FDA Shifts to Single Pivotal Trial Default and Updates Clinical Trial Participation Standards

The Food and Drug Administration announced a new policy that the default requirement for FDA approvals will be one robust pivotal trial plus confirmatory evidence, rather than two trials. The policy was published online February 18, 2026, in issue February 19, 2026.

Since 1997, the Food and Drug Administration has retained statutory authority to grant marketing authorizations on the basis of a single trial. The new policy formally shifts the default standard away from the two-trial requirement that has historically been the norm.

Separately, on December 15, 2025, the Food and Drug Administration finalized its guidance on Enhancing Participation in Clinical Trials, formally updating expectations for enrollment and trial design. While progress has been made since the draft guidance in 2020, many gaps remain among minority populations, older adults, and patients with comorbidities.

To promote the enrollment of a representative trial population, the FDA calls on sponsors to broaden eligibility criteria. By removing exclusions that lack a clear scientific or safety rationale, the study can assess a wider range of characteristics that may affect the drug's safety. Overly restrictive inclusion criteria are increasingly linked to limited generalizability, reduced label expansion opportunities, weakened payer and clinician confidence, and lower external validity of trial results.

The FDA recognizes that certain exclusions are appropriate to protect vulnerable patient groups but recommends reevaluating criteria in later stages of drug development as safety experience increases.

Continuing to reduce participation burden through remote assessments and decentralized or hybrid elements is critical for improving enrollment and retention. Providing flexibility in visit windows or decreasing the frequency of study visits can also address recruitment challenges by improving accessibility.

To reach populations historically underrepresented in clinical research, community-based recruitment and patient engagement are necessary. Reducing mistrust toward medical research requires intentional outreach through referral pathways such as community providers, advocacy groups, community leaders, or faith-based organizations.

Rare disease trials require tailored enrollment strategies due to limited populations and geographic dispersion, and communication with patient advocacy groups is key to understanding participant needs. Due to ethical access considerations, re-enrollment of participants from early-phase trials into later-phase randomized trials and open-label extension studies with broader inclusion criteria are recommended.

Studies that underrepresent intended-use populations often result in narrower indications and more conservative labeling. Lack of adequate safety data increases the likelihood of post-marketing requirements and additional studies. Incomplete safety and effectiveness evidence across diverse populations can delay physician confidence and adoption.