Randomized controlled trial (RCT) results diffuse into clinical practice slowly - the average time from trial completion to widespread adoption of a new treatment is nearly 20 years. These delays result in suboptimal treatment for patients with neurological diseases. In light of these delays and the enormous societal value of NINDS clinical trials findings, NINDS has recognized the need to accelerate implementation by promoting research to translate trial findings into routine care (T2 translational research). This application seeks to optimize translation of NINDS trials by personalizing clinical trial results ad addressing barriers to translation for clinicians and policy-makers. Using translational research methods, we can move from one-size-fits-all evidence-based medicine towards personalized medicine by estimating treatment benefit for individual patients. Other translational methods can evaluate and address stakeholder concerns that hinder translation. Because clinicians are often skeptical of trial results, changing practice requires convincing them not only that a treatment works in an RCT or that it works in academic medical centers, but that it will work for their patients. Similarly, if policy-makers and payers can be convinced that a new treatment is a good value (e.g., a favorable cost-benefit ratio), they can use their considerable influence on the healthcare delivery system to facilitate translation. Specifically, we will use translational research methods to address three important issues essential to improving trial translation: 1. estimating individual-level outcomes using multivariable outcome prediction 2. Estimating the impact of real world circumstances on outcomes using simulation analyses and 3. Cost effectiveness analysis. Results from these analyses can influence clinicians and policy-makers directly or through the use of tools, such as websites and mobile applications. This proposal has two key objectives. First, we will adapt translational research methods to clinical trials by addressing essential translation-relevant questions for the Carotid Revascularization Endarterectomy versus Stenting (CREST) trial. Second, we will develop a model to concurrently perform similar translational analyses in the Neurology Emergency Treatment Trials (NETT) network. These objectives will be addressed through 3 specific aims: 1. to estimate the expected net benefit of carotid endarterectomy (CEA) vs. carotid artery stenting (CAS) for individual patients in the CREST trial using refined multivariable outcome prediction methods. 2. To estimate the impact of personalized decision-making and real world circumstances (e.g., differing complication rates) on the net benefit of CAS vs. CEA for real world patients using simulation analyses. 3. To assess the feasibility of performing concurrent translational and cost analyses in NETT trials by evaluating a process implementation model in newly initiated and recently completed NETT trials. Dr. Burke has a unique background as a vascular neurologist with training in Translational research methodology through the highly regarded Robert Wood Johnson Clinical Scholars Program. In this proposal, Dr. Burke will develop the additional expertise in clinical trials, multivariable outcome prediction, simulation analyses and cost analyses to become a leader and independently-funded investigator in neurological translational research working to develop a new generation of NETT trials better designed to effectively inform real world clinical practice and improve patient outcomes. This proposal capitalizes on unique environmental strengths at the University of Michigan. Most importantly, Dr. Burke will be supported by an outstanding multi- disciplinary mentorship team including Dr. William Barsan the NETT Clinical Coordinating Center (CCC) principal investigator and a research leader in the emergency treatment of neurological diseases, Dr. Rodney Hayward a Professor of Internal Medicine and a pioneer in translational research and Dr. Lewis Morgenstern, a leader in neurological translational research. All three mentors have excellent track records in mentoring junior faculty and transitioning junior faculty to independence. In addition, Dr. Burke will have te opportunity to participate in a unique hands-on clinical trials immersion through the NETT to gain experience in clinical trial design, management and implementation. Finally, the University of Michigan has recently built the largest academic Translational Research center in the United States (the Institute for Health Policy and Innovation) which will support the advanced statistical methods required for this proposal.

Public Health Relevance

Dissemination of clinical trial results is slow - it takes almost 20 years on average for a new clinical trial finding to be widely implemented in clinical practice. For effective therapies, this process needs to be more efficient. The goal of this proposal is to provide essential translation-relevant information to clinicians and policy-makers by adapting methods from translational research to clinical trials. By improving clinician understanding of the value of a new therapy and policy-maker understanding of the societal incentives to implement a new treatment we seek to accelerate the translation of the next generation of treatments for neurologic disease.

Agency
National Institute of Health (NIH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS082597-02
Application #
8676950
Study Section
Neurological Sciences Training Initial Review Group (NST)
Program Officer
Hirtz, Deborah G
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Kelly, Adam G; Zahuranec, Darin B; Holloway, Robert G et al. (2014) Variation in do-not-resuscitate orders for patients with ischemic stroke: implications for national hospital comparisons. Stroke 45:822-7
Skolarus, Lesli E; Jones, David K; Lisabeth, Lynda D et al. (2014) The Affordable Care Act and stroke. Stroke 45:2488-92
Callaghan, Brian C; Burke, James F; Feldman, Eva L (2014) How neurologists can choose (even more) wisely: prioritizing waste reduction targets and identifying gaps in knowledge. JAMA 311:1607-8
Skolarus, Lesli E; Burke, James F; Freedman, Vicki A (2014) The role of accommodations in poststroke disability management. J Gerontol B Psychol Sci Soc Sci 69 Suppl 1:S26-34
Callaghan, Brian C; Kerber, Kevin A; Pace, Robert J et al. (2014) Headaches and neuroimaging: high utilization and costs despite guidelines. JAMA Intern Med 174:819-21
Sauser, Kori; Burke, James F; Reeves, Mathew J et al. (2014) A systematic review and critical appraisal of quality measures for the emergency care of acute ischemic stroke. Ann Emerg Med 64:235-244.e5
Burke, James F; Freedman, Vicki A; Lisabeth, Lynda D et al. (2014) Racial differences in disability after stroke: results from a nationwide study. Neurology 83:390-7
Skolarus, Lesli E; Burke, James F; Morgenstern, Lewis B et al. (2014) Impact of state Medicaid coverage on utilization of inpatient rehabilitation facilities among patients with stroke. Stroke 45:2472-4
Skolarus, Lesli E; Burke, James F; Brown, Devin L et al. (2014) Understanding stroke survivorship: expanding the concept of poststroke disability. Stroke 45:224-30
Burke, James F; Hayward, Rodney A; Nelson, Jason P et al. (2014) Using internally developed risk models to assess heterogeneity in treatment effects in clinical trials. Circ Cardiovasc Qual Outcomes 7:163-9

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