Developing Multimodal Therapies for Brain Disorders Proceedings of a Workshop (2017) / Chapter Skim
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5 Trial Designs to Establish Efficacy and Safety in Multimodal Therapies
5 Trial Designs to Establish Efficacy and Safety in Multimodal Therapies
Pages 37-46
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From page 37... ...
. • Response-adaptive randomization and enrichment increases effi ciency by shifting trial resources to the most promising treatments (Lewis)
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From page 38... ...
PLATFORM TRIALS AND ADAPTIVE TRIALS Lewis defined a platform trial as an experimental infrastructure built to efficiently evaluate multiple treatments or combinations of treatments, either in a disease or group of diseases, that is intended to survive the evaluation of any individual treatment. Efficiency derives from eliminating the need to repeatedly create and disable the clinical trial infrastructure as new treatments become available for testing (Berry et al., 2015)
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From page 39... ...
In tthe second stagge, shown in tthe secondd column, unbalanced rando omization favoors the arms tthat appear moost promising based on early e data (BCC, AC, and C)
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From page 40... ...
Planning a complicated adaptive trial requires the use of simulations to demonstrate the effects of adjusting trial parameters, including sample size, effect size, dropouts, etc. These additional evaluations through simulation before a trial begins can be extensive, said Lewis, but will save substantial time overall.
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From page 41... ...
The adaptiv ve approach sspecifically adddresses unceertainty by utilizing simulations overo the full range of unccertainty to ddeterminne how well the trial willl perform unnder certain cconditions, annd under which condittions the trial is less likely to perform w well. Allthough adapttive randomizzation1 has bbeen endorsedd by regulators, becausse of the noveelty of these approaches a thhe analysis annd interpretation of data emerging from f these sttudies will bee considered carefully onn a case-by-case basis, according to o Dunn.
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From page 42... ...
The result is current flow in the body, which produces physiologic changes that can be measured as clinical outcomes; however, the response itself is not the dose, but can be used to adjust the dose, for example, by moving the placement of the coil or dialing back on the intensity. Thus, because placement of the coil or electrode is one of the parameters that determines dose, two people getting DBS with the same delivery platform, for example, may be getting very different doses.
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From page 43... ...
Lutz added that within the field, there is debate about whether psychometric feedback over the course of treatment might provide additional information about treatment response that could lead to more optimized and personalized dosing strategies. This has led to the development of treatment prediction, selection, and adaptation tools (DeRubeis et al., 2014; Lutz et al., 2014; Rubel et al., 2015)
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From page 44... ...
Although these measures might interfere with psychosocial interventions, Lisanby noted that sensors are available to measure facial expression, facial intonation, the verbal content of speech, and other responses that reflect the social context and psychological state might be measured less intrusively. This is analogous, she said, to the measures used during multimodal therapy involving cognitive training in combination with brain stimulation, described earlier in the workshop by
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From page 45... ...
The complexities associated with obtaining reliable and objective measures of treatment response further highlight the challenge in studying and assessing the efficacy of multimodal therapies that include a psychosocial intervention component.
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