Does the FDA need to tighten its grip on drug trials in the U.S.? 

FDA drug trials

The U.S. Food and Drug Administration (FDA) is considered the gold standard of medical review across the globe. But lately, some studies have been calling for the FDA to take a tougher stance on certain drug approvals.

Claims that the FDA has been less rigorous with its standards for clearing drugs have cropped up over the past few years. In fact, a study conducted by the Oregon State University (OSU) in the U.S., reported that 24 out of the 37 drugs approved in 2022, were based on only one study. Moreover, only four drugs were greenlit after three or more trials were held.

Randomized controlled trials, which are crucial for minimizing bias in drug evaluation, were only used in about half of the studies, questioning the rigor of the drug approval process.

With this in mind, we looked at the current state of the FDA drug approval process and what it means for the biotech industry.

Table of contents

    Study finds trial results often undisclosed by the FDA

    According to the study mentioned above, only 25% of the trial results for the 37 drugs that received FDA approval were posted, meaning that 75% of the results were permitted to be kept under wraps. This includes studies run by biotechs and pharmaceutical companies as well as government-supported trials.

    “We know that there are more trials for these drugs in the registry than what is being reported in the FDA report. And we don’t see everything that the FDA reviewers are given,” said Veronica Irvin, co-author of the study and associate professor of the College of Health at OSU.

    Irvin explained that often, the public is kept in the dark about the supporting evidence for a FDA drug approval. The study also looked at how quickly trial results were reported on, the U.S. database for medical research. It found that only 6% of the study results were published within six months of the respective FDA drug approvals. These statistics have leached into 2023 and 2024 as well, according to Irvin.

    While the FDA does report harmful side effects that patients experience with a certain drug, and is quick to label drugs with warnings, Irvin pointed out that announcing the results of follow-ups is rare once they’ve been in the market for a few years.

    “There’s a requirement to report your results at the completion of your main primary outcome. But there’s no requirement and any regulations for what happens five or ten years down the road. At what point should a drug be evaluated for whether it is worth it? Very few are pulled (from the market),” said Irvin.

    How beneficial are FDA’s accelerated drug approvals many years down the line? 

    A study published in JAMA Network last week emphasized the importance of conducting follow-up research on drugs that are prescribed to patients, particularly those that received accelerated approval. The FDA introduced the Accelerated Approval Program back in 1992 to be able to bring drugs for life-threatening conditions quicker to patients. Although this move does fulfill the unmet needs of patients, expediting their entry into the market has raised concerns over safety and effectiveness, and whether it could even increase the risk of harm. 

    Most of the cancer drugs that were investigated in the study did not show benefit in overall survival or improve the quality of life of patients within five years of accelerated approval. Plus, a third of the drugs that were converted to regular approval failed to show significant improvement in the lives of patients. 

    “You have drugs, especially cancer, orphan drugs, rare disease drugs, getting to the public sooner, which is a benefit, but then there’s not as much review about the long-term effects and follow-up,” said Irvin.

    Moreover, the FDA has granted the use of surrogate measures to support the conversion from accelerated to regular approval, the study explained. This became more prevalent after the 21st Century Cures Act was passed in 2016, relaxing rules for priority conditions like cancer. 

    A surrogate endpoint is a clinical trial endpoint that is used as an alternative to a direct measure of a drug’s benefit. Instead, they help predict the clinical benefit of medicines. These measures have come under scrutiny as they do not provide enough clarity regarding the effectiveness or harm that the drug may have on patients’ lives.

    For example, when hunting for drugs that reduce the risk of a heart attack, measuring the surrogate marker of blood pressure aids the drug to go through the approval process faster. Although, reduced blood pressure does not definitely confirm the reduced risk of death from heart disease, Irvin explained.

    Null findings: not always reported

    Research has also shown that scientific research with null findings – where the results are not the expected outcomes – are not often reported. An analysis of 30,000 presentations at scientific conferences found that the ones with null results were far less likely to be published in journals compared to positive results, according to a report by Stat News.

    “I do think that it’s important for us to know that sometimes a null finding is okay. Just because there is a null finding once doesn’t mean that the drug shouldn’t ever be approved,” said Irvin. “I think it’d be good to know if there are multiple trials with null findings. I think it just makes it more transparent that, for example, in this study, at this dose with this population, a drug wasn’t effective, but at this dose with this population, it was. But that’s not easily findable right now.”

    Calls for FDA to improve transparency on clinical trial results

    One way that the FDA could boost transparency is by making summaries of trial data more accessible to the public. Irvin thinks that providing details of a clinical trial on Clinical – run by the National Institutes of Health (NIH) – in the form of a table could make it more reader-friendly, especially to the general public who find it hard to decode medical jargon. 

    “Oftentimes, it’s just a link to a paper, which has some benefits and weaknesses,” said Irvin. While a link to a research paper gives the full picture, people don’t always have access to the publications. 

    “Even if the results are reported, they’re very hard to follow. And, for those of us that have a PhD or an MD, reading through these is not easy, and so, for the general public, it’s very difficult to understand what that biomarker and the statistical tests were and what they meant,” said Irvin. “There should be a lay language requirement, at least a summary paragraph that makes it clear to the participants what is being measured, as it’s very difficult to interpret the results.”

    To add to that, a listing of all the trials that are ongoing and those that have been completed could make it easier for people to look them up as well.

    FDA proposes plans to cut down on clinical trials for drug approvals

    Meanwhile, the FDA has plans to reduce the number of clinical trials required to authorize treatments to one. A draft guidance titled ‘Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence,’ was welcomed late last year, that could allow researchers to perform a single study as long as there is also confirmatory evidence to back it. 

    The confirmatory evidence includes pharmacodynamic proof, evidence from an animal model that shows similarities in how the diseases manifest, clinical data from a similar indication, natural history evidence – which monitors how a disease develops in patients – and so on.

    However, Irvin wouldn’t increase the number of clinical trials that are required for therapies. For instance, in the case of rare diseases, it would be difficult to support multiple clinical trials as there are only a few patients diagnosed with the disease. 

    “For some drugs that work for certain conditions or patient groups, they should just be allowed to have the one trial. I do think that allowing some drugs to have the one trial approval is practical,” said Irvin. “But it allows other pharmaceutical drugs that could have many studies, only to have to report their best study, and not actually share all the other arms.”

    But this doesn’t entirely affect the trust that people in the U.S. have in the FDA, Irvin recounts, as it is quick to pull drugs from the market, and has review boards appointed to monitor research. 

    “I believe that there’s a lot of trust in the FDA. But I think that some consumers are surprised at what the FDA does and doesn’t regulate, and the level to which it is. I would think individuals would have more trust if they could go through and see the data,” said Irvin. “I just don’t know that it actually has an impact on their decision-making. If you have a serious health condition, then you’re most likely going to take that drug. But I think that there has been mistrust in healthcare since the pandemic in general, but I don’t know how that trickles over to the FDA.”

    The time taken for a drug to hit the market in the U.S. is shorter than in European nations and most other countries in the world. While it is notable that patients can get their hands on medicines to treat their illnesses quicker, Irvin advocates for more transparency in the way that these trials and therapies reach the public. 

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