Pharmacoepidemiology& Risk Management.

Drug Utilisation Studies and Access to Health Care Databases: Societal and Legal Challenges

Aurore Bergamasco, Caroline Tremblay, Alia Yousif, Yola Moride

Disclaimer

• YOLARX is a privately held company specialized in consulting and studyconduct in pharmacoepidemiology, pharmacovigilance and therapeuticrisk management

• Our current global customer base includes pharmaceutical companies aswell as regulatory agencies from across the world

• No funding was received for the present study

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Context

• Drug utilisation studies (DUS) are increasingly requested by health authoritieswhether these are regulatory agencies (EMA) or third-party payers (HAS)

• Optimizing the quality of the use of medicines

• According to the EMA, DUS belong to post-authorization safety studies (PASS)contributing to the evaluation of risk management plans

− Evaluation of the proper use of medicines in real life

Patient profile, indication, dosages, treatment duration, concomitant medication, …

− Evaluation of the effectiveness of risk minimisation measures

Implementation

Clinical outcomes

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DUS = Drug Utilization Study; HAS = Haute Autorité de Santé; EMA = European Medicines Agency; PASS = Post-Authorisation Safety Study

Objectives

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Determine the interest of health care databases for the conduct of DUS.

Identify the legislative and ethical frameworks relative to the conduct of DUS and, more particularly to the use of healthcare databaseses in different European countries.

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Methodology

• Literature Review− January – April 2015

• Two stages− Systematic review of the ENCePP electronic register of studies

Extraction of information regarding DUS (objectives, outcomes, data sources, regulatory requirement, …)

− Review of existing legislative sources in the European countries

Identification of the legal and ethical requirements applicable for the conduct of DUS and use of health care databases

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ENcEPP = European Network of Centers for Pharmacoepidemiology and Pharmacovigilance

Results – Phase I (ENCePP Register)

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EMA = European Medicines Agency; BMI= Body Mass Index

173 DUS(planned, ongoing or finalized)

74 (42,8%)conducted using existing health care

databases(secondary data sources)

99 (57,2%) using other data sources

(prospective studies, ad hoc data collection)

95 (54,9%) initiated upon request from a regulatorybody (EMA, national health authority, …)

Evaluation of drug utilisation modalities in real life clinical practice setting:

- Off-label use- Patient profiles

Specific objectives:- Disease characteristics

(biomarker, radiological examination, …)

- Patients characteristics(BMI, lifestyle factors, …)

- Specific characteristics of the indication

DUS Regulatory Framework

• Observational studies, also called Non-interventional studies (NIS)

• Important discrepancies across local legislations

• Heterogeneous legal and ethicalrequirements from different institutions regarding observational studies

- Ethics board approval

- Protocol format (national requirements)

Databases Accessibility

• Different modalities according to the countries and databases considered

- Authorization from data protection agencies

- Restricted access to certain institutions

- Access fees

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Results – Phase II (Legal Sources)

NIS = Non-Interventional Studies

Legal and Ethical Requirements – Examples

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CompetentAuthority

ANSMAgence nationale

de sécurité du médicament et des produits de santé

MHRAMedicines and

Healthcare products

Regulatory Agency

DHMADanish

Health and Medicines Authority

BfArMFederal Institute for Drugs

and Medical Devices

Paul-Ehrlich-InstituteVaccines, Biomedicines

AIFAAgenzia

Italiana del farmaco

AEMPSAgencia Española de Medicamentos

y Productos Sanitarios

Notification to the competentauthority

No

EXCEPT for studiesrequested by the

authorities

No Yes Yes No At the national-level:

NoAt the regional-

level:

Yes

Approval by a researchethic board

No Yes No Yes Yes Yes

Studyregistration

No No No Yes

VFA local register or clinicaltrials.gov

Yes

AIFA and Data

Protection Agency

No

Databases and Accessibility – Examples

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DatabasesSNIIRAM-PMSI EGB CPRD National registers GePaRD

Accessibility Authorizationfrom the CNIL

List of authorized institutions established by ministerial decree

Protocol approvedby a research ethicboard

Authorization fromthe Data Protection

Danish institutions authorised by Statistics Denmark

Project approval by the health insurance providers and local authorities

Persons employed by the BIPS Leibniz

Benefits Exhaustiveness ₋ Representa-tiveness

₋ Depth(20 years)

- Representativeness- Sample size (> 52 millions)- Follow-up duration- Data linkage

- Single identifier (linkage)

- Data accessthrough the internet

- Représentativeness- Sample size (17 millions)- Depth (> 10 ans)

Disadvan-tages

No clinical or environmentalinformation (lifestyle, …)

Sample Size (1/97th)

- Cost - Claims database- Time for access

Conclusion

• Health care databases= Opportunity for the conduct of DUS in a timelymannner

− Existing data

− Interesting for public health

Early identification of misuse situations

Implementation of appropriate corrective measures

Optimization of risk minimization measures

• Databases’ interest depends on study objectives and available data

• Utility of the database mapping to identify fit-for-purposes databases for the conduct of DUS

− Systematic and pragmatic literature review based on required data

− Matrix of identified databases including their characteristics

− Usefulness assessment to determine the most appropriate datasources for the DUS

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