Investigation: Biotechs and academics may be gaming clinical trial disclosure rules

Shoddy and in some cases possibly fraudulent clinical trial data management may be slowing down results reporting and hence medical progress, an investigation by The Scientist has found.

A reporter for the magazine reviewed multiple clinical trials listed on the American trial registry ClinicalTrials.gov. She found that publicly stated completion dates were often incompatible with the date at which recruitment for a trial ended.

For example, a trial only measuring short-term outcomes should be expected to have a “primary completion date” just weeks after the last patient was recruited. Instead, the publicly listed completion dates for several such trials were more than one year in the future.

Under U.S. federal law, many (but not all) trials are required to make their results public within one year of their primary completion date. Entering an incorrect completion date – whether accidentally or deliberately – effectively turns forward the disclosure clock because trial results that should have been reported long ago publicly appear as not yet due.

Missing Covid trial results

The reporter focused on Covid trials and found that:

“Our criteria yielded a dozen US trials with various sponsors—including biotech companies and major academic institutions—that ended enrollment months or years ago, yet are still listed as ‘active, not recruiting’ with estimated primary completion dates in 2022 or 2023.”

“The majority of these studies, launched before vaccines or treatments such as Paxlovid became widely available, have yet to release any results, and have thus offered little value in informing treatment decisions during the pandemic.”

“Most have postponed their estimated primary completion dates at least once after stopping recruitment, in some cases by more than a year at a time.”

Harm to patients

Making trial results public within one year of completion is required by U.S. law (FDAAA) and European law (EUCTR) for some trials, and is recommended by the WHO for all trials,

This benefits patients because it allows scientists and doctors to rapidly access new evidence on the safety and efficacy of drugs and medical devices.

In addition, keeping trial status information accurate on registries facilitates patient recruitment and health policy making.

Previous studies have shown that data on trial registries are often incorrect or out of date. The leading cause appears to be weak data management coupled with a lack of institutional and regulatory oversight, rather than malicious intent.

Honest mistakes or malicious intent?

It is unclear to what extent the inconsistencies detected are due to deliberate deception by the parties involved, as opposed to shoddy data management.

The journalist contacted multiple investigators and institutions for comment about apparent inconsistencies. Several conceded that they had omitted to keep their registry data up to date.

However, others declined to respond:

“In some other cases, The Scientist was unable to ascertain what had happened to a study. Memorial Sloan Kettering Cancer Center’s Phase 2 trial of tocilizumab, for example, stopped enrollment in November 2020 after recruiting just 9 patients, each of whom would be followed for 14 days, according to its record.”

“The primary completion date was postponed twice: initially to May 2022, and then, earlier this year, to May 2023—a date that would give it an official one-year reporting deadline in early 2024.”

“Neither the trial organizer nor the institution’s press office responded to requests for comment.”

Scale of problem unknown

It remains unclear how frequently estimated and actual primary completion dates are misreported across the database.

According to the journalist, “NLM is clear in a disclaimer on its website about its inability to check trial records beyond basic quality control for obvious errors.”

Meanwhile, an expert told the publication that research institutions could “invest more in monitoring and taking responsibility for the trials that they and their faculty are conducting… large research organizations should have professional staff with relevant expertise to oversee their trial records.”

The investigation by The Scientist can be accessed without paywall and is worth reading in full.

Comment by TranspariMED

This important investigation raises concerns that some players may be deliberately gaming the system, breaking the law, slowing down medical progress and harming patients.

TranspariMED strongly encourages meta-researchers to build on this work. In addition, institutional investors may want to check whether publicly listed companies might on occasion have purposefully delayed the disclosure of the results of selected trials.