3.1 - Clinical Trial Design

Good trial design and conduct are far more important than selecting the correct statistical analysis. When a trial is well designed and properly conducted, statistical analyses can be performed, modified, and if necessary, corrected. On the other hand, inaccuracy (bias) and imprecision (large variability) in estimating treatment effects, the two major shortcomings of poorly designed and conducted trials, cannot be ameliorated after the trial.. Skillful statistical analysis cannot overcome basic design flaws.

Piantadosi (2005) lists the following advantages of proper design:

  1. Allows investigators to satisfy ethical constraints
  2. Permits efficient use of scarce resources
  3. Isolates the treatment effect of interest from confounders
  4. Controls precision
  5. Reduces selection bias and observer bias.
  6. Minimizes and quantifies random error or uncertainty
  7. Simplifies and validates the analysis
  8. Increases the external validity of the trial

The objective of most clinical trials is to estimate the magnitude of treatment effects or estimate differences in treatment effects. Precise statements about observed treatment effects are dependent on a study design that allows the treatment effect to be sorted out from person-to-person variability in response. An accurate estimate requires a study design that minimizes bias.

Piantadosi (2005) states that clinical trial design should accomplish the following:

  1. Quantify and reduce errors due to chance
  2. Reduce or eliminate bias
  3. Yield clinically relevant estimates of effects and precision
  4. Be simple in design and analysis
  5. Provide a high degree of credibility, reproducibility, and external validity
  6. Influence future clinical practice