Trial data available in the FDA and EMA

Reports: A Cross-Sectional Study

Jeppe Bennekou Schrolla, MD, The Nordic Cochrane Centre Maher Abdel-Sattarb, PharmD, University of California

Lisa Berob, PhD, University of California

Background

Regulatory data can alter meta-analysis (Hart2012)

Regulatory data is only obtained in 3% of the Cochrane

reviews that obtained unpublished data (Schroll2013)

Lack of guidance on what agency to search

Recent changes by drug agencies could make previous

research outdated

Hart B, Lundh A, Bero L. Effect of reporting bias on meta-analyses

of drug trials: reanalysis of meta-analyses. BMJ 2012;344:d7202.

Schroll JB, Bero L, Gøtzsche PC. Searching for unpublished data for

Cochrane reviews: cross sectional study. BMJ 2013;346:f2231.

Background

United states:

Drug Approval Package

Medical Review

Statistical Review

etc

Europe:

Assesment report

European Public

Assesment Report(EPAR)

Purpose

To compare the accessibility, comprehensiveness and

usefulness of data available from the European Medicines

Agency (EMA) and Food and Drug Administration (FDA)

drug reports.

Methods

EMA and FDA websites searched for all new molecular

entities that were approved by both agencies

Data extraction from reports by two researchers

Accessibility

Comprehensiveness

Usefulness for metanalysis (benefit and harms)

Assessment of each agency

Descriptive analysis

Characteristics of documents

FDA EMA

Average number of pages1 (SD) 267 (158) 87 (27)

Table of contents and searchable % (n) 70% (19) 100% (27)

File partially redacted % (n) 100% (27) 0% (0)3

Reasons for redaction indicated % (n) 96% (26) 100% (27)

Lay summaries provided 0% 100%

Communication between regulator and applicant 100% 0%

Full trial reports /protocols available 0% 0%

Characteristics of trials and efficacy data

FDA % (n) EMA % (n)

Overview of trials with trial ID /trial name and summary 100% (27) 100% (27)

ClinicalTrials.gov ID or corresponding 0% (0) 0% (0)

Names of trial investigators and conflict of interest 0% (0) 0% (0)

Trial methodology assessed (risk of bias domains) 19% (5) 0% (0)

Patient population specified (inclusion, exclusion criteria) 96% (26) 96% (26)

Intervention and comparison group specified 89% (24) 93% (25)

Can the results be used in a meta-analysis? 100% (27) 96% (26 )

Harms

FDA EMA

Table of common adverse events 96% (26) 67% (18)

All important harms reported 93% (25) 26% (7)

Numerical results provided – safety 100% (27) 100% (27)

Risk management plan / pharmacovigilance 48% (13) 100% (27)

o further trials / studies required 78% (21) 48% (13)*

o follow up existing trials 22% (6) 22% (6)

o labeling restriction 4% (1) 100% (27)

REMS / Educational material 30% (8) 26% (7)

Discussion

Harms and efficacy data are available at the drug agencies

Lack of accesibility and guidance can be the reason why

data is rarely used

The trials cannot easily be linked to publications

Redaction of non-approved indications

Only agency to sponsor communications available

Conclusion

Both agencies provided data sufficient for meta-analysis

FDA provided more data on harms

EMA was more accessible and provided data on

withdrawn or rejected drugs

We recommend searching both agencies

Questions