Many clinical trial results are never published or publicly reported, raising ethical concerns about transparency of the findings.

A 2020 court ruling addressed this long-standing issue by requiring clinical trial sponsors to report missing data for trials conducted between 2007 and 2017 to ClinicalTrials.gov, a public database.1 “The failure to report trial results is the betrayal of the participants and a skewing of the evidence that the public can see,” says Harlan Krumholz, MD, director of the Center for Outcomes Research and Evaluation at Yale. When results are not reported, “it undoes the implicit pact between researcher and study participant,” Krumholz adds.

Study participants believe investigators are conducting their research to promote the public good and scientific advancement. But leaving trial data unpublished creates its own kind of bias, possibly harming the public. “This has the potential of leading people to incorrect conclusions about the evidence. In this case, evidence has been created, but hidden from public view,” Krumholz explains.

Patients who participate in clinical trials often do so out of a spirit of altruism. Participants are looking to “pay it forward” so future patients can benefit from new knowledge. “When trials go unpublished, it disenfranchises these patients,” says Erick Turner, MD, associate professor of psychiatry at OHSU School of Medicine in Portland, OR.

If critical evidence remains unpublished that could leave the false impression a drug is efficacious and safe, which is misleading to clinicians and patients. Notably, the 2020 court ruling addresses only the issue of reporting in the ClinicalTrials.gov database. The court did not address reporting in medical journal articles, where drug companies are free to publish or not as they see fit.

“Of those that are published, they are free to put ‘lipstick on a pig’ and make a negative trial look positive,” Turner says. Since, in contrast, ClinicalTrials.gov requires all trial results to be published, it provides a “useful reality check on what appears in journal articles,” Turner adds.

Patients are more likely to use ineffective or harmful treatments if clinical trial data are selectively reported. “When the answer to a question is known, but the answer is hidden from public view, researchers will enroll patients in experiments that don’t need to be done,” says Evan Mayo-Wilson, MPA, DPhil, an associate professor in the department of epidemiology and biostatistics at Indiana University School of Public Health-Bloomington.

That wastes time and money — and it also is unethical, because it exposes patients to avoidable harm. “Many organizations are reporting trial results because it’s the right thing to do,” Mayo-Wilson observes. “This ruling is an important step forward, and I hope manufacturers and universities will comply.”

To date, the FDA has not exercised its authority to issue civil monetary penalties to manufacturers and other organizations that fail to report trials of regulated products. The National Institutes of Health also can withhold funding from grantees that do not report trial results, including universities and academic medical centers. “This ruling is a reminder that penalties for noncompliance are long overdue,” Mayo-Wilson says.

Public awareness of this issue seems to be growing. “Across disciplines, scientists are facing essentially the same problem; that is, scientists test a lot of hypotheses and disproportionately report those tests with positive results,” Mayo-Wilson explains.

This happens whether the hypothesis is about the effect of a drug, the association between eating red meat and cancer, or the effect of body language on self-confidence. Because scientists do not report all tests with “negative” results, it appears as though their hypotheses are true more often than is the case. “We need to replace our current norms and incentives with ones that foster transparent and open science,” Mayo-Wilson says.

REFERENCE

  1. Seife et al. v. HHS et al., 18-cv-11462 (NRB) (S.D.N.Y. Feb. 24, 2020).