Engagement: A Path to Getting Research into practice Perspectives from a Former “PCORIAN” Kara Odom Walker, MD, MPH, MSHS, FAAFP Cabinet Secretary, Department of Health and Social Services May 15, 2017

About PCORI An independent research institute authorized by Congress in 2010 and governed by a 21-member Board of Governors representing the entire health care community Funds comparative clinical effectiveness research (CER) that engages patients and other stakeholders throughout the research process Seeks answers to real-world questions about what works best for patients based on their circumstances and concerns

PCORI’s Broad and Complex mandate “The purpose of the Institute is to assist patients, clinicians, purchasers, and policy-makers in making informed health decisions by advancing the quality and relevance of evidence concerning the manner in which diseases, disorders, and other health conditions can effectively and appropriately be prevented, diagnosed, treated, monitored, and managed through research and evidence synthesis... --from PCORI’s authorizing legislation … and the dissemination of research findings with respect to the relative health outcomes, clinical effectiveness, and appropriateness of the medical treatments, services...”

Increasing Value and Reducing Waste 2009 estimate: As much as 85% of research funding is avoidably wasted Stages in research production that lead to waste. Moher et al. Bold estimate made by two thought leaders in research and evidence-based medicine in 2009 up to that 85 % of biomedical research (including basic science to translational) was avoidably wasted---due to issues such as lack of publication, biased or incomplete reporting, or focus on low priority issues. Concerns were arrayed across all stages in research production—from question formulation through design and conduct, regulation and management, to full and complete, unbiased reporting. These were outlined in a series of detailed articles addressing opportunities for funders, scientific societies, professional medical associations, academic institutions, and scientific publishers to comprehensively consider “how should the entire scientific enterprise change to produce reliable and accessible evidence that addresses the challenges faced b society and the individuals who make up those societies?” Avoidable waste in the production and reporting of research evidence. Chalmers I, Glasziou, P. Lancet 2009; 374: 86-89. Increasing value and reducing waste in biomedical research: who's listening? Moher D, et al. Lancet 2015; Online: Sept.28

Engagement as a Path to Useful, High-Quality Research Proposal Review; Design and Conduct of Research Topic Selection and Research Prioritization Dissemination and Implementation of Results Evaluation

Does Engagement Make a Difference? A systematic review* provides the first international evidence of the impact of patient and public involvement on research on health and social-care research. Literature search from 1995-2009 identified 66 studies Analysis showed patient and public involvement enhanced quality and appropriateness of research Impacts were described for all stages of research But authors note the evidence base on impact of engagement still needs significant enhancement *Health Expectations 2014; 17(5): 637–650.

Patient-Centeredness

What is comparative effectiveness?

Why we need CER “ . . . for want of appropriate studies, innumerable practical decisions facing patients and doctors every day do not rest on a solid foundation of knowledge about what constitutes the best choice of care.” Institute of Medicine Report June 2009

Evidence of evidence gaps Among 16 current guidelines reporting levels of evidence including 2,711 recommendations: Level of evidence A – 11% Level of evidence C – 48% Data Sources and Study Selection Data from all ACC/AHA practice guidelines issued from 1984 to September 2008 were abstracted by personnel in the ACC Science and Quality Division. Fifty-three guidelines on 22 topics, including a total of 7196 recommendations, were abstracted. Data Extraction The number of recommendations and the distribution of classes of recommendation (I, II, and III) and levels of evidence (A, B, and C) were determined. The subset of guidelines that were current as of September 2008 was evaluated to describe changes in recommendations between the first and current versions as well as patterns in levels of evidence used in the current versions. Results Among guidelines with at least 1 revision or update by September 2008, the number of recommendations increased from 1330 to 1973 (48%) from the first to the current version, with the largest increase observed in use of class II recommendations. Considering the 16 current guidelines reporting levels of evidence, only 314 recommendations of 2711 total are classified as level of evidence A (median, 11%), whereas 1246 (median, 48%) are level of evidence C. Level of evidence significantly varies across categories of guidelines (disease, intervention, or diagnostic) and across individual guidelines. Recommendations with level of evidence A are mostly concentrated in class I, but only 245 of 1305 class I recommendations have level of evidence A (median, 19%). • Level of evidence A: recommendation based on evidence from multiple randomized trials or meta-analyses • Level of evidence B: recommendation based on evidence from a single randomized trial or nonrandomized studies • Level of evidence C: recommendation based on expert opinion, case studies, or standards of care. JAMA. 2009;301(8):831-841

More evidence: variability in practice “Variation in surgical rates is high and represents both gaps in outcomes research and poor patient decision quality.” A Dartmouth Atlas of Health Care Series http://www.dartmouthatlas.org/downloads/reports/Cerebral_aneurysm_report_09_30_14.pdf

Comparative Effectiveness Research Research that . . . Compares benefits and harms of at least two different existing methods to prevent, diagnose, treat, or monitor a clinical condition or to improve care delivery Is performed in real-world populations Informs a specific clinical or policy decision (“decisional dilemma”) Adapted from Initial National Priorities for Comparative Effectiveness Research, Institute of Medicine of the National Academies

Patient-centered outcomes research Patient-centered outcomes research, or PCOR, is a relatively new form of comparative effectiveness research Considers patients’ needs and preferences while focusing on the outcomes most important to them Investigates what works, for whom, under what circumstances Helps patients and other health care stakeholders make better- informed decisions about health and health care options

Comparative effectiveness - ALLHAT A total of 33,357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor  Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15,255); amlodipine, 2.5 to 10 mg/d (n = 9,048); or lisinopril, 10 to 40 mg/d (n = 9,054) for planned follow-up of approximately 4 to 8 years. Key question: What is the optimal first line therapy for hypertension? Abstract CONTEXT: Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. OBJECTIVE: To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. DESIGN: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. SETTING AND PARTICIPANTS: A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. INTERVENTIONS: Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. MAIN OUTCOME MEASURES: The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). RESULTS: Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). CONCLUSION: Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy. JAMA 2002; 288; 2981-97.

They should be preferred for first-step antihypertensive therapy. Key conclusion: Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy. Over a patient’s lifetime, chlorthalidone was always least expensive (mean $4,802 less than amlodipine, $3,700 less than lisinopril) Adding quality of life did not change these results ALLHAT sought to determine which of four agents performed best in terms of fatal CAD and nonfatal MI. The study enrolled patients with essential hypertension and at least one additional CAD risk factor. The study drug was instituted and additional open-label agents were added to achieve BP goals. The pragmatic ALLHAT found that, compared to amlodipine, chlorthalidone performed similarly in reducing overall incidence of CAD, but decreased the incidence of CHF. Compared to lisinopril, chlorthalidone reduced overall CAD by 10%, stroke by 15%, CHF by 19%, and angina by 11%. The doxazosin arm was terminated prematurely because of a significantly increased risk of CHF compared to chlorthalidone noted during an interim analysis. Following ALLHAT, thiazides became widely used as first-line agents for essential hypertension. While ALLHAT studied chlorthalidone, the related thiazide hydrochlorothiazide (HCTZ) has been the most commonly prescribed diuretic for hypertension in the US. This has largely to do with such things as drug cost, availability, side-effect profile, and the assumption that the benefits of chlorthalidone represent a class effect among thiazides. However, there is little direct evidence that HCTZ specifically reduces the incidence of CVD among hypertensive individuals. There is some evidence that HCTZ has worse 24 hour BP control than chlorthalidone.  Additionally, the MRFIT trial (1990)  amended its protocol to include chlorthalidone rather than HCTZ because of a non-significant trend for worse outcomes with HCTZ.

Comparative Effectiveness- ALLHAT How do the results of ALLHAT help patients and clinicians make decisions? Provides information on harms and benefits of three major antihypertensives. chlorthalidone amlodipine lisinopril Large enough to allow subgroups to be examined. Age <65 vs. >65 Men vs. women Black vs. nonblack Diabetes vs. no diabetes JAMA 2002; 288; 2981-97.

Comparative effectiveness

Rising numbers of Citations for “patient-centered outcomes research” in PubMed (n=290) Extending patient-centered outcomes to all research Extend engagement to policy and social determinants of health

Improving the flow and relevance of research evidence for implementation R Lobb, GA Colditz. Implementation science and its application to population health. Annu Rev Public Health. 2013;34:235–251

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