July 29, 2014
A clinical research report, published in Contemporary Clinical Trials, illustrates the advantages of the above-mentioned adaptive trial design for rare diseases. Adaptive crossover trial designs, giving patients the option to opt out or ‘escape’ the assigned treatment, can improve outcome efficiency and statistical significance. Increasingly designed to investigate new treatments for rare diseases, crossover trials involve two or more treatments administered in a set order to each patient and for set periods throughout the study. Patient 1 will receive treatment A followed by treatment B, whilst Patient 2 will receive treatment B followed by treatment A for the same period. Crossover trials therefore minimize patient exposure to ineffective treatments and increase efficiency since patients act as their own control and response to treatment is rapidly measured.
A randomized, double blinded, placebo controlled crossover trial was designed to test a new treatment for familial Mediterranean fever (FMF), a rare genetic auto-inflammatory disorder, characterized by recurring fever attacks. Patients received one of four treatment sequences alternating rilonacept (R) and placebo (P): RPRP, PRPR, RPPR and PRRP. Patients who experienced at least two FMF attacks during one course of treatment were allowed to escape to the other treatment arm until the end of that course. Participants then resumed the assigned treatment sequence. The investigators indicate that escape options helped reduce patient dropout from clinical trials and, contrary to Mullins et al.‘s views (mentioned in the previous article), increased study efficiency and significance. Where clinical trials for rare disease treatments are challenging, typically due to small patient numbers, crossover trials with early escape options increase patient motivation, minimize adverse effects, maximize treatment benefits and improve the significance of collected data.