LSHC Horizons Brochure 2024 - Flipbook - Page 36
Hogan Lovells | 2024 Life Sciences and Health Care Horizons | Clinical Trials
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Single-trial approvals: Key trial design considerations
Between the lines of the September 2023
draft guidance discussed in our “Spotlight on
Single-trial approvals” is a critical message
to any sponsor intending to rely on a single
trial for product approval. Although the draft
guidance provides greater detail regarding
the quantity, quality, and appropriate
sources of confirmatory evidence, it is critical
to recognize and address the challenges
associated with relying on one clinical trial
when seeking approval. To that end, the draft
guidance includes recommendations for early
engagement with the FDA for sponsors who
intend to seek approval using this approach.
Sponsors must be mindful of the inherent
challenges associated with pursuing an
approval based on one pivotal study. Multiple
adequate, well-controlled clinicals trials
will typically yield the most robust evidence
of effectiveness, especially when using a
randomized double-blinded, concurrently
controlled superiority design. Even so, other
types of study designs can also convincingly
establish effectiveness – such as non-inferiority
studies or designs utilizing external controls.
of evidence should be evaluated by appropriate,
pre-determined statistical methods. Expanding
upon the statistical framework, criteria for
determining the reliability of the confirmatory
evidence, including meaningful effect sizes
and uncertainty surrounding estimates,
should be considered. Additionally, sponsors
should address how these metrics relate to the
primary endpoints of the clinical investigation.
Sponsors should also consider potential
sources of bias or confounding that may affect
the interpretation of the confirmatory evidence,
including selection and performance bias.
This will prove particularly useful for sponsors
who may need to employ external validation
techniques, such as replication studies, to
validate the confirmatory evidence.
Applications supported by a single adequate
and well-controlled clinical investigation
and confirmatory evidence can raise unique
challenges on the path to approval. Hogan
Lovells will continue to work closely with
sponsors as they engage with FDA on this
approval pathway.
In situations where a sponsor will rely
on a single pivotal trial for product
approval – regardless of whether the trial
measures standard clinical endpoints or
surrogate endpoints – the trial should show
a clinically meaningful effect and the strength
Robert F. Church
Partner
Los Angeles
Eman S. Al-Hassan
Senior Associate
Los Angeles
Mike Mortillo, Ph.D.
Senior Regulatory
Specialist
Washington, D.C.
