A framework for applying unfamiliar trial designs in studies of rare diseases
ABSTRACT Rare diseases may be difficult to study through conventional research methods, but are amenable to study through certain uncommonly used designs. We sought to explain these designs and to provide a framework to assist researchers in identifying the most appropriate design for a given research question.
We systematically searched for literature describing rare disease research frameworks, trial designs, and trials that applied them. We present the advantages and disadvantages of each approach using these published examples, and a practical framework to help researchers in selecting between design choices.
When research participants are limited, researchers should consider using: 1) a crossover design; 2) n-of-1 trials; or 3) one of the following adaptive designs: a) a response-adaptive randomization design, b) a ranking and selection design, c) an internal pilot design,or d) a sequential design. Bayesian analysis may be applied to conventional designs, or to any of these uncommon designs. Several of these approaches may also be used in combination. The choice between methods should be guided by factors related to the intervention, disease,anticipated recruitment duration and success, and current state of knowledge about the treatment.
These techniques may facilitate research in rare diseases.
- SourceAvailable from: Paul Wicks
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- "Trials for rare conditions inherently face small sample sizes and are continuously looking for ways to improve the ability to detect treatment differences, such as expanding a trial to several different countries . Bayesian and adaptive trials offer alternatives for circumstances when researchers are faced with this scenario   . The additional benefit offered by Bayesian and adaptive approaches for participants in rare condition trials is that patients will not remain in a trial for an extended period of time without good reason. "
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