OBJECTIVE: 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. STUDY DESIGN AND SETTING: 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. RESULTS: 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. CONCLUSION: These techniques may facilitate research in rare diseases.
OBJECTIVE: 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. STUDY DESIGN AND SETTING: 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. RESULTS: 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. CONCLUSION: These techniques may facilitate research in rare diseases.
Authors: Linda Kwakkenbos; Linda M Willems; Frank H J van den Hoogen; Wim G J M van Lankveld; Hanneke Beenackers; Toon F van Helmond; Eni S Becker; Cornelia H M van den Ende Journal: J Clin Psychol Med Settings Date: 2014-12
Authors: Lisa V Hampson; John Whitehead; Despina Eleftheriou; Catrin Tudur-Smith; Rachel Jones; David Jayne; Helen Hickey; Michael W Beresford; Claudia Bracaglia; Afonso Caldas; Rolando Cimaz; Joke Dehoorne; Pavla Dolezalova; Mark Friswell; Marija Jelusic; Stephen D Marks; Neil Martin; Anne-Marie McMahon; Joachim Peitz; Annet van Royen-Kerkhof; Oguz Soylemezoglu; Paul A Brogan Journal: PLoS One Date: 2015-03-30 Impact factor: 3.240