Researchers plan to conduct a randomized, double-blind, placebo-controlled, crossover trial to assess the efficacy of orally administered AKL1 (a botanical mixture in capsule form) in addition to standard asthma therapy. Adults with suboptimally controlled asthma despite current therapy will be recruited. The study will consist of the following 4 periods, during which subjects will continue their normal asthma treatments:
A 4-week single-blind baseline period, during which subjects will receive a placebo
A 12-week double-blind active treatment period, during which subjects will receive either AKL1 or placebo
An 8-week single-blind washout period, during which subjects will receive a placebo
A second 12-week double-blind active treatment period, during which subjects will be crossed over from ALK1 to placebo or vice versa.
Daily diaries will record key measurements: peak expiratory flow and symptoms; spirometry; validated symptom and health status questionnaire scores; and adverse events monitored at study visits. Based on this information, which of the following statements is most likely true?
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This question describes the design of a crossover study aiming to assess the efficacy of orally administered AKL1 (a botanical mixture) capsules in addition to standard asthma therapy. In a crossover study, each subject receives different treatments (eg, active, placebo) during different times in the study phases. For example, a typical crossover study comparing an active treatment to placebo will have the following design:
There is an initial baseline period (eg, 4-week single blinded placebo) before randomization.
Subjects are then randomly assigned to receive either active treatment or placebo for a set time (ie, first treatment phase).
After this initial treatment phase, subjects undergo a washout phase to remove the effects from the first treatment.
Once the washout phase is completed, the subjects then cross over into a different treatment for a set time (ie, second treatment phase) and the process starts over.
Each subject in a crossover study receives all treatments and acts as his or her own control. This contrasts with studies that have a parallel arm design, in which subjects receive a single treatment throughout the duration of the study. Because each subject receives all treatments, crossover design studies usually yield more precise estimates of treatment effects compared to parallel design studies.
However, crossover studies may take longer to complete than parallel arm studies because subjects have to move from one phase to another multiple times during the study phases (Choice C). Another disadvantage of the crossover design is the carryover effect (ie, the influence of the first treatment phase carrying over to the second treatment phase). One way to minimize the carryover effect is to incorporate a lengthy washout phase.
(Choice A) Because each subject acts as his or her own control, crossover studies generally require smaller sample sizes than their parallel arm counterparts.
(Choice B) Each subject will be treated with both AKL1 and placebo (assigned in random order) because the study has a randomized, placebo-controlled, crossover design.
(Choice E) Subjects will continue to receive their standard asthma treatment for the duration of the study; therefore, they will also receive asthma treatment during the washout phase. The washout phase will allow any remaining physiological and psychological effects of the first treatment to dissipate.
Educational objective:
Studies that use a crossover design usually require smaller sample sizes and yield more precise estimates of treatment effects than studies that use a parallel arm design. However, they may take longer to complete and may be affected by the carryover effect.