An unreported clinical trial… from the FDA themselves

Our FDAAA TrialsTracker provides a public list of all trials required to report under the FDA Amendments Act of 2007 (FDAAA). We update every weekday with live data showing who has, and has not, reported their results in accordance with the law. You can read our full methods in our preprint paper.

One unreported trial last week stood out: this trial was sponsored by the FDA, the agency in charge of enforcing the reporting requirements of the FDAAA. We raised this in public; journalist Ed Silverman, from Pharmalot at STAT, picked up the story and contacted the FDA. He wrote about the trial in STAT, where a spokesperson for the FDA provided the following statement:

“Upon our review of the available information for NCT02821338, we determined that this study was mistakenly registered as a Phase 4 trial, when in fact this type of bioequivalence study is considered to be a Phase 1 trial, and therefore not an applicable clinical trial (ACT) to which the ClinicalTrials.gov requirements apply (see 81 FR 65016). Although this study is not an ACT and is not required by law to be registered or have results information submitted, for purposes of transparency, the FDA intends to submit the results of the study as soon as they are available. The CT.gov record will be updated accordingly.”

This response raises many interesting issues.

Firstly, while certain types of bioequivalence study are indeed exempt from reporting, we are delighted to hear that the FDA have decided to report the results of this trial and hope they will do so soon. The FDAAA contains many loopholes and exemptions for reporting, which we have faithfully implemented in our tool, using all available public data. But the global ethical standard is that all trials should report results.

Secondly, It’s good that the FDA plan to update their trial’s registry entry since this trial was, as they state, “mistakenly registered as a Phase 4 trial”. The ability to frequently update the FDAAA TrialsTracker is a major advantage of our tool over a static academic journal paper that simply documents the extent of the trials transparency problem at a single point in time. If the FDA change the designation of their trial from Phase 4 to Phase 1, so that it is provably no longer covered by the FDAAA, then this unreported trial will drop from our tracker within one working day. Audit data that changes over time, as performance changes, is a far better incentive to sponsors for quality improvement.

Lastly, we think it’s really important for public accountability that ClinicalTrials.gov and the FDA work together to ensure that all trials covered by FDAAA are clearly, prominently, and publicly identified. We would therefore also be interested to know if they will add flags to the data to identify those rare bioequivalence studies that are not Phase 1 trials but also not covered by the FDAAA reporting requirements. As we have previously discussed, including in our preprint paper: the FDA and ClinicalTrials.gov have decided to withhold important data denoting whether trials are covered by the law. This has forced us to make various conservative assumptions in making our tool. As a consequence of the FDA and ClinicalTrials.gov withholding data, we will be missing several trials that are in fact covered by FDAAA. In our view this should not be necessary. We welcome any efforts by the FDA and ClinicalTrials.gov to improve transparency and public accountability in trial reporting.

We will have more interesting news on the issue of individual unreported trials shortly.