Peter Pitts, Chief Regulatory Officer, Adherent Health, LLC
The debate around clinical trial transparency is certainly nothing new, with some arguing that the ClinicalTrials.gov registration requirement in the Food and Drug Administration Amendments Act (FDAAA) isn't being properly implemented and that more transparency (and oversight) is needed to satisfy full public disclosure and address the issue.
Unfortunately, it’s just not that simple.
As the former senior government official in charge of clinicaltrials.gov, I think it’s important to look at the facts - and the numbers.
In 2000, the National Institutes of Health (NIH) launched ClinicalTrials.gov to provide public access to information on clinical studies. Although it initially contained information primarily on NIH-funded research, it has been expanded to include both publicly and privately supported clinical research. Since the launch of the site, it has been enhanced to significantly increase data sharing, and the database now includes information on nearly 140,000 clinical trials in all 50 states and 182 countries.
And it’s being utilized. The NIH reported last year that ClinicalTrials.gov “receives more than 95 million page views per month and 60,000 unique visitors daily.”
As we progress through the many factors involved in data transparency, here are some issues we need to consider:
The FDA is at the nexus of vast amounts of patient-level clinical data – what role will transparency play in making such information available? How might the agency accomplish such a task, how would it be funded – and where does such an initiative fall on the agency’s long list of urgent priorities?
Should transparency be a government dictate or a working collaboration between interested parties both private and public – and what role should patients play? Should there be formalized transparency consortia? Should it be global?
Can transparency become a competitive advantage as well as a public health imperative?
According to Dr. Richard Moscicki, CDER’s Deputy Director for Science Operations, there’s a “transparency dichotomy” of “the promise versus fear and loathing.” As to “why” transparency is promising, he offers reproducibility and re-analysis of the potential to identify new information (placebo effects, biomarkers, endpoints, trial designs). According to comments Moscicki made at a recent conference on this issue, one group that is silently against transparency is academics – because they don’t want to be cornered into making studies public if it impacts their ability to publish.
The FDA’s impediment to data sharing, per Moscicki, is legal (data ownership, HIPAA/privacy, proprietary information), technical/practical (format, data standards, CDISC, redaction), a question of resources and the agency’s need to focus on its key mission.
On that last point, he shared that the FDA does not view (at least as of right now) the issue of clinical trial data transparency as a key agency agenda item – unless there was a move to move it to the head of the regulatory queue via user fees. But transparency is important and, per Moscicki, “inevitable” – and to that end he discussed the agency’s recent Federal Register notice (Masked and De-identified Non-Summary Safety and Efficacy Data).
Moscicki stressed that FDA’s approach has been under development for several years and the agency is not contemplating routine preparation and release of de-identified and masked clinical and non-clinical study data. The agency is encouraging independently organized efforts to create, curate and share clinical trial datasets from all sources.
Sir Alasdair Breckenridge, former Chairman of the MHRA and currently the Chair of United Kingdom’s Department of Health Emerging Science and Bioethics Advisory Committee, noted that transparency is “a process without a beginning or an end. It is a continuum.” And, “Transparency is like feeding a hungry dog – the more you give it, the more it wants.”
Sir A. suggested four key questions:
(1) Should the public have access to data based on which regulatory decisions are taken?
(2) What are the advantages and disadvantages of increased transparency?
(3) What are the key distinctions between transparency and communication (specifically the issue of public health literacy and numeracy – and the “road testing” of released information)?
(4) Will increased transparency lead to increased trust in regulators and the industry?
On that last point, Dr. Breckenridge points out that increased transparency does not lead to increased trust. Trust depends on perceptions of honesty and competence, and transparency may expose inherent inefficiencies in a system. And that’s a good thing – if we really mean to make the most of transparency.
Transparency cannot be “for thee but not for me.”
And he offers five keystones for moving forward:
(1) Agreement on timing of release of information
(2) Agreement on nature of information to be released
(3) Standards of protection of personalized data
(4) Standards for meta-analyses
(5) Rules of engagement for observational studies
Maybe the FDA’s incremental and collaborative approach is best. Slow and steady isn’t always attractive, but with respect to public sharing of clinical trials data, it is in the best interest of public health.