Clinical trial designs for rare diseases: studies developed and discussed by the International Rare Cancers Initiative

Jan Bogaerts, Matthew R Sydes, Nicola Keat, Andrea McConnell, Al Benson, Alan Ho, Arnaud Roth, Catherine Fortpied, Cathy Eng, Clare Peckitt, Corneel Coens, Curtis Pettaway, Dirk Arnold, Emma Hall, Ernie Marshall, Francesco Sclafani, Helen Hatcher, Helena Earl, Isabelle Ray-Coquard, James Paul, Jean-Yves Blay, Jeremy Whelan, Kathy Panageas, Keith Wheatley, Kevin Harrington, Lisa Licitra, Lucinda Billingham, Martee Hensley, Martin McCabe, Poulam M Patel, Richard Carvajal, Richard Wilson, Rob Glynne-Jones, Rob McWilliams, Serge Leyvraz, Sheela Rao, Steve Nicholson, Virginia Filiaci, Anastassia Negrouk, Denis Lacombe, Elisabeth Dupont, Iris Pauporté, John J Welch, Kate Law, Ted Trimble, Matthew Seymour, Jan Bogaerts, Matthew R Sydes, Nicola Keat, Andrea McConnell, Al Benson, Alan Ho, Arnaud Roth, Catherine Fortpied, Cathy Eng, Clare Peckitt, Corneel Coens, Curtis Pettaway, Dirk Arnold, Emma Hall, Ernie Marshall, Francesco Sclafani, Helen Hatcher, Helena Earl, Isabelle Ray-Coquard, James Paul, Jean-Yves Blay, Jeremy Whelan, Kathy Panageas, Keith Wheatley, Kevin Harrington, Lisa Licitra, Lucinda Billingham, Martee Hensley, Martin McCabe, Poulam M Patel, Richard Carvajal, Richard Wilson, Rob Glynne-Jones, Rob McWilliams, Serge Leyvraz, Sheela Rao, Steve Nicholson, Virginia Filiaci, Anastassia Negrouk, Denis Lacombe, Elisabeth Dupont, Iris Pauporté, John J Welch, Kate Law, Ted Trimble, Matthew Seymour

Abstract

Background: The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research.

Settings: The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed.

Results: The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design.

Interpretation: Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases.

Keywords: Bayesian; Clinical trials; Frequentist; Methodology; Multi-arm; Randomised controlled trials; Rare cancers.

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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