5. Designs of Comparison Trials

There are a number of different types of comparison trials possible:

  • Superiority to demonstrate that the investigational medicine is better than the control;
  • Equivalence to demonstrate that the endpoint measure is similar (no worse, no better) than the control;
  • Non-inferiority to demonstrate that the investigational medicine is not worse than the control;
  • Dose-response relationship trials to determine various dose parameters, including starting dose and maximum dose.
When the aim of a randomised controlled study is to demonstrate that one treatment is superior to another, a statistical test is employed and the trial is called a superiority trial. Often a non-significant superiority test is wrongly interpreted as proof of no difference between the two treatments. With statistical tools at most, one can show that they are equivalent. This type of study design is often used to test the effectiveness of a treatment compared to placebo.

In an equivalence trial, the statistical test aims at showing that two treatments are not too different in characteristics. These trials are designed to demonstrate that one treatment is as effective as another.

Finally, a non-inferiority trial, is designed to demonstrate that a treatment is at least not (much) worse than a standard treatment. Non-inferiority comparison trials are often used for efficacy studies and the control is a medicine already available to patients.

Dose-response relationship trials are a class of trials that determine an optimal dose (Maximum Tolerated Dose (MTD) or Optimum Biologic Dose (OBD)) of a specific medicine. The dose response of a medicine is important in pharmacology, pharmacokinetics and toxicology. Dose response studies may be part of larger research to develop new treatments or to supplement existing knowledge of a medicine whose benefits may have already been established.

Dose-response relationship comparison studies investigate:
  • The shape and location of the dose-response curve.
  • The appropriate starting dose.
  • The optimal strategies for individual dose adjustments.
  • The maximal dose beyond which additional benefit would be unlikely.
Typically randomised controlled trials adopt the parallel groups design. Cross-over, cluster and factorial designs are not as common. An analysis of the 616 Randomised Controlled Trials (RCTs) indexed in PubMed during December 2006 found that 78% were parallel group trials, 16% were cross-over, 2% were split-body, 2% were cluster, and 2% were factorial.