FDA will now approve new drugs with one clinical trial instead of two, reversing a 60-year standard
The two-trial rule was created after thalidomide caused birth defects in 10,000 children in Europe
On February 18, 2026, FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research (CBER) Director Vinay Prasad co-authored a perspective article in the New England Journal of Medicine titled 'Rethinking the Standard for Drug Approval.'
The article announced that FDA would default to requiring only one pivotal clinical trial — plus 'confirmatory evidence' — for new drug approvals, replacing the longstanding expectation of two independent pivotal trials. Announcing regulatory policy through a journal article rather than through formal notice-and-comment rulemaking under the Administrative Procedure Act was itself unprecedented; Yale law professor Joseph Ross noted FDA 'skipped the formal public comment process that is supposed to accompany major regulatory changes.'
Key Concepts
Essential concepts and terms to understand this topic
Iron Triangle
A stable three-way alliance between congressional committees, federal agencies, and interest groups that dominates policymaking.
Federal Court Limits
Jurisdictional limits on federal courts based on state sovereign immunity.
Rule-Making Power
Authority of federal agencies to create legally binding rules through notice-and-comment procedures.
Advice and Consent
The Senate''s power to approve or reject presidential appointments and treaties.
Administrative Procedure Act
1946 law governing how federal agencies develop regulations and make decisions through rulemaking and adjudication.
Independent Agencies
Federal agencies with legal protections from presidential control to ensure impartial decision-making.
Notice-and-Comment Rulemaking
APA process requiring agencies to publish proposed rules and accept public comments before finalizing.
Executive Power Vested
Article II's opening clause vesting all executive power in a President, creating the constitutional foundation for presidential authority.
Federal Agencies
Government organizations that implement and enforce laws within the executive branch.
Key People
8MM
Marty Makary
FDA Commissioner (Trump appointee, confirmed Feb. 2025)
Makary co-authored the NEJM article announcing the policy change and testified before Congress defending it the following week. A Johns Hopkins surgical oncologist and Substack health commentator before his appointment, Makary has consistently argued that FDA's approval standards create 'innovation bottlenecks' that deny Americans access to treatments available in Europe. His joint authorship with Prasad signaled alignment between the two top FDA officials.
VP
Vinay Prasad
CBER Director (FDA Center for Biologics Evaluation and Research); co-author
Prasad — an oncologist and prominent critic of what he calls 'evidence-free medicine' — has argued for years that FDA's two-trial standard is excessive for well-understood drug classes. His CBER directorship gives him oversight of vaccines, gene therapies, and biologics. His joint authorship of the NEJM article indicates the policy applies to his center's products as well as the drug centers.
RP
Richard Pazdur
Former FDA Office of Oncology Products Director (1999–2025); resigned in protest
Pazdur's 26-year tenure made him one of the most consequential regulatory officials in FDA history — he personally oversaw approval of dozens of breakthrough cancer drugs. His public resignation protest — stating he was 'handed a press release' and told to endorse a policy he disagreed with — was the most significant internal institutional signal of the policy's departure from FDA scientific norms.
AK
Aaron Kesselheim
Professor, Harvard Medical School; Director, Program on Regulation, Therapeutics, and Law
Kesselheim provided the most cited expert critique of the policy change, calling it 'a ratcheting down of FDA evidence standards.' His research has documented specific instances where single-trial approvals were subsequently reversed after the approved drug failed in broader post-market use.
Joseph Ross
Professor, Yale School of Medicine; health policy researcher
Ross identified the procedural problem with the NEJM announcement — that FDA skipped the formal notice-and-comment process the APA requires for major regulatory changes. His critique opened a potential legal challenge pathway: if the policy is treated as a legislative rule rather than a guidance document, it may be vulnerable to APA challenges for procedural non-compliance.
Peter Marks
Former CBER Director (2016–2025); resigned March 2025
Marks resigned as CBER director in March 2025 — before Prasad's appointment — after reportedly being pressured by RFK Jr. to change FDA's vaccine approval processes. He was replaced by Prasad. His departure, combined with Pazdur's, represented a loss of two of FDA's most experienced senior officials within months of the administration taking office.
Bernie Sanders
Senate HELP Committee Ranking Member (I-VT)
Sanders held an emergency hearing on the FDA policy change in late February 2026, calling it 'a giveaway to pharmaceutical companies dressed up as regulatory reform.' He cited the history of accelerated approvals that were subsequently withdrawn after failure in confirmatory trials and demanded Makary publicly commit to publishing the internal analysis used to support the change.
Robert F. Kennedy Jr.
HHS Secretary; FDA's organizational superior
The NEJM article did not mention RFK Jr., but the policy aligns with his broader critique of FDA's approval process as captured by pharmaceutical industry interests. He has separately called for faster access to alternative treatments and reduced regulatory barriers. Whether the policy change was initiated by Makary and Prasad independently or coordinated with RFK Jr.'s HHS office was not publicly clarified.
What you can do
Track new drug approvals after this policy takes effect — note which use one trial vs. two
education
FDA publishes approval decisions and their evidentiary basis through the Drugs@FDA database and the Center for Drug Evaluation and Research (CDER) monthly new drug approval reports. After the February 2026 policy change, you can track whether one-trial approvals increase and what confirmatory evidence is accepted. STAT News and MedPage Today provide detailed coverage of approval decisions.
Contact your senators about the Drug Approval Integrity Act
civic action
Senate HELP Committee Democrats introduced legislation on March 1, 2026 to write the two-trial standard into statute for drugs with revenues over $500 million. If you believe two independent trials should remain the default for blockbuster drugs, contact your senators to support the bill. If the Senate HELP Committee holds a markup, public attention matters.