Beyond Placebo: Alternative Options to the Randomized Control Trial Design in Rare Disease Studies

Abstract

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. This review paper discusses the usage of placebo and when other options could be
taken into consideration while creating the protocol, specifically with consideration to rare disease studies. 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.