“I write regarding concerns about the lack of compliance by medical product sponsors with requirements to report certain clinical trial results information to the ClinicalTrials.gov database. The law requires that certain clinical trial sponsors report results to ClinicalTrials.gov to expand the knowledge base, support additional research, and provide important safety and efficacy information to health care providers and researchers. These important goals depend on adequate compliance with applicable requirements and appropriate enforcement.”
Category Archives: oa.usa.fda
US congress committee calls for tougher action on trial sponsors who fail to meet reporting deadlines | The BMJ
“A US congress committee has criticised the Food and Drug Administration (FDA) and National Institutes of Health (NIH) for taking “only modest compliance action” against clinical trial sponsors who have not published results.1
Under US law, clinical trial sponsors are required to submit their results within one year of the completion date. Research looking at compliance in recent years found, however, that over 5000 trials were in “violation of applicable reporting requirements,”2 while over half (37 of 72) of reviewed trials that were funded by the NIH had failed to comply with applicable reporting requirements.3
The US Congressional Committee on Energy and Commerce has written to ask why the FDA and NIH have failed to sanction trial sponsors who break reporting rules….”
Discrepancies between FDA documents and ClinicalTrials.gov for Orphan Drug-related clinical trial data
Abstract: Clinical trial registries such as ClinicalTrials.gov (CTG) hold large amounts of data regarding trials. Drugs for rare diseases are known as orphan drugs (ODs), and it is particularly important that trials for ODs are registered, and the data in the trial record are accurate. However, there may be discrepancies between trial-related data that were the basis for the approval of a drug, as available from Food and Drug Administration (FDA) documents such as the Medical Review, and the data in CTG. We performed an audit of FDA-approved ODs, comparing trial-related data on phase, enrollment, and enrollment attribute (anticipated or actual) in such FDA documents and in CTG. The Medical Reviews of 63 ODs listed 422 trials. We used study identifiers in the Medical Reviews to find matches with the trial ID number, ‘Other ID’ or ‘Acronyms’ in CTG, and identified 202 trials that were registered with CTG. In comparing the phase data from the ‘Table of Clinical Studies’ of the Medical Review, with the data in CTG, there were exact matches in only 75% of the cases. The enrollment matched only in 70% of the cases, and the enrollment attribute in 91% of the cases. A similar trend was found for the sub-set of pivotal trials. Going forward, for all trials listed in a registry, it is important to provide the trial ID in the Medical Review. This will ensure that all trials that are the basis of a drug approval can be swiftly and unambiguously identified in CTG. Also, there continue to be discrepancies in trial data between FDA documents and CTG. Data in the trial records in CTG need to be updated when relevant.
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….”
FDA looks on while major U.S. institutions violate medical research rules
“The FDA has issued warnings to only a handful of the companies and institutions with the worst track records of violating a key clinical trial disclosure law, a new report finds.
Out of 51 large US-based companies and institutions that have failed to make five or more clinical trial results public, only three have been contacted by the U.S. drug regulator, and only one has received a final warning, FDA enforcement data show.
Failing to rapidly make clinical trial results public on the American trial registry harms patients because it slows down medical progress, leaves gaps in the medical evidence base, and wastes public funds. …”
Prospective Clinical Trial Registration: A Prerequisite for Publishing Your Results | Radiology
“The ICMJE requires that clinical trial results be published in the same clinical trial depository where the trial is registered. These results are in the form of a short (?500 words) abstract or table (6,7). Full disclosure of the existing results publication in a clinical trial registry should be explicitly stated when the manuscript is submitted for publication. The Food and Drug Administration (FDA) has indicated it will enforce trial results reporting related to ClinicalTrials.gov (8). The FDA is authorized to seek civil monetary penalties from responsible parties, including additional civil monetary penalties. In the United States, the sponsor of an applicable clinical trial is considered the responsible party, unless or until the sponsor designates a qualified principal investigator as the responsible party. The FDA issued its first Notice of Noncompliance in April 2021 for failure to report results in ClinicalTrials.gov based on a lack of reporting the safety and effectiveness results for the drug dalantercept in combination with axitinib in patients with advanced renal cell carcinoma (8).
Finally, as of July 1, 2018, manuscripts submitted to ICMJE journals that report the results of clinical trials must contain a data sharing statement. Clinical trials that begin enrolling participants on or after January 1, 2019, must include a data sharing plan in the trial registration. (for further information, see www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html). Since most clinical trials take 2 or more years for results to be reported, the Radiology editorial board had expected such mandatory data sharing plans to be reported in the current year. However, because of the COVID-19 pandemic, many clinical trials were halted. Thus, journal publication requirements to include data sharing statements are more likely to impact authors beginning in 2023. Data sharing statements required for Radiological Society of North America (RSNA) journals may be found at https://pubs.rsna.org/page/policies#clinical.
In conclusion, prospective clinical trial registration is a mechanism allowing us to ensure transparency in clinical research conduct, honest and complete reporting of the clinical trial results, and minimization of selective result publications. Since its inception in 2004, this requirement has evolved into a policy that is practiced by major medical journals worldwide, is mandatory for publication of trial results, and, in some circumstances, is enforced by the FDA. Further, ICMJE journals, including RSNA journals, are expecting manuscripts that report trial results to include statements on data sharing. As each clinical trial design is unique, we encourage authors to refer to the full description of the current ICMJE policy at icmje.org for additional information pertaining to their specific circumstances.”
FDA threatens second company with fines over missing clinical trial results
“The U.S. Food and Drug Administration has just fired a warning shot across the bow of a second drug company over its failure to make a clinical trial result public as required by law….”
Opinion | Joe Biden Made a Promise to Scientists. He Can Still Keep It. – The New York Times
“Researchers who receive federal help consistently fail to report their results to the public. The government should hold them accountable….
Researchers using federal funds to conduct cancer trials — experiments involving drugs or medical devices that rely on volunteer subjects — were sometimes taking more than a year to report their results to the N.I.H., as required. “If you don’t report, the law says you shouldn’t get any funding,” he said, citing an investigation I had published in Stat with my colleague Talia Bronshtein. “Doc, I’m going to find out if it’s true, and if it’s true, I’m going to cut funding. That’s a promise.”
It was true then. It’s true now. More than 150 trials completed since 2017 by the N.I.H’s National Cancer Institute, which leads the $1.8 billion Moonshot effort, should have reported results by now. About two-thirds reported after their deadlines or not at all, according to a University of Oxford website that tracks clinical trials regulated by the Food and Drug Administration and National Institutes of Health. Some trial results are nearly two years overdue. Over all, government-sponsored scientists have complied less than half the time for trial results due since 2018. (A spokeswoman for the N.I.H. said, “We are willing to do all measures to ensure compliance with ClinicalTrials.gov results reporting.”)…
In 2016, Dr. Francis Collins, the director of the National Institutes of Health, announced that the agency would begin penalizing researchers for failing to comply with its reporting requirements. “We are serious about this,” he said at the time. Yet in the years since, neither the F.D.A. nor N.I.H. has enforced the law. …”
NIH warns drug and device companies to post missing trial data
“Hundreds of drug companies, medical device manufacturers, and universities owe the public a decade’s worth of missing data from clinical trials, federal officials warned last week.
New rules issued last week in the wake of a federal court ruling in February instructed clinical trial sponsors to submit missing data for trials conducted between 2007 and 2017 “as soon as possible.” For years, many trials conducted during that span have largely been exempted from reporting their data to ClinicalTrials.gov, a public database, meaning a decade of data about approved drugs and medical devices has never been made public.
The court’s ruling, and the federal government’s decision not to appeal it and instead to urge trial sponsors to submit the missing information, represent a major win for transparency advocates, who for years have fought to recover the decadelong gap in publicly available clinical trial data. …
The court ruling, and the resulting change in federal policy, come after years of reporting that has detailed how federal research agencies routinely fail to enforce their own rules regarding clinical trial transparency — which advocates say is critical for the public’s understanding of a given medicines’s safety and efficacy. …”
FDA fails to collect over one billion dollars in fines from law-breaking pharma companies and universities | transparimed
“The FDA Amendments Act was originally introduced to prevent companies from burying research results that show their drugs to be harmful or ineffective. Negative publicity around past disasters linked to hidden clinical trials seems to have pushed pharma companies into compliance. Today, the leading drug companies publish their trial results as required by law nearly all of the time, though some of the less prominent commercial trial sponsors continue to do badly.
In contrast, even some of the major universities and nonprofits perform dismally….
If the FDA was enforcing the law, New York University School of Medicine alone would be facing a $7,647,109 fine for its illegal and unethical behaviour. However, to date, the FDA has not collected a single cent in fines….
The FDA has recently signalled that it may in future start selectively imposing fines on some occasions. Transparency advocates have sharply criticized the FDA’s plan for lacking teeth. …”