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Principles of Designing a Clinical Trial: Optimizing Chances of Trial Success

  • Neuromodulation (C Stagg, Section Editor)
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Abstract

Purpose of Review

Clinical trials are essential to advance health care and develop new therapies. In this review, we discuss the underlying principles of clinical trial design with an emphasis on assessing design risks that lead to trial failure as well as negative trials. While of general interest, this is perhaps particularly timely for the neuromodulation community, given the paucity of well-designed trials in the field. We give some examples from the phantom limb pain (PLP) literature.

Recent Findings

It is critical to gather as much preliminary data as possible and to know how to interpret it in order to choose an appropriate trial design. Therefore, the investigator needs to effectively assess the likely trial design risk/benefit ratio with a view to maximizing the chance of a meaningful outcome, whether this outcome rejects or fails to reject the null hypothesis. This analysis is especially important in a complex and heterogeneous disorder such as PLP, which has had many negative trials.

Summary

We discuss the factors pertaining to a strong trial design benefit/risk assessment, how late trial phases require greater support from preliminary data, how to design trials to minimize risks, maximize benefits, and optimize internal validity as well as the chances of a positive outcome. We highlight the need for investigators to incorporate best practice in trial design to increase the chances of success and to always anticipate unexpected challenges during the trial.

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Funding

F.F. is funded by a NIH R01 grant (1R01HD082302-01A1).

Author information

Author notes

  1. Mirret M. El-Hagrassy and Dante G. G. Duarte contributed equally to this work.

Authors and Affiliations

  1. Neuromodulation Center, Spaulding Rehabilitation Hospital, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA

    Mirret M. El-Hagrassy, Dante Duarte, Aurore Thibaut, Mariana F. G. Lucena & Felipe Fregni

  2. Coma Science Group, GIGA-Research, University and University Hospital of Liege, Liege, Belgium

    Aurore Thibaut

  3. Neuromodulation Center, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, 79/96 13th Street, Charlestown, MA, 02129, USA

    Felipe Fregni

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  1. Mirret M. El-Hagrassy
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Correspondence to Felipe Fregni.

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Conflict of Interest

Some of the authors have been involved in a number of the trials referenced in this paper.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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El-Hagrassy, M.M., Duarte, D., Thibaut, A. et al. Principles of Designing a Clinical Trial: Optimizing Chances of Trial Success. Curr Behav Neurosci Rep 5, 143–152 (2018). https://doi.org/10.1007/s40473-018-0152-y

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