Regulatory & Policy

Small US biotechs cite FDA barriers to first-in-human trials: survey

Category: Clinical Trial Reform | Regulatory Body: FDA | Geography: United States | Policy Instrument: Initiative launch

Small US biotechs cite FDA barriers to first-in-human trials: survey

The Biotech Consortium to Accelerate Innovation (BCAI), in partnership with Cambridge, Massachusetts-based MassBio, published survey findings showing that small US biotech executives see FDA regulatory requirements as a significant deterrent to conducting first-in-human (FIH) trials in the United States. The survey, conducted between December 2025 and March 2026, gathered responses from 37 US biotech executives, the majority from small, early-stage companies developing therapies for rare and serious neurological, oncological, and immunological conditions.

Of respondents, 76% identified the US as their first-choice location for FIH trials when FDA review is predictable and consistent, yet 72% said they are hesitant to conduct those same trials under the agency's historical regulatory framework. Under that framework, Australia ranked ahead of the US when respondents considered the historical regulatory environment, with a mean preference rank of 2.67 versus 4.03 for the US. A total 73% of respondents cited delays and financial costs tied to FDA clinical holds and rework as the leading reason sponsors are moving trials offshore — not scientific infrastructure or patient population access; 54% said they are now less likely to test new drugs in the US than previously, with executives referencing "current turmoil at the FDA with high turnover" as a contributing factor.

A specific technical concern also emerged: 85% of respondents support reforming the FDA's application of the "1/10 rule" — the tenfold safety margin used to establish maximum safe starting doses — which sponsors argue some reviewers are effectively applying as a ceiling on subsequent dose escalation rather than as a framework for establishing the initial safe starting dose. Additional remedies proposed by respondents include restoring predictable review timelines, strengthening sponsor-reviewer communication, aligning benefit-risk frameworks with disease severity and patient voice, and centralizing institutional review board (IRB) review for first-in-patient studies.

For rare and serious disease developers — where patient populations are small and disease progression is rapid — clinical holds and iterative rework carry disproportionate consequences. Small biotechs, which represent the majority of survey respondents, are acutely exposed to capital inefficiency; a clinical hold can derail a program entirely or force a pivot to a more permissive regulatory environment abroad. The 1/10 rule concern is particularly pointed in this context.

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BCAI's stated mission to keep American clinical trials in the US positions the survey as a policy advocacy instrument. The survey's findings arrive alongside a related government initiative: HHS launched Operation Trialblazer in June 2026 specifically to reverse the offshoring of early-phase clinical research, signaling that the trend documented by BCAI and MassBio has reached the level of federal policy concern. BCAI argues that migration of FIH trials to Australia, Europe, or China can delay US patient access to investigational therapies and shift clinical trial infrastructure and investigator experience overseas.


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