HTA and Managed Entry Practices in Europe Industry Perspective … · ... Key principles for the...

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HTA and Managed Entry Practices inEurope

Industry Perspective

Dr Mercia PagePIPERSKA WORKSHOP,

GLASGOW 9th July 2009

OUTLINE

• Research and Innovation• Healthcare environment• HTA principles in practice

– Horizon scanning– Added therapeutic value– QALYs– Patient access schemes

• Conclusions

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Research and innovation

• Innovation– Bringing new/ improved technologies to

market that enhance the health of patientsand thereby bring value to patients, carers,families healthcare professionals and widersociety

• How to value innovation?

Innovation

• Extent of unmet need• Disease prevalence• Condition severity• Condition resolution vs stabilisation• Duration of benefit• Availability of alternative treatments• Patient convenience/ compliance

1960

1980

2000

Clofibrate

Carvedilol

1970

1990

Esmolol

Atenolol

Pindolol

Nadolol

Doxazosin

Terazosin

Prazosin

Phentolamine

Propranolol

Metoprolol

Sotalol

Labetalol

Timolol

Verapamil

Captopril

Nifedipine

Colestipol

Pronethanol

Losartan

Irbesartan Eprosartan

Acetalozamine

ChlorthiazidesFurosemide

Triamterene

Chlorthalidone Amiloride

Enalapril Lisinopril

BFGPeptides

Gemfibrizol

Lovastatin

QuinaprilRamipril

Benzapril

Perindopril

Pravastatin

Simvastatin

Atorvastatin

Diltiazem

AmlodipineNicardipine

Felodipine

Nimodipine

Isradipine

RosuvastatinMajor classes of innovative medicines introduced for CV disease

Source: The Impact of Therapeutic Reference Pricing on Innovation in Cardiovascular Medicine, Desmond Sheridan& Jim Attridge, 2006, Pharmacoeconomics, 24 Suppl.2, 40

““Vicious CircleVicious Circle””

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Health careresources are limited

Reimbursement ofinnovativetechnologies is achallenge in eachhealth care system

Without reimbursementpatients cannot getaccess to these life-saving technologies

Return on R&Dinvestment isreduced, innovativetherapies are moreexpensive

Source: Dr. Zoltán Kaló, Director, Health Economics Research Centre (HERC)Eötvös Loránd University, and President, Hungarian Health Economics Association &ISPOR Hungary Chapter, from presentation made 14 October 2008

Continually evolving context• Unprecedented economic downturn in addition to ageing, rising

expectations, greater incidence and prevalence of chronicconditions etc

• Impacts of economic downturn likely to be felt in a number of waysin the health care sector:– Unemployment on the rise and evidence that unemployed have higher

health needs than employed– Increase in ill health in the population as even employed become

worried– Delay of improvements in lifestyle behaviours (eg putting off quitting

smoking) and perhaps more poor lifestyle behaviours– Potential for ‘real’ budget cuts for health– Unclear extent or focus of cuts but perhaps prevention and other ‘soft’

targets such as medicine budgets

Together these all suggest even greater need for appropriate ways toinform inherently difficult resource allocation decisions

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Guiding principles for HTA

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Structure of HTAprogrammes Methods of HTA Processes for

conduct of HTAUse of HTA in

decision making

1. The Goal and Scope ofthe HTA Should BeExplicit and Relevant to ItsUse2. HTA Should Be anUnbiased andTransparent Exercise

3. HTA Should Include AllRelevant Technologies

4. A Clear System forSetting Priorities for HTAShould Exist

5. HTA Should IncorporateAppropriate Methods forAssessing Costs andBenefits

6. HTAs Should Considera Wide Range ofEvidence and Outcomes

7. A Full SocietalPerspective Should BeConsidered WhenUndertaking HTAs

8. HTAs Should ExplicitlyCharacterize UncertaintySurrounding Estimates

9. HTAs Should Considerand Address Issues ofGeneralizability andTransferability

10. Those ConductingHTAs Should ActivelyEngage All KeyStakeholder Groups

11. Those UndertakingHTAs Should Actively SeekAll Available Data

12. The Implementation ofHTA Findings Needs to BeMonitored

13. HTA Should Be Timely

14. HTA Findings Need toBeCommunicatedAppropriately to DifferentDecision Makers15. The Link Between HTAFindings and Decision-Making Processes Needs toBe Transparent and ClearlyDefined

Source: International Group for HTA Advancement (also called Drummond et al 2008), Key principles for the improved conduct of health technologyassessments for resource allocation decisions, International Journal of Technology Assessment in Health Care, 24:3 (2008), 1–15

Managed entry in the UK … more than HTA… full lifecycleNational……Regional……..Local

National Influence

Horizon scanningNHSC (National Horizon Scanning Centre)UKMI (UK Medicines Information)NPC (National Prescribing Centre)

HTA centresNICE (National Institute for Health andClinical Excellence)SMC (Scottish Medicines Consortium)AWMSG (All Wales Medicines Strategy Group)

Post-launch guidanceUKMI (UK Medicines Information)NPC (National Prescribing Centre)

Regional Influence

LNDG - London New Drugs Group LCNDG – London Cancer New Drugs Group MTRAC – Midlands Therapeutic Review and

Advisory Committee Wolfson Unit – Northern and Yorkshire

regional drug and therapeutics centre Berkshire Priorities Committee South Thames Regional MI Group – Guys,

NeLM Wessex drug and medicines information

centre SHAs Regional Specialised Commissioning Groups

(SCGs) Managed Clinical Networks – Scotland RMSC (Regional Medical Services

Consortium) – NI

Local Influence

APCsD&TCsPCOs – formularies/guidelines/incentivesPBCsPractices – practiceformulariesCancer Networks andother clinical networks


National Horizon Scanning begins

NICE topic selection starts

Other Horizon Scanning Bodies start

Formulary Notification

Updates to additional databases groups

Early engagement with NICE

Primary/secondary carefinancial planninganalysis

Overview of horizon scanning

-3 yrs -2.5 yrs -2 yrs -1.5 yrs -1 yrs -0.5 yrs launch

Electronic Systems Access

HTA submissions start

Dialogue start with SMC/AWMSG plus keyarea Rxing committees


Joint Work on UK HorizonScanning

• Commitment in 2009 PPRS for:

– “a single, unified horizon scanning process to identify newtechnologies in development by the industry. This process will bedeveloped in co-operation with the National Institute for Healthand Clinical Excellence (NICE), the Scottish MedicinesConsortium (SMC), the All Wales Medicines Strategy Group(AWMSG), the National Prescribing Centre (NPC), UKMedicines Information (UKMi) and the National HorizonScanning Centre (NHSC)”

• This coherent UK approach seems to be fit for purpose

• European level work via EIFFEL by EUnetHTA

11Source: DH, 2009 PPRS, http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/DH_091825


Biologics and biosimiliars:We need to think carefully about interchangeability

• A biologic is medicinal product made from living organisms• Non-identical nature of a biosimilar to originator product can lead to

variations in bioactivity & immunogenicity• Clinical trials should be required to demonstrate safety, efficacy & lack of

deleterious immunogenicity of a biosimilar• Impact of interchangeability cannot be feasibly assessed due to required

size of clinical trial• All biologics should have unique names for distinguishing in prescribing,

dispensing, and for pharmacovigilance purposes• Do support an accelerated pathway for development• Do support standards to appropriately characterize molecule including the

conduct of clinical trials• Do not support interchangeability• Do support protecting incentives for innovations• Do support use of unique naming for Biosimilars12

Added Therapeutic Value: SomeApproaches

Swedish TLV explicitlycharged with ‘stimulatinginnovation’ though’ usingcost effectiveness from a‘societal perspective’.

Italian reimbursementcriteria make transparentdeterminations on thedegree of innovation

France – Amelioration duService Medical Rendu (ASMR)“Improvement in the MedicalService” (ASMR) criterionrelates to a medicine’s degree ofinnovation relative to the existingsituation/available treatments.

I. Major: ‘Major therapeutic progress’ II. Important: ‘Important improvement’ III. Modest: ‘Modest improvement’ IV. Minor: ‘Minor improvement’V. No improvement

Other codified criteria include: Severity & prevalence of disease Availability of existing treatments ‘Size’ of the therapeutic effect

Innovation scored on aScale of 1-5

Decision making based on three criteria: Human value principle Need and solidarity principle Cost-effectiveness principle

Added Therapeutic Value and JointAdvice• Emerging trend of greater interest by regulatory

agencies and HTA agencies• Opportunities to learn from this work:

– EMEA is currently looking at the potential for a risk –benefit ranking system which could summarise therelative benefits of products

– Early Scientific Advice in England - NICE– Joint Scientific Advice in UK planned – MHRA and

NICE– Joint Scientific Advice in Sweden - TLV and MPA

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QALYS

• Issues remain over the use of the QALY as themeasure of benefit– Different methods of underpinning the QALY result in

different answers, and not as yet consensus onappropriate method (EQ 5D, HUI3 etc)

– Bias towards life saving technologies– QALYs can discriminate against the old (less life

years left to live) and other groups– Ignores wider benefits, for example carers’ health

status may be improved if dependents’ health statusimproves

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5. HTA Should IncorporateAppropriate Methods forAssessing Costs andBenefits

Thresholds• Range of thresholds for cost/QALY used across Europe• No empirical underpinning• Much debate over appropriate scale of the threshold

(£20-£30,000k range currently used by NICE but othershave suggested it should be lower)

• Needs consideration of both:– Willingness to pay for health outcomes– Opportunity costs (what will be displaced by using a

particular technology)• And other factors which could be used to alter the

threshold (eg severity of disease as a modifier to thethreshold) as used in some countries (eg Sweden, beingexplored in Netherlands)

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TLV approach to cost/QALY thresholdin Sweden

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Flexibility• There is considerable uncertainty over a products value at launch• Modelling and appropriate sensitivity analysis within economic

evaluation component of HTA can explore this• However, uncertainty will still remain in what the full value is and

when it will become evident....• Suggests flexibility is required within HTA and it’s resulting

recommendations• New guidance to NICE Appraisal Committees to take into

consideration when the following criteria are met:– The treatment is indicated for patients with a short life expectancy, normally less

than 24 months and;– There is sufficient evidence to indicate that the treatment offers an extension to

life, normally of at least an additional 3 months, compared to current NHStreatment, and;

– No alternative treatment with comparable benefits is available through the NHS,and;

– The treatment is licensed or otherwise indicated, for small patient populations.

• Too early to determine the impact of this change18


Source, NICE, Dec 2008, http://www.nice.org.uk/media/88A/F2/SupplementaryAdviceTACEoL.pdf

Surrogate markers

• Need to recognise that there will always be risksand uncertainties at a given point in time

• May not be able to measure final outcome givenpractical constraints (may require large trial popn

and long follow up)• Surrogate markers (eg CD4 counts in HIV)

provide an opportunity to measure meaningfuloutcome(s) as a predictor for final outcome

• Area where there needs to be further work todetermine when and which surrogate outcomesare appropriate in HTA19


Releasing funds for innovation• Reduces waste or increasing efficiency could

release funds for innovation• But again, this is hard….• Needs refocused efforts on the part of HTA

agencies to consider technologies and otheractivities in the system which do not bring benefitsand are of limited value

• HTA can identify what to do less of…but otheragencies may need to influence and implementchanges to release funds

• Suggests joint working across the system bydifferent agencies

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3. HTA Should Include AllRelevant Technologies

Patient access schemes

• UK has seen a number of patient accessschemes

• Still relatively early to assess their success inachieving access at acceptable costeffectiveness

• Likely other countries will find the principlesjointly developed between ABPI and the DHuseful

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15. The Link Between HTAFindings and Decision-MakingProcesses Needs to Be Transparentand Clearly Defined

UK NHS agreed to a payer-rebate schemewith J&J for Velcade to treat Multiple Myeloma in 2007

Company: J&JLocation: UKYear: 2007Product: VelcadeDA: Multiple Myeloma

Benefits

• Patients receive effective treatment for lifethreatening disease with few alternatives

• Unique working arrangement with NHSindicated willingness of J&J to engage ininnovative pricing

• May lead to closer working relationshipswith NHS

• Additional sales in UK and reducedPR concerns

Challenges

• Clinical outcomes are not always measurable• Complex issues regarding partial response;

patients who reach 48% reduction non-reimbursable but do have benefit

• May encourage over-use as non responderswill be reimbursed

Payer Rebate

Outcomes

Market access

Takeaways

• Definition of appropriate clinical endpoints iscritical to effective outcomes risk sharing

• May be challenging to implement without post-marketing study of actual (non-trial) use inapproved markets

• Approach predicated upon existing clinical data(observed effectiveness inother countries)

High

Medium

LowMarginal

Incremental

Novel

Other

Acute

Chronic

Patient

Physician

Hospital

Non-reimbursed

Restricted

Unrestricted

Generic

Comparable

Novel

Low

Significant

High

Cash pay

Private

Single payerKey info

Background• No consensus treatment for Multiple Myeloma• Velcade clinically effective in 38% of patients; approved in US in 2003, EU 2004• Cost of one cycle of Velcade is approximately £3,000; results in base-case analysis of

approximately £38,000 per QALY

Structure• Treatment continued for patients with complete or partial response (reduction in serum M

protein of 50% or more)• Response is measured using serum M protein after a maximum of four cycles

of treatment• Rebate for full cost of Velcade after a maximum of four cycles of treatment if patients has

less than a partial response

Outcome• Agreement covered England and Wales — still no coverage in

Scotland as of Oct 2008

Method

Lessons

TreatmentcostInnovation

Diseasetype AdministerPayer

Reimbur-sement

Compe-titionUnmet need

Biogen, Schering,Teva/Aventis, Serono MS Risk SharingScheme for Beta Interferons and Glatiramer Acetate in UK in

2002 and ongoingCompany: Biogen, Schering,

Teva/Aventis, andSerono

Location: UKYear: 2002–ongoingProduct: Avonex, Betaferon,

Copaxone, RebifDA: Muttiple Sclerosis

Background• Annual cost per patient of the beta interferons in the UK in 2002 was £7,259 (Betaferon),

£9,061 (Avonex) or £9,088/£12,068 (lower dose/higher dose Rebif ) and glatiramer acetatewas £6,650

• Significant variation in estimates of cost per QALY; £10,000 per QALY (an estimate derivedfrom commercial-in-confidence data) to over $3 million per QALY (an American researchgroup’s findings)

• Significant uncertainty in clinical benefits in the long termStructure• Target of £36,000 per QALY• 5,000 patients monitored on Expanded Disability Status Scale• Future price reductions could be asked for if fail to achieve this target• Compared against historical Canadian cohort of patients• Specialist nurses funded by manufacturers

Outcome• Widespread patient access to what was then the only treatment

options available• Only report on outcome to date concludes: demonstrates practical,

but highlights political tensions• No data available on cost per QALY estimates and/or if price

reductions have occurred

Benefits

• Patient access• Increased number of specialist nurses

Challenges

• Lack of infrastructure hindered implementation• Conflicts on ownership of data and intellectual

property led to change of contractor tocomplete analysis

• Questions raised about whether a longer termRCT would have been more appropriate

• Change in epidemiology of disease sincescheme set up

Budget

Takeaways

• First example of patient access scheme in UK• Schemes require investment in governance

arrangements

High

Medium

LowMarginal

Incremental

Novel

Other

Acute

Chronic

Patient

Physician

Hospital

Cash pay

Single payer

Non-reimbursed

Restricted

Unrestricted

Generic

Comparable

Novel

Low

Significant

HighKey info

Method

Lessons

Sources: http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_4012214.pdfhttp://www.mstrust.org.uk/research/risksharingscheme/http://www.mstrust.org.uk/downloads/rss.pdfhttp://www.bmj.com/cgi/content/extract/326/7385/388http://www.pharmj.com/Editorial/20020803/news/news_ms.htmlhttp://www.msrc.co.uk/index.cfm?fuseaction=show&pageid=1893&CFID=7878852&CFTOKEN=40510486http://pn.bmjjournals.com/cgi/reprint/3/4/194.pdfhttp://www.parliament.uk/post/pn168.pdfhttp://www.nice.org.uk/guidance/index.jsp?action=byID&o=11441http://www.biomedcentral.com/content/pdf/1471-2377-9-1.pdf

TreatmentcostInnovation

Diseasetype AdministerPayer

Reimbur-sement

Compe-titionUnmet need

Pricing by indication

Maintain market

Private

Patient access schemes: DH and ABPI Principles(1)

• Arrangements must respect the role of NICE in providing the NHS with an independentassessment and appraisal of the evidence on an intervention.

• Schemes are to be discussed first and agreed in principle by the Department and the company.NICE’s principal role is to assess the impact of such proposals on cost-effectiveness taking intoaccount the details of the proposed scheme.

• The full costs to the NHS of any such arrangements should be included in the costs consideredby the Appraisal Committee.

• Schemes should be clinically robust, clinically plausible, appropriate and monitorable (e.g. if it is aresponder scheme, there must be a relatively straightforward way to measure a patient’s clinicalresponse).

• Any scheme should be operationally manageable for the NHS without unduly complex monitoring,disproportionate additional costs and bureaucracy. Any burden for the NHS should beproportionate to the benefits of the scheme for the NHS and patients. Clarity is also required onthe exact duration of any agreement and the circumstances in which it might be terminated.

• It is important that the cumulative administrative burden of such schemes remains manageablefor all parties involved in their operation, including front-line NHS staff. It is reasonable for theDepartment to take this issue into account when considering the viability of individual schemes.Priority is likely to be given to schemes that deliver the greatest benefits to patients, for examplein enabling the NHS to address a previously unmet need.

24Source: DH, 2009 PPRS, http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/DH_091825

• Schemes should be consistent with existing financial flows in the NHS and with localcommissioning (e.g. payers must be able to calculate the effective price for theirpatient population, so the costs and savings accrue to those local services makingcommissioning and treatment decisions).

• The NHS in England and Wales must be consulted on patient access schemes, inparticular where these involve additional data collection beyond that associated withthe conventional purchase of medicines – for example in relation to patient numbers,or the monitoring and recording of a patient’s condition over and above that for thenormal management of a patient. The Department will set out in more detail thenature of that consultation.

• The more systematic use of such schemes will need to be reviewed in light ofexperience. The timing of such a review will be jointly agreed but will be initiated notlater than two years after the commencement of this agreement.

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Patient access schemes: DH and ABPI Principles(2)

Source: DH, 2009 PPRS, http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/DH_091825

HTA and the broader system• Useful to remind stakeholders of how HTA fits in the broader system• Can we ever expect HTA to deal with all the factors that influence

medicines expenditure?• Will always need a suite of tools to enable the system to deliver

optimal value from all inputs• Must also recognise HTA is continually evolving:• “Health technology assessment will have to evolve from an

expression of rationalism in the form of establishing normativebehaviours (e.g., how practitioners should use a given technology)to a means of providing information that will contribute toelucidating preferences. The next phase in its evolution willrequire a major shift from simple, linear dissemination to the morecomplex interactive communication of information with a view toassisting people in making decisions.” (1)

• Much to learn from other countries and networks involved in HTA

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(1) Battista, RN and Hodge, MJ The evolving paradigm of health technology assessment: reflections for the millennium JAMC 1999; 160 (10):1464-67

HTA as a Continuum in Informing Decisions

• Decisions are taken at a number of levels in the system:– Patient level– Provider level (eg Hospital)– Regional level (eg County Councils in Sweden, PCTs in England)– National level

• There can be tensions if the decisions are made on a differentbasis

• HTA can be a aid to consistency in theory (although questionsremain over how far HTA can and has delivered consistency inpractice)

• Must recognise always need for flexibility to fit the local context

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Conclusions

• Pharmaceutical R&D is costly, risky and takesconsiderable time

• Health care systems and wider economic environmentcontinually changing

• Current economic downturn places even greater focuson difficult resource allocation decisions

• HTA can inform these decisions, and should be guidedby principles for ‘good’ HTA

• Flexibility is useful in structures, methods, processes,and use of HTA in decision making, whilst respectingprinciples for HTA

• HTA links to patient access schemes directly but theytoo need flexibility and to be guided by principles for‘good’ schemes

• Still much work to be done, but increasingly networkedworld of HTA with expertise to draw on across the globe

• Ongoing dialogue will be required28

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Thank you!

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