Beyond Placebo: Alternative Options to the Randomized Control Trial Design in Rare Disease Studies.
Unique difficulties and challenges can arise for rare diseases and orphan disease indications within a clinical trial. Some of the challenges encountered by trials that are working on rare diseases can include recruitment and enrollment.
One of the explanations for the challenges that are encountered in rare disease trials is because of the trial design of study, where the investigational product is being compared to the placebo.
It is essential for the investigators and those designing the protocol to consider alternative options from the standard randomized controlled trial. The aim of this paper is to review alternative trial design options. The trial designs discussed in this review paper include crossover trials, single arm studies and historical data, and n-of-1 trials.
The obstacles encountered in rare disease studies for enrollment can also be significantly amplified if the study necessitates emergency care and critical care situations; this can be intensified yet another time if the protocol has strict time windows for enrolling and dosing the patient. Some examples of emergency trials.
As the number of rare diseases is growing, the Food and Drug Administration will be seeing more submissions with data from smaller clinical trials where the regulators will be in an uneasy role of having to determine safety and efficacy with less than ideal data. The authors mention that when the study is for a rare disease, the constraints for studying a small group of patients can convert these obligations into great hurdles.
Clin Trial Pract Open J. 2020; 3(1): 1-4. doi: 10.17140/CTPOJ-3-110