No records found for 220 clinical trials of orphan drugs approved by the FDA

A new study has found widespread gaps and inconsistencies in clinical trials of orphan drugs, suggesting suboptimal data management by the FDA and failures by some pharma companies to consistently register clinical trials and keep public registry records up to date.

The study team compared publicly available FDA documents and ClinicalTrials.gov registry data for 63 orphan drugs approved between 2009-2019.

FDA documents identified 422 clinical trials linked to these drug approvals, but the team was only able to find 202 related trials in the ClinicalTrials.gov registry. 220 trials could not be located on the registry.

For those trials with data available in both types of sources, the number of trial participants recruited did not match in over 30% of cases.

The team commented that:

“There are various possible reasons why we could not find a trial in ClinicalTrials.gov.

(i) The studies may have run before ClinicalTrials.gov was established.

(ii) Phase 1 trials were not required to be registered until the [FDAAA] Final Rule of 2017.

(iii) In the United Kingdom, an audit has found that 12% of trials have not been registered and a certain fraction of trials may remain unregistered in the US as well.

(iv) It is possible that we were unable to identify the ClinicalTrials.gov match of some studies although such a match did exist.”

Regarding the data inconsistencies, they commented that:

“If there are discrepancies in such a simple number [as patient enrolment], it throws into doubt the veracity of other information in the registry or submitted to the FDA.”

The difficulties involved in matching up FDA approval documents with registry data are well known. FDA Commissioner Scott Gottlieb has yet to deliver on his 2018 promise to fix the issue.

Widespread data gaps and inconsistencies in trial registries are also well documented. These make it difficult for regulators, researchers and clinicians to determine the relevance and outcomes of clinical trials.

The new study can be accessed here.