Multidimensional Phase I Dose Ranging Trials for Stroke Recovery Interventions: Key Challenges and How to Address Them.

2021-08

Dalton, Emily J

Churilov, Leonid

Lannin, Natasha A

Corbett, Dale

Campbell, Bruce C V

Hayward, Kathryn S

clinical trials

dose

maximum tolerable dose

phase I

stroke rehabilitation

upper limb

Journal Article

0000-0003-3920-8530

0000-0003-0217-4576

0000-0002-9807-6606

0000-0001-5240-3264

10.1177/15459683211019362

Despite an increase in the amount of published stroke recovery research, interventions have failed to markedly affect the trajectory of recovery poststroke. We argue that early-phase research to systematically investigate dose is an important contributor to advance the science underpinning stroke recovery. In this article, we aim to (a) define the problem of insufficient use of a systematic approach to early-phase, multidimensional dose articulation research and (b) propose a solution that applies this approach to design a multidimensional phase I trial to identify the maximum tolerated dose (MTD). We put forward a design template as a decision support tool to increase knowledge of how to develop a phase I dose-ranging trial for nonpharmaceutical stroke recovery interventions. This solution has the potential to advance the development of efficacious stroke recovery interventions, which include activity-based rehabilitation interventions.

link

Neurorehabilitation and neural repair 2021; 35(8): 663-679

Neurorehabilitation and neural repair