Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system

Abstract

Study design

Narrative review.

Purpose

To provide an overview of adaptive trial designs, and describe how adaptive methods can address persistent challenges encountered by randomized controlled trials of people with spinal cord injury (SCI).

Results

With few exceptions, adaptive methodologies have not been incorporated into clinical trial designs of people with SCI. Adaptive methods provide an opportunity to address high study costs, slow recruitment, and excessive amount of time needed to carry out the trial. The availability of existing SCI registries are well poised to support modeling and simulation, both of which are used extensively in adaptive trial designs. Eight initiatives for immediate advancement of adaptive methods in SCI were identified.

Conclusion

Although successfully applied in other fields, adaptive clinical trial designs in SCI clinical trial programs have been narrow in scope and few in number. Immediate application of several adaptive methods offers opportunity to improve efficiency of SCI trials. Concerted effort is needed by all stakeholders to advance adaptive clinical trial design methodology in SCI.

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Fig. 1: Summary of comparison of conventional and adaptive clinical trial programs.

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Acknowledgements

This paper is the fifth of a series facilitated by STUDI. Donald Berry, Ph.D., Daniel Graves, Ph.D., and Megan Moynahan, MS, contributed to initial discussions about the scope of this review paper. Megan Moynahan, Jane Hsieh, MSc, Armin Curt, MD, and James Fawcett, MD, Ph.D., provided constructive reviews of the manuscript.

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MJM organized the workgroup and facilitated workgroup conference calls that ultimately defined the scope of the paper. She reviewed the relevant literature and wrote the initial draft of the paper. She made iterative revisions based on feedback from co-authors and others and engaged input from those with expertise in adaptive designs. She facilitated small group meetings where major revisions were reviewed for consensus. She confirmed co-authors’ agreement with the content of the final manuscript and obtained approval from those acknowledged to recognize them in the acknowledge section by name. LATJ contributed to the dialog that defined the scope of the paper. She reviewed the literature and provided substantial feedback on each of the drafts, and contributed to decisions made in the small group consensus meetings. She reviewed and approved the final manuscript. FR contributed to the dialog that defined the scope of the paper. He provided substantial feedback on content about RCT and adaptive designs. He reviewed and approved the final manuscript. RR contributed to the dialog that defined the scope of the paper. He provided substantial feedback drafts of the paper. He reviewed and approved the final manuscript. JLKK provided substantial feedback on drafts of the manuscript. He reviewed and approved the final manuscript. SK contributed to the dialog that defined the scope of the paper. He provided feedback on drafts of the paper, and reviewed and approved the final manuscript. AB contributed to the dialog that defined the scope of the paper. He provided feedback on drafts of the paper, and reviewed and approved the final manuscript. DL provided feedback on drafts of the paper. He reviewed and approved the final manuscript. JDG contributed to the dialog that defined the scope of the paper. He provided substantial feedback on each of the drafts and contributed to the decisions made in the small group consensus meetings. He reviewed and approved the final manuscript. JDS contributed to the dialog that defined the scope of the paper. He provided feedback on each of the drafts, and contributed to the decisions made in the small group consensus meetings. He reviewed and approved the final manuscript.

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Correspondence to M. J. Mulcahey.

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Mulcahey, M.J., Jones, L.A.T., Rockhold, F. et al. Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system. Spinal Cord (2020). https://doi.org/10.1038/s41393-020-00547-8

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