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

Dalton, Emily; Чурилов, Леонид; Lannin, Natasha A.; Corbett, Dale; Campbell, Bruce; Hayward, Kathryn S

doi:10.1177/15459683211019362

Cited by 8 publications

(5 citation statements)

References 61 publications

(151 reference statements)

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“…This suggest that in addition to being individually tailored according to the level of the participants’ skills, the ACT-ING program should also emphasize individualization of duration and frequency for effective promotion of adherence [ 49 ]. Therefore, there is a need for further research on the most optimal intervention dose (i.e., duration, number of sessions, session length and density, and task length, difficulty, and intensity) within the resources available and how optimal dosing is influenced by factors such as age, sex, comorbidities, primary etiology, or physical fitness [ 10 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Early Feasibility of an Activity-Based Intervention for Improving Ingestive Functions in Older Adults with Oropharyngeal Dysphagia

2023

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There is growing awareness about the use of combined strength- and skill-based swallowing training for improving swallowing physiology in the event of dysphagia. Such an approach involves focusing on coordination and timing as well as swallowing strengthening in the context of increased exercise complexity in eating and drinking activities. This study aimed to determine the early feasibility of a newly developed 12-week intervention, named the ACT-ING program (ACTivity-based strength and skill training of swallowing to improve INGestion), in older adults with dysphagia and generalized sarcopenia. In a multiple-case-study design, seven participants above 65 years of age (five women and two men) with slight to severe dysphagia and indications of sarcopenia underwent the intervention during hospitalization and in the community after discharge. The ACT-ING program met most of the feasibility marks in terms of demand (73.3% of those invited accepted participation), safety (100%), no reports of adverse events, tolerance (85.7%), usability (100%), and acceptability (100%). Three putative mediators of change (experienced autonomy support, in-therapy engagement, and perceived improvement in swallowing capacity) appeared to have been best accomplished in participants with slight to moderate dysphagia. The ACT-ING program showed preliminary evidence of early feasibility, warranting further early-phase dose articulation and proof-of-concept trials.

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Section: Discussionmentioning

confidence: 99%

Early Feasibility of an Activity-Based Intervention for Improving Ingestive Functions in Older Adults with Oropharyngeal Dysphagia

2023

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“…Effects or markers that are presumably related to the intervention and that either are considered unacceptable or show the desired level of effect has been achieved and a further increase in dose is not required. 8…”

Section: Dose Limiting Criteriamentioning

confidence: 99%

Enhancing quality and impact of early phase dose-finding clinical trial protocols: SPIRIT Dose-finding Extension (SPIRIT-DEFINE) guidance

Yap,

Rekowski,

Ursino

et al. 2023

BMJ

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SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 provides guidance for clinical trial protocol writing. However, neither the original guidance nor its extensions adequately cover the features of early phase dose-finding trials. The SPIRIT Dose-finding Extension (DEFINE) statement is a new guideline that provides recommendations for essential items that should be provided in the protocols of these trials. It details extensions to the SPIRIT 2013 guidance, incorporating 17 new items and modifying 15 existing items. The purpose of this guideline is to promote transparency, completeness, reproducibility of methods, and interpretation of early phase dose-finding trial protocols. It is envisioned that the resulting improvements in the design and conduct of early phase clinical trials will ultimately reduce research inefficiencies and inconsistencies, driving transformational advances in clinical care.

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“…2 also highlights an important aspect of why measurement and evaluation of active ingredients is critical. Rather than serve as "post-hoc" explanations of findings, addressing these issues in earlyphase pre-clinical trial stage can help narrow down the optimal decision at the end of a trial 24 . For example, if the active ingredient changed but there was no effect on overall outcome, there are two potential decisions to be made -(i) continue with the therapy, but increase the dosage of the ingredient, or (ii) switch to a different therapy.…”

Section: Measurement and Evaluation Of The Effect Of Active Ingredientsmentioning

confidence: 99%

Scientific basis and active ingredients of current therapeutic interventions for stroke rehabilitation

Ranganathan

Doherty

Gussert

et al. 2022

RNN

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Background: Despite tremendous advances in the treatment and management of stroke, restoring motor and functional outcomes after stroke continues to be a major clinical challenge. Given the wide range of approaches used in motor rehabilitation, several commentaries have highlighted the lack of a clear scientific basis for different interventions as one critical factor that has led to suboptimal study outcomes. Objective: To understand the content of current therapeutic interventions in terms of their active ingredients. Methods: We conducted an analysis of randomized controlled trials in stroke rehabilitation over a 2-year period from 2019-2020. Results: There were three primary findings: (i) consistent with prior reports, most studies did not provide an explicit rationale for why the treatment would be expected to work, (ii) most therapeutic interventions mentioned multiple active ingredients and there was not a close correspondence between the active ingredients mentioned versus the active ingredients measured in the study, and (iii) multimodal approaches that involved more than one therapeutic approach tended to be combined in an ad-hoc fashion, indicating the lack of a targeted approach. Conclusion: These results highlight the need for strengthening cross-disciplinary connections between basic science and clinical studies, and the need for structured development and testing of therapeutic approaches to find more effective treatment interventions.

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

Cited by 8 publications

References 61 publications

Early Feasibility of an Activity-Based Intervention for Improving Ingestive Functions in Older Adults with Oropharyngeal Dysphagia

Early Feasibility of an Activity-Based Intervention for Improving Ingestive Functions in Older Adults with Oropharyngeal Dysphagia

Enhancing quality and impact of early phase dose-finding clinical trial protocols: SPIRIT Dose-finding Extension (SPIRIT-DEFINE) guidance

Scientific basis and active ingredients of current therapeutic interventions for stroke rehabilitation

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