What is a registrational, or pivotal, clinical trial?
A registrational trial, also called a pivotal trial, is a clinical study designed to give regulators the main evidence on whether a drug works and is safe. Its results are meant to support an application to sell the drug.
Also known as: pivotal trial, pivotal study, registration trial
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What makes a trial pivotal
New drugs are tested in people in stages, from small safety studies to larger efficacy trials. A pivotal study is normally a Phase 3 study designed to provide the data a regulator needs for a decision. That is how the European Patients' Academy (EUPATI) defines it. It adds that such a study is generally randomized and controlled, and of adequate size.
The nonprofit Friends of Cancer Research says the FDA reviews data from all of a drug's trials. The pivotal trial is the one that tests the drug in its intended patients. It uses the final dose and formulation that would appear on the label.
The words "registrational" and "pivotal" can describe the same study. Recursion's October 2026 SEC filing uses both words for its planned REC-4881 trial.
What the FDA looks for
For a new drug, the FDA looks for "substantial evidence" that it works. Under federal rule 21 CFR 314.126, adequate and well-controlled studies are the main basis for that judgment. Such a study compares the drug with a control. The control can be one of these:
- a placebo, an inactive look-alike;
- another dose of the same drug;
- no treatment;
- a known effective therapy;
- in special cases, historical data on the disease.
The rule says uncontrolled or partly controlled studies cannot be the sole basis for approving a drug's claims of effectiveness. If carefully done, they can still back up well-controlled studies.
In a September 2023 draft guidance, the FDA described how one adequate and well-controlled trial plus confirmatory evidence can meet the standard. As of October 2026, the FDA's page still labels it a draft that is not for implementation.
An example from AI drug discovery
Recursion's TUPELO study of REC-4881 is open-label, so patients and doctors know the treatment. Recursion said on October 15, 2026, that it anticipates starting a registrational trial in 2027, pending FDA discussions. Its filing lists a risk that the FDA may not agree with its proposed pivotal trial design.
Sources
- Pivotal Study, EUPATI (European Patients' Academy on Therapeutic Innovation)
- Pivotal Trial, Friends of Cancer Research
- 21 CFR 314.126 -- Adequate and well-controlled studies., Electronic Code of Federal Regulations (eCFR)
- Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence, U.S. Food and Drug Administration
- Recursion Pharmaceuticals, Inc. Form 8-K Current Report, October 15, 2026, Recursion Pharmaceuticals (SEC filing)
