The document outlines the integral role of biostatistics in clinical trials, including the process of study planning, protocol development, and FDA evaluation of biostatistical data. It emphasizes the importance of selecting a qualified biostatistician and the distinction between statistical and clinical significance in assessing trial outcomes. Furthermore, it discusses FDA expectations for submissions regarding scientific evidence of safety and effectiveness.

1. Practical Biostatistics for Clinical Trials,
or How to Find and Use Your Biostatistician
Scott Brown, Ph.D.
NAMSA

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Overview
 Biostatistics Process
 Finding Your Biostatistician
 How Does the FDA View and Use Biostatistics?
 Statistical vs. Clinical Significance
 What Does FDA Expect?

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Biostatistical thinking is an integral part of
the design – not to mention analysis and
presentation – of nearly every clinical trial

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Biostatistics Process
Clinical Study
Planning
Development of
Protocol / SAP
“Operational”
statistics: tables,
listings, figures
Output: clinical
study reports,
scientific
communications
Interpret:
internal /
external consult,
regulatory,
reimbursement,
customers

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Finding Your Biostatistician

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Optimal situation:
 biostatistician with clinical and regulatory experience including
previous FDA submissions, collaboration with non-statisticians
including physicians, and working knowledge of disease state
and therapeutic area

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Reasonable approach:
 consultant biostatistician with similar levels of experience

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My take:
 you want a biostatistician who is willing to take ownership of your
project, to treat it as his or her own

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For larger studies or a series of studies, a
team of biostatisticians may be employed,
with tasks suited to skillsets and interests

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How Does the FDA View and
Use Biostatistics?

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FDA’s Division of Biostatistics within the
Center for Devices and Radiological
Health (CDRH) is a section of the Office of
Surveillance and Biometrics

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Statisticians tend to work across different
therapeutic areas and may or may not
have knowledge of the specific disease
state or treatment under consideration

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Biostatistical analysis is a tool to help
interpret data, not a sole means of
reaching conclusions about approvability
 The FDA statistician will not be the one signing the approval
letter

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This point cannot be overstated: FDA
evaluates “the totality of the data”
 That is, hitting your primary endpoint does NOT imply FDA
approval of the application – for that matter, failing to hit your
primary endpoint does not imply disapproval

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Statistical vs. Clinical
Significance

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P-values tell us nothing about the size or
relevance of an observed benefit – only
whether the benefit can be explained by
chance
 For example, a large study can detect small, clinically irrelevant
differences as being statistically significant

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Conversely, a large clinical benefit can fail
to be statistically significant if the trial is
small or poorly designed
 Clinical significance depends on the magnitude of the effect and
the importance of the outcome

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Clinical significance is not a statistical
issue, but rather an matter of judgment

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What Does FDA Expect?

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Statutory directive: for PMA submissions,
rely upon valid scientific evidence to
determine whether there is reasonable
assurance that the device is safe and
effective

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For a PMA (or 510(k)) submission, certain
endpoints will be prespecified in the
protocol and possibly the statistical
analysis plan (if one exists)

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 To view the complete series about Practical Biostatistics for
Clinical Trials, or How to Find and Use Your Biostatistician
 Visit NAMSA Seminars
 For information about NAMSA’s clinical services
 Check out our Clinical Research page
 For additional information on this topic
 Download our brochure on Clinical Research
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 Contact us at clientcare@namsa.com.