Methodologic challenges in the design and conduct of hyperacute stroke research
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Published on: August 18, 2015
1School of Nursing & Department of Neurology, Comprehensive Stroke Center, University of Alabama at Birmingham, RWUH M226, Birmingham, AL 35249, USA. annealex@uab.edu
Insights
Designing hyperacute stroke clinical trials is challenging due to patient and disease variability. New strategies are needed to improve trial design and enrollment for stroke treatments.
Area of Science:
- Neurology
- Clinical Trials
- Emergency Medicine
Background:
- Stroke is a leading cause of death and disability in the US.
- Current treatments, like tissue plasminogen activator for ischemic stroke, have limited efficacy.
- Hemorrhagic stroke lacks effective medicinal treatments.
Purpose of the Study:
- To describe challenges in designing and conducting hyperacute stroke trials.
- To review factors hindering enrollment in stroke studies.
- To discuss strategies for enhancing trial design and enrollment.
Main Methods:
- Review of challenges in hyperacute stroke trial design.
- Analysis of sample heterogeneity (pathophysiology, territory, hemodynamics, risk factors, healthcare access).
- Discussion of endpoint controversies and enrollment strategies.
Main Results:
- Significant heterogeneity in stroke mechanisms, neurovascular territories, hemodynamics, and patient profiles complicates trial design.
- Patient access to specialized healthcare services presents a barrier to enrollment.
- Controversies exist regarding the designation of appropriate clinical endpoints.
Conclusions:
- Hyperacute stroke trials face substantial design and enrollment challenges.
- Addressing sample heterogeneity and improving healthcare access are crucial for future research.
- Enhanced trial designs and endpoint strategies are recommended to advance stroke treatment research.
Abstract:
Stroke is the third leading cause of death in the United States and the leading cause of adult disability, consistently ranking in the top 10 of leading diagnostic categories encountered by practitioners in emergency and critical care settings. Despite its prevalence and clinical significance, only tissue plasminogen activator for ischemic stroke has been shown to reduce 3-month mortality and disability in phase III clinical trials, whereas for hemorrhagic stroke, no medicinal treatment has yet to demonstrate a similar reduction in mortality or disability. This article describes challenges inherent in the design and conduct of hyperacute stroke trials. Sample heterogeneity associated with pathophysiologic stroke mechanisms, the neurovascular territory implicated, systemic and intracranial hemodynamics, risk factor profiles, and patient access to requisite healthcare services are reviewed as contributors challenging enrollment into well-designed studies. Current controversies associated with designation of endpoints are presented and strategies to enhance trial design, and subsequent enrollment, are discussed. Recommendations are made for future clinical research into phenomena associated with hyperacute stroke.
