As I enter the room for my weekly clinical trial visit, I am met with tired smiles from my home-based participants. These patients, who suffer from transthyretin-mediated amyloidosis, a progressive and fatal condition, eagerly participate in a clinical trial for a new drug. Despite not directly benefiting from the research themselves, they hope that their involvement will lead to a better future for their children, grandchildren, and younger relatives. However, the toll of participating in a clinical trial is immense. In addition to managing their disease, these patients endure invasive tests, grapple with new side effects, and live with the constant worry of potential harm. It is disheartening to think that their efforts might be in vain if the data from the trial is never reported, the results are never published, and the study is rendered useless.
Clinical trials are the backbone of evidence-based medicine. To ensure transparent decision-making by patients, physicians, and regulators, it is crucial that all trial results, whether positive, negative, or neutral, are made publicly available. Without complete data, there is a risk of distorting the evidence, downplaying the harms and overstating the benefits. Unfortunately, the current state of clinical trial reporting is far from satisfactory.
A History of Insufficient Reporting Requirements
In the United States, reporting clinical trial results within a year of study completion has been a legal requirement since the FDA Amendments Act of 2007 (FDAAA). However, less than half of the trial results are reported on time, and thousands of results are missing altogether. Even trials for orphan drugs and those involving vulnerable populations, such as children, have disappointingly low reporting rates. Prior to 2007, there were scant laws mandating clinical trial reporting, and the pharmaceutical industry took advantage of this loophole, leading to instances of data concealment and the introduction of ineffective or dangerous medications into the market.
Furthermore, the problem extends beyond the pharmaceutical industry. Public and philanthropic sponsors, including government organizations, universities, and charities, are also guilty of underreporting their research results. While their motives may not be financially driven, the failure to report research contributes to unnecessary duplication and wastes taxpayer dollars. Shockingly, approximately half of taxpayer-funded research conducted by the National Institutes of Health (NIH) in recent years remains unreported, and in some cases, delinquent trialists have even been rewarded with new grants.
The Need for Mandated and Enforced Reporting
The solution seems straightforward: mandated and enforced results reporting. The FDAAA requires all applicable clinical trials to upload their results to the ClinicalTrials.gov database within a year of study completion. However, the legislation lacks teeth. It grants the FDA sole enforcement discretion, without compelling the agency to enforce the law or collect fines. Additionally, the FDAAA exempts trials completed before its enactment, which poses challenges when comparing the safety and efficacy of new drugs against older ones due to incomplete data.
Although grassroots campaigns by organizations like AllTrials and TranspariMED have made progress in increasing reporting rates, much remains to be done. Thankfully, there is growing political pressure to address the issue. Congressional committees have demanded evidence of enforcement actions, and initiatives like threats to cut funding for delinquent trialists have been proposed. Activist groups like the Universities Allied for Essential Medicines (UAEM) have taken action by filing petitions, highlighting the harm caused to patients and the scientific community due to the FDA’s inaction.
Addressing the clinical trial reporting crisis necessitates continued pressure on the FDA to take substantive action. Supporters can write letters of support and add them to the FDA petition. Additionally, redefining the language in the FDAAA statute can eliminate discretionary powers and enforce stringent reporting standards. By doing so, the FDA can align itself with global efforts to promote transparency and accountability in clinical research, drawing from the World Health Organization’s best practices in trial registration and reporting.
Furthermore, when enforcement begins, trials funded by public agencies, such as the NIH, must be prioritized to prevent the waste of taxpayers’ money. A comprehensive overhaul is needed to prioritize the American population’s well-being and align with the global commitment to fostering trust and transparency in clinical research.
Improving clinical trial reporting is crucial for the advancement of evidence-based medicine. Patients, physicians, and regulators rely on transparent data to make informed decisions. However, the current state of clinical trial reporting falls short. The FDAAA, despite being a step in the right direction, lacks enforcement and accountability provisions. It is evident that significant changes are needed to ensure all trial results are reported, regardless of their outcomes. By addressing these issues, we can foster an environment of trust, transparency, and patient-centered research. The time for action is now.