Pragmatic Clinical Trials. Disclosure/Conflict of Interest. Learning Objectives 7/15/2015. Friedly: No disclosures

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1 Pragmatic Clinical Trials Jerry Jarvik M.D., M.P.H. Department of Radiology Janna Friedly M.D. Department of Rehabilitation Medicine Disclosure/Conflict of Interest Friedly: No disclosures Jarvik: HealthHelp consultant RSNA Faculty PhysioSonics patents/stockholder Learning Objectives After reviewing this lecture, you will be able to: Define pragmatic clinical trial. Describe key differences between explanatory and pragmatic trials. Understand the rationale for the increasing investment in pragmatic trials. Define the PRECIS tool. List two national initiatives that lead research in the area of pragmatic trials. Describe the role of pragmatic trials in healthcare decision making for individuals and policy makers. 1

2 Overview Challenges with traditional clinical research: 1. Traditional randomized controlled trials (RCTs) are slow and expensive. 2. Traditional RCTs study efficacy in highly select populations under ideal conditions therefore hard to translate findings into clinical practice.* 3. Despite publication of over 18,000 RCTs/year, patients and providers still lack evidence to effectively inform a wide range of problems. *after an average of 17 years, only 14% of research findings will have led to widespread changes in care. 1 A response to the challenges Pragmatic Clinical Trials What are pragmatic clinical trials (PCT)? PCTs determine whether an intervention works in real world conditions and not to answer how or why. Patients: selection reflects routine practice Intervention: useful in current practice Comparator: routine practice (vs. placebo) Outcomes: patient centered Timing: timescales important to stakeholders Setting: where everyday care happens, (community clinics, hospitals, and health systems) reflecting routine clinical practice. 2

3 Key features of pragmatic clinical trials (PCTs) Stakeholder engagement: (health systems, providers, and patients as partners) improves integration/dissemination of results to clinical care. Large sample size: accounts for heterogeneity encountered in usual clinical settings Cluster randomization: improves efficiency and allows intervention to be applied on a large scale Use of EHRs: improves efficiency and allows intervention to be applied on a large scale s Key differences between RCTs & PCTs GOALS Traditional/Explanator y RCT To determine causes and effects of treatment Pragmatic Clinical Trial To improve practice and inform clinical & policy decisions DESIGN Tests intervention against Tests two or more real world placebo using rigid protocols treatments using flexible & minimal variation protocols & local customization PARTICIPANTS Carefully defined & selected Broad inclusion criteria MEASURES RESULTS Require data collection outside routine clinical care Rarely relevant to everyday practice Brief and designed so data can be easily collected in clinical settings Useful in everyday practice, especially clinical decision making 8 The RCT PCT continuum No clinical trial is completely explanatory or pragmatic. RCTs and PCTs exist on a continuum. Explanatory Trial Can an intervention work under ideal conditions? Pragmatic Trial Does an intervention work under usual conditions? 9 3

4 The Pragmatic Explanatory Continuum Indicator Summary (PRECIS) Tool A tool to illustrate the degree to which a trial is pragmatic or explanatory. 10 domains plotted on a spoke and wheel diagram: 1. Eligibility criteria 2. Intervention flexibility 3. Practitioner expertise (experimental) 4. Comparison intervention 5. Practitioner expertise (comparison) 6. Follow up intensity 7. Primary outcome 8. Participant compliance 9. Practitioner adherence 10. Primary analyses PRECIS: PCT vs. ECT PRAGMATIC STUDY EXPLANATORY STUDY Figure from Thorpe KE, et al. Canadian Medical Association Journal,

5 The Lumbar Imaging with Reporting of Epidemiology (LIRE) Trial Jerry Jarvik, M.D., M.P.H. University of Washington LIRE (pronounced leer)- From the French verb, To Read The Lumbar Imaging with Reporting of Epidemiology (LIRE) Trial Patients: all pts undergoing L spine imaging Intervention: epi info added to report, cluster randomized Comparison: usual care (usual reports) Outcome: spine related care collected from EHR Timing: months of follow up Setting: multiple, large integrated care orgs 5

6 Background and Rationale Lumbar spine imaging frequently reveals incidental findings These findings may have an adverse effect on: Subsequent healthcare utilization Patient health related quality of life Disc Degeneration in Asx LIRE Hypothesis For patients referred from primary care, inserting epidemiological evidence in lumbar spine imaging reports will reduce subsequent diagnostic and therapeutic interventions, including cross-sectional imaging (MR/CT), opioid prescriptions, spinal injections and surgery. 6

7 The Intervention: GHC Test Template Intervention Text The following findings are so common in normal, painfree volunteers, that while we report their presence, they must be interpreted with caution and in the context of the clinical situation. Among people between the age of 40 and 60 years, who do not have back pain, a plain film x ray will find that about: 8 in 10 have disk degeneration 6 in 10 have disk height loss Note that even 3 in 10 means that the finding is quite common in people without back pain ~ ~86 160,000 7

8 Stepped Wedge RCT Advantages of SW Design Controls for external temporal trends More efficient than parallel design Assures all sites receive intervention Participation more palatable for interventions viewed as desirable LIRE PRECIS 8

9 Growing recognition that more pragmatic research is needed Number of RCTs labeled pragmatic or practical from 1990 to Figure provided by Sean Tunis, MD, Center for Medical Technology Policy 0 26 Patient Centered Outcomes Research Institute Established as part of Affordable Care Act Non governmental entity (.org and not.gov) Started funding comparative effectiveness research in 2012 Strong emphasis on engaging patients and stakeholders in research 9

10 PCORI: 5 National Priorities for Research and Research Agenda 1. Prevention, Diagnosis and Treatment 2. Improving Healthcare Systems 3. Communication and Dissemination Research 4. Addressing Disparities 5. Accelerating Patient-Centered Outcomes Research and Methodological Research PCORI Funding Up to 3 years, $500K/year (direct costs) Must have key stakeholders engaged early and throughout research process Patient and stakeholder engagement plan Involved in study design and monitoring conduct Involved in dissemination of findings Stakeholders Involved from C to C : Conception Completion Advisory panels, teleconferences, focus groups Patients Caregivers Clinicians Patient advocacy groups Community groups 10

11 Summary Defined pragmatic clinical trial. Described key differences between explanatory and pragmatic trials. Defined the PRECIS tool. Described PCORI and NIH Health Care System Collaboratory Why Pragmatic Trials Are Important CECORC Comparative Effectiveness, Cost and Outcomes Research Center (CECORC) Director: Jerry Jarvik, MD, MPH Center Director: Zoya Bauer, MD, PhD 11

12 CECORC Ongoing Projects: BOLD/BOLDER LESS/LESSER LIRE Back Pain Outcomes Using Longitudinal Data (BOLD) Agency for HealthCare Research and Quality: $10 million ARRA CHOICE award PI: Jerry Jarvik, MD, MPH 1R01HS www. backpainproject.org BOLD SITES HMO Research Network Andy Avins, MD Kaiser Permanente Northern CA David Nerenz, PhD Henry Ford Health System- Detroit Srdjan Nedeljkovic, MD Harvard Pilgrim/Harvard Vanguard- Boston 12

13 BOLD CHOICE: 3 Aims 1. Establish BOLD cohort 1. Conduct observational cohort study of early imaging 2. Conduct RCT of epidural steroid injections plus local anesthetic (LA) vs. LA alone: LESS Trial LESS (Lumbar Epidural Steroid Injections for Spinal Stenosis) Trial LESS: Objective To conduct a double-blind RCT testing the hypothesis that the effectiveness of ESI plus local anesthetic (LA) is greater than epidural injections of LA alone in older adults with lumbar spinal stenosis. 13

14 LESS Study Design Multi-center, randomized, double-blind trial Intervention: TF or IL ESI Control: TF or IL local anesthetic injection Recruitment target: 400 older adults with lumbar spinal stenosis Subgroups: TF/IL, Caucasian/Non-Caucasian PCORI: LESSER Goals: 1. Obtain funding for 2 year follow-up for LESS 2. Learn more about outcomes important to patients with spinal stenosis 3. Provide data back to patients and see if this changes behavior 14

15 The Lumbar Imaging with Reporting of Epidemiology (LIRE) Trial NIH COLLABORATORY UH2 AT /1 UH3 AT FUNDING VIA COMMON FUND UH2/UH3 MECHANISM UH2 PILOT PHASE: YEAR 1 (COMPLETED) UH3 IMPLEMENTATION PHASE: YEARS 2-5 PI: JERRY JARVIK, MD, MPH Lumbar Imaging with Reporting of Epidemiology (LIRE) Four Implementation Sites: Mayo Clinic/Health System Henry Ford Health System (Detroit) Kaiser Permanente of Northern CA Group Health Cooperative (Seattle) Data Coordination Center: University of Washington (Seattle) 15

16 Macro for MRI (under 40 years): The following findings are so common in normal, pain-free volunteers that while we report their presence, they must be interpreted with caution and in the context of the clinical situation. Among people under the age of 40 who do not have back pain, an MRI will find that about: 5 in 10 have disk degeneration 3 in 10 have disk signal loss (desiccation) 3 in 10 have disk height loss 4 in 10 have a bulging disk 3 in 10 have a disk protrusion Note that even 3 in 10 means that the finding is quite common in people without back pain. Overall Hypothesis The benchmark information will influence subsequent management of primary care patients with low back pain Fewer subsequent imaging tests Fewer referrals for spine-related procedures (injections, surgeries etc.) Less narcotic use CECORC: future goals Build on infrastructure created in BOLD, LESS and LIRE to conduct large pragmatic trials in nonoperative spine care Expand collaborations to conduct spine-related research Expand national efforts to develop national registries for non-operative spine care (e.g. Musculoskeletal Outcomes Research Collaborative) 16