1 Comparative Effectiveness Research Scott R. Smith, PhD Director, Pharmaceutical Outcomes Research Agency for Healthcare Research & Quality

2 Today’s Outline A. Brief background on AHRQ’s Effective Health Care program. B. Peter Juhn, Johnson & Johnson, Inc. C. Jennifer Bright, Society for Healthcare Epidemiology of America. D. Gail Shearer, Consumers Union. E. Summary, more information & questions.

Medicare Modernization Act

4 Section 1013 of the MMA To improve the quality, effectiveness and efficiency of health care delivered through Medicare, Medicaid and the S-CHIP programs To improve the quality, effectiveness and efficiency of health care delivered through Medicare, Medicaid and the S-CHIP programs $15 million was appropriated in fiscal years 2005, 2006, 2007 (pending) for AHRQ to conduct and support research with a focus on $15 million was appropriated in fiscal years 2005, 2006, 2007 (pending) for AHRQ to conduct and support research with a focus on – outcomes – comparative clinical effectiveness and – appropriateness of health care items and services (including pharmaceutical drugs), – including strategies for how these items and services are organized, managed and delivered.

5 Types of comparisons Drug vs drug. Surgery vs watchful waiting. Inpatient versus outpatient treatment. Implantable device versus drug therapy. Specialty approach 1 versus specialty approach 2. Models of care (12-step, case management, skills training).

Working Framework for Comparative Effectiveness 6

7 Scientific Resource Center Methodology resource Methodology resource Stakeholder input Stakeholder input Dossier process Dossier process Formative help Formative help Research coordination Research coordination

Effective Health Care Program A. Evidence synthesis (EPC program) – Systematically reviewing, synthesizing, comparing existing evidence on treatment effectiveness. – Identifying relevant knowledge gaps. B. Evidence generation (DEcIDE, CERTs) – Development of new scientific knowledge to address knowledge gaps. – Accelerate practical studies. C. Evidence communication/translation (Eisenberg Center) – Translate evidence into improvements. – Communication of scientific information in plain language to policymakers, patients, and providers. 8

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1. Evidence Synthesis Evidence-based Practice Centers Evidence-based Practice Centers Created in 1997 Created in centers 13 centers Produce evidence reports/technology assessments Produce evidence reports/technology assessments Work with public and private sector partners Work with public and private sector partners User driven User driven 10

11 Methods of Systematic Review Systematic and comprehensive literature search Systematic and comprehensive literature search Uniform extraction and tabulation of data from studies Uniform extraction and tabulation of data from studies Qualitative and quantitative synthesis of data Qualitative and quantitative synthesis of data Critical appraisal of studies to identify factors that may lead to biased results Critical appraisal of studies to identify factors that may lead to biased results

12 First Published Comparative Effectiveness Reviews Management strategies for gastroesophageal reflux disease. Management strategies for gastroesophageal reflux disease. Benefits and safety of analgesics for osteoarthritis. Benefits and safety of analgesics for osteoarthritis. New diagnostic technologies for breast cancer screening. New diagnostic technologies for breast cancer screening. Epoetin and darbepoetin for managing anemia in cancer. Epoetin and darbepoetin for managing anemia in cancer. Off-label use of atypical anti-psychotic medications Off-label use of atypical anti-psychotic medications Renal artery stenting for mild renal artery stenosis. Renal artery stenting for mild renal artery stenosis. Therapies for localized prostate cancer. Therapies for localized prostate cancer. Oral medications for diabetes management. Oral medications for diabetes management. Medications for depression management. Medications for depression management. Drug therapies and other interventions for osteoporosis. Drug therapies and other interventions for osteoporosis.

13 2. Evidence Generation DEcIDE (Developing Evidence to Inform Decisions about Effectiveness) Network. DEcIDE (Developing Evidence to Inform Decisions about Effectiveness) Network. – Capitalizing on data – New methods – Answers for questions that don’t require multi-year, multi-million $ trials

14 Evidence Generation DEcIDE Research Network The main purpose of the DEcIDE network is to expeditiously develop valid scientific evidence about the outcomes, clinical effectiveness, comparative effectiveness, safety, and appropriateness of health care items and services. The network is comprised of academic and clinic-based centers with access to electronic health information databases and the capacity to conduct accelerated research.

15 What Does DEcIDE Primarily Do? A.Analyze existing health care databases to compare the effectiveness & outcomes of treatment. B.Analyze existing disease, device, and other registries. C.Conduct methodological studies to improve research on clinical effectiveness of treatments. D.Ability to conduct prospective studies including registries and practical clinical trials.

16 Summary &“Unofficial” DEcIDE Statistics 13 DEcIDE centers. 13 DEcIDE centers. Over 60 core clinical scientists. Over 60 core clinical scientists. Over 500 affiliated personnel. Over 500 affiliated personnel. Access to >120 different health databases. Access to >120 different health databases. Health data on over 50 million Americans. Health data on over 50 million Americans. Nation’s largest network of researchers in therapeutic effectiveness. Nation’s largest network of researchers in therapeutic effectiveness.

17 Other DEcIDE Resources International data International data – all 570,000 residents of British Columbia – GPRD (5% sample of UK) 11 Medicaid programs, incl some SCHIP 11 Medicaid programs, incl some SCHIP Commercial pharmacy & lab vendor data Commercial pharmacy & lab vendor data – Ingenix – PharmMetrics – Medstat (private health plans) Electronic Medical Records e.g., Intermountain Health Electronic Medical Records e.g., Intermountain Health Registries heart failure, CAD, breast cancer, HIV, and Hep C Registries heart failure, CAD, breast cancer, HIV, and Hep C

Other Capabilities of DEcIDE Design & implement prospective studies. Conduct clinical economics studies. Develop algorithms to identify inappropriate drug prescribing patterns. Evaluate the effects of benefit and formulary structure on health outcomes. Conduct simulations and modeling. Carry out evaluations of innovative healthcare services. Evaluate patient and prescriber decision- making tools. Examine clinical benefits of genetics testing. 18

19 Advantages of Observational Studies RCT’s rarely powered for ADE’s. RCT’s have poor external validity. –May not generalize to the patient population for whom the intervention may be applied. Women, children, minorities, very elderly are under-represented. Multiple drug choices and alternatives. Co-morbid conditions. RCT setting, health care providers is “artificial”. Longer term follow-up is usually achievable. Facilitates risk management and risk minimization. Enables better translation. –Interventions that are efficacious under a highly specific set of circumstances often fail to replicate across a wide variety of settings, conditions, patients.

20 Key Challenges Methods Data Sorting out interaction between setting and intervention. Comparing therapies on the relevant clinical endpoints.

21 Other challenges Reducing the timeline from question to answer –Building data systems that answer policy questions Data: wealth of data available from large healthcare databases.

22 Example DEcIDE Studies Completed Use of Clopidogrel in Stents (JAMA) Comparative Effectiveness of Beta-blockers (American Journal of Cardiology) Antipsychotic Treatment in Older Adults (CMAJ) Antidepressants and Aspiration Pneumonia (J Clin Epi) In Progress Bariatric Surgery in Patients with Type II Diabetes Mellitus Effectiveness & Safety of DMARDs Drug Therapies for COPD ACE-I Exposure in Pregnancy Coronary & Cardiac Stents Federated data networks Medication Therapy Mgmt

23 Methods Tools AHRQ’s Registries for Evaluating Patient Outcomes: A User’s Guide Purpose: serve as a guide the design and implementation of patient registries, the analysis and interpretation of data from patient registries, and the evaluation of the quality of a registry or one of its components.

24 User’s Guide Broad, multi-stakeholder involvement –Authors: 39 selected contributors with relative equal distribution from industry, academia, government and services providers –Reviewers: 35 reviewers including NIH, FDA, CMS, OHRP, OCR, IOM. –Case Studies: 20 case studies from 28 contributors –Sections: Creating, Operating, Evaluating

25 Obtaining User’s Guide AHRQ's Clearinghouse ( ). Download from –Registries for Evaluating Patient Outcomes: A User’s Guide (Long Form) AHRQ Pub. No. 07-EHC001-1 –User’s Guide to Registries for Evaluating Patient Outcomes: Summary (Short Form) AHRQ Pub. No. 07-EHC001-2 –Announcing…Registries for Evaluating Patient Outcomes: A User’s Guide (Flyer) AHRQ Pub. No. 07-M029

26 Published Monday: Emerging Methods in Comparative Effectiveness & Safety A series of 23 articles by AHRQ researchers on new approaches in comparative effectiveness methods are compiled in a special October edition of Medical Care. A valuable new resource for scientists committed to advancing the comparative effectiveness and safety research. All articles available for free download on AHRQ’s website or from AHRQ’s Clearinghouse (Pub. No. OM ). DEcIDE program

27 3. Evidence Translation Translate scientific evidence and make it accessible to patients, providers, and policy- makers to promote informed health choices Translate scientific evidence and make it accessible to patients, providers, and policy- makers to promote informed health choices Conduct research to communicate complexities of decision-making and inform development of health care information products and decision aids Conduct research to communicate complexities of decision-making and inform development of health care information products and decision aids Construct prototypes for decision aids and house MMA 1013 related decision aids Construct prototypes for decision aids and house MMA 1013 related decision aids

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Comparative Side Effect Information for Antidepressants Based on systematic review of literature from EPC program. 30

31 Opportunities Growing international interest in effectiveness research and comparative effectiveness studies. Converging interest of federal agencies in drug safety (e.g., Sentinel Network). Part D data. NIH’s CTSA program. IOM Reports. EHR/PHR. Collaborations with pharmaceutical & devices industries.

33 Program Outputs Research Reports Systematic Reviews Consumer Guides

34 More Information? Clancy CM, Slutsky JR. Commentary: A Progress Report on AHRQ's Effective Health Care Program. Health Serv Res Oct;42(5):xi-xix. Clancy C. The effective health care program: evidence-based medicine joins the consumer age. MedGenMed Feb 27;8(1): Garrison LP Jr, Neumann PJ, Erickson P, Marshall D, Mullins CD. Using Real-World Data for Coverage and Payment Decisions: The ISPOR Real-World Data Task Force Report. Value Health Sep-Oct;10(5): From the Institute of Medicine… Institute of Medicine Learning What Works Best: The Nations Need for Evidence on Comparative Effectiveness in Health Care. er%20(F).pdf

Scott R. Smith, PhD Even More Information

Thank you! 36