European Medicines Agency Policy 0070: an exploratory review of data utility in clinical study reports for academic research

Abstract

BackgroundClinical study reports (CSRs) have been increasingly utilised within academic research in recent years. European Medicines Agency (EMA) Policy 0070 ‘Phase 1,’ which came into effect in January 2015, requires the publication of regulatory documents such as CSRs from central applications in an anonymised format. EMA Policy 0070 requires sponsors to demonstrate careful consideration of data utility within anonymised CSRs published within the scope of the policy, yet the concept of data utility is not clearly defined in the associated anonymisation guidance.ObjectiveTo review the use of data from CSRs in published academic research and to hypothesise the potential data utility of CSRs anonymised under the objectives of EMA Policy 0070 for future academic research.MethodsReview of the objectives, research methodologies and findings of academic research reports using unpublished data from CSRs (prior to EMA Policy 0070). Semi-structured interviews with authors of academic research reports, including questions related to data utility of anonymised CSRs published under EMA Policy 0070.ResultsThirteen academic research reports were identified and reviewed. The research purposes ranged from assessment of reporting bias, comparison of methods and results with published data sources, detailed evaluation of harms and adverse events, re-analysis and novel analyses including systematic reviews and meta-analysis. All of the examples identified required access to the methods and results sections of CSRs (including aggregated summary tables) and research purposes relating to evaluation of adverse events also required access to participant narratives. Retaining anonymised participant narratives relating to interventions, findings and events, while maintaining an acceptably low risk of participant re-identification, may provide an important gain in data utility and further understanding of drug safety profiles.ConclusionsThis work provides an initial insight into the previous use of CSR data and current practices for including regulatory data in academic research. This work also provides early guidance to qualitatively assess and document data utility within anonymised CSRs published under EMA Policy 0070.

Can synthetic data be a proxy for real clinical trial data? A validation study

“…Another type of secondary analysis is to assess bias in trial design, misreporting or selective outcome reporting where 'keeping the same conclusions and comparable numerical results of all primary, secondary and safety endpoints […] is of utmost importance'. 2 The data synthesis approach we presented here achieves these objectives by including the primary and secondary endpoints in the generative model to ensure that relationships with other covariates are maintained, and it does not synthesise adverse event data to maintain the accuracy of safety data. More generally, a review of protocols found that most secondary analysis of clinical trial datasets focused on novel analyses rather than replication or validation of results.…”

“…Specifically, for clinical trial data, secondary analysis of data from previous studies can provide new insights compared with the original publications 1 and has produced informative research results including those on drug safety, evaluating bias, replication of studies and meta-analysis. 2 Therefore, there has been strong interest in making more clinical trial data available for secondary analysis by journals, funders, the pharmaceutical industry and regulators. [3][4][5][6][7][8] For example, the International Committee of Medical Journal Editors (ICMJE)'s data sharing policy 9 indicates that articles reporting the results of clinical trials must include a data sharing statement when they are submitted to ICMJE journals for publication.…”

Benefits and harms of Risperidone and Paliperidone for treatment of patients with schizophrenia or bipolar disorder: a meta-analysis involving individual participant data and clinical study reports

“…Platforms such as the YODA project and the Clinical Study Data Request [102] where the public can access IPD and CSRs from the manufacturers remain key and should be utilised more by systematic reviewers where possible. However, incorporating these data into systematic reviews requires better awareness of where these data can be sourced and greater resources [103][104][105]. In terms of data sourcing, regulatory agencies such as the European Medicines Agency [37] and Health Canada [106] have committed to releasing CSRs for trials on products that are centrally licenced.…”

Optimizing the synthesis of clinical trial data using sequential trees

“…In the case of clinical trials, the reanalysis of data from previous studies can provide new insights compared with the original publications. 1 Secondary analysis has produced informative research results including on drug safety, evaluating bias, and replication of studies, and for meta-analysis, 2 with the most common purposes being new analyses of the treatment effect and the disease state. 3 Also, there has been strong interest in making more clinical trial data available for secondary analysis by academia, the pharmaceutical industry, and regulators.…”