Unpublished clinical-study reports (CSRs) are more than twice as likely to provide complete information on patient-relevant outcomes than publicly available sources, a new analysis has found.
The study by Beate Wieseler and colleagues from Germany’s health technology assessment agency, the Institute for Quality and Efficiency in Health Care (IQWiG), will add momentum to the continuing drive by campaigners such as AllTrials for more transparency in the dissemination of clinical-trial data.
A central tenet of those efforts – and indeed of the European Medicines Agency’s plans to open up access to study data from the beginning of next year – is that clinical-trial documents not subject to restrictions on access to commercially confidential information or personal data should be available to download once the EMA has published its European public assessment report on an application for centralised marketing authorisation.
Whether CSRs do contain commercially confidential information or patient data that raise privacy concerns is a bone of contention between the biopharmaceutical industry and regulators/campaigners in the European transparency debate.
CSR outcomes
In the analysis by Wieseler et al published online in the open-access journal PLOS Medicine, the researchers compared the information available in clinical study reports, which IQWiG routinely requests from manufacturers for its product assessments, with reports from publicly available sources including journals and registries.
Specifically, Wiesler and colleagues took a sample of 101 trials with full CSRs received for 16 health technology assessments (HTAs) of medicines completed by IQWiG between 15 January 2006 and 14 February 2011.
In analysing the CSRs and publicly available sources for the same trials, the researchers assessed for each document type the completeness of information on all patient-relevant outcomes included in the HTAs (e.g., benefit outcomes such as mortality, symptoms or health-related quality of life; harm outcomes such as adverse events) and characterised these as “completely reported” or “incompletely reported.”
The proportion of outcomes with complete information was calculated both per outcome category and overall for each document type.
Complete information
The researchers found that the CSRs provided complete information on 86% of outcomes, compared with just 39% of outcomes in the combined publicly available sources.
With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes against 20% to 53% of these outcomes in the combined publicly available sources.
There was also a marked discrepancy in reporting of harm outcomes. The CSRs provided complete information on 84% to 92% of these outcomes, while the corresponding figures for the combined publicly available sources were 27% to 72%.
Study limitations
The authors acknowledged that the study sample was not representative as it only included CSRs provided voluntarily by pharmaceutical companies on request.
Moreover, the sample covered only a limited number of therapeutic areas and was restricted to randomised controlled trials of medicines.
Nonetheless, the analysis suggests that access to CSRs “is important for the unbiased evaluation of clinical trials and for informed decision-making in healthcare”, Wieseler et al commented.
They called for CSRs to be made publicly available for both past and future clinical trials, in line with the objectives of the AllTrials initiative.
