In 1962, mainframe computers occupied entire rooms, available only to a handful of institutions. There was no internet, no personal computing, no cloud storage, no high-throughput data analysis. Clinical trials were documented on paper, statistical methods were elementary, and our understanding of disease mechanisms was superficial. Genomics and advanced imaging were still science fiction.
Biomarkers were virtually nonexistent; artificial intelligence was not even a serious concept. In this environment of limited tools and profound uncertainty, Congress enacted the Kefauver-Harris Amendments in 1962, amending the Federal Food, Drug, and Cosmetic Act by requiring pharmaceutical companies to demonstrate not only safety of their drugs but also efficacy through “adequate and well-controlled investigations.” The statute’s use of the plural “investigations” prompted the FDA to adopt a standard practice of requiring at least two independent pivotal trials to confirm results and guard against statistical flukes or unreproducible findings.
We inhabit a radically different scientific landscape than we did in 1962. Genomes are sequenced in hours, not years. AI models predict molecular interactions with remarkable precision. Electronic health records and wearable devices generate vast real-world evidence streams. Advanced biomarkers offer mechanistic confirmation of drug effects. Yet until recently, the default expectation of two trials remained largely intact. That rigidity has imposed enormous costs, delayed breakthrough products reaching patients, and stifled innovation at a time when science has never moved faster.
The FDA’s February 18, 2026, announcement that it is moving away from the informal two-trial requirement is a necessary step to promote medical innovation that recognizes contemporary science. The agency will now evaluate “substantial evidence” of effectiveness more flexibly: a single high-quality pivotal trial, bolstered by robust confirmatory evidence—such as mechanistic data, validated biomarkers, real-world outcomes, or prior knowledge—can suffice.
Commissioner Makary has been clear that the agency will still require two trials in some cases when appropriate, reflecting how the agency’s one-trial standard is simply a new default. The agency still retains its flexibility to require more evidence in extraordinary cases. This policy shift acknowledges that modern science provides multiple pathways to confidently demonstrate a drug’s safety and efficacy.
The average cost to bring a new drug to market exceeds $2.6 billion, with the lion’s share consumed by clinical development. Large trials routinely run into hundreds of millions of dollars each and stretch across years. Mandating duplication — when a single well-designed study powered appropriately already yields compelling evidence — has added billions in aggregate expense while contributing marginal additional certainty. Those resources could instead fund entirely new research programs. Analysts at Jefferies project that FDA’s new policy will raise R&D spending as the policy reduces the capital intensity of late-stage development.
Not surprisingly, some critics worry that this one-trial default could risk funding for Contract Research Organizations (CROs), entities that run clinical trials who benefit from greater development costs. These criticisms are an example of the broken window fallacy, in which governments can create jobs by creating useless redundant tasks (i.e., breaking windows to create jobs in the window repair market). Ultimately, such redundancies divert resources from more useful forms of production. In this case, every dollar the government forces developers to spend on redundant trials is a dollar that could have been spent on more research for new life-saving cures.
Critics who claim this move will jeopardize safety ignore that, in therapeutic areas like oncology and rare diseases — where the FDA has long accepted single pivotal trials with supportive evidence — innovation has flourished without compromising patient safety. In 2024, according to a review conducted by AgencyIQ, 66 percent of New Molecular entities were approved based on one pivotal trial, demonstrating the approach’s reliability.
The FDA policy shift is long overdue, as Congress has long recognized that one trial is appropriate. Congress first explicitly authorized the one-trial flexibility in the Food and Drug Administration Modernization Act (FDAMA) of 1997, which allowed the FDA to deem one adequate and well-controlled trial plus confirmatory evidence sufficient for substantial evidence of effectiveness.
Patients will be the ultimate beneficiaries. Faster development timelines will translate into earlier access to many transformative therapies and lower drug prices. Conditions that afflict millions—cardiovascular disease, neurodegenerative disorders, metabolic syndromes—have historically faced the strictest duplication demands, slowing progress relative to orphan indications. Expanding flexibility across broader populations will shorten the gulf between discovery and patients, potentially bringing drugs to market years earlier than if the old policy remained in effect.
This is a meaningful step forward, but policy announcements must be matched by consistent action. The statutory standard is substantial evidence that a drug is safe and effective. An application is considered by weighing the risks vs the benefits of the drug which can be inherently subjective. That subjectivity makes predictability essential: therapy developers investing hundreds of millions of dollars and years of work need clear, consistent agency guidance about what the FDA will deem necessary and acceptable to satisfy that standard. A one-trial default is a positive step, but there needs to be transparent and consistent application.
This announcement recognizes that requirements put in place years before America landed on the moon should be modernized to fit modern America. Modern tools like AI-assisted trial design, surrogate endpoints, and real-world evidence can offer assurance that rivals or exceeds a redundant traditional trial. Aligning regulatory requirements with modern capabilities should result in a more dynamic pipeline of cures and treatments, renewed investor confidence, lower drug costs, and—most critically—more lives enhanced or saved.
