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OSI Public Health Program Seminar

Safety of Medicines

Presentation byPaul Lalvani, Pharmacist, MBA

Executive Director, RaPID

March 6, 2007

Implementing Drug Safety in 90 days

“Some remedies are worse than the disease” Publilius Syrus, Roman writer, 1st century BC.

Rapid Pharmacovigilance Implementation in Developing Countries

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O r ganizat ion f o r Innovat ion

Impl ement at ionand Impac t

O3i

O r ganizat ion f o r Innovat ion

Impl ement at ionand Impac t

O3i

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“Primum non nocere” (First do no harm)Hippocrates 500BC

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Overview of Presentation

What is P’vigilance

(PV)

WhyP’vigilance

is Important

Current Status of

P’vigilance

The RaPID™ Approach

Conclusions

P’vigilanceand Public

HealthPrograms

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Pharmacovigilance

Pharmacovigilance is defined as

“the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problems”

The Safety of Medicines in Public Health Programmes: Pharmacovigilance an essential tool, World Health Organization, 2006

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Objectives of Pharmacovigilance

• improve patient care and safety

• improve public health and safety

• encourage safe, rational and appropriate use of drugs

• promote understanding, education and clinical training in pharmacovigilance

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Sample Adverse Drug Reaction Report (

ADR Report)

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Pharmacovigilance Reporting Process

(movement of information)

HIV/AIDS, TB, Malaria

Hematology

Pulmonary/Chest

Emergency

Surgery

Endocrinology

All other

RaPID’s Focus

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Illustrative Representation of National Pharmacovigilance Programs

National Pharmacovigilance Program

HIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

Other

HIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

Other

HIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

Other

HIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

Other

HIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

Other

HIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

OtherHIV/AIDS

Hematology

Pulmonary/Chest

Emergenc

y

Surgery

Endocrinology

Other

Zon

e 1

Zone 2

HIV/AIDS

Hematology

Pulmonary/Chest

Emergency

Surgery

Endocrinology

Other HIV/AIDS

Hematology

Pulmonary/Chest

Emergency

Surgery

Endocrinology

Other

HIV/AIDS

Hematology

Pulmonary/Chest

Emergency

Surgery

Endocrinology

Other

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Illustrative Representation of National Pharmacovigilance Programs

National Pharmacovigilance Program

Department ofPharmacovigilance

Data Entry &Report

GenerationVigiflow®

Data MiningSignal Analysis

TriageReview by Experts

Policy Recommendations andFine tuning of Public Health Programs

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Overview of Presentation

WhyP’vigilance

Is Important

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Impact of ADRs in USA

• 1.2 million hospitalized patients in 20041

• Cost of drug-related morbidity and mortality >$177.4 billion2

• ADRs are the 4th - 6th leading cause of death3

1 Exilhauser, Owen AHRQ 20072 Ref. Ernst & Grizzle J Am Pharm Assoc. 41: 192(2001)3 Lazarou et al JAMA 1998;279: 1200 - 1205

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Examples of Product Recalls and Product Safety Concerns

• Even developed countries with stringent regulatory authorities, have withdrawn several drugs from the market in the past few years• Experience/data shows 4% to 5% of drugs on the market are withdrawn and about 20% receive ‘black box’ warnings (safety concerns not previously identified)

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Importance of pharmacovigilance

• Complete safety data (especially for unexpected and serious adverse events) can only be captured through pharmacovigilance

• It cannot be captured through clinical trials which are conducted in an “artificial environment.” – In clincial trials patients

• are not taking any other medications• do not have concomitant infections• are taking the drug short-term (during the

duration of the trials only) and• are not part of vulnerable groups (e.g.,

children, pregnant women, elderly, etc.)

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Safety concerns with Anti-Retrovirals

Product Potential ADRs and Risks

Abacavir Hypersensitivity, potentially fatal, up to 5%

Didanosine • Pancreatitis – often fatal, very difficult to manage

• Neuropathy

Indinavir

Ritonavir

Saquinavir

• Lipodystrophy--disfiguring change of fat distribution identifies HIV+ patients on ARV treatment

• Leads to discontinuation

• Severe skin reactions – potentially fatal

Safety of ARVs in pediatrics is largely a ’black box’

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Adverse effects associated with antiretroviral medicines have been reported to occur in up to 30% of HIV-infected children on antiretroviral therapy. [Examples of ADR’s included]: hepatotoxicity, raised serum amylase without symptomatic pancreatitis, zidovudine-(AZT-) induced anaemia, nevirapine- (NVP-) inducedrash, didanosine- (ddI-) induced pain in the abdomen, stavudine- (d4T-) induced angioedema.

Most of the adverse effects are reversible by modifying the dosage or omitting the offending medicine.

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We are accelerating the use of new drugs in new environments, which are mostly devoid of pharmacovigilance activites

• Faster scale up of public health programs due to availability of new funding from major donors such as the Global Fund, World Bank, PEPFAR, UNITAID, etc

• New drugs are reaching developing countries in greater numbers and more quickly because of new funding from several donors, including the Bill and Melinda Gates Foundation

Importance and URGENCY of

pharmacovigilance

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The RaPID™ Approach

“All things are a poison and none is without poison; it is the dose that determines it is a poison.”

Paracelsus "father" of toxicology (1500AD)

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RaPID Overview

Current situation in countryRaPID’s Approach

Mission Principles

Process Activities

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Mission

• To conduct pharmacovigilance on behalf of public health programs

and

• To strengthen national pharmacovigilance capacity in developing countries

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Guiding Principles

• Establish complementarity with National Programs

• Strengthen local capacity• Focus on the big three killers (AIDS, TB,

Malaria)• Focus on the most vulnerable

populations• Implement quickly using a ‘RaPID™

Force’—in months, not years• Leverage IT to connect global specialists• Use the findings to formulate policies

for patient safety• Ensure sustainability

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RaPID Overview

Current situation in countryRaPID’s Approach

Mission Principles Process Activities

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Data GatheringIn-countrypartners

Data Analysis

Data S

haring3 Key Activities of the

RaPID™ Program

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Data Entry &Report

GenerationVigiflow®

Data MiningSignal Analysis

TriageReview by Experts

Department ofInformation

System

Department ofPharmacovigilance

RaPID Office

Data Sharing

National Pharmacovigilance Program

Pulmon-ology

Hema-tology

OtherHIVProgram

ARTCenters

ARTCenters

ARTCenters

ARTCenters

TBProgram

TBCenters

TBCenters

TBCenters

TBCenters

Malaria+ Other

Focus of RaPID™

Data A

nalysisD

ata Gathering

Overall Architecture of RaPID™ Program

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Pulmon-ology

Hema-tology

OtherHIVProgram

ARTCenters

ARTCenters

ARTCenters

ARTCenters

TBProgram

TBCenters

TBCenters

TBCenters

TBCenters

Malaria+ Other

Focus of RaPID™

PV activities

RaPID™ Process Flow

Dailytransmission

WeeklyReporting

1

2 3

4

5

Data A

nalysis

Data Sharing

Data Entry &Report

GenerationVigiflow®

Data MiningSignal Analysis

TriageReview by Experts

Department ofInformation

System

Department ofPharmacovigilance

RaPID Office

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Key activities and roles of partners

Analyze Pharmacovigilance Capacity In-Country

Assess PublicHealth Programs

for HIV/TB/Malaria

Assess PharmacovigilanceCapacity of Country

Assess DonorAnd Partner Support

for Pharmacovigilance

Implementing Org

In-country PV Dept, WHO, RaPID team

Customize ADR forms

Establish RaPID InfrastructureIn-Country

Develop a Customized RaPID Pharmacovigilance Approach for Program

Establish aProtocol For ImplementingRaPID

Co-Develop RaPID Pharmacovigilance

Approach for Country

In-country PV Dept, WHO, RaPID team

WHO/UMC to TrainCountry Program

Officers and PV team

Dedicated ‘RaPID Force’ to Gather

ADR Data

Gather Data and Ensure Quality

Data Screened

for Accuracy and Quality

Data Transferred toRaPID’s DataEntry Office

WHO/UMC to Train New

In-Country RaPID Staff

UMC, WHO, Swissmedic, In-country PV Dept, RaPID team

Conduct Causality

Assessments and Produce Reports

Share Reports with Global Experts for

Review

Analyze Data

Enter ADRData into

National Vigiflow®Database

RaPID Data entry team, In-country PV Dept, UMC, WHO

Provide Support

in Policy Generation

Share Data Globally

Provide Support for Policy Change

Present Analysisand Findings

to the Country Program

In-country PV Dept, WHO, UMC, Swissmedic,RaPID team

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Ongoing Pharmacovigilance Activities

Pharmacovigilance Capacity Assessment:

Development of Protocol for Assessing antimalarials

Assessment of ADR/AE Reports

Data Gathering and Assessment of Pharmacovigilance data in ART Centers:

• In collaboration with UNAIDS, CHAI, WHO and various donors for providing support to National AIDS Control Organization in India

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Current Consortia Partners

Uppsala Monitoring Centre (UMC)

An independent centre of scientific excellence, the Uppsala Monitoring Centre is responsible for the collection of data about adverse drug reactions from WHO member states from around the world, and the generation of signals of drugs which might possibly have problematic side-effects. Currently 82 countries are actively contributing to the database.

Ecumenical Pharmaceutical Network (EPN)

Swissmedic will collaborate with RaPID on a project basis with a focus on Vigiflow®

In discussions with: MSF, CHAI, PSI, IDA, MC, among others

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Contacts

RaPID™ Program, O3i11 West 42nd Street,

3rd Floor, New York, NY 10036; Tel: +1-212-208-2447

The Uppsala Monitoring Centre, Stora Torget 3, S-753 20 Uppsala;

Sweden;Tel:+46-18-656060

Email: info@rapidpharmacovigilance.orgWebsite: www.rapidpharmacovigilance.org