Perhaps, It is Not a Good Idea to Do Only One Clinical Study?

Typically, it does take more than one clinical study to insure . . .

A lower number of Clinical Studies: WASHINGTON — The Food and Drug Administration plans to begin requiring one clinical study, instead of the standard two, for medical products before consideration for approval, FDA Commissioner Marty Makary announced late in 2025. 

While historically the FDA has required two trials for added assurance of a drug’s safety and efficacy, it has become increasingly flexible and many drugmakers already submit just one pivotal clinical trial for approval. Makary said that while the agency will still require two in some cases, the default will be one trial. Preliminary partial as taken from STAT which has a paywall.

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Lowering FDA’s Drug-Approval Standards Is a Lose-Lose | MedPage Today

While FDA Commissioner Marty Makary, MD, MPH, was announcing plans to officially lower the standard for the number of clinical trials needed to approve a new drug (from the long-standing expectation of at least two trials to just one). Backlash was swift. Critics worried the move was politically motivated and it signaled a retreat from the rigorous dual trial requirement that once made FDA approval the global gold standard.

Those concerns are understandable. In reality, this is not a sudden shift or a new philosophy. It is the continuation of a trajectory beginning quietly and years ago. The effort met with little public scrutiny. It was gaining traction after President Obama signed the 21st Century Cures Act in 2016. The effort to shorten approval has been carried forward informally by the first Trump administration, the Biden administration, and now the second Trump administration.

In 2023, the FDA advanced the one-trial standard through draft guidance titled, “Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence.” The guidance was never finalized.

prior to FDA approval, industry-supported researchers had only disclosed results from about one in four completed studies. Even 5 years later, results from about half of the completed studies remained unreported. For 28% of drugs approved in 2017, the only publicly available results were from the single trial used for approval.

This is not a minor procedural gap. When a pharmaceutical company runs multiple studies, statistically, at least one in 20 is expected to yield a “positive” finding (p<0.05) by chance alone. If only that one is made public, and the rest remain in a file drawer, the FDA — and the public — may be basing decisions on a false signal.

The founders of modern clinical epidemiology understood this danger long before today’s debates. Archie Cochrane and Austin Bradford-Hill emphasized that evaluating medical interventions requires answering three distinct questions: Can it work? Does it work? Is it worth it?

The first question — proof of principle under ideal circumstances — is what randomized controlled trials are designed to answer. But demonstrating that a treatment works in the real world, across diverse patient populations and clinical settings, requires multiple trials, pragmatic studies, and observational evidence. Demonstrating that a treatment is worth the cost requires economic evaluation — an element that is present in many of our peer nations, but almost entirely absent from FDA decision-making.

A single, tightly controlled trial might answer the first question. It seldom answers the second or third.

Officially lowering the evidentiary bar creates a predictable risk: more companies may highlight their most favorable study while downplaying or withholding less supportive results — data the public may never see. We cannot accurately judge the safety of new treatments if we are only allowed to read the results that the manufacturer chooses to publish. Requiring more than one trial is not bureaucratic red tape; it is the core safeguard that helps us separate true clinical benefit from statistical noise, optimistic marketing, or incomplete science.

Data from the pre-21st Century Cures Act era, when multiple studies were the norm, suggest that adverse drug reactions requiring boxed warnings or withdrawals occurred in about 10% of approved drugs. In contrast, there has been an increase in the number of boxed warnings since 2017, with 90 new warnings in 2023 alone. Nearly 80% of these problems were identified in post-marketing studies. Disclosure of more pre-approval study findings may have identified these problems before the drugs went to market.

Americans already pay some of the highest drug prices in the world. We should not also bear the burden of lower scientific standards. Patients deserve medications that have been thoroughly tested, transparently evaluated, and proven to work — not just in one trial under perfect conditions, but in the real world where medicine is actually practiced.

At a moment when public trust in institutions is fragile, lowering the bar for evidence is exactly the wrong move. Instead, we should strengthen the FDA’s commitment to transparency, reproducibility, and multiple, independent trials. Innovation matters. But equally important is the confidence that the medicines we rely on are safe, effective, and worth their extraordinary cost.

Lowering FDA’s Drug-Approval Standards Is a Lose-Lose, MedPage Today