L

eading clinical research authorities are calling for more aggressive enforcement of requirements for public reporting of the results of experimental drug trials, in response to a recent STAT investigation that found widespread failures by eminent universities and pharmaceutical firms to file data on their clinical trials.

STAT’s findings, along with a separate report published in the medical journal BMJ Open, “have confirmed beyond all doubt” that trial reporting compliance is “unacceptably low,” two leaders from the World Health Organization said in a statement.

Marie-Paule Kieny, an assistant director-general at the WHO, and Dr. Vasee Moorthy, a leader of WHO’s vaccine programs, called reporting failures “unethical,” because they can “lead to exposure of future volunteers to risks already identified but not publicly available.”

advertisement

STAT’s reporting identified such risks. In one case, a University of Indiana scientist studying breast cancer failed to report results of a controversial drug, Avastin, that proved so harmful to trial volunteers that the research was terminated prior to completion. Many patients and doctors using or considering Avastin would have benefited from knowing about those ill effects, yet the data were not made public. Years later, the Food and Drug Administration said Avastin should not be used to treat breast cancer.

The investigation found that some of the nation’s most prestigious research institutions routinely flouted a federal law requiring timely reporting of the results of clinical studies to ClinicalTrials.gov, a public website operated by the National Institutes of Health. The law mandates reporting results within a year of a trial’s completion or termination.

Among the worst offenders: Stanford University, Memorial Sloan Kettering Cancer Center, and the University of Pennsylvania, all of which violated the law at least 95 percent of the time. That sometimes left patients and doctors in the dark as they mapped out the dangers and assessed the efficacy of drugs for breast cancer, diabetes, and other ailments.

Clinical trial reporting lapses visualized

STAT examined data reporting for all institutions – federal agencies, universities, hospitals, nonprofits, and corporations – required to report results to ClinicalTrials.gov for at least 20 human experiments since 2008. This visualization shows the first comparative analysis of their performance. Among the groups, just two companies provided trial results within the legal deadline more than half the time. Most – including the National Institutes of Health, which oversees the reporting system – violated the law the vast majority of the time.

Percentage of clinical trials by entity that have late or no results:

“Currently, evidence-based decision making is seriously undermined by the incomplete and untimely disclosure of clinical trial data,” the WHO statement said.

Dr. Francis Collins, the NIH director, called a prepublication overview of STAT’s findings “very troubling.”

Dr. David Kessler, a former FDA commissioner, said STAT “pointed out a weakness in the system that needs to be corrected.” He expressed confidence that fixes will be made now that the problem has “light shining on it.”

But he said compliance with the reporting law is “is just the beginning.” The law requires some trial data to be reported in summary form, but Kessler said “full clinical trial data needs to be in the public domain.”

The reporting law was written with pharma companies in mind. They sometimes hid failed trials or equivocal results to safeguard sales and marketing efforts.

The investigation found poor compliance by many drug companies. Overall, corporations filed required results late — or not at all — 74 percent of the time. The FDA is empowered to fine companies up to $10,000 a day for violations, but so far has not levied a single penalty.

Jarilyn Dupont, an attorney who directs regulatory policy for FDA, said that ClinicalTrials.gov often has missing or incorrect information that creates enforcement challenges.

Due to the complexity of the law and of trial records, enforcement actions require considerable effort, she said, and FDA is not funded to look comprehensively at the thousands of possible reporting violations. The agency has, so far, drafted 14 “pre-notice” letters of possible violations — an effort that took nine months of work with available enforcement staff. In each case, Dupont said, the company brought its trials into compliance or argued successfully that the trial was exempt.

Collins said the FDA and NIH would have a stronger basis for enforcing the law next year, after regulatory rules are refined and approved.

At that time, “if the data is better, it will help in analyzing some of the data quicker,” Dupont said, but added that it was impossible to predict any effect on the efficiency of FDA’s enforcement process, or if any violators might face fines.

STAT found that on the whole, universities and nonprofits did even worse than corporations. Clinical reports from academic institutions arrived late or not at all 90 percent of the time. Even the NIH’s own scientists violated the law 75 percent of the time.

Former FDA Commissioner Margaret Hamburg, who stepped down earlier this year, said the reporting process is not just a formality, as some researchers seem to believe. “There are multiple reasons for greater transparency in the publication of clinical trials,” she said, including reducing unnecessary risks to patients and guiding researchers planning new studies.

Addressing STAT’s findings, Hamburg said: “The focus on clinical trial reporting is valuable.”

The story has been updated to include comments from Jarilyn Dupont, a lawyer for the FDA.

Leave a Comment

Please enter your name.
Please enter a comment.

Sign up for our Morning Rounds newsletter

Your daily dose of news in health and medicine.