FDA may accept one pivotal study

The Food and Drug Administration is not quietly tweaking a technical rule. It is trying to change the default logic of drug approval. In a February 19, 2026 commentary, FDA Commissioner Marty Makary and top agency official Vinay Prasad said the agency’s “default position” will now be that one adequate and well-controlled clinical study, plus confirmatory evidence, can support approval of a new drug or biologic (ajmc.com). That sounds abrupt. In one sense, it is. In another, it is the FDA finally saying out loud what the law has allowed for years. The legal backbone for this shift is not new. The FDA has long had authority to approve products on the basis of one strong trial backed by other evidence, and the agency put that flexibility into draft guidance in 2019 and then again, more explicitly, in 2023 (fda.gov, fda.gov). What changed in 2026 is the posture. For decades, drug companies treated two pivotal trials as the safe expectation because that was how the FDA usually behaved. Makary and Prasad are trying to kill that expectation and replace it with a new one: quality first, duplication second (biopharmadive.com). That distinction matters because “one trial” does not mean “one study and good luck.” The FDA’s 2023 draft guidance says a single adequate and well-controlled investigation still has to be reinforced by confirmatory evidence, which can come from sources such as mechanistic data, evidence in related populations, pharmacodynamic findings, animal models, or certain forms of real-world evidence (fda.gov). In other words, the agency is not lowering the statutory standard on paper. It is changing what kind of package can satisfy it. The burden shifts away from repeating a large preapproval experiment and toward building a broader web of supporting proof. That web is easier to imagine in rare disease, where the old model often made little sense. In September 2025, the FDA launched its Rare Disease Evidence Principles process for therapies aimed at ultra-small populations, generally fewer than 1,000 people in the United States, when the disease is driven by a known genetic defect and causes rapid decline or death (fda.gov, fda.gov). There, the agency openly acknowledged the obvious problem: if only a few hundred patients exist, demanding multiple traditional trials can be less a mark of rigor than a recipe for paralysis. But once that logic escapes rare disease, the tradeoff changes. Fewer preapproval patients usually means less mature safety data at launch. Rare toxicities often do not show up until a drug reaches broader use, in older patients, sicker patients, and people taking other medicines. The FDA’s own rare-disease framework says products approved through that route may face additional postmarketing requirements (fda.gov). That is the real center of gravity in this policy. If one pivotal study becomes normal, then surveillance after approval stops being a back-end administrative chore and becomes part of the evidence plan from the start. That will force sponsors to design launches differently. Real-world data systems, active safety monitoring, and faster label updates become more important when the preapproval file is thinner. The FDA’s new stance may indeed shorten development and reduce the cost of running redundant late-stage trials (clinicaltrialsarena.com). It also means the first years on the market will carry more of the uncertainty that used to be absorbed before approval. The concrete detail is buried in the agency’s own language: one trial may get a drug over the line, but the missing second look does not disappear. It moves into the postmarket period, where patients become the larger study population (fda.gov, fda.gov).