- Prospective registration of clinical trials and subsequent comprehensive publication of the trial results can support the full and accurate evaluation of drugs, but occurs too infrequently despite the efforts of regulators.
- Wider access to clinical trial data sets could help validate findings and facilitate secondary analyses, but concerns surrounding copyright and licensing, patient confidentiality, and potential erroneous analysis of the data by third parties are a barrier to the wider adoption of open data sharing policies.
An article published in Science and Public Policy highlights the ongoing disconnect between the number of clinical trials conducted and the number fully published in the medical literature. The article, by Habeeb Razack et al, outlines the four key components to clinical trial transparency:
- trial registration
- data documentation
- data sharing
- publishing trial outcomes.
The authors describe how journals have made progress towards supporting and encouraging greater transparency. International Committee of Medical Journal Editors (ICMJE) Guidelines require authors of clinical trial publications to provide trial registration details and many publishers also request data sharing statements. Some journals follow the Transparency and Openness Promotion Guidelines (TOP) from the Center for Open Science (which also publishes the related TOP Factor that ranks academic journals based on their commitment to research transparency and reproducibility).
Elsewhere, there are various mandates in place to encourage transparent reporting of trial data. These include the US Food and Drug Administration Amendments Act (FDAAA) Final Rule, which sets a deadline of within one year of trial completion for applicable trials to have their results posted to the ClinicalTrials.gov registry. However, compliance with the FDAAA mandate is reported to be low, as highlighted in a recent analysis. The All Trials campaign, which calls for the mandatory registration and reporting of results from all clinical trials, provides ongoing monitoring of FDAAA compliance via the FDAAA Trials Tracker website. Razack et al underline the importance of reporting data from all trials, as the evaluation of a drug should be based on all available data for that drug and not just data that has been selected for publication.
The latest Good Publication Practice Guidelines (GPP 2022) encourage the publication of all clinical trial data (and at a minimum, trials reporting Phase II and Phase III data) in a peer-reviewed journal —a policy supported by the authors, who point out that posting results on clinical trial registries does not directly contribute to the medical literature. The authors direct researchers to guidelines such as CONSORT (Consolidated Standards of Reporting Trials) for clinical trials, and those available on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) website for other study types, to improve the rigour and consistency of health research reporting.
“The finish line of a clinical trial is when it gets published.”
The authors make some suggestions to encourage increased data sharing, including a common data sharing repository and data reporting policy that would make the process less onerous for clinical trial sponsors. They suggest that complementary sharing of data could improve the accuracy of meta-analyses and reduce the need for additional trials. Interestingly, the authors highlight a study that found a positive correlation between articles that include a link to a data repository and citation counts. The authors note a high number (>10,000) of clinical trials related to COVID-19 listed in the WHO International Clinical Trials Registry Platform (ICTRP), for which open research practices could be transformative in expediting research validation, particularly given the need for rapid research dissemination and treatment uptake.
“Maintaining data transparency is a [part] of the obligation that the pharmaceutical industry has towards the public.”
The authors also highlight potential barriers to adopting transparent data sharing practices, of which the most commonly cited appears to be uncertainty surrounding copyright and licensing. There is also the issue of patient privacy and confidentiality. To fully understand how a clinical trial was conducted may require access to study materials, including the raw data, which may include patient-level data. One suggestion to allow patients to opt in to a data sharing clause during the informed consent process is countered by the risk of creating bias in secondary analyses due to patients choosing to opt out. Furthermore, there is a risk that third parties accessing trial data may use inappropriate analyses and reach erroneous conclusions that undermine trust in the original trial findings. Finally, the authors question whether increased availability of data and study materials, including complete clinical study reports, may undermine the availability of novel findings for publication.