Dr Michael Silverman, principal at BioStrategics Consulting Ltd, discusses clinical trial sample size as an important aspect of the clinical trial protocol.

This week I would like to discuss certain considerations around clinical trial sample size in defining a successful clinical trial protocol.

Sample size for early stage clinical studies that are not out to prove statistically-relevant efficacy tend to be smaller in size, although the larger the number of patients that meet the criteria of the market population one hopes to treat, the great the likelihood that one will generate data that will be predictive of a later stage larger or pivotal study. In deciding the size of an early stage trial, it is important to remember that there should be a reason for every patient included in the study. Early stage trials are often exploratory or pilot in nature to test feasibility, define a dose range, and/or help identify the appropriate methods to measure changes and differences.

It is typical in dose-response studies, to ascertain a dose at which the drug may be used, to enroll several patients at each dose before escalating to the next in the hope of identifying any side effects or adverse events that would define the upper limit of the dose range. Similarly, in early efficacy-indicating studies, one would prefer to include as many patients as possible at doses likely to be used commercially to observe the variation and level of effectiveness of the drug using as many assessment criteria as possible.

For later stage and larger clinical trials, the sample size must be large enough to minimize the possibilities of false-positive or false-negative trial results, but not so large as to overwhelm the team’s logistical capabilities or extend the timelines beyond reason. Consultation with a biostatistician is essential to balance these factors and determine the mathematically most efficient sample size that will allow the trial to meet its primary objectives. Important factors that are considered in determining sample size include:

One of the biggest problems I have observed in later stage studies designed to demonstrate the efficacy of a drug in comparison to the current standard of care is the tendency to under size the study by overestimating the efficacy of the drug and underestimating the efficacy of the standard of care. Great care should be taken also from overemphasizing what is seen in early stage uncontrolled studies where bias can creep in and overestimate the potential of the new drug.

Dr Michael Silverman is the principal clinical consultant at BioStrategics Consulting Ltd., a clinical development consulting company based in Marblehead, MA, with business interests around the globe. Dr Silverman would be delighted to hear your thoughts on today’s blog, your experiences, or anecdotes and of course, your questions. To make comments or ask questions, click on this link.



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Copyright © 2011 BioStrategics Consulting Ltd.


About BioStrategics Consulting Ltd

BioStrategics Consulting Ltd provides a range of management-level clinical development consulting services to the pharmaceutical and biotechnology industries
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