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

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