On February 18, 2026, FDA announced that one adequate, well-controlled trial plus confirmatory evidence is now the default bar for marketing authorization, instead of two trials. A companion Plausible Mechanism framework goes further for rare disease programs. Here is what sponsors need to plan for, and what it means for your data.
Free sandbox · No credit card · 21 CFR Part 11 aligned
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Feb 18, 2026
single pivotal trial default announced
Feb 23, 2026
Plausible Mechanism draft guidance released
Apr 27, 2026
comment period closes
1
trial now expected to carry the full evidentiary weight
What changed
Both are directional as of this guide. Treat the specifics as subject to change until final guidance is issued.
FDA Commissioner Martin Makary and CBER Director Vinay Prasad said one adequate and well-controlled study, combined with confirmatory evidence, will generally support approval, a shift from the long-standing two-trial expectation.
FDA says the pivotal trial is expected to be generalizable to US practice, reflect a broad population across multiple sites, include a control arm reflecting the current standard of care, and use a clinically meaningful primary endpoint.
A February 23, 2026 draft guidance formalizes a "Plausible Mechanism" framework, allowing substantial-evidence determinations to rely on strong mechanistic rationale for individualized therapies targeting specific genetic conditions, where a randomized trial in an ultra-rare population is not feasible.
FDA is accepting comments on the Plausible Mechanism draft guidance until April 27, 2026. Build your data practices to the higher bar now rather than waiting for the final text.
What this means for your data
When two trials shared the evidentiary burden, a data quality gap in one was easier to absorb. Under a one-trial default, your edit checks, audit trail and query resolution are what convince a reviewer the trial is reliable enough to stand alone.
Edit checks / auto-queries
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Operator
Greater than
Value
180
Priority: High
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80
Priority: Normal
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Value 192 violates limit (180). Please verify.
Multi-site, multi-arm
If your one pivotal trial needs to reflect a broad, representative population across multiple sites, your EDC needs to make adding a site simple. QR-code enrollment, site-level participant numbering and by-site exports let you scale sites without scaling your data team.
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Before you switch
Every plan, including the free sandbox, includes edit checks, calculated fields and the audit trail.
21 CFR Part 11-aligned controls throughout; documentation available on Enterprise to support your own validation.
AI drafts your visit schedule and forms from a protocol; most teams have a working build the same day.
Bring an existing study or a prior protocol’s forms across as a starting template.
Email support, typically under 24 hours, plus documentation for your own assessment on Enterprise.
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FDA Commissioner Martin Makary and CBER Director Vinay Prasad said the agency’s default position is now that one adequate, well-controlled study combined with confirmatory evidence can support marketing authorization, rather than the long-standing expectation of two trials.
It is described as a default position, not an absolute mandate. FDA can still request additional evidence for a specific program, and sponsors can still propose more than one trial.
A February 23, 2026 draft guidance describing a pathway for individualized therapies that target specific genetic conditions with a known biological cause, allowing a strong mechanistic rationale to support a substantial-evidence determination when a randomized trial in an ultra-rare population is not feasible.
No. The Plausible Mechanism framework is a draft guidance, and FDA is accepting public comments until April 27, 2026. Treat the details in this guide as directional until final guidance is issued.
A single pivotal trial needs to withstand more scrutiny on its own. A field-level audit trail, automatic edit checks and the ability to add sites quickly matter more when there is no second trial to share the evidentiary weight.
Capture is not a regulatory consultant and does not advise on submission strategy. What it provides is the same flexible build, audit trail and lab data handling any rare disease program needs, so your underlying data supports whatever pathway your regulatory team pursues.
Nothing to start. The free sandbox has no credit card and no time limit.
Keep exploring
EDC for rare disease clinical trials
Built for the small cohorts this framework is aimed at.
Audit trail software for clinical trials
The field-level record a single pivotal trial leans on.
Query management software
How auto-raised queries keep data submission-ready.
CRF builder for clinical trials
AI-drafted forms and edit checks from your protocol.
ICH E6(R3) guide for clinical trial teams
Another 2026 regulatory shift worth tracking alongside this one.
Free sandbox with every feature. No credit card, no sales call.