An Academic presentation byDr. Nancy Agnes, Head, Technical Operations, PepgraGroup:  www.pepgra.comEmail: pepgrahealthcare@gmail.com

POST AUTHORIZATIONSTUDIES FORCLINICAL RESEARCHPURPOSES

Today's Discussion

In-Brief

Introducing Post-Authorization Safety Studies (PASS)

Aims of PASS

Actions to foster PASS collaboration and bridge pharmacovigilance

and pharmacoepidemiology

Changes in PASS

Conclusion

OUTLINE

In Brief

Have a look at post-authorization safety studies and importantpharmacoepidemiologic and pharmacovigilance aspects in clinical

research in this Pepgra blog. PASS covers different types and limitationsof surveillance programs, such as the use of large databases and

disparate data sources for rapid signal detection, as well as novel andadvanced design and analysis approach for causal interference from

observational information.

IntroducingPost-AuthorizationSafety Studies(PASS)

A PASS, an authorization of a study carried outafter a medicinal product, to obtain furtherinformation on a medicinal product's safety or tomeasure the effectiveness of risk-managementmeasures.

The purpose of the PASS is to evaluate the safetyand benefit-risk profile of a medicinal product andto support regulatory decision-making.

The protocols and results of PASS's access iswith the Pharmacovigilance Risk AssessmentCommittee (PRAC)

Aims ofPASS

Identify, characterize, or quantify a safety hazard;

Confirm the safety profile of a medicine; or,

Measure the effectiveness of risk-managementmeasures.

PASSs can either be clinical trials or non-interventional studies.

Under the EU legislation, a post-authorization studyis classified as a PASS when the main aims forinitiating the study include:

Contd..

Quantification of risks or providing evidence about the absence of risks.

Evaluation of risks in populations with limited or missing safety data.

Assessment of patterns of drug utilization that gives information on the safety profile.

Measurement of the effectiveness of a risk minimization activity.

The British Journal of Pharmacology analysis showed that 74% of PASS had a focuson investigating safety concerns, while 34% focused on drug utilization, and 25%on the effectiveness of risk minimization.

Contd..

In one-third of the PASS, more than one of these objectives present in the protocol.Some 35% of the PASS had effectiveness endpoints as well as safety ones.

It may reflect the fact that PASS is expensive and long-term commitments forsponsors, with the result that it is desirable to capture routine effectiveness data inthe real world.

Concerning the study population, 12% of the overall PASS are of pregnancyregistries, and 18% included pediatric patients only. Also, 22% of PASS targetedhealthcare professionals, with the great majority of these (94%) aimed at assessingthe effectiveness of risk minimization efforts and drug utilization.

Actions to FosterPASS Collaborationand BridgePharmacovigilanceand Pharmaco-epidemiology

The currently available information on PASSoffers critical insights into design and conduct ofPASS under the new Europeanpharmacovigilance legislation.

The new analysis indicates that there is scopefor further improvements in transparency fromboth regulators and MAH.

The EMA could increase the availability ofprotocol assessments within the EU-PAS, whilePASS sponsors could improve access to anddocuments in the register.

Contd..

The large number of PRAC comments involving in the methodological issues andfeasibility concerns should alert PASS stakeholders for the need for improved studydesign, based on current guidelines and pharmacoepidemiological principles.

Looking ahead, it will be vital to building cooperation between PASS stakeholders tosupport transparent and methodologically sound studies that align with other riskmanagement approaches.

This collaborative generation of knowledge will be integral to strengthening thecapacity of the EU to deliver better and safer therapies.

TRANSPARENCY:

The EMA is working on new mechanisms toincrease data transparency and compliance bysponsors with ENCePP standards andrequirements (code of conduct, checklists, EU-PAS registration).

Contd..

Changesin PASS

A considerable number of PRAC comments related to methodological issues andfeasibility concerns should raise awareness among PASS stakeholders of theneed to design more thoughtful studies, according to pharmacoepidemiologicalprinciples and existing guidelines.

Currently, most PASS is detailed studies, involving a simple, long-term,descriptive analysis of patients who have taken the drug, with no comparator.

Hybrid studies involving both primary and secondary data collection present morefrequently in future.

METHODOLOGY:

Contd..

Today's pharmacoepidemiological toolbox offers many additional options, such asthe ability to model links between exposure and outcomes. Such approaches couldimprove the design of PASS.

Also, new guidelines for post-authorization efficacy studies (PAES) 8 have just beenreleased, with a final version expected in 2017; this is likely to lead to increasingnumbers of requests by regulatory authorities for PAES in addition to PASS.

Clinical trial design options for designing of PAES includes explanatory andpragmatic trials.

Contd..

In the EU Clinical Trial Regulation, the new description of PASS will rise intoeffect, impacting classification of it.

It results in, and some studies classification will be observational studies,resulting in a different review process and pose a challenge for study sponsors inthe coming year.

Also, when the new clinical trial regulation comes into force, it will becomeessential to scrutinize possible rules in the ethics committee decision-makingacross Europe and their impact on the conduct and the implementation of PASS.

DEFINITIONS:

Contd..

In future, there will be more joint studies involving multiple products, sponsors,academics and CROs within a therapeutic category.

Such tasks will need new governance structures.

EU initiatives, such as the IMI accelerates the development of vaccine benefit-riskcollaboration in Europe (ADVANCE) project.

The EMA initiative for patient registries represents promising opportunities toexpand joint efforts using new governance models, with the potential to deliverrobust results with statistical significance.

GOVERNANCE:

Contd..

Conclusion

These are the few important topics that everyclinical researcher should possess knowledgeof post-authorization services.

Pepgra has stated many essential aspects andchanges in the clinical research field to helphealthcare data analytics services.

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