FDA secrecy surrounding falsification of data or violations in adverse event reporting detected during clinical trials is undermining the integrity of the scientific evidence base on drugs and medical devices, experts warn.
Writing in JAMA, they note that inspection reports compiled by the U.S. Food and Drug Administration are often kept from the medical research community, to the detriment of patients and public health:
"Despite their importance, FDA inspection reports are not proactively disclosed... In certain cases, information regarding the FDA’s findings and actions can be found in publicly available [documents]... Still, most reports are extensively redacted... making it difficult to link the FDA inspections to specific drugs or published trial reports... [T]he frequency with which research irregularities are uncovered is not known..."
Apixaban. Fraud affected as many as 24 of 36 sites in China during a trial of the anticoagulant apixaban. The FDA noting that if data from one of the sites were excluded, the statistically significant benefit of apixaban on all-cause mortality would be lost. Nonetheless, the approved labeling of the drug cited a reduction in all-cause mortality, and results from the trial have since been incorporated into numerous publications, guidance documents, and meta-analyses
Rivaroxaban. FDA site inspections identified deficiencies that affected half of the trial’s 16 clinical sites, and the FDA determined that the extent of the violations warranted exclusion of the entire trial from regulatory assessment. However, these data integrity issues were not discussed in a journal article describing the trial's outcomes. That article has since been cited more than 1,100 times.
The authors conclude that the FDA should consider making inspection reports proactively available on the FDA website and on clinical trial registries such as ClinicalTrials.gov.
They argue that greater FDA transparency could produce numerous benefits.
Journal editors could independently assess elements of trial quality in publication decisions
Systematic reviewers, meta-analysts and authors of clinical practice guidelines could take these reports into consideration
Funders and institutions could adopt preventative and corrective measures
Other regulators, including the European Medicines Agency, could use this information to inform their own decision-making
Sharing information on trial quality issues could support harmonization in assessments and actions across regulatory agencies
The authors conclude that:
"FDA trial inspection reports have been largely hidden from public view, but access to information on the integrity and quality of clinical trials that underpin a product’s assessment is critical, particularly when irregularities or misconduct are identified. Public availability of these reports is required to meet current standards for clinical trial transparency and uphold the integrity of the scientific evidence base."
Till Bruckner, founder of TranspariMED, said:
"With hundreds of clinical trials of potential COVID-19 treatments and vaccines now underway, regulatory transparency is more important than ever. Without access to this information, public health decision-makers, doctors, and patients will be unable to assess the reliability of evidence, potentially exposing patients to ineffective treatments that may do more harm than good."
TranspariMED today filed a Freedom of Information request with the MHRA to gain access to the UK regulator's clinical trial inspection reports.
The article, titled "Increasing Access to FDA Inspection Reports on Irregularities and Misconduct in Clinical Trials", was written by Rafael Dal-Ré, Aaron Kesselheim, and Florence Bourgeois. It is freely accessible online.