Generating Real-World Evidence

Transcription

1 Generating Real-World Evidence The Emergence of Pragmatic Clinical Trials Liz Wing, MA Senior Science Writer/Editor Jonathan McCall, MS Senior Science Writer/Editor

2 The NIH Health Care Systems Research Collaboratory was established by the National Institutes of Health Common Fund through a cooperative agreement (U54 AT007748) from the Office of Strategic Coordination within the Office of the NIH Director. The views presented here are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

3 Part 1 Why do we need pragmatic clinical trials (PCTs)?

4 Most clinical research fails to be useful not because of its findings but because of its design. J. Ioannidis PLOS Med 2016

5 If we want evidence from trials to be used in clinical practice and policy, trialists should make every effort to make their trial widely applicable, which means that more trials should be pragmatic in attitude. S. Treweek and M. Zwarenstein Trials 2009

6 What makes a trial pragmatic? Key characteristics*: Research question Setting Participants Intervention design Outcomes Clinical relevance *Adapted from Zwarenstein M, Treweek S, Gagnier JJ, et al. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ. 2008

7 Research question Traditional Efficacy: Can the intervention work? Pragmatic Effectiveness: Does the intervention work when used in normal practice? Example: In patients living with heart disease, what is the best dose of aspirin to use to prevent a heart attack or stroke?

8 Setting Traditional Well-resourced, ideal setting Pragmatic Normal practice including primary care, community clinics, and hospitals Example: Patients with end-stage renal disease receiving a hemodialysis intervention at a standalone dialysis facility

9 Participants Traditional Highly selected Pragmatic Little or no selection beyond the clinical indication of interest Example: Adult patients in the U.S. living with heart disease

10 Intervention design Traditional Tests the intervention against placebo, enforcing strict protocols and adherence Pragmatic Tests two or more realworld treatments using flexible protocols Example: Intervention tests two common aspirin doses: 81 mg vs. 325 mg

11 Outcomes Traditional Often short-term surrogate endpoints or process measures Pragmatic Clinically important endpoints Example: Trial results clarify the effectiveness of a treatment: its relative benefits, harms, and risks

12 Clinical relevance Traditional Indirect not usually designed for making decisions in real-world settings Pragmatic Direct purposely designed for making decisions in real-world settings Example: An American College of Surgeons policy summit scheduled in the final years of the pragmatic trial will facilitate rapid translation of trial results into national policy

13 Examples Three current healthcare system-based pragmatic research studies: STOP CRC NIH Collaboratory Demonstration Project ADAPTABLE PCORnet Demonstration Project Diuretic Comparison Project Veterans Affairs Cooperative Studies Program

14 STOP CRC NCT Testing an EHR-based method to improve colorectal cancer screening rates in people who receive care at safety net clinics Conducted in a community-based network of federally qualified health centers Enrollment goal: 20,000 Estimated completion: 2017

15 ADAPTABLE, the aspirin study NCT Testing which of 2 common aspirin doses is more effective at preventing heart attacks or strokes in adults living with hypertension Conducted at large partner health systems Analyzes data from both clinical and patient-powered networks Enrollment goal: 20,000 Estimated completion: 2018

16 Diuretic Comparison Project NCT Testing which of 2 common hypertension meds is more effective at preventing cardiovascular outcomes in Veterans >65 living with hypertension Conducted at 2 VA healthcare systems Enrollment goal: 13,500 Estimated completion: 2023

17 Key takeaways for communicators 1. Partnerships with diverse stakeholders 2. Dissemination of results among stakeholders 3. Need for knowledge curation

18 Randomized trials conducted in the context of clinical practice often called pragmatic clinical trials may be the most important source of knowledge in the future. R. Califf Regulatory Affairs Professionals Society blog May 2016

19 The NIH Collaboratory s Living Textbook A Case Study of Knowledge Dissemination in Patient-Centered Pragmatic Research

20 Disclosures Jonathan McCall is a salaried employee of the Duke Clinical Research Institute (DCRI), an academic research organization affiliated with the Duke University School of Medicine. He currently works on projects funded by the DCRI, the National Institutes of Health, the Clinical Trials Transformation Initiative, and the U.S. Food and Drug Administration.

21 Origin stories Dr. Eugene Stead. Photo credit: NIH Dr. Robert Califf. Photo credit: Duke Medicine

22 (The) Collaboratory aims to improve the way clinical trials are conducted by creating a new infrastructure for collaborative research with healthcare systems. The ultimate supports Data, goal tools, is the ensure and design that healthcare resources and providers rapid produced and execution patients can by make decisions based on the best available clinical evidence. The Collaboratory also supports of the the pragmatic improve design Collaboratory and rapid the clinical execution way are of clinical trial pragmatic made Demonstration clinical trials available are to Projects that address questions of major public health importance and engage the healthcare Projects delivery conducted greater systems that research in research address by partnerships. creating community questions Data, a new tools, and of to resources produced by the Collaboratory are made available to the greater infrastructure promote major public partnerships for health collaborative importance with healthcare research and community to promote partnerships with healthcare systems and propel a transformation systems engage in how with healthcare clinical and research propel is conducted. delivery a transformation systems. Dissemination systems efforts in include the Collaboratory s Knowledge Repository, Living Textbook, and weekly Grand Rounds webinar how series. clinical research is conducted research partnerships

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24 What is the Living Textbook? Our goal in creating Rethinking Clinical Trials is to provide a living document to guide the many different people with an interest in practical (or pragmatic ) clinical trials and health systems research. We hope that this living textbook will be useful to a broad spectrum of users, including the public, healthcare professionals and administrators, personnel working in academic and industry-funded clinical trials, and full-time clinical trialists. A living document to guide the many different people with an interest in practical (or pragmatic ) clinical trials and health systems research.

25 Organization & governance Primary oversight provided by Coordinating Center leadership Materials contributed by Collaboratory members or partners may also fall under review of Publications, Presentations & Products Committee A. Tasneem, 2013

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29 Contractor (writing/ editing) 1 Admin Support 1 Writer/ Editor 1 WordPress Developer 3 Writers/ Editors 1 Project Lead 3 Project Leads 1 SharePoint Developer Writer but was no ~1 single FTE; project contributor lead was is a dedicated resource FTE for but the attention project, and was % diffused varies. over entire Collaboratory project.

30 Challenges for the Communicator

31 Pragmatic, patient-centered research is different Audiences are diverse in terms of interest, motivation, and knowledge base Communication is multilateral, multidirectional, and multichannel and takes place in the setting of complex networks The learning health system model means that when everything works properly, the result is a constant positive feedback loop in which practice informs research and research is fed back into practice Patients are not subjects but partners/participants

32 Advantages Large networks of experienced research sites = deep bench of talent and imagination! Collaborative approach encourages sharing of experience and homebrewed tools for wider dissemination Curiosity drives attention to content and resources

33 Navigating (relatively) uncharted waters By Kattigara - Own work, CC BY-SA 3.0,

34 Hitting the target Photo credit: Darren Glanville from Acle, Norfolk, UK - Archery, CC BY- SA 2.0,

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36 Choosing the right platforms Public Domain, rid=

37 Finding and engaging subject matter experts Ury Lesser, Man with a Loupe. Public Domain,

38 Routine care and maintenance Titian, The Punishment of Sisyphus. Museo Prado

39 The constant need to evolve Image credit: Nobu Tamura

40 Key Lessons

41 1. Knowledge dissemination is like an iceberg 9/10ths of it is below the waterline.

42 2. Writing is important, but curation is absolutely essential.

43 3. Platforms and analytics matter.

44 4. In the era of pragmatic, patient-centered research, patients are becoming active participants in research and investigators, hospitals, and health systems are themselves becoming research subjects.

45 5. Incentives for knowledge dissemination in pragmatic research are not yet fully aligned with the needs of the larger research community.

46 Some final thoughts Pragmatic clinical research offers a set of unique challenges and opportunities for communications professionals Flexibility and willingness to cultivate diverse skillsets are at a premium Offers an unusual degree of variety and potential for personal/professional growth