Dr Michael Silverman, principal at BioStrategics Consulting Ltd, discusses clinical trial design as an important aspect of the Clinical Trial Protocol.

This week I would like to discuss the importance of clinical trial design in defining a successful clinical trial protocol.

Clinical trial design provides the operational details of the drug testing conditions. It includes the specifics of trial design, use of control agents, blinding, randomization and the drug-dosing regimen. All are critical components of the scientific success of a trial, and all are closely intertwined into the superstructure of the protocol.

The study design must be created based on its appropriateness to the objectives of the trial and, in turn, is influenced by the phase of development, nature of the disease under treatment, and the availability of alternative therapy. In early, smaller trials of safety or pharmacokinetics, it may be reasonable to employ an open-label design without a control group, a crossover design, or a dose-escalation scheme. Larger efficacy trials are most commonly conducted using a controlled, blinded design, although there are many variations on this schema. The choice of design parameters must be highly individualized. There are several types of controlled trial designs, including:

Noncurrent Controls

  • Historical
  • Crossover
  • Withdrawal
  • Factorial
  • Others

Concurrent Controls

  • Nonrandomized
  • Randomized
  • Untreated control
  • Active control
  • Placebo control

The choice of the drug-dosing regimen is determined to a large extent by the products pharmacology, pharmacokinetics, and previous clinical trial results (both safety and efficacy), along with the dosage form and route of administration. This decision is often straightforward but takes on particular significance in blinded and controlled clinical trials because of the need to match dosing across study groups. It is generally possible to use a matching placebo when all groups are receiving the same dosage forms (e.g. tablets or infusions), but when the new drug has unique physical properties (such as a hemoglobin solution) or the standard therapy has a different dosage form (such as comparing an oral with an intravenous antibiotic), considerable creativity may be needed to conduct a blinded, controlled trial.

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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