The early-escape design is another way to minimize an individual’s duration of exposure to a placebo. In the early-escape design, participants are removed from the study if symptoms reach a defined level or they fail to respond to a defined extent. The failure rate can then be used as the measure of efficacy. Thus, in a study with an early-escape design, participants are only briefly exposed to ineffective interventions. In such cases, the need to change treatment becomes a study endpoint.
Early Escape Design is used when
- The criteria for deciding whether these endpoints have occurred should be well specified, and
- The timing of measurements should ensure that patients will not remain untreated with an active drug while their disease is poorly controlled.
The primary difficulty with this trial design is that it may give information only on short-term effectiveness. The randomized withdrawal trial however, which can also incorporate early-escape features, can give information on long-termeffectiveness.
EET differ from randomized withdraw trials (RWT) in which patients are randomized to placebo or active treatment after the patient achieves a favorable clinical response following treatment with the test article. Unlike the RWT, the EET design randomizes the patients at baseline and allows the patient to escape from the treatment group to which they were randomly assigned if a pre-specified level of improvement is not achieved or if the disease worsens.
Both EETs and RWT are relatively new trial designs which minimize placebo exposure, or exposure to less effective treatment arms. Not surprisingly, these designs have proven to be more user-friendly than conventional parallel randomized controlled trial (RCT) designs. However, they present scientific, statistical and ethical concerns distinct from more conventional designs. Although commonly used in rare disease and/or small trial setting, EETs could be useful in a more general study setting.