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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reviews that obtained unpublished data (Schroll2013)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research outdated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 Searching for unpublished data for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