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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2013

Open Access 01-12-2013 | Review

Experimental designs for small randomised clinical trials: an algorithm for choice

Authors: Catherine Cornu, Behrouz Kassai, Roland Fisch, Catherine Chiron, Corinne Alberti, Renzo Guerrini, Anna Rosati, Gerard Pons, Harm Tiddens, Sylvie Chabaud, Daan Caudri, Clément Ballot, Polina Kurbatova, Anne-Charlotte Castellan, Agathe Bajard, Patrice Nony, and the CRESim & Epi-CRESim Project Groups

Published in: Orphanet Journal of Rare Diseases | Issue 1/2013

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Abstract

Background

Small clinical trials are necessary when there are difficulties in recruiting enough patients for conventional frequentist statistical analyses to provide an appropriate answer. These trials are often necessary for the study of rare diseases as well as specific study populations e.g. children. It has been estimated that there are between 6,000 and 8,000 rare diseases that cover a broad range of diseases and patients. In the European Union these diseases affect up to 30 million people, with about 50% of those affected being children. Therapies for treating these rare diseases need their efficacy and safety evaluated but due to the small number of potential trial participants, a standard randomised controlled trial is often not feasible. There are a number of alternative trial designs to the usual parallel group design, each of which offers specific advantages, but they also have specific limitations. Thus the choice of the most appropriate design is not simple.

Methods

PubMed was searched to identify publications about the characteristics of different trial designs that can be used in randomised, comparative small clinical trials. In addition, the contents tables from 11 journals were hand-searched. An algorithm was developed using decision nodes based on the characteristics of the identified trial designs.

Results

We identified 75 publications that reported the characteristics of 12 randomised, comparative trial designs that can be used in for the evaluation of therapies in orphan diseases. The main characteristics and the advantages and limitations of these designs were summarised and used to develop an algorithm that may be used to help select an appropriate design for a given clinical situation. We used examples from publications of given disease-treatment-outcome situations, in which the investigators had used a particular trial design, to illustrate the use of the algorithm for the identification of possible alternative designs.

Conclusions

The algorithm that we propose could be a useful tool for the choice of an appropriate trial design in the development of orphan drugs for a given disease-treatment-outcome situation.
Appendix
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Metadata
Title
Experimental designs for small randomised clinical trials: an algorithm for choice
Authors
Catherine Cornu
Behrouz Kassai
Roland Fisch
Catherine Chiron
Corinne Alberti
Renzo Guerrini
Anna Rosati
Gerard Pons
Harm Tiddens
Sylvie Chabaud
Daan Caudri
Clément Ballot
Polina Kurbatova
Anne-Charlotte Castellan
Agathe Bajard
Patrice Nony
and the CRESim & Epi-CRESim Project Groups
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2013
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-8-48

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