E S S E N T I A L D R U G S MONITOR - WHOapps.who.int/medicinedocs/pdf/s4940e/s4940e.pdf · all...

Lessons on improving 2–4drug regulation

Some results from a WHO/ 4–7Health Action Internationaldrug pricing survey

Pooled procurement reducing 7–8costs in the Caribbean

Are dispensing prescribers 9a threat to appropriatemedicines use? A reportfrom Zimbabwe

Improving medicines use 10–11through Drug and Thera-peutics Committees

25 years of the Essential 12–17Medicines List: somepersonal perspectives

Latin America’s Drug 17–18Utilization Group

Making a difference: 19the work of the GlobalTB Drug Facility

Antiretroviral use in a South 20–21African township

Indonesia: educating the 22–23community on how toimprove self-medication

A drug use study at an 23Indian hospital

WHO’s Model Formulary 24

E S S E N T I A L D R U G S

M O N I T O REssential Drugs Monitor E D I T O R I A L

No 32 (2003)

WORLD HEALTH ORGANIZATION

The Essential Drugs Monitor is producedand distributed by the WHO Departmentof Essential Drugs and Medicines Policy(EDM). It is published in Chinese, Eng-lish, French, Spanish and Russian, andhas a global readership of some 300,000to whom it is free of charge. The Monitorcarries news of developments in nationaldrug policies, therapeutic guidelines, cur-rent pharmaceutical issues, educationalstrategies and operational research.

WHO�s Department of Essential Drugsand Medicines Policy seeks to ensure thatall people � wherever they may be � areable to obtain the drugs they need at a pricethat they and their country can afford; thatthese drugs are safe, effective and of goodquality; and that they are prescribed andused rationally.

All correspondenceshould be addressed to:

The EditorEssential Drugs MonitorWorld Health OrganizationCH-1211 Geneva 27, SwitzerlandFax: +41 22-791-4167e-mail: [email protected]

I N T H I S A N N I V E R S A R Y I S S U E :

T

25 years of essentialmedicines progress

“Essential medicines are those that satisfy the prior-ity health care needs of the population. They areselected with due regard to public health relevance,evidence on efficacy and safety, and comparativecost-effectiveness. Essential medicines are intendedto be available within the context of functioninghealth systems at all times in adequate amounts,in the appropriate dosage forms, with assuredquality and adequate information, and at a pricethe individual and the community can afford.”

The Selection and Use of Essential Medicines. Report of the WHOExpert Committee, 2002, including the 12th Model List of EssentialMedicines. WHO Technical Report Series No.914.

HIS special edition of the Essential

Drugs Monitor celebrates twenty-five years of the essential medicines

concept. The historic first meeting of theWHO Expert Committee on the Selec-tion of Essential Drugs took place inGeneva from the 17�21st October 1977.Today, more than 150 countries haveadopted the concept and developed theirown national lists of essential medicines.

This issue includes a keynote addressgiven by the Director-General of WHO,Gro Harlem Brundtland, at the 25th anni-versary celebrations in Geneva, affirmingthe Organization�s commitment to theessential medicines concept. Stressingthe concept�s relevance for all countries,developed and developing, she spokeof WHO�s two critical functions foressential medicines � global normativeguidance and technical support forMember States. Promoting equity andsustainability would be the focus ofmedicines work. Dr Brundtland went on

countries have banded together topool their drug procurement ac-tivities to reduce prices andguarantee a reliablesupply. Sri Suryawatidescribes a communitylevel programme in In-donesia to ensure thatmothers understandabout the medicinesthey purchase. This in-novative approach hasbeen carefully evaluatedand has been shown to bevery effective in changingknowledge and behaviour.On the other side of theworld, Birna Trap andEbba Holme Hansen report on a studyof dispensing doctors in Zimbabwe,showing that if prescribers dispensemedicines themselves there are signi-ficant differences in their practices!Articles from India and Latin America

of the first articles to describe the effectof using antiretroviral medicines in apoor community, with nurses deliveringmost of the care. Measuring the price of

to emphasise the Organization�sneed to remain evidence-basedand totally independent fromcommercial interests and fromindividual donor decisions.(See p 12 for the full speech).Margaretha Helling-Borda,who attended the first ExpertCommittee meeting (and laterbecame Director of the EDMprogramme), shares some ofher memories of that importantoccasion in 1977. Both thesearticles stress the point that se-lection is only one componentof assuring access and ensuringrational use.

Other articles in our special issue fo-cus on some of these different aspects.Francis Burnett from St. Lucia writes ofa long-term, successful system in the Car-ibbean in which a group of small island

focus on drug utilization research in thetwo regions.

The challenge of addressing AIDSin Africa is described by a team workingin Cape Town, South Africa. This is one

medicines is the subject of an-other article from South Africa,by Aarti Kishuna. She reportson the use of a new drug pricingsurvey methodology that willbe described in more detail inthe next issue of the Monitor.We also feature a 10-countrystudy of drug regulation, and adescription of the Global DrugFacility�s work to increaseaccess to TB medicines.

The range and geographicaldiversity of these articles reflectthat what started at a meetingin 1977 to select an essentialdrugs list has blossomed into a

global movement to ensure access to wellselected medicines to treat commondiseases in the most rational way. We canonly hope that the next 25 years sees suchprogress continued. ❏

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Issue No. 32, 2003

ROBLEMS related to the safety and quality of medicines exist in manydeveloping and developed countries, some result in tragedy, oftenwith children as the victims. Such incidents have a variety of causes:the use of products containing toxic substances or impurities; medi-

cines whose claims have not been verified; medicines with unknown andsevere adverse reactions; substandard preparations; or outright fake andcounterfeit products. Effective drug regulation is required to ensure thesafety, efficacy and quality of drugs, as well as the accuracy and appro-priateness of the drug information available to the public. A recent WHOpublication, Effective Drug Regulation: A Multicountry Study, reports on asystematic assessment of drug regulation in 10 countries. Its purpose is tosynthesize their experiences and draw generic conclusions from which theparticipating countries and others may learn. In this review we focus onthese important lessons.

Improving drug regulation

P

In spite of all the efforts made, lessthan 20% of WHO Member States arethought to have a well developed drugregulation system, and those that do aremostly industrialised countries. Of theremaining Member States, about 50%implement drug regulation at varyinglevels of development and operationalcapacity. The other 30% either have nodrug regulatory authority (DRA) in place,or have only a very limited capacity thatbarely functions. Studies in some coun-tries show that about 20% of tested drugproducts fail to meet quality standardsand that the prevalence of substandardand counterfeit drugs is higher in coun-tries where drug regulation is ineffective.WHO�s recent assessment of regulatoryperformances in selected countries andits publication of the results are timely

in the subsequent chapters, and discussesthe authority, capacity and organiza-tion of drug regulatory agencies. Chap-ters 6�10 address the main drugregulatory functions: licensing of manu-facturing, distribution and retail sale;inspection and surveillance; productassessment and registration; control ofdrug promotion and advertising; anddrug quality control laboratories. Each ofthese chapters contains parallel sectionscovering powers, process, personnel,financing, regulatory functions, and plan-ning and performance. Chapter 11 setsout concepts, methods and indicators forassessing regulatory performance, anddiscusses country performance in rela-tion to various aspects of regulation. Thebook concludes with key lessons andstrategies for improving drug regulation,focusing on building regulatory struc-tures and processes. It is the latter thatwe highlight here.

BUILDING REGULATORYSTRUCTURES

In some countries studied legislationomits or exempts certain areas of phar-maceutical activity from the scope ofcontrol. Since legal structures form thefoundation of drug regulation, regulatorygaps and new challenges should beaddressed by modifying or extending ex-isting legislation, or introducing newlegislation. Drug regulation should coverall products for which medicinal claimsare made, and all activities in the publicand private sectors associated with drugmanufacture, importation, distribution,dispensing and promotion.

Overall accountabilityIn some countries drug regulatory

functions are assigned to two or moreagencies, at the same or different levelsof government. The study showed thatsuch fragmentation was a potentialimpediment to regulatory effective-ness, with an increased risk of lapsesin implementation, duplication ofeffort, wastage of resources and evenconfrontation.

Ideally, drug regulatory structuresshould be designed so that a central co-ordinating body has overall responsibilityand is accountable for all aspects of drug

regulation for the whole country. How-ever, restructuring the entire DRA willrequire a substantial amount of time andeffort, and there may be a need for inter-mediate options that allow improvementsin an existing divided structure. Anothersolution is to establish official structuresfor coordination and information systemswithin existing organizations. A systemwith formal channels of coordination andinformation flow should be created tosupport drug regulatory decision-makingat national level.

Multiple functions and conflictsof interest

The study showed that some drugregulatory authorities have been assignedmultiple functions and so cannot focussolely on drug regulation. If the author-ity responsible for drug regulation isassigned non-regulatory functions, suchas manufacturing, procurement and/ordelivery of services, conflicts of interestmay occur in respect of mandates

overseas markets. For example, drugsmanufactured or imported by state agen-cies may not have to be registered,whereas those from private businessesdo. Such systems mean that products maynot conform to the standards set by theDRA. Also therapeutic goods manufac-tured for export may not be subject to thesame standards as those consumed lo-cally. Use of double standards in the caseof exported products raises questions offairness in international public health.

Regulatory toolsThe study revealed that not all drug

regulatory authorities make availabledocumented standard operating proce-dures for registration, and that even fewercountries have documented guidelinesand checklists for inspection. When suchtools are lacking, application of the leg-islation may become erratic and even leadto questions about the transparency oflaw enforcement.

Standards and guidelines should beestablished in written form for all drugregulatory functions. These tools shouldbe used to guide practice, and be madepublicly available in order to ensurethe transparency of the drug regulatoryprocess.

ResourcesOne of the study�s main findings is

that shortage of qualified personnel is thegreatest problem faced by drug regula-tory authorities, partly due to the salariesoffered to employees. Another factor maybe the limited pool of pharmaceuticalprofessionals in some countries becauseof a lack of places in pharmaceuticaleducation.

Human and financial resources arecritical for successful drug regulation, andgovernments should employ people withthe required specialist knowledge andskills. Employees must have integrity

Drug legislationIn general drug legislation must:

◆ define the categories of medicinal products and activities to be regulated;◆ state the missions and goals of drug regulation;◆ create the administrative bodies necessary for implementing drug regulation, and

define their structural and functional relationships;◆ state the roles, responsibilities, rights and functions of all parties involved in drug

regulation, including those of the regulators and the regulated;◆ define the qualifications and standards required for those handling drugs;◆ create mechanisms to ensure that all responsible parties are licensed and

inspected, and ensure compliance with drug legislation and with the standardsand specifications laid down for persons, premises and practices;

◆ define the norms, standards and specifications necessary for ensuring the safety,efficacy, and quality of drug products, as well as the appropriateness andaccuracy of product information;

◆ state the terms and conditions for suspending, revoking or cancelling licences toimport, manufacture, export, distribute, sell, supply or promote drugs;

◆ establish the administrative measures and legal sanctions that will be applied ifdrug legislation provisions are violated;

◆ create mechanisms for ensuring the transparency and accountability of drugregulatory authorities to the government, the public and consumers;

◆ create mechanisms for ensuring government oversight.

Box 1

In the countries reviewed, the drugregulatory authorities all: belong tothe government; are specialisedagencies; have centralised authority;employ advisory boards/committeesto provide technical support.

contributions to efforts to improve thissituation.

The publication, Effective Drug Regu-lation: A Multicountry Study, gives anoverview of the development of drugregulation in 10 countries, as well as theresources available and the strategiesused when the studies were conducted in1998�1999. An analysis of systems�strengths and weaknesses in the countries� Australia, Cuba, Cyprus, Estonia, Ma-laysia, the Netherlands, Tunisia, Uganda,Venezuela and Zimbabwe � is also pro-vided. Data collection was based onarchival studies and key informant inter-views, using a standardised tooldeveloped by WHO, and refined by theparticipating investigators and researchadvisers. The tool, which is included asAnnex 1 of the publication, is useful forcountries and organizations wanting toassess drug regulation performance.

The report includes a brief profile ofeach country, and compares a number ofbackground features relevant to drugregulation. It then presents conceptualframeworks to be used in the analysisand synthesis of overall drug regulation

Staff shortages appear to be aserious problem in all 10 countriesstudied. Difficulty in recruiting staffwas cited in six countries, while therewas difficulty retaining staff in four.

and resource allocation. Distribution ofhuman and other resources to coverall these functions has a significantimpact on the adequacy of support forregulatory activities.

Regulatory double standardsNot all drug regulatory requirements

are applied equally. Exemptions aresometimes made, depending on wherethe drug comes from, who manufacturedor imported it, where the drug is distrib-uted or whether it is sold on domestic or

A N N I V E R S A R Y I S S U E

3E S S E N T I A L D R U G S M O N I T O R

Issue No. 32, 2003

and should be well remunerated. This isparticularly important because regulationinvolves various stakeholders with com-mercial interests who may try to exertpressure on the authority in order to se-cure decisions favourable to themselves.Adequate and sustainable financingmechanisms are clearly crucial.

Government budget is the mainmeans of financing the DRA in eight outof the 10 countries, while all 10 DRAscharge fees for their services � althoughthe sum charged is almost always muchlower than the actual cost of performingthe regulatory function. Fees collectedby government-financed DRAs aretransferred to the government treasury.Countries vary both in the type of serv-ice for which fees are charged and in thelevel of fees. Only two of the 10 DRAsare entirely self-financed from theircharges.

Clearly, government resources aloneare insufficient to promote effective drugregulation in most of the countries stud-ied. The report recommends that DRAsin these countries should set fees at a levelthat reflects the real cost of drug regula-tory services, and should be allowed toretain the fees. The fee system shouldcover all services provided, including li-censing, inspection, quality control andcontrol of promotion and advertising. Butthe DRA should not be entirely depend-ent upon the fees charged for its services.Governments should be fully committedto ensuring the sustainability of drugregulation. Financing for the authorityshould therefore be structured so that abalance is struck between a sufficiently

procedures for products imported fromthose countries. Alternatively, it may de-cide to consider functions certified inthose countries as legally valid in its owncountry. Prioritisation and streamliningof work processes can be used to enhanceefficiency, with each product or facilityclassified according to its �risk�. Undersuch a scheme, products and facilitiesclassified as low-risk receive less intensescrutiny, freeing staff for high-risktargets.

BUILDING REGULATORYPROCESSES

Formal and informal sectorsThe study showed that drugs distrib-

uted through the informal sector receivelittle attention compared with thosedistributed through the formal sector.Counterfeit products, products of dubi-ous quality and faulty information �especially exaggerated claims of efficacy� are often widespread in the informalsector. It is very important that monitor-ing of pharmaceutical activities coversboth sectors.

Balance of prioritiesRegulatory functions should be car-

ried out in such a way that each receivessufficient attention and resources, butexperiences in the countries indicate thatdifferent functions receive varying de-grees of emphasis. Disparities are foundin three key areas:

Pre-marketing versus post-market-ing product assessment: Drug legislationin all the countries assigns two types ofpower to DRAs � the authority to assesspharmaceutical products and determinewhether they should be registered, andthe authority to monitor and changethe information and registration statusof a drug after it has been marketed.However, much more time is assignedto pre-marketing assessment than topost-marketing review. Yet even ifpre-marketing assessment has been thor-oughly conducted, it may be insufficientto guarantee the efficacy and, especially,the safety of drugs. Emphasis should alsobe placed on post-marketing surveillance.

Product registration versus regula-tion of distribution: The study showedthat product registration is considered amajor responsibility by all the DRAs. Incontrast, regulation of drug distributionand information does not seem to enjoythe same level of attention. This is par-ticularly so in countries where licensingand inspection of distribution channelsare assigned or delegated to anotheragency or another level of government.But the regulatory objective of ensuringpublic health and safety in the use of phar-maceuticals can be achieved only whenevery pharmaceutical activity operatesproperly, from the source to the user.

GMP versus distribution-channelinspection: In many countries,Good Manufacturing Practices (GMP)inspection receives more attention andresources than inspection of distributionchannels. But it is not in the interests ofthe consumer if a product that has beenproduced according to GMP is later storedand distributed under adverse conditions.Inspection of distribution channels shouldbe given equal emphasis, particularly in

countries where the drug distribution sys-tem has several intermediate levels andthe climate may be unfavourable.

ImplementationBesides structural constraints, such as

human and financial resources, the wayin which DRA employees perceive theirjobs and how they perform are key fac-tors in drug regulation performance.Staff need a clear sense of mission ifregulatory processes are to be pursuedconsistently.

Regulatory processes should be sys-tematically monitored in order to identifyproblems and determine whether actualactivities match those planned.

Assessment of DRA performanceSeveral approaches can be employed

to assess a DRA�s performance.Self-assessment: Self-assessment can

help an organization to learn about itsown strengths and weaknesses. A DRAthat routinely conducts self-assessmentand continuous quality improvementcan greatly enhance drug regulatoryperformance.

Review by supervisory body: Drugregulatory legislation normally specifiesthe official chain of command and thesupervisory body to which the DRA mustreport. Administrative and legislativesupervision is an important means ofaccountability if properly applied.However, supervision should not be usedas a means of political influence overlegitimate regulatory decisions.

Peer review: This involves setting upmechanisms for mutual review of drugregulation systems. It serves as a meansof external auditing, whereby the per-formance of one agency can be compared

Recommendations for effectivedrug regulation

◆ A clear sense of the mission of the regulatory authority is important in motivatingDRA staff to pursue regulatory processes in order to achieve drug regulation.Governments should state clearly the mission and objectives of drug regulation,so that it is easy to assess the attainment of intended objectives.

◆ Drug laws should be sufficiently comprehensive, covering all activities involvingdrug products and information, and they should be updated regularly.

◆ One central agency should be accountable for the overall effectiveness of drugregulation.

◆ Personnel engaged in drug regulation should have integrity and be appropriatelytrained and qualified. Human resources development programmes should bemade available to help staff to improve their knowledge and skills, and to enablethem to cope with developments in pharmaceutical science and technology. Staffshould also have access to the latest scientific and technological information tofacilitate their work.

◆ Appropriate standards and guidelines should be developed and used as tools forthe application of all regulatory processes. They should be freely available to allstakeholders, including the public, in order to increase the transparency of theDRA’s operations. The same standard of regulation should be applied to alldrugs, whether they are imported and/or manufactured by the public or theprivate sector, and destined for domestic consumption or for export.

◆ Sustainable financing is essential to promote effective drug regulation. Drugregulatory authority financing should strike a balance between fees covering thefull cost of services and government support. Fees should provide increasedrevenue to the authority, so that it can perform effectively, and serve to discour-age clients from “flooding” the system with applications that do not meet officialrequirements.

◆ Every regulatory function contributes to ensuring the safety quality and efficacyof drugs. The action taken by the authority should cover all drug regulatoryfunctions in a balanced fashion. Support for drug regulation should not becompromised by other non-regulatory tasks with which the DRA may also becharged.

◆ The regulatory process should be systematically monitored in order to identifyproblems and determine whether actual activities match the intended actions.Moreover, the DRA should become a learning organization, which routinelyconducts self-assessment and continuous quality improvement. There should beadministrative and legislative supervision in order to guarantee accountability.Peer review by drug regulatory authorities in other countries can serve as ameans of external auditing, whereby the performance of one agency can becompared with that of its peers.

◆ Any inefficiency in the regulatory process delays decision-making and may leadto shortages of critically needed drugs, thus endangering lives. Drug regulatoryauthorities should employ various strategies to increase efficiency of resourceuse. Examples include: prioritisation and streamlining of the work process; jobenlargement and job enrichment for regulatory staff; pooling of internationalinformation resources; and sharing and pooling of international quality controlresources.

◆ Drug regulatory authorities should communicate regularly with their clients. Theyshould also acknowledge the right of citizens to be provided with accurate andappropriate information on drugs marketed in their country. Educating citizensabout the efficacy, safety, quality and rational use of drugs will ultimatelyenhance the achievement of regulatory objectives.

Box 2

high fee to cover the cost of services andprovision of government support. Also,the salaries of DRA employees and theremuneration of expert committee mem-bers performing reviews should not bedirectly linked to specific fees or to theagency�s overall earnings. This will helpto ensure that regulatory decisions are notinfluenced by payment of fees.

The report recommends a numberof other possible ways of overcominghuman resources problems, includingmulti-skilling approaches and greatercoordination between the DRA andeducational institutions to increase thenumber of people with the requisiteskills. Module-based educational pack-ages could also be developed throughcollaboration between countries.

Pooling of information resources mayhelp to reduce the regulatory workload.Networks of information sources andusers may be built up to facilitate thetransfer of information and technologies,particularly between developed anddeveloping countries. Quality controllaboratories with sufficient capacity andwhich adhere strictly to good laboratorypractice could be accredited, and coun-tries with fewer resources send productsto them for testing. To reduce its work-load while not compromising on quality,a DRA may also identify countries withstrong drug regulation and waive some

Nine of the 10 countries studiedhave a system for monitoringadverse drug reactions, each basedon a voluntary reporting system byhealth professionals.

...cont’d on page 4 ➠

In addition to testing for pre-marketing quality control, the DRAlaboratories in six of the countriesalso collect drug samples for testingas part of post-marketing qualitysurveillance.



Issue No. 32, 2003

with that of others. Systems for interna-tional peer comparison of quality controllaboratories are one example, with pro-ficiency tests showing each participatinglaboratory how well it is performing incomparison with the others.

These approaches are not mutuallyexclusive: they may complement oneanother in appraising performance, aswell as helping to identify areas forimprovement.

The key to all review methods is thatperformance should be systematicallyand regularly assessed, to allow objec-tive and comprehensive appraisal andidentification of strengths, weaknessesand measures for improvement.

Communication with clientsand consumers

The DRA�s task is to serve the public

and its operations must be transparentto both clients (for example, drugmanufacturers) and to consumers. Com-munication with clients should be aroutine activity throughout the regulatoryprocess. Information on its functions andthe results of decisions should also becommunicated regularly to the public.

Consumer empowermentTraditionally drug regulation has been

considered as a process involving two ac-tors, the DRA and the regulated firms.But policies that foster such arrangementsrun the risk of encouraging corruption.Since consumers are the end-users ofdrugs, all drug regulatory efforts shouldlead, ultimately, to protection of the con-sumer. Consumer groups or publicinterest groups can contribute to theseefforts by participating both in the devel-opment of regulatory policies and inregulatory activities. They can act asindependent �attorney generals� and

Drugregulatorystructures

Drugregulatoryprocesses

Healthoutcomes

Drug regulationoutcomes

Environment

Environment

Good outcomes

Bad outcomes

positive

negative

positive

negative

• Better treatment of illness• Better prevention of

disease• Decreased morbidity and

mortality

• Safe, effective, good quality drugsavailable

• Appropriate information• Rational prescribing• Appropriate dispensing practice

• Substandard, counterfeit, toxic anduseless drugs

• Inappropriate information• Irrational prescribing• Inappropriate dispensing

practice

• Drug resistance• Treatment failure• Adverse drug reaction• Increased morbidity and

mortality

Inspection ofmanufacturersanddistributors

Productassessmentandregistration

Monitoringqualityof drugs

Controlof drugpromotionandadvertising

Adversedrugreactionmonitoring

CentralState/provinceDistrictCommunity

Regulation level

((((

Policy, legislation, regulationsHuman resourcesFinanceInfrastructure

Administrative elements

((((

StandardsSpecificationsGuidelinesProcedures

Technicalelements

((((

Regulatory functions

Licensing ofpremises,practicesandpersons

Figure 1Study framework showing key components of drug regulation

Figure 2Drug regulation: interconnections between structures, processes andoutcomes

Drug pricing surveyin KwaZulu-Natal

D➢ AARTI KISHUNA*

IVIDED into nine provinces, South Africa has a population of approxi-mately 45 million1, about 80% of whom rely on public sector healthservices. The rest use the private sector, which includes a very smallprivate-not-for profit element. In 1996 South Africa introduced its Na-

tional Drug Policy,2 and also adopted the Essential Drugs Programme, currentlyonly implemented in the public sector.3 Only drugs registered by the SouthAfrican Medicines Control Council can be used in the country.

Patients who attend public sector hos-pitals are charged a fee that is inclusiveof the drugs dispensed, while at primarylevel patients are treated free of charge.The majority of patients attending privatesector facilities have medical insurance.Most health care providers are contractedto these insurance companies and makedirect claims to them for services provided,including the drugs that are dispensed.

The pilot study on drug pricing tookplace in the Province of KwaZulu-Natal,which has a population of approximately8 million.1 In the public health sectorthere are approximately 300 clinics4 and

Centrally:• confirming list of drugs• sampling geographical areas

+ public sector facilities• seeking permission• data collection team + training• collecting public sector drug prices

In the field:• selecting private sector facilities• collecting private sector drug prices

• entering data• analysis• results• reporting

60 hospitals.1 There are also 28 privatehospitals1, and the majority of privatesector dispensers are either retail phar-macists or dispensing doctors. Theflow-chart below shows the main drugpricing survey activities undertaken inKwaZulu-Natal.

Data were collected at selected facili-ties from the public and private sectorsin four geographical areas. As the private-not-for profit sector is small it wasexcluded from the study. Public sectorhospitals were chosen from a list offacilities, according to the area. The pri-vate sector included the nearest retail

pharmacy and dispensing doctor withina five kilometre radius from the publicfacility. The study also included a privatehospital in each geographical area.

Drug procurement in the public sec-tor is through a closed tender system.

The tender process is managed nation-ally with input from the provinces. Oncethe tenders are awarded, provinces orderdirectly from the recommended suppli-ers who deliver to the provincial depots.Health care facilities are charged the priceof the drugs plus a fixed levy by the de-pot. The prices paid by all health carefacilities are the same, so data were notcollected at individual public health fa-cilities but from the provincial depot.Table 1 shows the number of facilitiessampled per geographical area.

Drug prices

In analysing drug prices, ratioswere used, with South African pricescompared with international indexprices (reference prices) which had beenconverted into local currency. The inter-national index prices were taken fromManagement Sciences for Health�sInternational Drug Price IndicatorGuide 2000,4 and the Australian Phar-maceutical Benefits Scheme.5 Survey

Improving drug regulation...cont’d from pg. 3

protect the public from undue pressurefrom industry or politicians. Supportfrom the DRA and other organizations isneeded to empower consumers so that theycan make an appropriate contribution.

Educating consumers about the effi-cacy, safety, quality and rational use ofdrugs can also enhance the achievementof regulatory objectives.

Effective Drug Regulation: AMulticountry Study does not intend toprescribe ready-made strategies for drugregulation. Rather it sheds new light onthe regulatory environment, providing newperspectives on constraints and optionsfor improving the way systems work.

WHO�s study reinforces the message thatif public health is to be protected gov-ernments must establish strong nationaldrug regulatory authorities with a soundorganizational structure and the legalpower and resources to carry out theirduties. ❏

Effective Drug Regulation: A MulticountryStudy, by S. Ratanawijitrasin and E.Wondemagegnehu is available fromWorld Health Organization, Marketing andDissemination, CH 1211 Geneva 27, Swit-zerland. Tel: + 41 22 791 2476, fax: 4122 791 4857, e-mail: [email protected]: Sw.fr.20/US$18, and in developingcountries Sw.fr.14.



Issue No. 32, 2003

KwaZulu-Natal Table 1Number of facilities sampled per area

Area 1 Area 2 Area 3 Area 4

5 public health 5 public health 5 public health 5 public healthfacilities (1) facilities (1) facilities (1) facilities (1)5 retail 4 retail 5 retail 5 retailpharmacies (5) pharmacies (2) pharmacies (5) pharmacies (5)1 private 1 private 1 private 1 privatehospital (1) hospital hospital (1) hospital5 dispensing 5 dispensing 5 dispensing 5 dispensingdoctors (1) doctors (1) doctors (3) doctors (5)

A total of 43 private sector facilities were sampled. Data were collected from 29. The numbers in bracketsindicate the number of facilities, from those sampled, that actually provided data. All the facility managerswere asked for permission to carry out the survey.The information from the private hospitals was included with the data from the retail pharmacies, for analysis,since each private hospital has a private retail pharmacy.For the public sector data were collected from the depot.Time constraint was the reason most often given by those facilities that did not want to participate in thesurvey.Data were collected by four data collectors, all based in the selected geographical area.Data collection, in the field, was undertaken in a week.

KwaZulu-Natal Table 2Average price difference for the three sectors compared with thereference price

Sector Brand Most sold generic Cheapest generic

Private 24.26 (0.31–119) 14.05 (1.8–56.19) 13.86 (1.0–56.19)Public 1.64 (0.05–16.91)

The figures in brackets indicate the range of ratios that exist from the lowest to the highest.

The public sector procures just one product.

KwaZulu-Natal Table 3Public sector drug price components of amoxicillin, 250mg capsule,500s

Tariff Size as a percentage Cost

R60.72 (ex-manufacturer)Value added tax (VAT) 14% R70.60 (ex-manufacturer,

including VAT)Distribution levy 6% R75.11 (price charged to

institutions by depot)

KwaZulu-Natal Table 4Private sector drug price components of amoxicillin, 250mg capsules,500s

Tariff Size as a percentage Cost

R61.19 (ex-manufacturer towholesaler, excluding VAT)

Wholesaler mark-up 34.43% (recommended R93.33 (wholesaler sellingmaximum is 21.22%) price to retailer, excluding VAT)

Retail mark-up 41.52% (recommended R159.60maximum is 50%. Discountsvarying from 0–30% canbe offered to cash patientsor medical insurance)

VAT 14%Dispensing fee, 0.5%–1% R161.08 (price paid bybroken bulk etc. patient)

The ex-manufacturer�s price was collected from the wholesaler. The prices quoted above in the cost column,apart from the last row, do not include VAT. However, each supplier, from manufacturer to wholesaler toretailer, charges 14% VAT on their mark-ups. These are then claimed back from the receiver of revenue.(8 Rand = US$1 approximately).

Price composition

One product, amoxicillin 250mg cap-sules, pack size 500, was followedthrough the distribution chain, in bothsectors, to determine the components thatmake up the final price.

Table 4 shows that the patient endsup paying approximately 2.6 times themanufacturer�s selling price of thedrug. Information on how the manu-facturer makes up the price of theproduct, before it leaves the factory, wasunavailable.

Affordability

Table 5 shows the number of days thelowest paid government worker needs towork in order to afford a course ofamoxicillin treatment in the private sec-tor. The annual wage of the lowest paidgovernment worker is US$2793.91(Rand 24036),6 and the daily wage isUS$ 7.78.

Results indicate that the brandedproduct costs the lowest paid governmentworker the most, while the cheapest ge-neric costs the equivalent of half a day�spay for a course of treatment.

Need for change

The survey results show that SouthAfricans are paying high prices for theirdrugs, especially in the private sector.

The following recommendations aremade in the light of these findings:

➤ All sectors need to improve theirprocurement practices. A standardreference price should be agreed uponto assist this process.

➤ A review of the mark-ups levied bywholesalers and retailers is needed.Also manufacturers need to be moretransparent with their exit prices. For-tunately this process is presentlyunderway in South Africa as a resultof the National Drug Policy�s pricingcomponent.

➤ The government needs to reviewits levying of VAT on essentialmedicines, as it is the patient whoultimately carries the final burden ofthis tax. ❏

* Aarti Kishuna is a consultant on publichealth and a member of the Advisory Boardof the WHO/HAI drug pricing project.

References

1. Day C, Gray A. Health and related indicators. SouthAfrican Health Review 2001. Durban: Health Systems;2001. Available at URL: http://www.hst.org.za/sahr/

2. National Department of Health. National drug policyfor South Africa. Pretoria: National Department ofHealth, South Africa; 1996.

3. National Department of Health. Essential Drugs Pro-gramme, South Africa, 1998. Pretoria: NationalDepartment of Health 1998. Available at URL:www.sadap.org.za/edl/

4. MSH. International drug price indicator guide. Bos-ton: Management Sciences for Health; 2000. Availableat URL: http://erc.msh.org

5. Australian Department of Health and Ageing. Austral-ian Pharmaceutical Benefits Scheme 010801. Woden:Australian Department of Health and Ageing.Available at URL: www.health.gov.au/pbs/

6. Pick W, Conway S, Fisher B, Kgosidintsi N, Kowo H,Weiner R. Measuring quality of care in South Africanclinics and hospitals. Technical Report to Chapter 14of the 1998 South African Health Review. Durban:Health Systems Trust; 1998.


KwaZulu-Natal Table 5Number of days required towork to afford a course ofamoxicillin treatment

Drug name Cost in days

Amoxicillin Original 1.37Most sold 0.66Cheapest 0.54


results are given in Tables 2�5.From Table 2 it is clear that the

branded products, in the private sector arethe most expensive, with one product 119times more expensive than the referenceprice. In the public sector prices areapproximately 1.64 times higher than thereference price, which is to be expectedas public sector prices are much cheaperthan those in the private sector.

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SOME PRELIMINARY FINDINGSFROM OTHER COUNTRIES

South Africa was one of a number of countries that conducted field tests as part ofthe WHO/Health Action International project to develop a drug pricing survey meth-odology. This will be a standardised method to collect and analyse medicine pricesand price composition within a country at a point in time and over time, and betweencountries. It is felt that armed with reliable analyses of medicine prices governments,NGOs and others can better evaluate the impact of pricing policies and be in a strongerposition to negotiate for more equitable prices. Below we present some prelimi-nary findings from other countries participating in the study. In Monitor No.33we will have a longer report on the project and on the accompanying manual,Medicine Prices: A New Approach to Measurement, which will be published inMay 2003.

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Measuring drug prices in Sri Lanka

The survey was carried out in four districts, with 15 pharmacies randomlysampled in each district. Price information was sought on 30 drugs, for both theirinnovator brand and the generic version most commonly sold in the country. Therewere 10 drugs on the survey list that were found in both brand and generic versions,in the targeted strength, in at least 3 or more surveyed facilities. Results in SriLanka reveal that the Median Price Ratio (MPR) for the 10 innovator brand nameproducts was 4.41, while the MPR for the same 10 most sold generic drugs was 1.19,just 19% over the international price. The lowest MPR among the 10 generics was0.14 (meaning that the local price was 14% of the international reference price), whilethe lowest MPR for brands was 1.46 (local price 46% over reference price). Thehighest brand MPR suggests that brand prices reach as high as six and a half times theinternational generic reference prices.


Issue No. 32, 2003

Drug pricing survey... cont’dfrom pg. 5

Armenia Table 2Affordability of monitored drugs in Armenia

Monitored Drugs Cost of course therapy Lowest paid government worker

ARD US$ Necessary Possible to buyto work/ Rice Sugar

day kg kg

Most expensive drugsAciclovirBrand drug 85963 154 148.4 318 344Most sold generic 44687 80 77.1 166 179Lowest priced generic 34536 62 59.6 128 138CeftriaxoneBrand drug 62426 111 107.7 231 250Most sold generic 39530 71 68.2 146 158Lowest priced generic 34180 61 59.0 127 137SimvastatinBrand drug 34509 62 59.6 128 138Most sold generic 34262 62 59.1 128 138Lowest priced generic 34262 62 59.1 128 138DiclofenacBrand drug 28635 51 49.4 106 115Most sold generic 5472 10 9.4 20 22Lowest priced generic 4121 7 7.1 15 17FluoxetineBrand drug 28707 51 49.5 106 115Most sold generic 18941 34 32.7 70 76Lowest priced generic 16573 30 28.6 61 66BeclomethasoneBrand drug 21173 38 36.5 78 85Most sold generic 14868 27 25.7 55 60Lowest priced generic 14868 27 25.7 55 60RanitidineBrand drug 11234 20 19.4 42 45Most sold generic 1987 3.5 3.4 7 8Lowest priced generic 1865 3 3.2 7 8The cheapest drugFurosemideBrand drug 227 0.4 0.4 0.8 0.9Most sold generic 143 0.3 0.2 0.5 0.6Lowest priced generic 128 0.2 0.2 0.5 0.6Mean of republic levelBrand drugs 20728 37.0 35.8 77 83Most sold generic 9731 17.4 16.8 36 39Lowest priced generic 8776 15.7 15.1 32 35

ARD = Armenian dram (national currency).

Armenia Table 1A regional analysis of drug price ratios in the Armenian pricingsurvey

Marzes Mean of All Maximum of all Minimum of allPharmacies pharmacies pharmacies

YerevanBrand drugs 4.6 14.1 0.3Most sold generic 3.2 19.3 0.2Lowest priced generic 2.8 19.3 0.2

KotaykBrand drugs 3.9 9.6 0.2Most sold generic 2.8 16.1 0.2Lowest priced generic 2.6 16.1 0.2

ShirakBrand drugs 4.2 12.2 0.2Most sold generic 3.4 16.8 0.2Lowest priced generic 3.1 16.8 0.2

SyunicBrand drugs 5.9 11.3 0.3Most sold generic 3.2 11.3 0.3Lowest priced generic 3.1 11.3 0.3

TotalBrand drugs 4.6 14.1 0.2Most sold generic 3.2 19.3 0.2Lowest priced generic 2.8 19.3 0.2


Some results from ArmeniaThe pilot study took place in Armenia in October and November 2001, with

40 private for-profit pharmacies sampled, 65% of them in the capital, Yerevan,and the rest in three regions (known as Marzes). Table 1 gives a regional levelanalysis of drug prices.

Relating drug prices to people�s earnings, the study found that the highest pricefor an average length course of a branded version of aciclovir was US$154 (see Table2), meaning that the lowest paid Government worker in the country would have towork for 148 days to pay for the course. The same money would buy 318 kg of rice or344 kg of sugar, enough for 10 years. In the case of the cheapest generic drug theprice of a course of treatment comes down 60% � not enough to solve the problem formost Armenians.

M. Aristakesyan.

Sri Lanka TableDrug price variations across Sri Lanka: medians, for different geographic regions, of private outlet prices(expressed as a ratio over international generic supplier price)

Median Price Ratio found within Region

Colombo Kegalle Matale Moneragala MaxMPR/Drug Name Drug type MedPR MedPR MedPR MedPR MinMPR*

Amoxicillin Innovator Brand 6.56 6.56 6.56 6.10 8%Amoxicillin Most Sold Generic 1.16 1.16 1.16 1.16 0%

Beclomethasone inhaler Innovator Brand 1.46 1.46 1.38 1.46 6%

Captopril Most Sold Generic 0.47 0.47 0.47 0.49 4%

Ciprofloxacin Most Sold Generic 1.23 1.24 1.23 1.24 1%Cotrimoxazole suspension Innovator Brand 6.35 6.74 5.60 6.74 20%Furosemide Innovator Brand 3.70 3.70 3.70 3.41 8%Furosemide Most sold Generic 0.81 0.81 0.81 0.81 0%Ibuprofen Innovator Brand 4.68 4.70 4.73 3.97 19%Nifedipine Most Sold Generic 1.40 1.09 1.06 1.14 32%Omeprazole Most Sold Generic 0.14 0.13 0.14 0.15 10%Prednisolone Most Sold Generic 0.89 0.89 0.89 0.89 0%Ranitidine Innovator Brand 5.65 5.65 5.65 5.59 1%Salbutamol inhaler Innovator Brand 2.83 2.83 2.83 2.83 0%Salbutamol inhaler Most Sold Generic 1.61 1.62 1.62 1.62 1%

* This column gives the relative increase going from the minimum to the maximum from the other 4 columns.

The table shows price variationacross regions within Sri Lanka. Theseare all the targeted drug products thatwere found at several facilities in eachof the four survey regions. MedianMPRs within regions are presented.Several drug products are preciselyconsistent in terms of price across re-gions. However, for other drugs, suchas cotrimoxazole, ibuprofen and nife-dipine, price differences between regionsas high as 32% were found for the sameproduct.

R. Wickremasinghe, K. Balasubrama-nium, U. Jayarathna, S. Jayarathna, C.Abeywardena, S. Ranwella, A. De Silva,B. Hettiarachchi.

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■ ■ ■ ■ ■

shows that there were only four drugswith prices lower than the internationalmedian, all of which are available generi-cally and have been used in Kazakhstanfor some time. Fourteen out of 49 drugs

The survey in KazakhstanIn Kazakhstan the monitoring

survey of prices and availability of85 medicines in 21 pharmacies inKaraganda City was conducted from

December 2000 to May 2001.A cost calculation per unit was made,

with a unit defined as a tablet/capsule,an ampule, a vial, or gram of ointment.

The Table on the following page

(29%) were 100�199% higher than theinternational median; 21 out of 49 drugs(43%) were 200�499% higher; and 10 ofthe 49 drugs were 500�700% higher.T. Nurghozian.


Issue No. 32, 2003

F➢ FRANCIS BURNETT

INANCIAL constraints have made it increasingly difficult for developingcountries to adequately finance the supply of drugs to health facilities.The countries comprising the Organisation of Eastern Caribbean States(OECS) have recognised that improving the use of existing resources

could be achieved by efficient procurement practices. Of the four areas ofdrug supply management cycle (selection, procurement, distribution, and use)efficient procurement provides the greatest opportunity for cost-savings.1

The OECS/Pharmaceutical Procurement Service (OECS/PPS) is a self-financing public sector monopsony or buyers’ cartel that covers its operatingcost from a 15% surcharge. This article considers the success of the OECS/PPS, (formerly the Eastern Caribbean Drug Service) in implementing improvedpharmaceutical procurement as a cost containment strategy, and outlines es-sential elements for successful pooled procurement for other resource-constrainedcountries.

Reducing costs throughregional pooled procurement

The core function of the OECS/PPSis the pooled procurement of pharma-ceuticals and medical supplies for thenine Ministries of Health (MOHs) of theOECS countries. During the 2001/02tender cycle, the annual survey on a mar-ket basket of 20 popular drugs showedthat the regional prices were 44% lowerthan individual country prices2 (Figure1). The continuous annual cost-savingsaccrued after 16 years of the joint pur-chasing arrangement have reinforcedthe Procurement Service as an excellentcost-benefit model of economic and func-tional cooperation among OECS membercountries.

Centralised tenderThe OECS/PPS presented suppliers

with a public sector monopsony or a pur-chasing cartel so that products tenderedby the Service are purchased exclusivelythrough annual contracts. Prior to theestablishment of OECS/PPS, the OECScountries purchased drugs individuallyfrom suppliers by direct negotiation. Thecost of pharmaceuticals in any countrydepended on the following factors: the

professional attitude andnegotiating skills of thesupplies officer, the gov-ernments� payment trackrecord and the sourceof supply. Consequently,drug prices for similarproducts used to varywidely among OECScountries.

The PharmaceuticalProcurement Serviceoperates a centralised,restricted tendering sys-tem in which all ap-proved suppliers arepre-qualified by a ven-dors� registration question-naire. Pre-qualification isnecessary to assess thequality standards, techni-

monitors delivery and supplier perform-ance. OECS/PPS does not warehousesupplies, but instructs suppliers to shipconsignments directly to participating

Anguilla

AntiguaBarbuda

British VirginIslands

Puerto Rico

Dominica

Grenada

Montserrat

St. Kittsand Nevis

St. LuciaSt. Vincentand theGrenadines

Barbados

Tobago

Trinidad

ArubaBonaire

Turks & CaicosIslands

Haiti

DominicanRepublic

Guadeloupe

St. Martin

Martinique

St. Croix

Caribbean Sea

OECSCountries

Political will andfinancial commitment

Political will was an essential in-gredient for success, with the PrimeMinisters of the Eastern Caribbean Statesagreeing to establish the OECS/PPS in1986. The countries deposited one-thirdof their annual pharmaceutical budget toindividual country drug accounts at theEastern Caribbean Central Bank (ECCB)in order to assure prompt payment tosuppliers and to maintain a revolvingdrug fund. This was a concrete sign ofpolitical will and financial commitment.

Establishing OECS/PPSThe OECS/PPS is an agency of the

OECS, a formal grouping of nine EasternCaribbean countries: Anguilla, Antiguaand Barbuda, British Virgin Islands,Dominica, Grenada, Montserrat, St. Kittsand Nevis, St. Lucia and St. Vincent andthe Grenadines. Their combined popu-lation is approximately 550,000. TheOECS/PPS was established under aproject funded by USAID, and by 1989the scheme was financially self-sufficient.

55

50

45

40

35

30

25

BVI

St. Lu

cia

Antig

ua

St. Ki

tts

St. Vi

ncent

Dominic

a

Montse

rrat

Angu

illa

Grenada

% un

it co

st re

ducti

on

Country

Figure 1Average % unit cost reduction for a market basket of 20 populardrugs 2001/2002 compared with individual country prices

cal competence and financial viabilityof competing suppliers. After solicitingbids from over 75 international suppli-ers, the Service awards annual contracts,places orders directly with suppliers, and ...cont’d on page 8 ➠


Kazakhstan TableMedian drug prices in Karaganda, compared to the international median – Average of December 2000 and May 2001

Median drug prices, in Karaganda compared to international median (MSH) December 2000 – May 2001*

Less than international median prices % 100–199% % 200–499% % More than 500–7000% %

Ciprofloxacin 19 Ascorbinic acid 117 Nystatin 204 Phenoxymethyl-penicillin 567Bromhexine 29 Tetracycline ointment 128 Ergocalciferol 214 Oral rehydration salts (Rehidron) 574Papaverine 54 Salbutamol 131 Cephazolin 227 Amoxicillin 644Propranolol 74 Ampicillin 133 Acetylsalicylic acid 229 Amitriptylline 661

Gentamicin 137 Prednisolone 231 Benzatinbenzyl-penicillin 672Vitamin A 142 Captopril 239 Diazepam 830Nifedipine 153 Theophylline 247 Metronidazole 883Chloramphenicol 160 Sulfadimezine 249 Hydrochlorothiazide 1130Furosemide 178 Heparin 253 Mebendazole 3964Verapamil 180 Spironolactone 256 Aciclovir 6803Erythromycin 186 Nalidixic acid 276Betamethasone 189 Paracetamol 322Diphenhydramine 192 Doxycycline 333Rifampicin 194 Cimetidine 343

Betamethasone 346Folic acid 354Glibenclamide 356Atenolol 406Indometacin 420Digoxin 428Co-trimoxasole 489

* Of 60 main list drugs, only 49 were in theInternational Drug Price Indicator Guide.

Kazakhstan drug pricing survey continued


Issue No. 32, 2003

countries which in turnreimburse their respectiveEastern Caribbean CentralBank (ECCB) drug ac-counts. The procurementand payment cycle is shownin Figure 2.

Recognising the successwith the pooled procurementof pharmaceuticals, OECS/PPS has rapidly expanded itsproduct portfolio to includemedical supplies, contracep-tives and x-ray consumables.The Service has now been

1.00.90.80.70.60.50.40.30.20.10.0

St. Ki

tts

Montse

rrat

Angu

illa BVI

Antig

ua

Dominic

a

Grenada

St. Vi

ncent

St. Lu

cia

US$

millio

ns

Country

Figure 3Annual value of purchases for OECS 2001/2002

an unreliable supplier mayraise the cost of a drug toseveral times the originalcontract price.3 Apart fromthe cost implications, poorsupplier performance canseriously hurt the credibilityof health programmes anddemoralise health workers.

Prior to the adjudicationof contracts, the past per-formance of suppliers isreviewed in detail. The fac-tors considered in evaluatingsupplier performance includedelivery times, the numberof partial shipments per pur-chase order, expiration dates,

comprehensive quality assurance pro-gramme to ensure that each imported drugis efficacious and acceptable. The pro-gramme encompasses pre-qualificationof selected suppliers, contractual pur-chasing agreements, and regular testingof priority drugs at three laboratories. TheOECS/PPS Tenders Sub-committee hasshort-listed 13 critical drug entities withinherent bio-availability problems in-cluding phenytoin, digoxin, warfarin andslow release oral dosage forms.

The OECS/PPS produces a biennialRegional Formulary Manual which is acompilation of core essential medicinescommon to the nine participating mem-ber states. A core list of essential drugshas also significantly reduced wastagebecause funds are not tied up in overstocks and non-essential items. Themanual is not merely a drug list, but con-tains drug information to aid prescribersin appropriate drug use.

Lessons for other countriesThe experience of the OECS/PPS,

after 15 years of successful centralisedtendering for pharmaceuticals and relatedmedical supplies, has demonstratedthat improved procurement can reducecosts and enhance the efficiency of healthservice delivery. Following a WHO-sponsored workshop in Fiji in April 2001,seven Pacific islands have developed

Some keys to the success ofOECS pooled procurement

◆ Political will and financialcommitment

◆ A core list of essential drugs toreduce wastage

◆ Participatory decision-making

◆ Careful selection of suppliers

◆ Prompt payment of suppliers

◆ Provision of training and techni-cal assistance to participatingcountries, including a qualityassurance service

Reducing costs...cont’d from pg. 7 Figure 2

OECS/PPS procurement and payment cycle

Aggregate CountriesForecast (Sept)

Reimburse Accounts(Continuous)

Prompt Payment toSuppliers (Continuous)

Place Orders(Jul, Oct, Feb)

Invite Tenders(Nov)

Award Contracts(Mar)

a three-year action plan to pursue thepooled procurement of pharmaceuticalsalong the OECS/PPS model.

Against the background of severe dif-ficulties that are confronting the globaleconomy and the subsequent negativeimpact on developing countries, othercountries should explore all strategies touse their scarce health sector resourcesefficiently. Better procurement methodshave been shown to produce significantcost-savings. ❏

Francis Burnett is Managing Director,OECS/PPS, P.O. Box 3093, Castries, St.Lucia. Tel: +758 452-5058/452-5895, fax:+ 758 453-0227, e-mail: [email protected]

References1. World Health Organization. Financing essential drugs:

report of a WHO Workshop in Harare, Zimbabwe.Geneva: World Health Organization; 1998.

2. Organisation of Eastern Caribbean States. Pharmaceu-tical Procurement Service Annual Report 2001. St.Lucia: OECS; 2001.

3. Quick JD, Rankin JR, Laing RO, O�Connor RW,Hogerzeil HV, Dukes MN, Garnett A, eds. Managingdrug supply, 2nd ed. West Hartford CT: KumarianPress; 1997.


mandated to explore the feasibility ofpurchasing dental and laboratory sup-plies. During the 2001/2002 tender cycle,the Unit purchased US$3.5 million worthof supplies for the nine OECS memberstates2 (see Figure 3).

Organizationaldevelopment andinstitutional alliances

The ECCB, the monetary authorityfor the stable Eastern Caribbean dollar,facilitated the prompt payment of theforeign exchange to suppliers at no addi-tional cost to participating countries. Theformal country-based committees ofthe OECS/PPS, ensure participatorydecision-making and commitment byMinistries of Health. The OECS/PPSPolicy Board comprises Ministers ofHealth (assisted by their Permanent Sec-retaries), the OECS Director General, theECCB representative and the OECS/PPSManaging Director; the Board exercisesoverall responsibility for the Unit�sPolicy directives.

Two sub-committees report to thePolicy Board: the Technical AdvisoryCommittee (TAC) and Tenders Sub-Committees. The TAC comprises a seniordoctor and the Supplies PurchasingOfficer from each Ministry. The TendersSub-Committee is a subset of TAC andincludes only the Supplies Officer fromeach country. OECS/PPS� managementis part of the sub-committees; the PolicyBoard and the Sub-Committees meet an-nually and are chaired on the principalof alphabetical rotation by host country.These formal relationships are central tothe participation and ownership ofOECS/PPS� constituent countries. In ad-dition, the collective decision-making ofthe Tenders Sub-Committee reduces thepossible influence by drug company rep-resentatives on the adjudication process.

The tendered items are extracted fromthe OECS/PPS� Regional Formulary andTherapeutics Manual which is reviewedannually by TAC. The Tenders Sub-Committee reviews bid offers and awardscontracts to successful suppliers. Thepooled procurement list represents largevolume and/or high cost items for whichthere is a consistently high demand.

Choice of currency,foreign exchange andterms of payment

The OECS/PPS solicits bids in USdollars to provide one standard monetaryunit for easy price comparison. The

Eastern Caribbean (E.C.) dollar is peggedto the US dollar at a rate of 2.7 and hasremained stable at this rate for the last25 years. The use of the US dollar pricesthrough the OECS/PPS procurement sys-tem allows OECS countries to forecastdrug costs in the E.C. dollar withoutconcern about fluctuations betweeninternational currency, or between theE.C. dollar and the U.S. dollar. Thestability of the E.C. dollar and theavailability of the US dollar are bothadvantages that many developingcountries, including some Caribbeancountries, do not have.

One of the most critical elements ofOECS/PPS� initial success in reducingthe cost of pharmaceuticals was the abil-ity to pay suppliers promptly in foreignexchange within 60 days of receipt ofgoods at country-level. In recent years,however, the reputation for promptpayment which OECS/PPS initially es-tablished has become tarnished becauseof slow reimbursement of the countrydrug accounts by some member countrieswhich are experiencing economic diffi-culties. Suppliers responded to tardypayments by withholding shipmentsto both defaulting and non-defaultingcountries.

Past performanceof suppliers

The selection of suppliers has a pro-found impact on both the quality and costof drugs. Inadequate quality assurance inthe selection process may result in thepurchase of drugs that are ineffective andunsafe. Hidden costs caused by late de-liveries, default on confirmed orders,losses due to poor packaging, short ex-piry date and other factors attributable to

the quality of packaging and labelling,the quality of documentation, quality as-surance of products and proficiency ofthe customer service department.

Other OECS/PPS benefitsApart from pooled procurement,

OECS/PPS provides the countries witha wide range of related services, whichinclude training and technical assistance,a common drug formulary manual, drugutilisation studies and quality assurance.

OECS/PPS has regularly conductedContinuing Medical Education (CME)seminars in the member states to keephealth practioners up-to-date on thebest practices of rational drug use. Inconjunction with CME seminars, theService has conducted a series of drugutilisation reviews on chronic diseasessuch as hypertension, diabetes mellitus,epilepsy, mental disorders and asthma.The purpose of the reviews is two-fold:to assess doctors� prescribing practices,and to devise intervention strategies toenhance prescribing behaviour.

Since inventory control is an impor-tant aspect of drug supply management,OECS/PPS has convened seminars oninventory management to ensure that thehealth facilities have a regular supply ofquality pharmaceuticals. In addition,the countries have been equipped withINVEC, a highly sophisticated tailor-made database computer programme,that maintains a perpetual inventoryrecord of all issues and receipts. TheOECS countries have now developedbetter techniques for forecasting quanti-ties which have decreased the incidenceof stock outs, expired items, obsolescenceand expensive emergency orders.

OECS/PPS has implemented a


Issue No. 32, 2003

P➢ BIRNA TRAP AND EBBA HOLME HANSEN*

RESCRIBING and dispensing are two important aspects of access tomedicines. Although respective roles differ according to circumstances,it is generally accepted that dispensing is an area of competence ofpharmacy staff rather than the medical profession. In many countries,

the functions of prescribing and dispensing are kept separate, principally toavoid a conflict of interest on the part of the prescriber, who could profit fromboth prescribing and selling medicines. This separation also optimises rational-ity of therapy by having pharmacy staff or pharmacists, who are specialists inthis area, review prescriptions and ensure good practices in dispensing. How-ever, prescribers who also undertake dispensing can provide an importantalternative access to medicines in areas where there are no pharmacy services,so dispenser prescribing is common in many developing countries, especiallyat primary health care level.

Dispensing prescribers – a threatto appropriate medicines use?

appropriateness of the prescribed treat-ment. A score sheet was developed basedon assessment by a panel of experts, andthis served as a reference for the assess-ment of appropriate prescribing of theantibiotic, cotrimoxazole.

Major differencesThe study identified major differences

between the prescribing of DDs andNDDs. DDs prescribed significantlyhigher amounts of medicines, injections,antibiotics, mixtures, cough prepara-tions and analgesics per patient thanNDDs1,2,3. The higher prevalence of pre-scriptions was strongly associated with�symptomatic treatment� (i.e. a drug wasprescribed for every symptom), generalover-prescribing of antibiotics and pre-scription of medicines with lower clinicalvalue2,3.

Injections, particularly procaine peni-cillin, were prescribed three times morefrequently by DDs than by NDDs in thetreatment of upper respiratory tract in-fection3. DDs� choice of antibiotics inthe treatment of these infections was ingeneral appropriate. When compared toNDDs, the antibiotics most frequentlyprescribed by DDs were chloramphe-nicol and aminoglycocide3. However,sub-curative doses of antibiotics wereprescribed to almost one-fifth of DDs�

patients. Sub-curative dosages of cotri-moxazole were prescribed two and ahalf times more frequently by DDs thanNDDs � in 23 % of encounters versus9%2. DDs prescribed analgesics andpsycholeptics more frequently in treat-ment of upper respiratory tract infectionthan did NDDs3. Consultation time wasshorter for DDs compared to NDDs � 8.7minutes versus 13.0 minutes.

The study analysed some of the fac-tors influencing prescribing practices,in particular characteristics of the prac-tice (clinic), the physician, working styleand attitude. Consultation time was re-lated to the location of the practice, highor low urban density and race. Caucasianprescribers were found to have longerconsultation times, which could alsobe related to seeing fewer patients perday. Prescription practice was influencedby race and the doctor�s place of educa-tion. The practice of polypharmacy andprescribing more �symptomatic treat-ment� seemed to be related to site ofeducation. Prescribers educated inZimbabwe had better prescribingpractices compared to those educatedelsewhere. This could perhaps be relatedto the inclusion of the essential drugsconcept and standard treatment guide-lines in the curriculum for medicalstudents in Zimbabwe. Although thestudy did not fully investigate howconfounding factors such as gender,race, location of the practice, place ofeducation and patient load influenceprescribing, it can still be concludedthat prescriber dispensing is associatedwith less clinically and economicallyappropriate prescribing.

Serious implicationsThese findings give cause for con-

cern, especially in view of the currenttrend in many developing countries to-wards increased numbers of �for-profitdispensing prescribers�, with little or nomonitoring or control of their practices.This may have serious implications for

appropriateness of treatment and pa-tient care. The study demonstrated that,regardless of how a society ensures thatmedicines are available and accessible,the authorities need to set standards andto regulate dispensing, medicine manage-ment and activities related to pharmacypractices. Moreover, the study showedthat self-regulation by the medical pro-fession has failed. The profession hasaccepted a practice by some of its mem-bers that is against the ideology and ethicsof that profession � a practice which putsthe interest of DDs before the interest ofthe patient.

While this study was done in a devel-oping country, differences in prescribingquality between DDs and NDDs havealso been documented in studies inother developing and in developed coun-tries4,5,6. The general practitionersincluded in this study were of multi-ethnic origin, with 30�50% having non-African race or education. The studyfindings might therefore be valid out-side Zimbabwe, and be an importantpointer for DDs in relation to �for-profitprescribing� throughout the world. ❏

* Birna Trap works for the Euro HealthGroup, Tinghøjvej 77, 2860 Måløv, Den-mark, Phone: + 45 39 69 68 88, fax: + 4539 69 58 88, e-mail: [email protected] She previously worked forthe Zimbabwe Essential Drugs Action Pro-gramme. Ebba Holme Hansen is Professorin the Department of Social Pharmacy,Royal Danish School of Pharmacy, Uni-versitetsparken 2, DK-2100 Copenhagen,Denmark. (The material in this article waspublished in Health Policy and Planning in2002, see reference 1).

References

1. Trap B, Hansen EH, Hogerzeil HV. Prescription habits

of dispensing and non-dispensing doctors in Zim-

babwe. Health Policy and Planning, 2002:17(3):

288�295.

2. Trap B and Hansen EH. Cotrimoxazole prescribing by

dispensing and non-dispensing doctors: do they differ

in rationality? Tropical Medicine and International

Health; 2002:7(8):878�885.

3. Trap B and Hansen EH. Treatment of upper respira-

tory tract infections � a comparative study of dispensing

and non-dispensing doctors. Journal of Clinical

Pharmacy and Therapeutics, 2002:27:289�298.

4. Nizami SQ, Khan IA, Bhutta ZA. Drug prescribing

practices for general doctors and paediatricians for

childhood diarrhoea in Karachi, Pakistan. Social

Science and Medicine, 1996;42 (8):1133�1139.

5. Morton-Jones TJ. Prescribing costs in dispensing

practices. British Medical Journal, 1993; 306:1244�6.

6. Stewart-Brown S, Surender R, Bradlow J, Coulter A,

Doll H. The effects of fundholding in general practice

on prescribing habits three years after introduction

of the scheme. British Medical Journal, 1995;311:

1543�7.

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Increasingly dispensing may involvepayment for medicines, creating conflictof interest related to the profit motive forhealth workers who both prescribe anddispense medicines. Many problemsexist for such payment schemes to besuccessful. The focus has been on will-ingness and ability to pay, but little isknown of how the quality of prescribingand patient care is influenced by the fi-nancial and for-profit motive related toprescribing by dispensing prescribers.Research in Zimbabwe in 1997 providesnew information on rational prescribingby dispensing (for-profit) prescribers.The research was done by the ZimbabweEssential Drugs Programme, The RoyalDanish School of Pharmacy and theUniversity of Zimbabwe, with financialsupport by The Danish Agency forDevelopment Assistance (DANIDA).

Assessingprescribing practices

The study was designed as an analy-tical, cross-sectional, comparative surveyof 29 randomly selected private sectordispensing doctors (DDs) and 28 non-dispensing doctors (NDDs) all in Harare,Zimbabwe�s capital. By selecting prac-tices in Harare with a pharmacy nearby,easy patient access to dispensing ofmedicines was ensured for both typesof practices.

Data on prescribing were collectedfrom patient records. The quality of pre-scribing was assessed, based on expertopinion, focusing on well-knownprescribing problems and applying�gold standards� � standard treatmentguidelines as clinical assessment criteria.

The study compared the WHO/International Network for RationalUse of Drugs (INRUD) rational druguse indicators for DDs and NDDs, andassessed how upper respiratory tract in-fections were treated by the two groupsof prescribers. Moreover, by using apanel of experts (three private practition-ers and one pharmacist) it was possibleto assess prescribing by looking at therecorded diagnoses and assessing the

2.5

2.0

1.5

1.0

0.5

0

Aver

age n

umbe

r per

pres

cript

ion

Drugs

NDDDD

Injections Antibiotics Mixtures

2.3

1.7

0.30.1

0.720.54

0.430.25

P=0.0001

P=0.002

P=0.006

P=0.005

Figure 1Prescribing indicators by DDs and NDDs in Zimbabwe



Issue No. 32, 2003

INCE 1998 WHO/EDM has been working to promote Drug andTherapeutics Committees. A WHO manual on this important topicwill be published in 2003 and will be featured in the next issue ofthe Monitor. The article below describes the process used to de-

velop the manual and the training course which is being used worldwideto try to ensure an increase in the number and effectiveness of Commit-tees. We would welcome readers’ comments on their experiences withDrug and Therapeutics Committees, particularly successful strategies andlessons learned. Contact details are on page 1.

Drug and therapeutics committees:vehicles for improving rationaldrug use

S

➢ TERRY GREEN, ALIX BEITH,JOHN CHALKER*

During the past half century therehave been great advances in the treatmentof many medical conditions, especiallyinfectious diseases. Unfortunately, theuse of inappropriate drugs to treat thesehas led to serious health care problems,resulting in increased morbidity, mortal-ity, costs and, more recently, emergingantimicrobial resistance (AMR).

Irrational use of drugs in hospitals indeveloping countries is a major problemand little has been published on how toimprove it. A suggested starting point isto develop hospital Drug and Therapeu-tics Committees (DTCs) to act as agentsof change. This was one of the recom-mendations from the first InternationalConference on Improving Use of Medi-cines (ICIUM), held in Thailand in1997 (see box p. 11 for details of ICIUM2004). The recommendation was basedon lessons from developed countries,where more has been published about theeffectiveness of such Committees.

In many hospitals the selection proc-ess for antimicrobials does not followan evidence-based methodology andantimicrobials are overused, producingan environment conducive to the devel-opment and spread of AMR. The WHOGlobal Strategy for Containment of An-timicrobial Resistance,1 published inSeptember 2001, recommends settingup DTCs, as one way of helping in theefforts to contain the increase in AMR.

Among other problems that occurwith inappropriate use of drugs is an in-crease in adverse drug reactions (ADRs),medication errors and the use of rela-tively unsafe drugs. It has been estimatedthat in the USA 10.8% of hospital in-patients suffer from an ADR, at anannual cost of between US$1.4 billionand US$4 billion, and ADRs are betweenthe 4th and 6th most common cause ofdeath.2 A DTC can establish mechanismsthat have the potential to reduce ADRs.

Many countries already have DTCs todeal with the problems of drug selection,procurement, distribution and use, and toaddress the continuing and emerging

problems of AMR. The majority ofDTCs are in developed countries, includ-ing Australia, the USA and Europeancountries. In Australia, 92%3 and in theUK (in 1990), 86% of hospitals haddeveloped some type of hospital thera-peutic committee. In the USA, DTCs orsimilar committees are required in orderto receive accreditation. In differentsettings they may also be known as aPharmacy and Therapeutics Committee,a Pharmacotherapy Committee, a Formu-lary Committee or a Rational Drug UseCommittee.

What do DTCs do?DTCs are organizations within a hos-

pital or primary care clinic that areresponsible for evaluating the clinical useof drugs, developing policies for manag-ing drug use and administration, andmanaging the formulary system. A forumto evaluate and discuss all aspects ofdrug therapy, they advise the medical,nursing, administrative and pharmacydepartments on drug-related issues.

The main functions of Drug andTherapeutics Committees are:◆ evaluating and selecting drugs for

the formulary and providing forits periodic revision. This includesdeveloping rigorous evidence-based criteria for selection ofdrugs, taking into accountefficacy, safety, quality and cost;

◆ assessing drug use to identifypotential problems;

◆ promoting and conductingeffective interventions to improvedrug use (including educational,managerial and regulatorymethods).

In addition Committees may:

◆ manage adverse drug reactions;

◆ manage medication errors;

◆ promote infection controlpractices.

Who should be on aCommittee?

A successful Committee needs tohave the appropriate leadership andmembers, and to meet regularly. It mustbe dynamic, resourceful and use all mem-bers� skills. It is crucial that all keystakeholders in the hospital are on theCommittee, and that hospital managersgive members the necessary time to con-tribute in a sustainable and effective way.Membership structure varies in differentcountries. Ideally a Committee has astrong chairperson, who is an opinionleader and who commands the respect ofhospital and health leaders. Membersoften include: specialists from medicine,surgery, obstetrics and gynaecology,psychiatry and infectious diseases, phar-macists, a clinical pharmacologist, adrug information specialist, and nurses(either clinical or administrative nurserepresentatives), an infection controlnurse, and the administrative officer orother high level hospital administrationofficial.

For a Committee to be effective theremust be a structured drug selection sys-tem that is explicit in its methodology,and that is transparent and evidence-based. The Committee must have theability to design and implement inter-ventions to improve the use of drugs. Thehospital administration must give theCommittee authorisation and support tocarry out its functions, and have madeexplicit a clear line of authority to topadministration officials. There is a needfor regular meetings with published min-utes and close follow up on all activities.When a functioning Committee has thesekey features, it can be expected that itwill be effective and that the result willbe improved patient outcomes.

A combination of interventions, insti-tuted by the DTC, will have the mostsignificant effect on drug use and AMR.4

These include the appropriate selectionof formulary drugs, the development offormulary-based guidelines, monitoringand evaluating drug use, surveillance,detection and appropriate care of patientswith resistant organisms, and promo-tion and monitoring of basic infectioncontrol practices.1

Are DTCs effective?In developed countries, studies have

shown that DTCs can have a significantimpact in promoting rational drug use,monitoring drug use and controlling drugcosts.3,5 In developing countries the evi-dence is less compelling, but there issufficient evidence to show that the indi-vidual functions of a DTC provideeffective interventions to improve druguse and control costs. Proven successful

interventions include: establishing andimplementing a formulary list or an es-sential medicines list6 and standardtreatment guidelines;4 and using educa-tional techniques, especially interactiveproblem-oriented methods in face-to-facesettings, and repeat sessions with differ-ent prescribers.4,7 Success has also beenachieved through establishing and imple-menting audit and feedback (includingdrug use evaluation) of provider prescrib-ing;8 and supervising and monitoringprescribing habits using indicators orsimple protocols.4 A well-organized DTCwill provide the structure to facilitatemanagement of all of these well provenactivities, and so it is reasonable toassume that it can be effective.

Promoting DTCs indeveloping countries

WHO/EDM in cooperation withManagement Sciences for Health (MSH)is developing a manual on how to estab-lish and maintain a DTC at hospital level,to help developing countries instigatebasic DTC activities and so improve drugmanagement in hospitals. The manualwill be published in 2003.

At the same time MSH�s RationalPharmaceutical Management Plus (RPMPlus) programme in cooperation withWHO, has developed an 8�10 day DTCtraining course. The course promotes thecreation of DTCs, trains potential andactual Committee members and promotesthe effective functioning of DTCs on for-mulary management and drug use. It isdesigned for physicians and pharmacistswho are interested in improving therational use of drugs through DTCs, orwho will be able to provide training andtechnical assistance to other DTCs.

For effective formulary management,DTC members need to make their deci-sions on inclusions or exclusions usingevidence-based drug management prin-ciples. Participants need information onthe principles, concepts, approaches andtools of clinical pharmacology (drug ef-ficacy), pharmacoepidemiology (drugsafety), pharmacoeconomics (drug costs)and pharmaceutics (drug product qual-ity). The course also covers effectivemethods of improving drug use, aggre-gate and indicator methods for assessingdrug use, and successful methods ofimplementing and monitoring change.The exchange of experiences and ideasamong participants adds depth to thelearning process in this highly participa-tory course. The methodology is basedon brief interactive presentations, withgroup and plenary discussions followedby exercises and field visits.

As far as possible sessions are inte-grated, so, for example, during the STG



Issue No. 32, 2003

exercise participants are given all the datato develop evidence-based STGs forpneumonia and surgical prophylaxis forCaesarean section. Then these STGs areused when making drug utilization re-view (DUR) criteria. On the field visitsto local hospitals the STG/DUR protocolsare used to look at practice and costs.These practical exercises during fieldtrips can have important results. For ex-ample, when looking at drugs and dosesin surgical prophylaxis for Caesareansection at one hospital, it was found thatby not following the STG and using un-necessary antimicrobials, the cost paidper patient was US$6.47�13.6 timesmore than necessary.

Follow-upTraining courses on their own rarely

result in sustainable behaviour change,so participants are asked to develop aone-year work plan for their institution,which is followed up to assess progressand give advice when needed. Follow-up is done in different ways. For localcourses someone visits or telephones theparticipants, but the challenge is greaterwith international courses, and e-mail anda course web site are used. The site stimu-lates interactive learning for those whohave been on a course. Each team�s workplan and updates on its progress areposted, along with personal profiles andphotos of participants. Successes andfailures are shared through a discussionboard, so that people learn from eachother. The site also provides links toimportant DTC resources. In addition,the RPM Plus web site (www.msh.org/projects/rpmplus) has valuable informa-tion on DTCs, including a fact sheet,links to training course sessions, andDTC course announcements.

ProgressTo date, the training course has been

presented in 10 countries to 295 parti-cipants from 42 different countries.Locations have included: Internationalcourses in Indonesia (June 2001), Kenya(October 2001) and India (September2002): Regional courses in Bolivia (De-cember 2001), Guatemala (February2002), Moldova (June 2002) and Jordanin December 2002: and National coursesin the Philippines (February 2001), Tur-key (July 2001), Nepal (December 2001)and South Africa (March 2002).

While a significant number of partici-pants have been lost to follow-up, weknow that many others are involved inpost-course DTC activities, including:

➤ Further courses � so far there havebeen 14 courses and nine more areplanned in eight countries.

➤ DTCs are being created or restructuredin 11 countries.

➤ Three countries have introducednew processes for drug selection,improving formulary management.

➤ STGs have been developed in at leastthree countries.

➤ DURs have been conducted in fourcountries. ABC and VEN analysis ofpharmaceutical purchases completedin two countries and ADR and medi-cation error reporting programmes areunderway in two countries.

All of these activities facilitate iden-tification of potential problems. Giventhat most of the courses took placevery recently it is expected that manymore participants will provide us withinformation about achievements intheir DTC-related work activities in thefuture.

Great potentialIn hospitals in developing and devel-

oped countries a DTC can be a keyinstrument in improving drug selectionand drug use. Yet in many cases DTCsare not functioning optimally. This is of-ten because the chairperson is notcommitted, the membership is not repre-sentative of all stakeholders, or lacksadequate training, or the administrationis not supportive in terms of recognitionand remuneration for the time needed forCommittee work.

The DTC training course is proving amajor step towards promoting effectiveDTCs internationally, and we now need

to develop a longer-term, sustainable,framework for presenting and follow-ing up this course. Our focus will beon determining the main factors thatmake DTCs as effective as possible indeveloping country settings.

DTCs offer the opportunity and envi-ronment to improve drug managementwithin hospitals and primary caresettings. Overall these important Com-mittees can provide the link to controland manage drug use, improve patientoutcomes, and contain AMR. ❏

* Terry Green, Alix Beith and John Chalkerwork for the Rational PharmaceuticalManagement Plus Program, Center for Phar-maceutical Management, ManagementSciences for Health, 301 North FairfaxDrive, Suite 400, Arlington, VA 22203,USA. Tel: + 1 703 524-6575, fax: + 1 703524-7898, e-mail: [email protected]

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References

1. WHO global strategy for containment of antimicrobialresistance. Geneva: World Health Organization; 2001.pp 34�35.

2. Lazarou J, Pomeranz, Corey P. Incidence of adversedrug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA, 1998 Apr15;279(15):1200�1205.

3. Weekes LM, Brooks C. Drugs and therapeutics com-mittees in Australia: expected and actual performance.Br. J Clin Pharmacol, 1996, 42:551�557.

4. Interventions and strategies to improve the use ofanti-microbials in developing countries, a review.Drug management program. Geneva: World HealthOrganization; 2001. WHO/CSR/DRS/2001.9.

5. Soumerai SB, Avorn J. Efficacy and cost-containmentin hospital pharmacotherapy: state of the art and futuredirections. Milbank Memorial Fund Quarterly Healthand Society, 1984, 62:447�474.

6. Laing RO, Hogerzeil HV, Ross-Degnan. Ten recom-mendations to improve use of medicinces in developingcountries. Health Policy and Planning 2001; 16(1):13�20.

7. Wade W, Spruill WJ, Taylor AT, Longe L, Hawkins DW.The expanding role of pharmacy and therapeutics com-mittees: the 1990s and beyond. Pharmacoeconomics1996 Aug;10(2):123�128.

8. Thompson O�Brien MA, Oxmas AD, Davis AD,Haynes RB, Freemantle N, Harvey EL. Audit andfeedback: effects on professional practice and healthcare outcomes. Cochrane Collaboration Abstract.November 1997.

Enjoying the sunshine in Mumbai, India – participants at the highly acclaimed international training course on Drug and TherapeuticsCommittees, held in 2002

Announcing ICIUM 2004collaboration with Management Sci-ences for Health, Boston UniversitySchool of Public Health and HarvardMedical School, are also supporting theevent.

ICIUM 2004 aims to build an inter-national consensus on effective andinnovative interventions for improvingdrug use, particularly in developingcountries. It will also seek to define anew global research agenda relevantto current conditions and unfoldingdevelopments in international health.A range of options and challengeswill be explored across six main areas:international policies and systems;national policies, systems and pro-grammes; hospitals, inpatient andspecialty care; primary care, focusing

on health providers; primary care,focusing on the community; andspecial topics.

This stimulating, interactive eventwill be of great interest to policy-makers, health ministry officials,programme managers, clinicians,researchers, advocates and donors.Individuals are encouraged to submitabstracts for presentation at the Con-ference. A limited number of schol-arships, covering registration fees,travel and accommodation will beavailable to participants from poorercountries who have abstracts acceptedor who are key policy-makers. ❏

Further information is available on the Con-ference web site: www.icium.org orenquiries can be e-mailed to: [email protected]

THE first International Confer-ence on Improving Use ofMedicines (ICIUM) was held in1997, and brought together a

wide range of participants and a wealthof interesting and important materialson how to improve medicines use (seeMonitor No. 23, available at: http://www.who.int/medicines/information/infmonitor.shtml). Following this suc-cess, ICIUM 2004 will be held inChiang Mai, Thailand, from 30 Marchto 2 April 2004. Once again the mainorganizer is the International Networkfor Rational Use of Drugs (INRUD),with the local involvement of theThai INRUD group and the Instituteof Health Research at ChulalongkornUniversity, Bangkok. WHO/EDM, in


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Issue No. 32, 2003

“I


T is a great pleasure for me tojoin you in the celebration of the25th anniversary of the firstWHO Model List of Essential

Medicines. To understand the revolu-tionary nature of the idea behind theModel List, and the tremendous impor-tance of this List over the past quartercentury, we must take a minute to

Access to essentialmedicines: a globalnecessity

Guinea, Peru, Sri Lanka, and Tanzania.In October 1977, WHO produced

the first Model List of Essential Drugsand, in 1978, the Declaration of AlmaAta identified �provision of essentialdrugs� as one of the eight elements ofprimary health care. The Model List hasclearly filled a need. By the end of1999, 156 countries had a national list

artemether-based anti-malarialmedicine on the Model List. Ournew Essential Medicines Librarynow brings together all WHO�score evidence and normative infor-mation on all essential medicines.

The new WHO Model Formu-lary was issued for the first timetwo months ago, based on theModel List of Essential Medicines.It presents all relevant medicineinformation and summaries ofmost WHO�s clinical guidelines. Itis available in hard copy and as asearchable web version. This hasled to a complete renovation andre-actualisation of the wholeessential medicines concept.

The new WHO Model QualityAssurance System has, for the

� and the wider debate � on intellec-tual property, where it is relevantfor public health. The basis for our

Dr Brundtland, WHO’s Director-General, gave akeynote speech, quoted here, at anniversarycelebrations in Geneva

look back. The twentiethcentury opened with onlyone widely available mod-ern medicine: aspirin. In the1940�s, the first antibiotic,the first mass producedantimalarial, and the firstantitubercular were intro-duced. The 1950s and1960s saw the rapid introduction of oralcontraceptives, diabetes medicines, andthen medicines for mental illness, manyinfectious diseases, cardiovasculardiseases and cancer.

By the 1970s, effective medicines �though not always ideal � existed fornearly every major illness we know.Yet, for half the world�s population, itwas as if they were still living inthe 1880s. For them, modernmedicines were unavailable,unaffordable, of poor qualityor ineffectively used. TheWorld Health Assemblyof 1975 was a water-shed. This Assemblyintroduced the conceptsof �essential drugs� and�national drug policy�.Seeing how central and eve-ryday these concepts havebecome to public health, it isimpressive to think that they are notmuch more than 25 years old.

The Assembly hoped to begin clos-ing the huge gap between those whowere benefiting from the pharmaceuti-cal harvest of the mid-1900s and thosewho could not access these medicines.It began developing this bridge bybuilding on precedents set in Scandi-navia, on the North America formularyliterature, and on pioneering efforts bycountries as diverse as Papua New

of essential medicines; three-quartersof these lists had been revised in thefive preceding years. Over the past fewyears, the Model List has developedrapidly on several fronts in response toa growing global demand for wideraccess to essential medicines.

The new pro-cedures for updating and disseminatingthe WHO Model List were approved in2002; a process that was strongly sup-ported by the Executive Board and theAssembly.

In April 2002, WHO included 12antiretroviral medicines and the first

“The last decade has seen inequitiesin health care increase, with reducedpublic budgets and increased relianceon the private sector.”

position is very clear: no clause in anytrade agreement should work in a waythat denies � to those who need them �access to life-saving medicines forcommon diseases. This applieswherever they live and whatever theirability to pay. In accordance withthis position, WHO has formulatedglobal guidance and is giving practicaladvice to Member States on the con-sequences and possibilities that lie inthe rules on intellectual property beingnegotiated within the World TradeOrganization.

first time, led to the pre-qualificationof manufacturers and products forHIV and malaria on behalf of all UN

“For many the reality isstark: no cash, no cure.”

agencies.The last decade has seen

inequities in health careincrease, with reducedpublic budgets and in-creased reliance on theprivate sector. There is

now a global cry forequitable access toessential medicinesfor the prevention and treatmentof HIV/AIDS. This also appliesfor access to other essentialmedicines, especially those for

common childhood diseases,major infectious diseases and

chronic conditions such as diabetes,hypertension, epilepsy and mentaldisorders, which benefit fromlong-term treatment.

New international agreements,including the WTO TRIPS Agreementand the WTO Agreement on TechnicalBarriers to Trade (TBT), will undoubt-edly affect access to medicines indeveloping countries. The recent UKCommission on Intellectual PropertyRights provides a very comprehensiveanalysis of the potential impact. WHOis closely involved in the negotiations

“Access to essential medicines de-pends on a nucleus of key factors:rational selection, affordable prices,sustainable financing and reliablesupply systems.”

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Issue No. 32, 2003

“WHO needs to remain evidence-based and totally independent fromcommercial interests so that we canensure an independent developmentof normative work. Member Statesshould always feel confident about theindependence of our policy advice.”

We have come a long way since1977. But the challenges ahead aregreat. For too many of the world�s poorpeople � those with an income of one

“For our future work, this means continued support tocountries, with a focus on results.

◆ Within country support, more focus will be put oncapacity building through normative information, practicalpolicy guidance and training.

◆ More focus will be put on supporting Member States inaspects of good governance and formulation of essentialgovernment functions, such as promoting the right mixbetween public and private functions and regulating theprivate sector.

◆ We will continue development of the evidence base fordrug selection, based in part on WHO’s independenceas a source of scientific information. Scientific andnormative work benefits all Member States and needsto remain independent from individual donor decisions.It is certainly part of WHO’s core functions and willremain so.

prices, sustainable financing andreliable supply systems. These fourcomponents of the strategy are inter-dependent. Lower prices attract more

treatment are integrally linked. Spend-ing money on essential medicines � andon the systems needed to deliver themeffectively, equitably and safely � is agood health investment.

We need to find ways to respond tothese great challenges. Essential drugsare not an ordinary commodity. Accessto health care is a human right. Gov-ernments and international agencieshave an obligation to see that this rightis progressively realised. Access to es-sential drugs is part of this obligation.

The concept of essential medicineshas global relevance and is a global

◆ More focus will be put on strengthening the functions ofdistrict hospitals in ensuring equitable access to primary care.

◆ Access to essential medicines is part of the progressivefulfilment of the fundamental right to health. The rights-basedapproach will be further developed and supported as ameans of empowering NGOs and the general public inmaking their governments accountable.

◆ More focus will be put on further developing and supportinghealth insurance as an important approach in making healthcare more affordable for all, and in promoting access to cost-effective health care. WHO will follow a pragmatic approachto critical issues, such as affordability and the use of TRIPSsafeguards to ensure access, building on good governanceby countries.

◆ The promotion of the essential medicines concept will befurther intensified through close collaboration with otherclusters, other UN agencies, the World Bank and NGOs.”

WHO’s future work in essential medicines◆ ◆ ◆

pressure drugs and aspirin � given dailyto people at elevated risk of heart at-tack and stroke � can save the lives ofmillions of people at risk of cardiovas-cular disease each year on a globalbasis. This highly effective combina-tion therapy could be much morewidely used in the industrialised world,and is increasingly affordable in the de-veloping world. These medicines areoff-patent and relatively cheap. Thedrug combination would cost less than14 dollars for each person annually.Still, it might not be affordable topoor countries facing the traditionalburdens posed by communicablediseases and the growing burdenof noncommunicable and chronicdiseases.

The recent WHO Commission onMacroeconomics and Health high-lighted the need for major newinjections of resources from high in-come countries. It called for a majorincrease in the resources invested inhealth in the poorest countries over thecoming two decades. Moreover, it

or two dollars a day � nothing verymuch has changed at all. The onset ofserious illness in the family too oftenleads inexorably to death, disability andimpoverishment. Thirty-eight countriesspend less than two dollars per personper year on medicines, while many ofthese countries have large numbersof people living with AIDS. Overallhealth expenditure may be as little as10�12 dollars per person.

Inevitably, in such circumstances,the cost of care falls to the individualand the family. Few poor people haveaccess to health insurance. They haveto pay for drugs when they get sick.Out-of-pocket payments � a largeproportion of which go on medicines �constitute up to 90 per cent of totalhealth spending in some poor countries.For many the reality is stark: no cash,no cure.

Drug prices are only part of thischallenge. Access to essential medi-cines depends on a nucleus of keyfactors: rational selection, affordable

donor and governmentfinancing; radically in-creasing drug availabilityboosts health systemsdevelopment; more effec-tive supply systems meangreater coverage; and morecoverage increases salesrevenues.

High quality health caredepends on choosing thosemedicines with the bestcombination of safety, effi-

cacy, quality and health impact. Over1500 new medicines have been intro-duced during the last 25 years. Manyof these represent genuine therapeuticinnovations which can and should havea major public health impact. Healthsystems and health care providers eve-rywhere struggle to select those drugswhich best suit their needs.

New essential medicines are expen-

“The Model List of EssentialMedicines is a key tool.”

“Access to essential medicines ispart of the progressive fulfilment ofthe fundamental right to health.”

argued that the old dogma which saysdevelopment assistance is only cost-effective if it focuses on prevention �not treatment � is outdated. The recentdevelopments within a number ofdiseases, such as HIV/AIDS, TB andmalaria � and now with cardiovasculardiseases � show that prevention and

necessity. The Millennium Develop-ment Goals include access to essentialmedicines as one of 17 health indi-cators. The world is committed toexpanding access to essential medicinesand WHO is committed to supportingthis goal. WHO has two critical func-tions for essential medicines: to developand promote global normative guid-ance, and to give technical support toMember States. Some of the normativework and all technical support putsemphasis on promoting equity andsustainability, with a focus on fulfill-ing the needs of poor and marginalisedpopulations. WHO works with allstakeholders � both at the global leveland in the countries. Besides the min-istry of health, this includes especiallythe nongovernmental sector andacademia.

WHO needs to remain evidence-based and totally independent fromcommercial interests so that we canensure an independent developmentof normative work. Member Statesshould always feel confident about theindependence of our policy advice.

We are in the middle of a greatstruggle to increase investments inhealth as part of the fight to reduce pov-erty and achieve the Millennium Goals.We have to show that we have effec-tive means to achieve measurableimprovements in health. We need tofind effective ways of delivering basichealth care to all � also to the world�sone billion poorest people. A key partof this challenge will be to ensure awidening access to essential medicines.The Model List of Essential Medicinesis a key tool in this work. Let us all workto make the next 25 years even moresuccessful than the quarter century wecelebrate today.� ❏

sive. For example, the newartemether-lumefantrinecombination for malaria isabout 25 times as expensiveas chloroquine, even at thepreferential price negotiatedby WHO for the public sec-tor in developing countries.Treatment of multi-drug resistant tuber-culosis is about fifty times as expensiveas a simple DOTS regimen.

Last week, we presented newevidence which shows that a few com-monly available medicines such asstatins for the lowering of cholesteroland low-doses of common blood



Issue No. 32, 2003

The Drug Evaluation Panel includedmostly pharmacologists and clinicalpharmacologists, as safety of medicineshad been of major concern at WHO sincethe 1960s. But very few memberswere from developing countries wherethis discipline was rare. Dr Darmansjahfrom Indonesia and Dr Lionel from SriLanka, among the eight members ofthe 1977 Expert Committee, were excep-tions. The other Panel members consistedmainly of pharmaceutical technologists,and even fewer were from developingcountries. Mr Yeap Boon Chye fromMalaysia was selected because of hisconsiderable experience of collaboratingwith WHO.

Geographical distribution was an-other criterion for Expert Committeemembership selection. Four pharma-cologists/clinical pharmacologistsfrom teaching, research and clinical in-stitutions in Brazil, France, Italy andthe USA respectively (Professors Zanini,Lechat, Garattini and Azarnoff) werechosen from the Drug Evaluation Panel.Professor Babajan from the USSRwas also selected but could not attend.But there was no one from Africa oneither of the two Panels (nor on manyothers either). The Committee neededto have an expert from Africa; � some-one who would know about theproblematic situation of medicines inAfrica. I remember going to the WHOLibrary searching all the Panels for asubject that would come close to ortouch that of medicines. Dr Beausoleil,Director of Medical Services at theMinistry of Health, Ghana, was thusinvited. Dr Probst and Mr Richmanof UNICEF were the only represen-tatives from other organizations. Thepharmaceutical industry was only invited

to the second expert com-mittee in 1979, when dosageforms were added to theEssential Drugs List. Thecriterion of having a womanon an Expert Committeecame years later. Womenwere very rare on any Ex-pert Panel 25 years ago �it was truly a man�s worldin which we somehowsurvived.

Why such details on thecomposition of members?Because I am convinced thatthe eight competent commit-tee members, backed by asecretariat of four temporaryadvisers � all Drug Evalua-tion Panel members (DrsBorda, Lunde, Tognoni andUlianova) � and WHO staff(Drs Fattorusso, Nakajimaand me, together with ourexcellent secretary, MsBurford) � had a fine cata-lytic effect on each other. Werepresented a good balancebetween sound scientific

Approving every wordbefore closing

There is no such thing as a draft re-port from an Expert Committee. Everyword in the text and content of a Com-mittee has to have final approval beforethe Committee disperses on the last dayof the five-day meeting. But in 1977 wewere not of the computer generation.Most professionals wrote their materialby hand and gave it to a secretary for typ-ing, and I think that this favourablyreduced our �word output�. Moreover,none of the Committee members or thetemporary advisers were people of manywords. These may be the reasons why avery concise and clear main text of only12, A5 pages resulted from our work � atext that still stands the test of time. Intotal, the small blue booklet of 36 pagesincluded, apart from the text, the firstModel Essential Drugs List with 220main and complementary drugs, an al-phabetical index, recommendations forthe development of the WHO programmeon essential drugs, a glossary and a bib-liography. When published, TechnicalReport Series No. 615 became an instantWHO bestseller, which sold out in threemonths and had to be reprinted severaltimes.

Country situation analysesfollowing the Committeemeeting

Apart from serving in the WHO sec-retariat during the Expert Committee

Need for selection ofessential drugs

With the focus on developing coun-try needs, health priorities and primaryhealth care, Dr Hiroshi Nakajima, chiefof a small three staff unit (Drug Policiesand Management) at WHO Headquar-ters, in 1974 began preparations for theFirst Expert Committee on EssentialDrugs to be held in October 1977. Thework had strong backing from WorldHealth Assembly resolutions andWHO senior management, notablyDr Mahler, WHO�s Director-Generaland Dr Fattorusso, Director of the Divi-sion of Prophylactic, Diagnostic andTherapeutic Substances.

Dr Nakajima often spoke about theneed to have a limited list of about 150drugs that would cover the majority ofhealth needs and achieve the widestpossible coverage of the population. Inthe first Consultation on the Selectionof Essential Drugs that took place inOctober 1976, the annotated list ofessential drugs (active substances) cameto around 200.

The 1977 Expert Committeeon the Selection of EssentialDrugs

Preparing a WHO Expert Committeeis a complex task with strict rules andregulations. One major criterion is thatany person considered for an ExpertCommittee has to be on a WHO ExpertPanel. To place someone on a Paneltook a very long time so one had tochoose from people on existing Panels.In 1977 there were two Panels related todrugs: one for Drug Evaluation and an-other for Pharmaceutical Specifications.

I

Margaretha Helling-Borda

knowledge, common sense, vision andexperience, coupled with politicalawareness and astuteness.

The Model List andTechnical Report SeriesNo.615

Of course there were some heatedexchanges in the Committee, in an oth-erwise quite sophisticated and scientificatmosphere. One major issue waswhether or not explanatory text and jus-tification should be included for eachselected or rejected drug. Luckily wis-dom prevailed. The text of the ExpertCommittee only gives some examplesand lists scientific criteria and otherguidelines that need to be applied in theselection of essential drugs. In its reportit did not provide details of why each drugwas selected or not. It was felt that thiswould have led to endless discussionsafter the report�s publication, particularlywith the pharmaceutical industry. Thethree well-prepared and widely circulatedworking papers, including a draft ModelList, were excellent reference sources onwhich the Committee could base its fi-nal decisions and from which large partsof text could be used. The clinical com-ments � the ones not included in the finalExpert Committee text but so importantin the decision-making process � were inthe major working paper (DPM/WP/77.3I. Borda). These later became veryuseful when WHO undertook countrysupport in drug selection.

➢ MARGARETHA HELLING-BORDA*

N 1968 when I joined the WHO Research Project for Adverse DrugReaction (ADR) Monitoring after the thalidomide disaster, I started todevelop a Drug Dictionary for drugs in the ADR reports received fromthe 10 developed countries participating at that time. I remember being

amazed that so many brand names existed, and that the generic or nonpropri-etary names were so little used. The chemical name was often used to describethe active substance of a medicine in the then frequently unobjective and com-mercial drug information sources. In this plethora of names and substances andlacunae of good objective information how could prescribing physicians andothers be expected to practice rational drug use? For developing countries withtheir enormous needs and cost-constraints, the problem was even more seriousand their situation became acute in the 1970s. In 1974 a Chief Medical Of-ficer wrote to WHO “our latest indent is 105% more expensive than last year’s.I need hardly say that this makes complete nonsense of our financial estimates,and my Government cannot, in the near future, double the money allocated formedicines”. That Chief Medical Officer was Dr Ebrahim Samba of the Ministryof Health of The Gambia, now Regional Director for WHO’S Regional Officefor Africa.

Memories of the FirstExpert Committee Meetingand celebrating 25 years later


Phot

o: W

HO


Issue No. 32, 2003

N Geneva on the 21st October2002, the 25th anniversary ofWHO�s Model List of EssentialMedicines was marked by a day

of debate led by international experts.Discussions focused on many aspectsof what the List and the essential medi-cines concept mean to improving publichealth. One highlight was the keynotespeech by WHO�s Director-General, re-inforcing the message of the concept�scontinuing relevance (see p 12). Butcelebrations in Switzerland were beingmirrored around the world, and here wemention just some of these memorableevents.

The Christian Medical Associationof India organized a press conferenceon the 25th October 2002, in NewDelhi, to celebrate the anniversary.The Community Health MedicinalUnit of Patna �joined hands withWHO� by holding a two-day mediaorientation and awareness seminaron essential drugs and rational useof drugs. In Calcutta, West Bengal,the Community Development Medici-nal Unit hosted a CommemorativePanel Discussion, which attracted an

25 years of essential medicines:events around the world

enthusiastic audience of doctors andpharmacists. And at the Mumbai Inter-national Training Course on Drug andTherapeutics Committees, an eveningwas devoted to a talk on 25 years ofessential medicines.

I

“Twenty-five years is a longtime for successful implemen-tation of a programme. Yet, theproblem of providing equita-ble and affordable accessto safe, effective and quality-assured drugs to peoplearound the world is so vast andso complex that the journeyremains far from finished.”

Community Development MedicinalUnit, West Bengal, India.

Nicaragua’s birthday cake. A celebration for the WHO and Nicaraguan Essential Drugs Listsand the country’s Essential Drugs Programme was held in Managua – one of the manypopular events worldwide marking this important anniversary

In Rio de Janeiro, Brazil, the firstday of the 3rd International Seminar onAccess to Medicines � FundamentalRole of the State, a special session was

held to commemorate the anniversary.Eighty participants from 18 countrieswere unanimous in recognising the uni-versality and increased relevance of theessential medicines concept today.

Russia�s Pharmaceutical Newsletterfeatured a special article, �The purpose� ensuring access to medicines, to

celebrate the jubilee, and the 12th WHOModel List of Essential Medicines�.

See above for more about events inCambodia. ❏

Further information is available at: http://www.who.int/medicines/organization/par/anniversary.shtml

meeting, my own strong recollectionfrom the historic days 17�21 October1977 are my visits to the WHO medicalservices, preparing for the country visitsright after the Committee. Two vaccina-tions were mandatory then � againstcholera and against smallpox. I had bothduring that week. They put me in a stateof febrile euphoria and malaise. Perhapsthis was a premonition of what was tocome with the bouts of malaria anddiarrhoeal diseases that I experiencedduring my first trip to developingcountries � a real �eye opener�.

Only a few days after the committeemeeting closed, Dr H. Nakajima, Dr F.S.Antezana and I took off for our six coun-tries, six-week country situation analysistrip to Asia � to Sri Lanka, Indonesia, thenBurma, Nepal, Thailand and India. Andto be consistent with the �sixes� I alsolost six kilos in weight during thoseweeks. But I learnt a lot about the condi-tions in a developing country. I started tounderstand why a national essential drugslist and programme were needed. I real-ised that WHO had produced a great toolto get the process started and tried in mythen very inexperienced way to assess thesituation and write a prototype report ofthe pharmaceutical situation in �my threecountries�. These were Sri Lanka whereDr Lionel helped me, Indonesia whereDr Darmansjah guided me and Burma

(Myanmar) where I met with DrNakajima. When the three WHO �asses-sors� met again during a final three-dayperiod in Delhi, India, to try to get a graspof the problems in that huge country, Iremember retreating to my hotel in a stateof exhaustion, overwhelmed by all myimpressions. But that was 25 years ago.Hundreds of country visits, assessmentsand evaluations later on all continents, Iam very happy to see the great progresscountries have made. Nepal provides justone example. In 1977 pharmaceuticalswere handled by the Ministry of Forestryand there was only one pharmacist, DrSuwal. He was later responsible for build-ing up and modernising that country�spharmaceutical supply system.

25 years later –celebrating the anniversary

For 21 October 2002 I was invited toCambodia by WHO�s Regional Office forthe Western Pacific to participate in aninter-country workshop to evaluate Na-tional Drug Policy implementation.Twenty-seven participants from 14 coun-tries in the Region attended, from placesas diverse as Australia, Brunei, China,Fiji, Laos, Malaysia, Solomon Island, thePhilippines and Viet Nam. It was goodto see that at least half of the workshopparticipants were women � a great change

from 25 years ago when, as mentionedearlier, it was very much a man�s worldin this professional area.

The workshop coincided with the25th Anniversary of the WHO Model Listof Essential Drugs and a half-day semi-nar on this topic started the workshop. Iwas very pleased to be given the oppor-tunity to speak about the �WHO ModelList of Essential Drugs/Programme �start and evolution: global perspectiveand reflections�. For me it was a greatopportunity to hear about progress � butalso new, challenging and difficult prob-lems in Western Pacific countries. Forexample, I recalled my first visit in 1985to Viet Nam and the many subsequentvisits, to Mongolia in 1991 and 1992,Malaysia for the first time in 1977, toChina in the early 90s, the Philippines,and to Australia where an importantWHO-sponsored meeting on nationaldrug policy took place in 1995. I learntabout the host country, Cambodia, andits fine essential drugs programme, de-veloped in such a short time and after allthe difficulties the country had endured.It was gratifying to report to the work-shop that the essential drugs concept hasbecome nearly universal over a 25-yearperiod. More than 150 countries have anational list of essential medicines, ma-jor international agencies now base theircatalogue on the WHO Model List, 101

countries had a national drug policy in1999 (only five in 1985), and access toessential drugs has almost doubled be-tween 1977 to 1997. But one-third of theworld�s population still does not haveregular access to essential medicines.This preoccupying fact means that therestill is very much to do, and the essentialmedicines concept is therefore more validthan ever for the challenges of today, suchas the emergence of new epidemics ofHIV/AIDS, resistant malaria and tuber-culosis. Another challenge is to expandand introduce the concept�s use in theprivate sector.

I am indeed very grateful to have had� and to continue to have � the opportu-nity and privilege to work with so manycommitted, knowledgeable and fine peo-ple in and outside WHO, and in countries.We work together towards the worth-while cause of increased access to themost needed medicines, through the es-sential medicines concept and its core,an essential medicines list, modelled onWHO�s List � born at that first ExpertCommittee in 1977. ❏

* Margaretha Helling-Borda worked forWHO for over 25 years and was Directorof the Action Programme on EssentialDrugs from 1994 until 1996. She is now aconsultant on public health issues.

FELICIDADES OPS EN TUCENTENARIO Y EN TUS

VEINTICINCO AÑOS ESENCIALES



Issue No. 32, 2003

I➢ RICHARD LAING

N late 2002, I was asked to join agroup to write a review article on25 years of the WHO Model Listof Essential Medicines, which

will be published in the Lancet in early2003. As is normal with such articles,there are sections on history, data tablesanalysing the List over time and betweencountries, a discussion of the issues re-lated to the List, and a conclusion aboutfuture perspectives. As I wrote the pa-per, I reflected on how my personal andprofessional life has been intertwinedwith the List and the essential medicinesconcept that the List generated.

First exposureI was first exposed to the WHO Model

List in 1979. I was working in a rural hos-pital in pre-Independence Zimbabwe,struggling with issues around drugselection and procurement. A visitingprofessor with a few students from thelocal university came out to visit the hos-pital and showed me a much photocopied1977 List � the first ever compiled. Iremember clearly being struck by whata great idea this was, and I started touse the List to guide our selections forprocurement.

Soon after Independence, a smallbooklet called PEDLIZ (ProposedEssential Drug List for Zimbabwe) waspublished and circulated widely. It wasmeant to be in circulation for 18 monthsbut it took longer than that to producethe first EDLIZ (Essential Drug List forZimbabwe). It was a fairly revolutionarydocument, as it combined treatmentguidelines for common conditions withthe List, and also it was a �levelled List�.This meant that drugs could be desig-nated for use only at certain levels of thehealth system. The book was smallenough to fit in your pocket and doctorsin hospitals began to use it.

ZEDAP experiencesIn 1986, I was involved in establish-

ing ZEDAP (Zimbabwe Essential DrugsAction Programme). This programmerevolved around implementing thevarious elements of the essential drugsconcept, focusing on selection, manage-ment training and the promotion ofrational drug use. One of our first acti-vities was a nationwide survey, whichrevealed that while the EDLIZ was uni-versally available, it was not being used.We discovered that this was becausenurses working at primary health carefacilities thought that the book was for�experts� and not for them. To dispel thisperception we changed the way that thetreatment guidelines and the List weredeveloped. We involved end users in theprocess and found this to be very suc-cessful. This ZEDAP approach has now

Personal reflections on 25 years of theWHO Model List of Essential Medicines

been duplicated in other countries.1

But we also involved the industry inthe process of selecting the EssentialDrug List! Naturally industry represen-tatives had commercial incentives foradvocating selection of specific drugs,and they were successful in includingmany �me-too� drugs. Our List balloonedto be one of the longest in the world. Thisexperience convinced me of the need tohave clear criteria for selection, and ofthe dangers of involving pharmaceuticalindustry members in actual selectiondecisions. One other lesson we learnedwas the need to involve procurementsupply staff in the process. For example,at one time we changed the regimenfor treating gonorrhea from penicillinto kanamycin and neglected to informthe supply staff. Very soon we were outof stock of kanamycin and the penicillinthat had been procured was likely toexpire.

INRUD and ManagingDrug Supply 2

In 1990, I moved to the USA andbegan to coordinate the InternationalNetwork for Rational Use of Drugs(INRUD) and work on the revision ofthe first edition of the standard text,Managing Drug Supply.2

One of my early activities at thistime was to work with a young BrownUniversity undergraduate on a reviewof the first 15 years of the WHO ModelList, which was published in the Lancet.3

One of the key insights from this reviewwas that while the List was primarily usedfor public health purposes the selectionof the List was done by clinical phar-macologists. We suggested that themembership of the WHO Expert Com-mittee on the Use of Essential Drugs bebroadened.

I was also working on revising the textof Managing Drug Supply. The sectionof the book on selection is fewer than40 pages out of a total of over 800, andyet the key concepts that came to beimplemented in the next decade weredescribed in this section. The diagram ofthe �bull�s-eye with ears� to describe thelevelled List and the diagram to showthe many uses of an essential drugs listoccurred here for the first time.

Eritrean experienceMy first opportunity to put these new

ideas into practice occurred when I wasasked to assist the Eritrean Ministry ofHealth in the third revision of their na-tional Essential Medicines List. A greatdeal of preparation went into this. Allprescribers were contacted for sugges-tions which were collated, and referencematerials on therapeutics and pricingwere also collected. Then we held a largeconsultative meeting at which morethan 100 prescribers and pharmacists

reviewed the selection criteria, and then,working in groups, reviewed each com-ponent of the List. We asked each groupto report back at a plenary session bypresenting therapeutic evidence andcost comparative information on a sin-gle overhead transparency sheet. Thisprocess worked very well, with groupmembers searching text books and pric-ing lists to synthesize the information.What became clear to me in this processis that cost comparisons are only validwithin a therapeutic group of drugs, andthat documented evidence will alwaystriumph over undocumented experience.What also struck me was the need tomake systematic reviews available in anaccessible form to people making thesedifficult decisions.

Change from experienceto evidence

In 2000 and 2001 I attended a seriesof meetings held in Geneva to addressperceived problems in the process bywhich the WHO Model List was revised.The key concerns identified by WHO andthe Expert Committee in November 1999

revolved around the need to basedecisions on evidence rather than just ex-perience, and to improve the transparencyof the process and the speed at which theList would be published and translated.MSF had expressed concern that costwas being used as an absolute barrier toinclusion of expensive though effectivedrugs.

A meeting was organized by theMédecins Sans Frontières Access toMedicines Campaign and gave an addi-tional opportunity for the NGO andacademic community to make their casethat changes were needed. Senior mem-bers of EDM attended the meeting, takingthe many criticisms with a good grace,and agreeing that some changes in theprocess would be necessary.

The next meeting was an informalconsultation organized by EDM and at-tended by Committee members, healtheconomists, academics and field staff;there was also an open session withMember States. This was a very practi-cal meeting at which the problems whichexisted in the process were examined andsuggestions made for how they could beaddressed. For many issues there was a

CHWdispensary

Health center

Hospital

Referral hospital

Private sector

Registered medicines

S S

National listof essentialmedicines

Levels of use

Supplementaryspecialistmedicines

All thedrugsin theworld

List of common diseases and complaints

Treatment choice

Treatmentguidelines

Training andSupervision

Essential medicines list/National formulary

Financing andsupply of drugs

Prevention and Care

Relation between treatment guidelines and a list of essentialmedicines

The Essential Medicines Target



Issue No. 32, 2003

S

compromise between what was ideal andwhat was practical. The meeting resultedin a draft document which was circulatedto Member States. Their comments wereposted on the Web and a second roundof comments was invited. Reading andresponding to these was a very useful ac-tivity for me, as it forced me to reassessall of my assumptions about the ModelList.

Finally, after all of these reviews, adocument was submitted to the WHOExecutive Board that finalised theprocess. The document, Procedure toupdate and disseminate the WHO ModelList of Essential Medicines, is availableat URL: http://www.who.int/medicines/organization/par/edl/procedures.shtml

Having been involved in this process,my faith in the value of having a globalbody to provide technical leadershipwas reaffirmed. The final documentwhile a defined process for WHO wasalso a model process for any country.

2002–3 EML meetings

In 2002, I attended the meeting ofthe WHO Expert Committee on the Useof Essential Medicines, and it was a highpoint of my professional life. Here was agroup of very experienced people fromall over the world coming together toshare their expertise for the good of theworld. Many tough issues were debated,but in every discussion there was anemphasis on evidence and reaching thebest possible decision for those who aresick, wherever they may be. There wasan open session at which different pro-tagonists stated their points of view andthese were carefully considered. Atthe meeting the process approved byWHO�s Executive Board was formalisedinto specific activities. The inclusionof antiretroviral drugs was presentedusing an evidence-based format. I leftthe meeting confident that the newprocesses could be implemented both

at global and national levels.Within hours of completion of the meet-

ing the List was published on WHO�smedicines web site, and translations weremade very quickly.4

What lies ahead?

There are many challenges for bothWHO and countries in translating theideal of an essential medicines list pro-duced from evidence-based treatmentguidelines into reality. Who will do thework? Where is the evidence? Willcountries have the capacity to revise theWHO Model List to meet their specificcountry needs?

But I remain confident that this grandidea of identifying a few essential medi-cines that should be made universallyavailable will continue to energise peo-ple to work to ensure that sick people donot die or suffer from lack of access tomedicines.

Finally, I wonder when the originalessential medicines concept was pro-posed whether those involved could haverealised how they were changing theworld. I know that is has made a hugedifference to my own and many otherpeoples� lives. Long may it continue todo so. ❏

Richard Laing is Associate Professor in theDepartment of International Health, BostonUniversity School of Public Health, USA, andguest editor of this issue of the EssentialDrugs Monitor.

References1. Laing RO, Ruredzo R. The essential drugs programme

in Zimbabwe: new approaches to training. HealthPolicy and Planning, 1989;4(3):229.

2. Quick JD, Rankin JR, Laing RO, O�Connor RW, HogerzeilHV, Dukes MNG, Garnett A. (eds). Managing drugsupply, 2nd ed. Hartford, CT: Kumarian Press; 1997.

3. Howard NJ, Laing RO. Changes in the World HealthOrganization Essential Drugs List. Lancet, 1991;338:743�745.

4. http://www.who.int/medicines/organization/par/edl/eml.shtml

➢ HÉCTOR BUSCHIAZZO, ALBIN CHAVES,ALBERT FIGUERAS, JOAN-RAMON LAPORTE*

INCE the inauguration of the WHO European Drug Utilization ResearchGroup (DURG) in the 1970s1 similar networks have been set up in otherregions. In the case of Latin America this occurred in September 1991at the First Meeting of Latin American Groups for Drug Epidemiology

held in Barcelona. Discussions in Barcelona involved health professionals fromeight Latin American countries and representatives from Spain’s Ministry ofHealth, the Catalan Pharmacological Society and WHO/EDM. Participantsexpressed concern that in most Latin American countries drug utilization (DU)data were scarce and fragmentary. Some local drug regulatory authorities wereunable to guarantee the efficacy and safety of products marketed, and had noaccess to quantitative or qualitative drug consumption data. The few drug con-sumption studies that had been done showed an alarming situation in terms ofprescribing, dispensing and use of medicines. Agreeing that information onDU patterns would be a useful tool for designing drug policy and drug educa-tion programmes, delegates pointed out that the lack of local clinicalpharmacology research meant that data had to be extrapolated from studiescarried out in very different countries and cultural settings. Diminishing resourceswere limiting the efficiency of public health care systems and decreasingthe already eroded access to the health care, including essential medicines.DURG-LA was formed to help overcome these problems.

Drug utilization in LatinAmerica – the example of DURG-LA

Meeting a needin Latin America

DU research points to and profiles thegap between controlled research, thera-peutic practice and population healthneeds, and it is a tool for implementinginterventions to promote a healthier useof medicines.1 DURG-LA promotes suchresearch in Latin American countries, andexchanges experiences and informationamong the participating groups. It usesthe knowledge acquired to give technicaladvice to drug regulatory authorities andto guide pharmacology teaching. DURG-LA also produces and disseminates

Promoting drugutilization studies

Part of the initial core group partici-pated in the first multicentre collaborativeDU study, which was on self-medicationand self-prescription, carried out in asample of more than 240 pharmacies in11 regions in six countries.2

Since then the different participantgroups have made presentations on anumber of local and multicentre DUstudies, involving nearly all DU meth-ods. Methodologies include quantitativeand qualitative analysis of drug prescrip-tion and consumption, and time trends ofgeneral patterns of drug use, togetherwith analysis of specific areas of thera-peutics. Some of these studies have beenpublished in local or international jour-nals, spreading DURG-LA�s message toa wider audience. Cuba provides oneoutstanding example of success, withmore than 160 municipal centres forpharmacoepidemiology set up duringthe 1990s, run by general practitionerstrained in the discipline. The Cuban net-work is involved in problem-orientedcontinued medical education andtherapeutic information, drug utilizationresearch and pharmacovigilance, withover 20,000 adverse drug reactionsreported each year.3,4

The Third DURG-LA meeting in1997 called for the creation of a perma-nent observatory on the quantitativeand qualitative time trends of drug usein Latin America. By the end of the meet-ing a draft of the data collection form tobe used in this work was ready. A firstevaluation was done, including qualita-tive and quantitative analyses of the 50

most consumed products (both by numberand by value) in 11 countries (Argentina,Bolivia, Brazil, Chile, Colombia, CostaRica, Cuba, Ecuador, Nicaragua, Peruand Uruguay). Data were presented anddiscussed at the 1999 meeting (see Table1), and will soon be published. It is hopedthat funding will be found to set up apermanent observatory for the region.

Selecting essentialinformation

In parallel with the exchange of in-formation about participants� researchand support activities, DURG-LA groupshave been discussing another area ofconcern � the new challenges of the in-formation and telematics revolution inrelation to clinical pharmacology. Teach-ing, drug information, drug selectionat different levels of the health system,drug regulation, pharmacovigilance andresearch have all been debated. Whilescientific information grows and is moreaccessible, this does not necessarily meanthat knowledge � the ability to appropri-ately interpret and use information fordecision-making � increases accordingly;rather, an excess of information may con-tribute to confusion regarding therapeuticpriorities. In addition, access to scien-tific literature is more difficult for manyof the 400 million Spanish-speakingcommunity because of language barriers.

To address these concerns SIETES(Sistema de Información Esencial enTerapéutica y Salud; System of essentialinformation on therapeutics and health)


information aimed at improving druguse, and collaborates on training of healthprofessionals in pharmacoepidemiologyand therapeutics.

By the end of 2002 there had beeneight DURG-LA meetings, covering awide range of subjects (see Table 1).Other general topics, such as bioequiva-lence, and promotion of the use of drugpolicies and generic medicines, havebeen the focus at several meetings. Oraland poster presentations on specificDU studies are given frequently, andtheir design, results and interpretationdiscussed.



Issue No. 32, 2003

The example of DURG-LA...cont’d from pg. 17

was created, and the system was pre-sented at the Fourth DURG-LA meetingin 1998. It is a database of selected bib-liographic references, more than 30% ofthem with an abstract and/or a commentin Spanish. SIETES contains manuallyselected articles, short communications,letters, editorials, review articles andnews published in over 80 journals, in-cluding both the major general andspeciality medical journals, and leadingclinical pharmacology, therapeutics andpharmacoepidemiology journals. Be-tween 5,000 and 6,000 new referencesare added each year. By March 2003, theSIETES database contained more than60,000 references, which are retrievableby various means including use of key-words (there are over 8,000), name ofauthor, journal, year, terms in the title,the abstract or the text, etc.

SIETES, which receives support fromWHO/EDM, covers all areas of thera-peutics, with special focus on new drugevaluations, comparative drug evalua-tions, translation of evidence into clinicalpractice, natural history and epidemi-ology of diseases, research in drugutilization and pharmacoepidemiology,

Table 1

Main topics discussed at the eight DURG-LA meetings*

I Meeting (Barcelona, Spain – September 1991)– International collaborative experiences in DU– Opportunities for establishing a network of clinical pharmacology and

pharmacoepidemiology in Latin America– Pilot phase of the self-medication study1

II Meeting (Rio de Janeiro, Brazil – June 1994)– General discussion of the results of the self-medication study1

III Meeting (Cartagena de Indias, Colombia – September 1997)– Drug information, clinical pharmacology information and internet– Latin-America Drug Situation Observatory – design of data collection form

IV Meeting (La Habana, Cuba – September 1998)– Latin America Drug Situation Observatory – results of pilot phase– Problem-based learning in therapeutics14

– DURG-LA Web Page Project

V Meeting (La Plata, Argentina – September 1999)– SIETES system for information on drugs and therapeutics– Latin America Drug Situation Observatory – one year analysis– Problem-based learning in therapeutics14

– Presentation of the DURG-LA web page

VI Meeting (San Jose, Costa Rica – September 2000)– SIETES web page searchable engine presentation– e-farmacos discussion list presentation5

– Latin-America Drug Situation Study – perspectives and future; funding seeking– Problem-based learning in therapeutics14

– Joint meeting with EAMI

VII Meeting (São Paulo, Brazil – October 2001)– e-farmacos discussion list – the first year5,6

– Roundtable: Reform and drug policy in Latin American countries– Generics policy in Brazil

VIII Meeting (Mexico, DF, Mexico – September 2002)– Roundtable: Generic medicines policy in Latin America (Argentina, Brazil, Costa

Rica, Guatemala and Mexico)– Proposal of a multicentre study on drug use in secondary prevention of ischaemic

heart disease.

* Each meeting included oral presentations of one centre or multicentre drug utilization studies by theattending groups. The meetings in São Paulo and Mexico also included poster presentations.DU = drug utilization; SIETES = Sistema de Información Esencial en Terapéutica y Salud); EAMI =Encuentro de Autoridades Competentes en Medicamentos de los Países Iberoamericanos.

and methodology in all areas of clinicalpharmacology. Also covered are inter-national health, with a focus on globalinequalities, pharmacoeconomics andcost-effectiveness, pharmacology teach-ing, training, continuing education indrug prescribing, drug regulation, drugpolicy, and news of interest, focusing onSpain and Latin America.

In 1999 a CD-ROM version waslaunched, and since 2001 SIETES can beaccessed at: http://www.icf.uab.es orhttp://www.sietes.org Participants in

DURG-LA use it regularly, and promoteits use among health professionals andstudents in their respective countries.

Another successful initiative to pro-mote information exchange was launchedin 2000, when at EDM�s suggestion, theelectronic discussion list e-farmacoswas set up. This is the Spanish equiva-lent of the electronic list �E-Drug� (http://www.essentialdrugs.org) e-farmacosgenerates more than 400 messages peryear and has nearly 300 subscribers.5,6

Knowledge productionand sharing

DURG-LA was born and has grownin response to changes in the pharmaceu-tical sector. The past 10 years has seenextraordinary growth in the world medi-cines market, but globally inequalitiesin access to medicines have deepened.7

The WTO TRIPS Agreements, the Inter-national Conference on Harmonisation,and consensus between the global phar-maceutical industry and the regulatoryauthorities of the main pharmaceuticalmarkets may be seen to have contributedto accelerate market innovation andpharmaceutical company mergers. Thesecompanies may exert strong influenceon drug regulatory authorities8,9 andmay have an increasing, sometimesoverwhelming, presence in continuingeducation of physicians and other healthprofessionals.10,11

On the other hand, poor public invest-ment in health, privatisation of healthsystems and deregulation impose addi-tional barriers to access to good qualityessential medicines.12 Rational selection,prescribing and use are critical in improv-ing access to drugs, but they involve notonly providing the right drug at the cor-rect dosage and duration of use, but alsoproviding information and patient edu-cation on its use.13 DURG-LA works toensure the updating of continuing edu-cation and training programmes both inuniversities and health care organizationsusing independent problem-orientedinformation. The group sees one of themost exciting challenges for clinicalpharmacology as selecting those infor-mation materials which are essential,i.e., which help to build up knowledgeoriented to satisfying health needs in acost-effective, equitable and respectfulway. Problem-oriented learning, asdescribed in the very widely used Guideto Good Prescribing,14 is a basic meth-odological component of this strategy,and one which has been discussed

at numerous DURG-LA meetings.The group is going from strength

to strength. To date more than 80 healthprofessionals from 26 university depart-ments, drug regulatory authorities, andhospital and primary care centres from18 countries (Argentina, Bolivia, Brazil,Chile, Colombia, Costa Rica, Cuba, Ec-uador, El Salvador, Guatemala, Mexico,Nicaragua, Panama, Peru, Spain, Uru-guay, the US, and Venezuela) haveattended DURG-LA meetings on a regu-lar basis. And the group has attractedfunding from a wide range of sources.In the global society, networking andknowledge sharing are essential inorder to meet the research, teachingand service goals of clinical pharma-cology. We believe that the most originalcontribution of the DURG-LA is its spe-cific focus on sharing and transferringknowledge. ❏

* Hector Buschiazzo is Past President ofthe DURG-LA (1999–2002) and Director,Faculty of Pharmacology at the National Uni-versity of La Plata, Argentina. Albin Chaves,is President of DURG-LA and Director of theDepartament of Pharmacotherapy, CajaCostarican Social Security, San Jose, CostaRica. Albert Figueras works on InternationalCooperation at the Catalan Institute of Phar-macology, and is Associate Professor in theDepartment of Pharmacology, Therapeuticsand Toxicology at the Autonomous Uni-versity of Barcelona, Spain. Joan-RamonLaporte is Director, Catalan Institute ofPharmacology, and Professor in the Depart-ment of Pharmacology, Therapeutics andToxicology at the Autonomous University ofBarcelona, Spain.

References

1. MNG Dukes (ed.) Drug utilization studies. WHORegional Publications, European Series No. 45.Copenhagen, 1993: 5�22.

2. Drug Utilization Research Group, Latin America.Multicenter study on self-medication and self-prescription in six Latin American countries. ClinicalPharmacology and Therapeutics 1997;61:488�493.

3. Debesa F, Jiménez G, Figueras A, Diogène E, Pérez-Peña J, Ávila J, Laporte JR. Spontaneous reporting ofadverse drug reactions in Cuba: integrating continu-ous education, training and research in a networkapproach. British Journal of Clinical Pharmacology2002;54:335�336.

4. Diogène E, Pérez-Peña J, Figueras A, Furones JA,Debesa F, Laporte JR. The Cuban experience in focus-ing pharmaceuticals policy to health population needs:initial results of the National PharmacoepidemiologyNetwork (1996�2001). Pharmacoepidemiology andDrug Safety (accepted for publication).

5. WHO. Useful web sites and electronic discussiongroups on pharmaceutical issues. Essential DrugsMonitor 2001;30:8.

6. Figueras A, Laporte JR. Regulatory decisions in aglobalised world: the domino effect of phenylpropa-nolamine withdrawal in Latin America. Drug Safety2002;25(10):689�693.

7. Velásquez G, Boulet P. Globalization and access todrugs. Perspectives on the WTO/TRIPS Agreement.Revised. Health Economics and Drugs EDM SeriesNo. 7. Geneva: World Health Organization; 1999.

8. Moynihan R. Alosetron: a case study in regulatory cap-ture, or a victory for patients� rights? British MedicalJournal 2002;325:592�5.

9. Abraham J. The pharmaceutical industry as a politicalplayer. Lancet 2002;360:1498�1502.

10. Angell M. Is academic medicine for sale? New EnglandJournal of Medicine 2000; 342:1516�18.

11. Bodenheimer T. Uneasy alliance � clinical investiga-tors and the pharmaceutical industry. New EnglandJournal of Medicine 2000; 342:1539�1544.

12. Sachs JD. Macroeconomics and health: investing inhealth for economic development. Report of the Com-mission on Macroeconomics and Health. Geneva:World Health Organization; 2001.

13. Rawlins, MD. Education and training in rational useof drugs for health professionals and the population.In: WHO (ed.) Rational use of drugs. Report of theNairobi Expert Conference, 25�29 Nov. 1985. Geneva:World Health Organization; 1985.pp. 276�286.

14. de Vries TPGM, Henning RH, Hogerzeil HV, FresleDA. Guide to good prescribing. Geneva: World HealthOrganization; 1997.

Participants at the DURG-LA meeting in San Jose, Costa Rica, in 2000

Phot

o: D

URG

-LA



Issue No. 32, 2003

Global TB Drug Facility: improvingaccess to TB drugs

accordance with a nationalDOTS expansion plan to reachthe global targets by 2005.

In addition to grants inkind, the GDF direct procure-ment mechanism can supportcountries which have ade-quate funds for drugs, butlack efficient mechanismsfor procurement and qualityassurance. With the establish-ment of the Global Fund toFight AIDS TB and Malaria(GFATM) as a major fundingsource for programmes totackle these three diseases, itis likely that the direct pro-curement mechanism willgradually become the primarymeans of GDF support tocountries.

Since its launch in 2001 theGDF has reviewed nearly 60applications from countries,NGOs and states. Most of the37 countries approved for sup-port so far are in sub-SaharanAfrica, and South East and

partnership chain. The GDF currentlyhas three funding agencies, fivecontractual partners and over 10collaborative partners, in additionto the support provided by WHOregional and country offices.

3. Use product packaging as a meansto simplify logistics, promote ra-tional use by health workers, andenhance patient acceptability andcompliance.

For many years TB treatment hasbeen characterised by extraordinarydiversity. There are currently 19 TBproducts for six drugs on the WHOModel Essential Medicines List (andmany other products in use by na-tional programmes). WHO guidelinesinclude 11 treatment regimens inthree treatment categories, with tworecommended dosages (daily andintermittent), and three weight catego-ries (not always consistent). Added tothis complexity, there is a wide vari-ety of packaging available: blisters,foil wrapped tablets, and containersof loose tablets. Not surprisingly, thisresults in confusion for managers,clinicians, nurses and patients.

The GDF aims to address this by pro-viding a standardised catalogue of TBdrugs, and it promotes Fixed-DoseCombination (FDC) tablets suppliedin individual patient treatment pack-ages. Four and two drug FDCs are thecore products provided by the GDF,which will be provided as individualpatient packs containing a full courseof treatment (six to eight months).Using complete patient packs simpli-fies ordering and stock management,

ensures that health workers providethe correct combination of tablets topatients, and can assist in promotingpatient acceptance and adherence totreatment.

4. Use grants of drugs to catalyse im-provements in the quality of healthservice provision.

By linking grants of drugs to pro-gramme performance, and encour-aging partners to provide additionaltechnical and financial assistance, theGDF has demonstrated its ability tocatalyse improvements in several keyareas which are concerns of the GDF,but do not fall within its mandate.These include planning for DOTSexpansion, monitoring, and drugmanagement.

5. Establish a diverse funding base.

In addition to the grant makingmechanism, the GDF has alsoestablished a direct procurementmechanism, whereby countries andNGOs can use their own resources tobuy high quality low cost drugsthrough the GDF. This mechanismmay also be used by other fundingpartners (eg GFATM) for support tocountries.

The Facility demonstrates many keyaspects of the essential medicines con-cept. The TB drugs supplied are carefullyselected with a view to improving treat-ment success. Procurement of the drugsthrough international mechanisms hasreduced the price and increased the reli-ability of supplies. Distribution of thedrugs has been through international andnational organizations and the provisionof blister packs and the use of Fixed-DoseCombination products has facilitated theprocess. Improved use of the products isfacilitated by the supply of these drugsthrough a DOTS programme. ❏

* Ian Smith is Manager of the Global DrugFacility, Jacob Kumaresan is Executive Sec-retary, Global Partnership to Stop TB andGini Arnold, is Technical Officer, GlobalDrug Facility.

For further information about the GlobalDrug Facility contact Gini Arnold at: WorldHealth Organization, 1211 Geneva 27,Switzerland, e-mail: [email protected] andto find out more about the Global Partner-ship to Stop TB contact the ExecutiveSecretary, Global Partnership to Stop TB,World Health Organization, 1211 Geneva27, Switzerland, e-mail: [email protected]

■ ■ ■

D

➢ IAN SMITH, JACOB KUMARESAN,VIRGINIA ARNOLD*

ESPITE the availability of effec-tive treatment for over 50 years,tuberculosis (TB) continues topose a serious threat to global

health, with nearly 9 million new casesand 2 million deaths every year. In theearly 1990s, WHO promoted DOTS,(Directly observed treatment short-course) as an effective and multi-facetedTB control strategy. However, progressin expanding DOTS over the last decadehas been inadequate, and WHO estimatesthat only 27% of people with infectiousTB were diagnosed and treated in DOTSprogrammes in 2000. Without a rapid ac-celeration of DOTS expansion, the globaltargets of detecting 70% of people withinfectious TB and curing 85% of thosedetected will not be met until 2013. Drugshortages are a significant barrier to rapidDOTS expansion, and these are frequentand serious in many parts of the world.They are often caused by financial con-straints, inefficient drug procurementsystems, poor quality drugs and lack ofproduct standardisation.

The five componentsof DOTS:

◆ political commitment;

◆ diagnosis of infectious cases bysmear microscopy;

◆ short course chemotherapy(directly observed for at least thefirst two months);

◆ uninterrupted drug supplies;

◆ monitoring of treatment outcome.

The Global TB Drug Facility (GDF)has been developed by the Global Part-nership to Stop TB to address theseissues, with the aim of increasing andsecuring access to high quality TB drugs.With initial funding from the Govern-ment of Canada, the GDF was formallylaunched on 24 March 2001, and ishoused in WHO�s Stop TB Department.Further details of the GDF are availableon the web site at: http://www.stoptb.org/GDF/

With its budget of US$250 million,the Fund aims to provide treatment for10 million patients by 2005, avertingdeaths and reducing the risk of drug re-sistant TB. The GDF�s primary supportmechanism is in the form of �grants inkind� of first-line TB drugs. The Fund hasestablished an independent mechanismfor reviewing applications for support.The quantity of drugs provided is cal-culated on the basis of the number ofadditional patients to be treated, in

A powerful message from the Global TB Drug Facility

Central Asia, with over 1.8 million pa-tient treatments to be supplied. Drugshave been ordered for 30 countries,and delivered to 19. Four countriesare also using the direct procurementmechanism.

The development and progress of thisinitiative has attracted much interest.Several of the lessons learnt throughthe GDF could be extended to help in-crease access to medicines for diseasesother than TB, specifically HIV/AIDSand malaria. The lessons include theneed to:

1. Link demand, supply and monitor-ing, to facilitate increased accesswhile ensuring rational use.

By linking supply of drugs to objec-tive assessments of technicalsoundness and operational feasibility,and by monitoring drug use, treatmentoutcomes and drug resistance, theGDF has greater confidence thatdrugs are being used appropriately.

2. Establish a ‘virtual organiza-tion’ through a partnership ofagencies.

The GDF has created a �virtual net-work� of agencies around the world,each providing specific services to theGDF on a contractual or collabora-tive (no fee) basis. This network iscoordinated by the GDF secretariat inGeneva. These include procure-ment, manufacturing, quality control,freight/shipping, monitoring andquality assurance. Through a com-petitive bidding process, GDFidentifies organisations that pro-vide efficient, quality and low costservices, and creates an effective



Issue No. 32, 2003

F

➢ TOBY KASPER, DAVID COETZEE, FRANCOISE LOUIS,ANDREW BOULLE, KATHERINE HILDERBRAND*

EW areas of public health have generated as much debate, controversyand protest in recent years as the drive to expand access to antiretroviraltherapy – the drugs that have transformed AIDS from a death sentenceto a chronic condition – in developing countries. Several years ago, it

was a futile discussion: with a yearly cost of US$10,000 per patient, there waslittle possibility of widespread access in developing countries. But, largely as aresult of a potent combination of generic competition and activism, prices haveplummeted, with triple therapy now being available for as little as US$209 ayear1, causing a huge shift in the debate about availability.

Demystifying antiretroviraltherapy in resource-poor settings

Today, the debate centres on if anti-retroviral therapy is possible in severelyresource-constrained environments, and,increasingly, on the best ways to deliverthese drugs. In a poor township 30kilometers outside Cape Town, SouthAfrica, Médecins Sans Frontières set outto grapple with both of these issues.Khayelitsha has around 500,000 inhab-itants � a figure swollen by a steady influxof economic migrants from rural areas �of whom 50% are unemployed and morethan 70% live in shacks. HIV sero-prevalence rates at antenatal clinics areabove 24%, having risen with shockingrapidity over the past 10 years.

The provincial government of theWestern Cape decided to launch SouthAfrica�s first government-run programmeto prevent mother-to-child transmission(MTCT) of HIV in Khayelitsha. Zido-vudine (AZT), first became available inthe township�s two maternity wards inearly 1999, and the programme has sub-sequently become one of the continent�sbiggest, with more than 20,000 womenhaving accepted testing, and over 3,000having received antiretroviral therapy.Médecins Sans Frontières began support-ing this MTCT programme in 1999,before opening clinics to offer treatmentto the mothers, their infected children,and others with HIV from the broadercommunity at three government primaryhealth care centres in April 2000. Despitecatering solely to those with HIV, thecentres were called �infectious diseaseclinics�, out of a fear that labelling themHIV clinics would generate stigma anddeter people from accessing services.This concern turned out to be entirelymisplaced, as the community quicklybranded them AIDS clinics, and nonethe-less the queues steadily lengthened.Treatment was initially limited to oppor-tunistic infections � the conditions thatarise with increasing frequency as HIVerodes the immune system�s capacity toward off infections. But in May 2001, thiswas broadened to include antiretroviraltherapy, making the project the first touse antiretrovirals in government healthfacilities outside the context of clinicaltrials.

This step was motivated by bothhumanitarian and public health princi-ples: despite receiving quality care andprophylaxis for opportunistic infections,

patients were getting sick and dying atunacceptable rates and so needed accessto the only drugs that have been provento suppress HIV infection and thus ex-tend life. Further, there was a clear needto develop models for the delivery ofantiretroviral therapy in South Africa.Thus the project was intended to demon-strate that the use of antiretroviral therapyat primary health care level was feasible,affordable and replicable.

Impressive survival rates

Preliminary analyses recently pre-sented at the XIV International AIDSConference in Barcelona provide strongindications that poor black women andmen can indeed derive considerable ben-efit from antiretroviral therapy withoutundue toxicity. To date, 180 patients havebeen placed on this therapy, selected fromamong the 3,000 patients who have at-tended the MSF clinics in Khayelitsha(Box 1 gives details of the selection proc-ess). These patients were extremely sickwhen they began therapy, having a me-dian CD4+ T cell count of 43, with asmany patients initiating therapy withunder 10 CD4+ T cells as above 100. Incontrast, a typical CD4+ T cell count in aseronegative person would be in therange of 800�1200, and it is well-estab-lished that the risk of death increasessignificantly as the count drops below 50.Thus if untreated, the prognosis of this

group of patients would beextremely poor, with deathwithin a year the sad realityfor most.

However, on antiretro-viral therapy, their survivalwas impressive. After ninemonths of treatment, 88% ofthe patients were alive. Thereason for this dramaticimprovement is simple:patients with immune sys-tems weakened by HIVinfection are prone to getsick with infections that peo-ple with healthy immunesystems can normally fightoff. On antiretroviral the-rapy, the rates of theseopportunistic infectionswere significantly reduced

�gold standard� of undetectable levels ofviremia (less than 125 copies in the testavailable) or using a higher level thatsome have suggested is more appropri-ate to developing country contexts, asshown in Graph 3.

These encouraging results occurredwith very few serious adverse events.There were no deaths related to drug tox-icity, and while 46% of patients reportedat least one side-effect, most of thesewere minor, scoring only a 1 or a 2 onthe AIDS Clinical Trials Group gradingof adverse events, with 1 being the mostmild and 4 the most serious (64% weregrade 1, grade 2:19%, grade 3:11% andgrade 4:6%).

Three key factors

In analysing the programme�s successto date and assessing the possibilities touse it as a model in other settings, threekey aspects stand out.

First and most fundamentally, thedrugs must be affordable. In this case, itmeant beginning with brand-name drugswhich, although considerably cheaperthan in developed countries (or, indeed,in South Africa a few years earlier), werestill much more expensive than genericversions produced in countries such asBrazil, India and Thailand. These alter-natives were not registered in SouthAfrica, but after authorisation to use Bra-zilian generic antiretrovirals was receivedfrom the South African Medicines Con-trol Council, a change to Brazilian drugshas allowed twice as many patients to betreated.

The second key to success was theinvolvement of the community. This wasfacilitated by giving all treatment at pri-mary health care level, rather than at alarge reference hospital. Additionally, thecommunity was integrally involved in theprocess of selecting patients for therapy,which played a major role in guaran-teeing local ownership over the projectas a whole (see Box 1 for more on theselection process).

6.05.55.04.54.03.53.02.52.01.51.00.5

0

Oppo

rtunis

tic in

fecti

ons p

er pa

tient

–yea

r

Incidence risk ratio: 3.19 (95% CI: 2.62–3.91) N=159

69%

All (pre-ARV) All (on ARV)

➪

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

TB in

fecti

ons p

er pa

tient

–yea

r

Incidence risk ratio: 6.81 (95% CI: 3.02–19.00)

85%

TB (pre-ARV) TB (on ARV)

➪

250

200

150

100

50

050–9910–49<10

Base

line c

ount

Baseline 6 mont N=59h

100–199

Graph 1Impact of antiretroviral therapy on incidence rates of opportunisticinfections (all and TB only)

Graph 2Median CD4+ T cell counts at baseline andsix months, stratified by baseline count

(see Graph 1). The reduction was parti-cularly striking for tuberculosis, whichis one of the major killers of people withHIV/AIDS in South Africa.

Reduction in opportunistic infectionsis largely attributable to the considerableimprovements seen in immunologic sta-tus. After six months on therapy, the meanincrease in CD4+ T cell count was 143.This meant that while 54% of patientshad below 50 CD4+ T cells at the start oftherapy, only 2% were still below thislevel after six months; in contrast, nonewere above 200 at baseline, while at sixmonths 53% had climbed above thisimportant threshold. Interestingly, evenpatients with severely compromisedimmune systems at initiation of therapyexperienced large improvements afterbeginning antiretroviral therapy, as shownin Graph 2.

These improvements were possiblebecause antiretroviral therapy effectivelysuppressed viral replication in the largemajority of patients, thus allowing theimmune system to recover, instead ofhaving to concentrate its energy on fight-ing off HIV infection. This success wasevident whether measuring using the



Issue No. 32, 2003

Finally, the involvement of the pa-tients themselves has been essential.They are genuine partners in the projectat a number of levels:

➤ At the political level, when politicianshave questioned the validity of usingantiretroviral therapy in resource-poor settings, it was the patients whoresponded, writing letters to newspa-pers and speaking out in the media.

➤ At the community level, they play animportant role in the support groupsrun for patients on antiretroviraltherapy, with those who have been ontherapy for longer periods of timehelping mentor those beginning.Also, a number of patients workwith a South African NGO, the Treat-ment Action Campaign, on a majorcommunity education initiative.

➤ At the individual level, patients haveeducated themselves on the impor-tance of adherence, allowing themto take responsibility for their owntherapy, making it unnecessary to usemedical staff to observe them takingtheir pills (see also Box 2).

influx of patients with HIV,many of whom are dying,despite the best efforts of thestaff. When antiretroviralsare available, the staff�s roleshifts back from care of thedying to being able to helppatients return to goodhealth, with an obviousimprovement in morale.

Additionally, access toantiretroviral therapy pro-vides an important reasonfor patients to stay in themedical system: in Khay-elitsha, not a single patienton antiretroviral therapyhas been lost to follow up,in marked contrast with the

Box 1

Selecting patients for antiretroviral therapy◆ ◆ ◆

Patient selection is one of the more difficult aspects of setting up a programme, asthe need inevitably outstrips the supply of drugs available. However, it is importantto note that, contrary to popular perception, not all people with HIV should immedi-ately be placed on antiretroviral therapy. In Khayelitsha, the biological and clinicalcriteria used to select patients include:

◆ a CD4+ T cell count of less than 200, and a WHO disease stage of 3 or 4, bothin line with WHO’s recently-released guidelines on antiretroviral therapy inresource-poor settings;

◆ patients must live in Khayelitsha;

◆ patients must have regularly attended the clinics for at least three months(instituted in light of the highly mobile nature of Khayelitsha’s population).

These requirements plus the fact that some patients chose not to take antiretroviraltherapy mean that the number of patients who were ultimately candidates to bestarted on therapy has not overwhelmed the resources available.

Nonetheless, a system was introduced that involved the community in the processof selecting patients. A number of community representatives – typically peoplewith experience with people with HIV (and including those with HIV themselves) –met regularly to assess candidates and determine who would ultimately be placedon therapy. Deliberations are based on a number of factors, such as the health ofthe patient, their income level, the social support available to the patient and her/his openness about HIV infection, and if other members of the same family arealready on antiretroviral therapy. Although the process is time-consuming, it hasproven a valuable way to fairly and equitably allot spots in the treatment pro-gramme, as well as an important means of ensuring community ownership overthe programme.

Box 2

Patient-centred approaches to adherence◆ ◆ ◆

The issue of how to ensure that antiretroviral therapy is taken regularly and appro-priately has generated considerable discussion and controversy. Some even suggestthat the use of antiretroviral therapy in poor countries will only lead to the wide-spread development of resistance. They advocate either that resources are not putinto making the drugs available or that they are only administered under strictlycontrolled conditions, such as in the presence of medical staff (along the lines ofthe DOTS model for TB, although the comparison is complicated by the greaterfrequency of dosing of antiretroviral therapy and the fact that it is life-long ratherthan of a limited duration). However, in Khayelitsha, an approach centred oneducating patients and empowering them to be actively involved in the treatmentprogramme has yielded very positive results.

This begins with the careful selection of a regimen that is easy to take – for examplea combination of nevirapine and co-formulated AZT/3TC, which amounts to twopills twice a day – and setting the health care facilities within easy reach of thepatients (for example, at primary health care level). Once patients begin therapy(after an educational process), a tripartite programme supports adherence:

◆ Individual support is available in the form of trained counsellors available duringclinic hours to answer questions, and, more informally, through “treatmentassistants,” a household member or neighbour whom each candidate for therapyis requested to identify who can provide support on adherence;

◆ Peer support comes in the form of support groups run solely for patients onantiretroviral therapy, and which serve both as valuable spaces for patients todiscuss barriers to adherence with others sharing similar experiences and as aforum for ongoing education;

◆ Educational materials are provided to help patients fully appreciate the risks andbenefits of antiretroviral therapy, and understand the importance of adherence.

Research is ongoing to quantify the levels of adherence, but the dramatic improve-ments in the surrogate markers of changes in viral load and CD4+ T cell countsstrongly suggest that adherence is good.

“People must know that a poor person likeme living in a shack can take these drugsproperly. They are my chance to live.”Patient on antiretroviral therapy in Khayelitsha, SouthAfrica.

100%90%80%70%60%50%40%30%20%10%

0%Six monthsThree monthsBaseline

Perce

ntage

with undetectable viral loadN=76 (3 mths.)

with viral load <5000 copies/mlN=59 (6 mths.)

Graph 3Viral load (HIV RNA) at baseline, three andsix months

general experience in this highly mobiletownship. Finally, the significant de-creases in opportunistic infections (andthe resultant need for hospitalizations)suggest that those who argue thatantiretroviral therapy is unattainable,based on crude calculations of the costof drugs, are missing a fundamentalaspect of the provision of antiretroviraltherapy. That is that a considerablepercentage of the costs incurred by drugpurchases can be offset by drops inhospitalisations and opportunistic in-fections. This has been demonstrated inBrazil2, and is quite likely to be true inSouth Africa, a country that spends anestimated R4 billion (approximatelyUS$400 million) on care and treatmentof people living with HIV/AIDS.3 Re-search is ongoing in Khayelitsha toquantify the magnitude of this offsettingeffect.

Finally, in contrast to those who ar-gue that treatment and prevention areinextricably opposed and competing forresources, in Khayelitsha the synergy

The lessons

The project has revealed anumber of important lessons:

First and foremost, anti-retroviral therapy can be safelyand effectively used in resource-poor settings, and the time hascome to scale up from pilot projects towidespread access.

Managing patients on antiretroviraltherapy is often easier than managingpatients not taking antiretrovirals. Pa-tients in advanced HIV infection arefrequently ill with a variety of oppor-tunistic infections, many of which aredifficult to diagnose and treat, particu-larly at a primary health care level. Incontrast, patients on antiretroviral therapytypically experience rapid improve-ments in their health, and, particularlyafter the first few months on antiretroviraltherapy (when the bulk of side-effectsoccur), they can be followed by nurses.In Khayelitsha, this was facilitated bythe development of standardised tools toassist in the assessment and managementof adverse events.

The availability of antiretroviral therapybolsters the entire health system. SouthAfrica � and many other sub-SaharanAfrican countries � is experiencing amajor loss of medical staff, in part as aresult of poor working conditions andlow morale engendered by the enormous

between treatment and prevention hasbeen striking, with the availability oftreatment providing a powerful incen-tive to learn one�s status. It was thus nosurprise that a recent survey of nine sitesaround South Africa found that Khay-elitsha had the highest rates of HIVtesting, and desire to be tested amongthose who had yet to be tested, as well asthe highest levels of condom use.4 ❏

References

1. Médecins Sans Frontières. Untangling the web ofprice reductions: a pricing guide for the purchase ofARVs in developing countries. 2nd ed. Paris: Méde-cins Sans Frontières; 2002. Available at URL: www.accessmed-msf.org

2. Ministry of Health of the Federative Republic of Bra-zil. Response: the experience of the Brazilian AIDSProgramme. Brasilia: Ministry of Health; 2002. Avail-able at URL: http://www.aids.gov.br/final/biblioteca/reposta/resp_ingles.pdf

3. National Treasury of the Republic of South Africa.Intergovernmental fiscal review. Pretoria: NationalTreasury of the Republic of South Africa; 2001.

4. Parker W, Oyosi S, Kelly K, Fox S. On the move:the response of public transport commuters to HIV/

AIDS in South Africa. Johannesburg: Centre forAIDS Development, Research, and Education;2002. Available at URL: http://www.cadre.org.z a / p d f / O n % 2 0 t h e % 2 0 M o v e % 2 0 F i n a l %20Report.pdf

* Toby Kasper was Head of Mission for MSFSouth Africa at the time this paper waswritten, and now works for the Global Fund


to Fight AIDS Tuberculosis and Malaria.Francoise Louis works for MSF South Africa,PO Box 27401 Rhine Road, 8050 CapeTown, and David Coetzee, Andrew Boulleand Katherine Hilderbrand work in the De-partment of Public Health and PrimaryHealth Care, University of Cape Town,South Africa.


Issue No. 32, 2003

S

CBIA: improving the quality of self-medicationthrough mothers’ active learning

➢ SRI SURYAWATI*

ELF-MEDICATION is beneficial forthe treatment of minor ailmentsonly if there is sufficient know-ledge about the correct use of the

medicines. There are at least five piecesof information required for appropriateself-medication: information about theactive compound; indication; dosageand administration; side-effects; andcontraindications. However, a survey car-ried out in Yogyakarta, Indonesia, in 1993showed that the level of knowledge moth-ers had about medicine was consideredinadequate to support safe and effectiveself-medication (see Figure 1).

been limited. In a large country like In-donesia, with over 200 million people,it is impossible to rely on the limiteddrug information services available. Thecommunity should be empowered andequipped with skills to seek informationrapidly and correctly, using any availablesource of information. In short, there isan urgent need for an innovative publiceducation strategy that promotes activelearning; facilitates self-learning; em-powers the community with skills and acritical attitude in seeking information;and creates information-seeking behav-iour. The learning process should also betransferable.

When the necessary information is

all the medicines they haveat home, and in addition re-usable sets of medicines canbe provided. Each groupworks with one set of around30�40 preparations in ori-ginal packages, with pricelabels, consisting of severalclasses of medicine, such asantipyretics/analgesics, vita-mins/minerals and coughremedies.

The activity usually takes2�3 hours. A tutor beginswith an introduction on theadvantages/disadvantagesof self-medication, and thenparticipants are requested to

is used for caffeine and paracetamido-phenol for paracetamol.After completing the discussion,

participants are requested to collect theinformation needed for appropriateself-medication: the active ingredient, in-dication, dosage and administration,side-effects and contraindications. At thesame time, participants examine the clar-ity and completeness of information foundon each package. The expected impactof this exercise is to encourage partici-pants to read all information critically.

Is CBIA effective?

CBIA has been field-tested and evalu-ated in a controlled study, in comparisonwith a large seminar, which is a morecommon form of education. One hundredand twelve mothers of low to moderatelevels of education were recruited for thestudy, and randomly assigned to threegroups. Group A received CBIA, GroupB attended a large seminar to train themin the same skills, and Group C servedas the control.

The results showed that the scores ofthe five main components of knowledgeincreased significantly in both Group A(4.9±0.3 to 8.3±0.2; P<.001) and GroupB (4.5±0.6 to 6.4±0.3; P≤.05), in com-parison to controls, where there was nochange (4.2±0.4 to 4.8±0.3; NS). In ad-dition, the increase in knowledge in theCBIA group was significantly greater(P<.02) than among mothers attending

Contra-indication

100%

80%

60%

40%

20%

0%Side

effectsDosage

andadministration

IndicationActivecompound

(n=139)

4%

45%

65%

2% 2%

Perce

ntag

e

Figure 1Percentage of mothers who know the com-ponents of information of the medicinesmost commonly used in their households

Potential for disaster

The most common lack of informa-tion concerns the active compound.Mothers only know the brand-namedrugs marketed for a certain symptom,and therefore, they are sensitive to drugadvertisements. The direct effect of thislack of knowledge can be seen in house-hold drug consumption patterns, whereseveral brand-names with the sameactive compound are used concurrently.This is a waste of money, yet ironically,many studies show that a key factormotivating self-medication is cost-efficiency. But of course the impact ofself-medication cannot only be measuredin financial terms. Figure 1 shows thatthere is ignorance of side-effects andcontraindications, with the risk of usingdrugs incorrectly, for example, long-termuse of analgesics for �keeping healthy�,or the risk of contraindications. If it isnot done correctly the potential benefitsof self-medication can turn to disaster.

An innovative publiceducation strategy

If more information is needed toimprove the quality of self-medication,efforts must be made to equip users withknowledge about the five componentslisted above. Many types of public edu-cation have been tried, such as campaignsthrough the mass media, seminars andarticles in magazines, but their impact has

already available on drugpackaging in Indonesia, whyis it being wasted? As thisinformation is approved bythe Drug Regulatory Author-ity, it is considered reliable,and if it is used optimallypeople will have the factsthey need for appropriateself-medication.

CBIA: taking upthe challenge

CBIA is an abbreviationfor Cara Belajar Ibu Aktif(Mothers� Active LearningMethod). It is an educationalmodule developed by theDepartment of Clinical

Pharmacology, Gadjah Mada University,Yogyakarta, in 1993, aimed at improv-ing mothers� knowledge and skills toselect non-prescribed or over-the-countermedicines. CBIA uses a problem-basedapproach and self-learning process. In-formation printed on the pharmaceuticalpackage is used as training material. Thetraining is intended to empower mothersto seek and critically assess informationon the drugs that they commonly use, andto increase drug procurement efficiencyin households.

Conducting CBIA sessions

The CBIA module uses small-group(6�8 people), interactive discussions. Theprocess can be incorporated in regularmeetings of women�s grass roots organi-zations, as well as in other arrangedgatherings. Not only mothers but fathersand teenagers can all participate. Com-munity gathering points, such as houses,mosques and village offices, are excel-lent for conducting CBIA. Students orothers familiar with the contents of drugpackages can be recruited as tutors, andit is also possible to invite tutors fromthe target groups. Before carrying out theactivity, tutors familiarise themselveswith the problems relating to each drugpackage being used in the session. A phar-macist or physician can be invited as aresource person.

Each participant is requested to bring

10

8

6

4

2

0Control(n=32)

Seminar(n=42)

CBIA(n=38)

Scor

e of k

nowl

edge

(of m

axim

um sc

ore)

Before intervention

After intervention

Figure 2Average score of knowledge on themedicines most commonly used in theirhouseholds

form small groups. Using the medicines,they observe where they can find infor-mation on active ingredients, grouptogether over-the-counter drugs basedon their main ingredients (not theindications), and then discuss the findings.

Topics to cover

Discussion should, as a minimum,cover the following points, (although ex-perience shows that participants canidentify others, and sometimes come upwith surprising findings):➤ Active ingredients are always stated

on the package, and this informationis hardly ever found in drug adver-tisements. Incomplete and unclearinformation in drug advertisementscan be clarified by consulting the drugpackage.

➤ Brand names may be sold in many dif-ferent forms, e.g., syrup, tablet, etc.,with exactly the same active com-pound. Participants should learn thedifference between brand names with�Forte� or �Plus� included, and theirconventional forms.

➤ Though the brand names for adultsand children are often similar, theactive ingredients are sometimes dif-ferent. Participants should be awareof those differences.

➤ Prices vary between the drug forms,for example, syrups may be 10 timesmore expensive than tablets.

➤ Drug purchasing can be more efficient

10

8

6

4

2

0Control(n=32)

Seminar(n=42)

CBIA(n=38)

Numb

er of

bran

dnam

espr

ocur

ed in

one m

onth

Before intervention

After intervention

Figure 3Average number of brandnames procured inhousehold in one month

if people think about theprices in relation to thedose. Brand names with�Forte� in may be severaltimes more expensivethan the conventionalone, although there isonly a slight difference inthe amount of the activeingredients.

➤ For commercial pur-poses, the names ofactive ingredients areoften hidden in othernames, which are notcommonly known bythe public. For example,1,3,7 trimethyl-xanthine


(P<02)


Issue No. 32, 2003

A➢ G.B. SIMPSON, D. GOVINDA DAS

CCESS to standardised and vali-dated information on drug useis essential to verify patternsof drug utilization, identify prob-

lems and monitor the outcome ofeducational or other interventions. Veryfew studies of in-patient drug use havebeen reported from developing countries,but in April 2000 Osmania GeneralHospital in Hyderabad, India, began afour-year study to analyse drug utili-zation trends among its in-patients.Osmania is a tertiary level governmentteaching hospital with 39 wards, 21departments and 1168 beds, with pa-tients coming from throughout AndhraPradesh State. The research uses WHOdrug indicators, with the data collectedbecoming the basis for the design andevaluation of interventions. In line withWHO recommendations for such stud-ies, researchers are using the AnatomicalTherapeutic Chemical (ATC) classifica-tion system and the measuring unit isthe number of defined daily doses perthousand patient days (DDD/1000PDDefined Daily Dose). A DDD is the �typi-cal� dose of a drug, used to treat the mostcommon medical problem for whichthe drug is prescribed. Its use facilitatescomparison and discussion of differencesin drug use in internationally acceptedunits.1�5

Retrospective data from 1-4-2000 to31-3-2002 were collected and analysedfor the use of drugs and a two-year pro-spective study is underway for the period1-4-2002 to 31-3-2004. The retrospectivedata were used to design interventionsto change prescribing behaviour, andevaluate the outcome of interventions.

The statistical analysis consisted ofthe names and quantities of drugs usedfor a year, as well as the annual numberof patient days (the sum of all days whichall patients spent in a hospital for a year).

The total quantity of a drug used isdivided by the DDD for that drug and thenumber of DDDs used for a year is cal-culated. This number is further dividedby the number of thousands of days that

all patients have spent in OsmaniaGeneral Hospital for that year. Finally thedrug utilization is expressed in numberof DDD used per 1000 patient days.

The 20 most used drugs are shownin Table 1. Overall drug utilization inOsmania General Hospital was 4426.66DDD/1000PD during 2000�2001 and4484.35 DDD/1000PD during 2001�2002. On average each patient received4�5 drugs daily. In comparison in a Ser-bian study the drug utilization was7133.87 DDD/1000PD during 1997 and8597.03 DDD/1000PD during 1998.6

At Osmania Hospital two major pre-scribing irrationalities were observedafter an analysis of use of individualdrugs and drug groups.

CorticosteroidsThe use of corticosteroids during

2000�2001 was 508.42 DDD/1000PDand during 2001�2002 was 536.81 DDD/1000PD. In Serbia during 1997 the rateswere 325.00 DDD/1000PD and in 1998,320.70 DDD/PD.6 In Osmania Hospitalthere is widespread use of corticosteroids,which may lead to many toxic effects.Two categories of toxic effects resultfrom the therapeutic use of cortico-steroids, those resulting from withdrawalof steroid therapy and those resultingfrom continued use of supraphysiologicaldoses. The side-effects from both of thesecategories are potentially life threateningand a careful assessment of the risks andbenefits in each patient is essential.7

RanitidineRanitidine use was 380.42 DDD/

1000PD during 2000�2001 increasing to488.92 DDD/1000PD during 2001�2002.At Osmania, ranitidine is prescribed asprophylaxis against Non Steroidal Anti-Inflammatory Drugs (NSAIDs) inducedulcers, and treatment of peptic ulcer,gastroesophageal reflux disease, andnon-ulcer dyspepsia. Prophylactic use ofranitidine is not needed with short-termNSAIDs therapy in patients without anyhistory of ulcer disease.

Indian hospital drug use studyshows need to improve prescribing

Taking actionAn intervention programme to change

doctors� prescribing behaviour isunderway at Osmania General Hospital,through educational activities such aslectures, seminars, group teaching anddistribution of printed material to reducethe use of corticosteroids and ranitidine.Already another Indian study has shownthe benefits of such educational interven-tions to improve prescribing. In a drugutilization study done in GovernmentHeadquarters Hospital, Ooty, 46% ofpatients admitted were prescribed rani-tidine. After an educational programmea 30% decrease in ranitidine use wasnoticed after one year.8 ❏

Dr G.B.Simpson and Dr D.Govinda Das,Department of Clinical Pharmacologyand Therapeutics, Osmania MedicalCollege/Osmania General Hospital,Hyderabad-500012, India. E-mail: [email protected]

References

1. WHO. The use of essential drugs. Technical ReportSeries No.895. Geneva: World Health Organization;2000, 1�8.

2. WHO. How to investigate drug use in health facilities,Geneva: World Health Organization; 1993. EDMResearch Series No.7, 3�27.

3. WHO. How to develop and implement a national drugpolicy, 2nd ed. Geneva: World Health Organization;2001, 59�68.

4. Quick JD, Rankin JR, Laing RO, O�Connor RW,Hogerzeil HV, Dukes MN, Garnett A, eds. Managingdrug supply, 2nd ed. West Hartford, CT: Kumarian Press;1997, 430�449.

5. WHO. ATC index with DDDs. Olso: WHO Collabo-rating Centre for Drug Statistics Methodology; 2002.Web site: http://www.whocc.no/atcddd/

6. Jankovic SM. Drug utilization trends in �Kragujevac�clinical hospital centre from 1997 to 1999. Indian Journalof Pharmacology 2001; 33; 29�36.

7. A.Gilman, J.Hardman and L.Limbird, eds. Goodman& Gilman�s the pharmacological basis of thera-peutics. 10th ed. New York: McGraw-Hill Press; 2001,1666�1668.

8. Johnson G. Impact of drug utilization programme onranitidine in a South Indian Hospital. Indian Journal ofPharmacology 2001;33:43.

Table 1Top 20 drugs used in Osmania General Hospital(Drug use is expressed as number of DDDs/1000 PD)

Name of the drug 2000–2001 Name of the drug 2001–2002

1. dexamethasone 430.98 ranitidine 488.922. ranitidine 380.42 dexamethasone 442.223. diclofenac 330.42 declofenac 370.124. normal saline 287.73 normal saline 296.345. ampicillin 254.58 ringer’s lactate 243.886. ringer’s lactate 238.14 ampicillin 227.177. dextrose 5% 196.25 ciprofloxacin 198.468. dextrose saline 172.19 dextrose 5% 190.389. furosemide 146.61 dextrose saline 186.2010. atropine 145.71 furosemide 141.5011. ciprofloxacin 140.10 metronidazole 132.3212. CPM 117.61 CPM 108.3613. gentamycin 106.18 paracetamol 103.1814. metronidazole 102.54 gentamycin 101.1815. ibuprofen 95.43 vitamin C 99.8616. dextrose 25% 93.09 ibuprofen 72.7117. paracetamol 90.13 hydrocortisone 67.7118. ferrous sulfate 72.58 atropine 67.0819. vitamin C 61.60 phenytoin 54.4820. hydrocortisone 58.44 ferrous sulfate 54.39

TOTAL USE OF DRUGS 4426.66 4484.35

the large seminar (see Figure 2).Furthermore, the number of brand-

name drugs used in households in aone-month period reduced drasticallyin Group A (5.3±0.3 to 1.5±0.3; P<.001),while in the other groups the number ofmedications did not change (Figure 3).

Not only was the CBIA approach ef-fective in increasing knowledge andreducing the number of products used,but all of the mothers who underwentCBIA intervention found this type ofproblem-based learning enjoyable.

After dissemination of the field-test

results, CBIA was replicated by inter-ested colleagues in various settings.Feedback on use of the interventionshows that CBIA works well with groupsof mothers, fathers, the elderly, teenag-ers and primary school students. The bestresults were achieved with mixed groups.Experience shows that a forum consist-ing of mothers, fathers and familymembers living in an immediate neigh-bourhood resulted in a more sustainedimpact. A practical guide to conductingCBIA is available in English from theaddress below.

Maintainingthe momentum

Interested students at Gadjah MadaUniversity, Yogyakarta, can includeCBIA in their public service programme,a part of their formal training in the finalyear. CBIA has also been adapted andsuccessfully field-tested to improve thequality of information given by person-nel delivering medications to patientsin health facilities. Journalists becamevery interested after attending sessions,and articles about CBIA have appearedin leading national newspapers and a

popular womens magazine (Kompas,29 October 1995, Kedaulatan Rakyat,5 May 1997 Kartini, 25 September 1997).The message is now spreading furtherafield, with BBC London broadcast-ing an interview with the writer in June2002. ❏

* Dr Sri Suryawati is Head of the ClinicalPharmacology Department, Faculty of Medi-cine, Gadjah Mada University, Yogyakarta,Indonesia. Tel: + 62 274-563596, fax:+ 62 274-543711, e-mail: [email protected]



Issue No. 32, 2003

IN its efforts to promote safe andcost-effective use of medicines,WHO has recently released thefirst edition of the WHO Model

Formulary. The Formulary is the firstglobal publication to give comprehen-sive information on all 325 medicinescontained in the WHO Model List ofEssential Medicines. It presents informa-tion on the recommended use, dosage,adverse effects, contraindications andwarnings of these medicines. Correct useof this tool will improve patient safetyand limit superfluous medical spending.

A look at some statistics shows whythe need for such a formulary is so great.Bad prescribing habits are very commonin all countries of the world and overuse,under-use and misuse of medicines re-main widespread. For example, 30�60%of patients in primary health care centresreceive antibiotics (perhaps twice whatis clinically needed); 25�75% of antibi-otic prescriptions in teaching hospitalsare inappropriate; half of the 15 billioninjections given world wide each yearare not sterile; and many of these are noteven needed. Only one in two countriesactively regulate drug promotion, and lessthan 50% of people with chronicillnesses, such as diabetes and hyper-tension, adhere to prescribed treatment.Ineffective and unsafe treatment leads toexacerbation or prolongation of illnessand harm to the patient. In addition, in-appropriate treatment increases the coststo the patient, the insurance system or thegovernment.

Evidence-based selectionRational drug use depends heavily on

selecting essential medicines that reflectthe best combination of efficacy, safetyand comparative cost-effectiveness. Theirselection should be evidence-based andfree from commercial influence. In 2002,WHO introduced new procedures aimedat establishing a model selection processfor updating its Model List of EssentialMedicines. This new process now in-cludes tying selection directly totreatment guidelines, preparing system-atic reviews of the clinical evidence forproposed choices, and making this evi-dence publicly available in advance ofdecision-making meetings. This meansthat there is an opportunity for all stake-holders (including industry and patientadvocacy groups) to comment on pro-posed changes in the List, before takingthe final decisions in a closed meetingof independent experts, and publiclydocumenting the reasons for eachdecision.

Effective use of medicines also de-pends on the actions of health careproviders, formal and informal distri-bution channels, the pharmaceuticalindustry and the public. Over the lastdecade, through the efforts of the Inter-national Network for Rational Use

WHO’s new Model Formulary – promotingconsumer rights and patient safety

of Drugs (INRUD), and a host of op-erational research initiatives, much hasbeen learned about improving the use ofmedicines. For example, it has beenshown that interventions such asunfocused drug information, treatmentguidelines without active follow-up, andnon-interactive communication effortshave no measurable impact. On the otherhand, standard treatment guidelines sup-ported by effective training programmeshave been shown to reduce mortalityfrom acute respiratory infections in chil-dren. Targeted training of licensed drugsellers can increase dispensing of effec-tive treatment and reduce dispensing ofunsafe ones for diarrhoea and acute res-piratory infections; and interactive groupdiscussions involving prescribers andmothers can dramatically reduce theoveruse of injections. The challenge forhealth policy-makers is to learn fromthese lessons and act accordingly.

It is estimated that only two-thirds ofdeveloping country populations havesome form of access to essential medi-cines. For those countries, pharmaceu-ticals can represent as much as 40% ofthe health budget. Because of the con-siderable impact on the quality of careand the cost of treatment, the selectionof essential medicines, and their appro-priate use, constitute the most effectiveapproach to improving equitable accessto health care. This principle also appliesto industrialised countries, where detailsof medical insurance coverage are alwaysimportant concerns for the public, andcentral to policy debates. For example,in Europe and North America annualmedicine expenditure in-creases of 10�18% in1999�2001 are raisingconcerns among public reim-bursement schemes andhealth insurers. Prepaymentand insurance schemes have allfound that application of the es-sential medicines concept iscritical to the financial viabilityof such programmes � no insur-ance system can afford toreimburse all medicines availableon the market.

The WHO Model List of EssentialMedicines, recently updated to include12 essential antiretroviral medicines forthe treatment of HIV/AIDS, focusespharmaceutical efforts on priority condi-tions and quality medicines that are themost cost-effective, safe and affordablepossible. For instance, the vast majorityof medicines contained in the Model Listare well-known and well-establishedpharmaceuticals which are off patent andavailable from many sources.

Adapting to national needsThe new Formulary is primarily

intended as a model for national govern-ments and institutions, to be used as abasis for creating their own national for-mularies. It is particularly relevant fordeveloping countries, where commercialand promotional materials are often theonly available source of drug informa-tion for health workers, prescribers andpatients. The WHO Formulary may alsobe useful for individual prescribers � andfor this reason it is available at reducedcost for developing countries.

The Model List of Essential Medi-cines and the Model Formulary constitutethe backbone of the new WHO EssentialMedicines Library (www.who.int/medi-cines), which is being developed. Visitorsto this site will find the reasons drugswere included on the Model List, the un-derlying evidence, price information andnormative information, such as Interna-

tional Nonproprietary Names (INN), In-ternational Pharmacopoeia monographs,and the Anatomic, Therapeutic andChemical (ATC) and Defined Daily Dos-age (DDD) classifications. To makeaccess to information as wide as possi-ble, the WHO Model Formulary isavailable both in PDF format and as asearchable database. A CD-ROM versionis in preparation.

National and institutional committeescan also decide to use the WHO ModelFormulary as a starting point for theirown formularies. Rather than startingfrom scratch they can use the existingWHO text and adapt this to their localconditions. They can do this by eliminat-ing medicines which do not figure ontheir national list, entering other medi-cines from their national list, and addingspecific information on national prod-ucts, brand names, product specificationsand prices. It should be stressed, how-ever, that the availability of this WHOtext should not be used to cut short onthe development process of a national or in-stitutional formulary. An essential conditionfor the acceptability and use of a formularyis a development and review process whichinvolves wide consultation among future us-ers. Formulary committees interested in thisapproach should contact their national orregional WHO offices for advice. ❏


© WHO 2003

The WHO Model Formulary2002 is available from:World Health Organization,Marketing and Dissemination,1211 Geneva 27, Switzerland.Price: Sw.fr.40, US$36, and indeveloping countries US$20.

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