Not only have there been enacted measures with regards to disclosures of financial transfers of value between applicable parties in the medical products arena, but transparency of clinical trial data is on the precipice of a major expansion. After years of status quo, stakeholder demand for increased visibility has resulted in proposals from both regulatory authorities and industry associations for an increase of trial data dissemination. The question is – how much more data should be made available?
Currently in the U.S., most non-phase-1 interventional drug and device trials (aside from small feasibility studies and studies that use de-identified samples) are required to be registered on the ClinicalTrials.gov database, including summaries of study design and post-trial study results. The European Clinical Trials Register database houses descriptions of medicinal Phase II-IV adult clinical trials and Phase I-IV pediatric clinical trials, but with no trial results provided.
These efforts have not yet translated into comprehensive trial publication. A recent study (July 2013, Journal of Clinical Oncology) found that the results for almost half of U.S. cancer trials were not posted to ClinicalTrials.gov three years after study completion. Another study (2011, British Medical Journal (BMJ) noted that fewer than half of trials funded by the National Institute of Health were published in a peer-reviewed biomedical journal indexed by Medline within 30 months of trial completion; and after a median of 51 months post-trial-completion, a third of trials remain unpublished. BMJ cited possible reasons for these delays as: lack of incentive to disseminate negative or unsupportive findings; time constraints; limited resources; changing interests; or failure to have an article accepted by a journal for publication.
Regulatory authorities have initiated efforts to broaden the scope of required trial data dissemination. The US FDA recently sought public comment on a proposed initiative to make available de-identified and masked clinical and preclinical data derived from medical product applications. Meanwhile, the European Medicines Agency (EMA) released a draft policy in June, which proposes a 3-tiered system of accessibility, using both commercially confidential information and patient data as indicators for what information would remain out of the public sphere. After soliciting feedback from the public, the EMA plans to implement the final policy on January 1, 2014.
US and EU pharmaceutical and medical device trade associations have teamed up to put forth their own recommendations for data sharing, which are more limited in scope than the regulatory proposals. While the FDA/EMA draft guidelines have the potential to make study data available to the general public, the industry proposals would allow data access specifically to scientific and medical researchers – once a review board has approved the request as legitimate for research purposes. Also, patients participating in clinical trials would gain access to factual summaries of the corresponding trial results. These industry commitments would apply only to trial data published on or after January 1, 2014, and are endorsed by all member companies of both associations.
Proponents for the release of comprehensive trial data cite benefits including:
- Physicians’ ability to practice evidence-based medicine is enhanced when critical trial data results are not withheld.
- Accessibility to data on unsuccessful trials will enable researchers to plan more effective future studies through reviewing past efforts.
- Trial patients will gain visibility into how their efforts contribute to furthering clinical research – bolstering patient volunteer recruitments.
Advocates for limiting the availability of trial data have concerns such as:
- Non-contextualized data analysis by non-experts can lead to incorrect assumptions or conclusions.
- Competitors could utilize a submitter’s raw data to benefit the competing drug/device through shortened development cycles or patent grants.
- Patient privacy is placed at risk, as re-identification of patients based on anonymized information is possible.
The final outcome of the intense lobbying on this issue is yet to be realized. Both sides have salient points that need to be addressed, but the message is now clear that the trend is moving toward increased clinical trial data transparency.