Which treatment is better? Ascertaining patient preferences with crossover randomized controlled trials.

Abstract

The difference in patient-reported outcomes between study arms can often be difficult to ascertain in randomized controlled trials (RCTs) using a parallel design because of wide interindividual variations in baseline characteristics and how patients interpret the outcome measures. Furthermore, the minimal clinically significant difference is often not available for many outcomes, and even when available, not individualized for each patient. Crossover RCTs are designed for intraindividual comparisons, which can address these issues by asking patients to directly compare the interventions with regard to effectiveness, adverse effects, and ease of use and to provide an overall choice. We discuss the key design elements for crossover trials, their advantages and disadvantages relative to parallel designs, and their utility in palliative care research using a number of case examples. This is a narrative review. Crossover studies randomize patients to a sequence of treatments. In addition to facilitating intraindividual comparisons, they often require a smaller sample size for the same statistical power compared with parallel designs and are thus less costly. However, crossover studies are only feasible when the condition being studied is relatively stable and the intervention has a short-term effect. Crossover studies with inadequate washout periods may be difficult to interpret. The risk of attrition also may increase because of prolonged study duration. By facilitating intraindividual comparisons and eliciting patient preferences, crossover studies can provide unique information on the superior intervention. Crossover designs should be considered for selected palliative care studies.