Technology Assessment in Kaiser Permanente NAIC Health Innovations (B) WG May 30, 2008

1. Technology Assessment in Kaiser PermanenteNAIC Health Innovations (B) WGMay 30, 2008 Brent Barnhart Senior Counsel Kaiser Permanente

2. HI About Kaiser Permanente Nationwide Description: People: Facilities: Revenue: Nation’s largest nonprofit health plan Integrated health care delivery system 8.5 million members 14,000+ physicians 140,000+ employees 8 regions in 9 states and D.C. 32 hospitals and med centers 430+ medical offices $37 billion annually WA OR OH CO CA MD DC VA GA

3. A Prepaid Integrated Delivery System With Aligned Incentives The Permanente Federation Permanente Medical Group • Social Purpose • Quality Driven • Shared Accountability for Program Success • Integration along Multiple Dimensions • Prevention & Care ManagementFocus Health Plan Members Kaiser Foundation Hospitals Kaiser Foundation Health Plan

4. New Medical TechnologyAssessment Drugs Biologics Devices, Equipment and Supplies Medical and Surgical Procedures Support Systems, Organizational and Managerial Systems including IT Comparative Effectiveness • Entirely new technology • New applications of existing technology Systematic and comprehensive evaluation of the medical (safety, efficacy, and effectiveness), social, ethical and economic implications of development, diffusion, and use of health technology

5. Comparative Effectiveness • Within Kaiser Permanente, the Interregional New Technologies Committee (INTC) is one of a group of national committees that review new technologies, products and pharmaceuticals: • INTC • National Product Council • Pharmacy and Therapeutics Committee • Kaiser Permanente is also helping to fund a new Institute for Comparative Effectiveness Research (ICER) that will disseminate information to patients, clinicians, and insurers.

6. Interregional New Technologies Committee INTC • Monitors and evaluates new, and new applications ofexisting, medical and behavioral technologies • Evaluates the medical appropriateness based on demonstrated safety, efficacy and comparative utility • Tracks and analyzes emerging technologies as evidence becomes available. • Compares the new technology to existing alternative technologies • Recommendations, not coverage decisions; never patient-specific Under The Permanente Federation – the national physician arm of Kaiser Permanente

7. Establishment of the INTC Charge to develop an explicit process for evaluating new medical technologies. The goal is to evaluate available scientific evidence, determine if a new technology is safe and effective, and make recommendations to the KP Regions. The Executive Medical Directors chartered the INTC New recommendation language employed KP hires David Eddy MD, PhD Early 1980s 1993 1990 2004 2007 KP enters collaboration with BCBSA TEC Two court cases Involving IVF and Infant Liver Transplant

8. INTC • 18 members, all regions represented • Inter-regional • Inter-entity • 10/18 members are physicians • Quarterly meetings with approx. 8 topics each • Internal and external evidence reviews • PMG experts as clinical guests for select topics • PMG expert opinion gathered for all topics

9. Safety Efficacy Benefit of using a technology for a particular health problem in ideal conditions Substantial equivalence or comparison to placebo Intermediate, short-term outcomes Everything in the left column plus Effectiveness Benefit of using a technology for a particular health problem in general or routine conditions Comparisons to standard of care and experience relevant to members Long-term health outcomes Operational impact FDA and INTC Scope Compared FDA’s Scope INTC Scope 9

10. FDA: Medical Devices

11. Guiding Principles By Applying Principles of Evidence-based Medicine Base clinical and policy decisions on evidence of effectiveness & benefit. David Eddy, MD, PhD • Evidence of benefit Do it • Evidence of no benefit/harm Don’t do it • Insufficient evidence Be conservative • Use discretion • If it is new, recommend only within well designed trials Do things that work, don’t do things that don’t, use resources wisely.

12. Topic Selection • Needs and ideas from INTC members • Feedback on meeting minutes • Feedback from regions as they make operational decisions • Inquiry line database • Internal and external assessment topics • New evidence: medical journals and professional meetings • FDA approvals, panel meetings, minutes, reviews • Member and physician demand • Open agenda planning calls including non-KP colleagues Strict criteria are NOT used to select topics. Generous input and judgment are used to determine topic priority.

13. 2007 INTC Topics Topic Selection • Surgery for morbid obesity • CT colonography • Wearable cardiodefibrillator vest • CAD Mammography • Artificial cervical discs • Hip resurfacing • Remote electronic telemonitoring for CHF • Robot-assisted laparoscopic prostatectomy

14. Preparing a Topic • Determine interest level in new technology • Gauge potential operational impact and demand • Raise relevant benefit, media, legal and ethical issues • Learn how the technology might fit into PMG practice • Gather PMG input • Determine source of assessment • Consider internal and external resources, public and private • Supplement most current assessment, as needed • Select a speaker and prepare a presentation • Assist speaker in drafting a recommendation

15. Anatomy of a Technology Assessment • Background • Problem Formulation • Literature Search Strategy • Evidence Summary/Tables • Regulatory Information including FDA • External assessments, all sectors • Conclusion/Rationale • Bibliography Supplemented with PMG expert opinion and professional societies

16. Sources of Information The Permanente Federation (TPF) External Assessments Internal Assessments Hayes BCBSA TEC ECRI INTC Primarily SCPMG Also TPMG, TPF EPCs FDA AHRQ Cochrane CCOHTA NICE Inquiry Line Others: Advisory Board, HTC, etc. Internal Input: Permanente Medical Groups Regional Initiatives Inter-entity Interregional Initiatives The INTC manages the national agenda for new medical technology assessment with the input of numerous collaborators and resources.

17. New Technology Inquiry Line • Supports the needs of PMG physicians throughout all KP regions for evidence-based information on new technologies • Volume of Inquiries . . . • Total inquiries (1999-2006) – 4,531 • In 2006, the average number inquiries per day was 2.2 • In 2006, clients used the inquiry line for . . . • Patient-specific inquiry – 44% • General technology inquiry – 46%

18. INTC Website

19. The BCBSA TEC/KP Collaboration TEC's collaborative relationship with Kaiser Permanente began in 1993. This relationship has given TEC staff ready access to Kaiser's clinical experts on a wide range of topics. As a result of TEC's collaboration with Kaiser, David M. Eddy, M.D., Ph.D., Senior Advisor for Health Policy and Management, served for over 10 years as TEC's Scientific Advisor, until his retirement from the position in 2004. In addition, one Permanente physician, Jed Weissberg, M.D., is a voting member of TEC's Medical Advisory Panel. TEC Assessments and other publications are provided to Kaiser Permanente staff as drafts. Dr. Weissberg participates actively in the MAP discussions, sharing clinical opinion from Permanente physicians on the draft TEC products. TEC staff works with Kaiser Permanente's Technology Assessment staff to obtain input on topic selection and to gain access to Permanente's physician experts on a wide range of topics. Permanente clinical expertise may be used to help shape the actual research questions in TEC Assessments. In many cases, these are the same physicians that either chair or sit on committees that are responsible for developing practice guidelines at Kaiser Permanente.

20. More on BCBSA TEC • Founded in 1985 and pioneered the development of scientific criteria for assessing medical technologies through comprehensive reviews of clinical evidence. • TEC provides comprehensive evaluation of the clinical effectiveness and appropriateness of a given medical procedure, device or drug, averaging 20 to 25 assessments a year. TEC serves a wide range of clients in both the private and public sectors, including KP and CMS. • TEC Assessments are scientific opinions, provided solely for informational purposes and should not be construed to suggest that BCBSA, KP or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated. • TEC is headed by Executive Director, Naomi Aronson, Ph.D. Its core staff of research scientists consists of experienced physicians and doctorate-level scientists with a history of academic and primary research affiliations. • A Medical Advisory Panel, comprising independent, nationally recognized experts in technology assessment, clinical research and medical specialties, has scientific accountability for all TEC assessments. BCBSA TEC content is available at: http://www.bcbs.com/betterknowledge/tec/

21. BCBSA TEC Criteria TEC Assessments routinely use the five TEC criteria to evaluate whether drugs, devices, procedures and biological products improve health outcomes such as length of life, quality of life and functional ability. 1. The technology must have final approval from the appropriate governmental regulatory bodies. 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. 3. The technology must improve the net health outcome. 4. The technology must be as beneficial as any established alternatives. 5. The improvement must be attainable outside the investigational settings.

22. 2/07 ECRI Target #907 3/05 CCOHTAIssue 65 2/06Ontario 4/06Hayes 7/06Hayes 1/04Hayes 1/04 ECRI Tech Forecast 3/02 AHFMR 2/07 BCBSA TEC BD + C C 2002 2004 2005 2006 2007 - - 2a 2a 2/05 TPMG 4/05 SCPMG 8/06 INTC 6/07 INTC 8/05 INTC 6/06 SCPMG An Assessment Example: Hip Resurfacing — At a Glance — In May 2006, the FDA conditionally approved the Birmingham System and requested Smith & Nephew conduct two post-approval studies. In Feb 2007, the FDA voted in favor of approval with conditions for Corin’s Cormet 2000 hip resurfacing system and requested a postmarket study No coverage.

23. What the INTC Produces The INTC Recommendations: • There is sufficient evidence to determine that the technology is medically appropriate (or is a medically appropriate treatment/diagnostic option) for select patients. • There is insufficient evidence to determine whether the technology is medically appropriate for any patient. OR There is insufficient evidence to determine whether the technology is a medically appropriate treatment/diagnostic option for any patient. • no evidence • insufficient quantity and/or insufficient quality • conflicting or inconsistent • There is sufficient evidence to determine that the technology is generally not medically appropriate (or is not a medically appropriate treatment/diagnostic option) for any patients. Further describe characteristics of the evidence What the INTC Does Not Do: Cost-effectiveness studies Operational decisions Clinical practice guidelines Coverage policies Consultation for individual patient cases

24. Current Example: Cervical Arthroplasty Anterior Cervical Discectomy with Fusion (ACDF) • The goal is to decompress the disc space and stabilize the vertebrae, relieving pressure on the nerve to reduce back, neck and shoulder pain. • Disadvantages: • complications associated with grafting • loss of cervical mobility • growing evidence that fusion may contribute to adjacent-level degenerative disease versus Cervical Arthroplasty • Uses the same anterior surgical approach as cervical fusion • Eliminates need for donor bone • Aims to maintain motion of cervical vertebrae hoping to reduce future problems and not hasten DDD in adjacent discs Implanted Bryan Disc

25. Cervical Discs and the FDA Prestige-ST® by Medtronic On July 17, 2007, the FDA approved the Prestige-ST® for the treatment in skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and or myelopathy. Intractable radiculopathy and or myelopathy should be present with at least one of the following items producing symptomatic nerve root and/or spinal cord compression which is documented by patient history (e.g., pain [neck and/or arm], functional deficit, and/or neurological deficit), and radiographic studies (e.g., CT, MRI, x-rays, etc.): 1) herniated disc, and/or 2) osteophyte formation. The Prestige® is implanted via an open anterior approach. The FDA’s Panel recommended Medtronic be barred from claiming preservation of ROM could protect adjacent discs. The FDA recommended a post-approval study of a min. of 200 pts. with data collection at 5 and 7 years post-op.

26. Cervical Discs and the FDA Bryan by Medtronic On July 17, 2006, the Orthopaedic and Rehabilitation Devices Panel of the FDA recommended approval of the Bryan Cervical Disc but has not received final marketing approval at this time. The Bryan disc is indicated for use in patients similar to those for whom the Prestige device is indicated.

27. Cervical Artificial Disc Replacement—At a Glance— TEC draft soon expected 7/07ECRI Forecast 6/06ECRI Forecast 10/07ECRI Target Expected 9/06 HAYES Outlook 11/05NICE TBD 2004 2005 2006 2007 2008 TBD - - 11/06 INTC 11/04 INTC 7/03INTC 12/07 INTC There is currently not a policy on artificial cervical discs. In July of 2007, the FDA approved the Prestige® Cervical Disc System. At the same time, the FDA's Orthopaedic and Rehabilitation Devices Panel recommended approval of Byran® Cervical Disc System.

28. Selective Evidence by Disc Type Lind (2007), Bryan, n=11, Sears (2007and 2007b), Bryan, n=67 Shim (2006), Bryan, n=61 Coric (2006), Bryan, n=33, RCT Lafuente (2005), Bryan, n=46, prosp. series Hacker (2005), Bryan, n=46, RCT Goffin (2002, 2003), Bryan, n=146, prosp. series Duggal (2004), Bryan, n=26, prosp. Series Bertagnoli (2005), ProDisc-C, n=27, prosp. Series Pimenta (2004), PCM, n=53, prosp. Series Mummaneni (2007), Prestige, n=541, RCT Porchet (2004), Prestige II, n=55, RCT

29. Even More Selective: RCTs by Disc Type Coric (2006), Bryan, n=33, RCT Hacker (2005), Bryan, n=46, RCT (2005), Bryan, n=550 (not published) Mummaneni (2007), Prestige, n=541, RCT Sawin (2005), Prestige ST, n=118, RCT (not publ.) Porchet (2004), Prestige II, n=55, RCT

30. Mummaneni et al - Prestige IDE Trial • 28% of surgeons (20/72) had financial interest in Medtronic and contributed a total of 187 of 541 patients with all centers contributing 1-49 patients each. • A fixed non-inferiority margin of 10% was agreed upon in advance by Medtronic and the FDA (Hypothesis: The success rate of Prestige is not lower than control by 10%.) • The interim Bayesian statistical analysis was planned when all patients reach 12-months and 250 pts. reach 24 mos. Primary endpoint is a composite of pain and functional disability, neurological status, adverse events, secondary surgical interventions and a radiographic functional spinal unit (FSU) height determination.

31. The Bayesian Interim Analysis • The FDA issued draft guidance on Bayesian statistics in medical device trials in May 2006 http://www.fda.gov/cdrh/osb/guidance/1601.pdf • “Bayesian statistics is a statistical theory and approach to data analysis that provides a coherent method for learning from evidence as it accumulates. Traditional (frequentist) statistical methods formally use prior information only in the design of a clinical trial. … In contrast, the Bayesian approach uses a consistent, mathematically formal method called Bayes’ Theorem for combining prior information with current information on a quantity of interest. …“ • “When good prior information on clinical use of a device exists, the Bayesian approach may enable FDA to reach the same decision on a device with a smaller-sized or shorter-duration pivotal trial.”

32. Previous INTC Recommendation (11/06) There is insufficient evidence to determine whether cervical arthroplasty is a medically appropriate treatment option for single-level cervical degenerative disc disease, including disc herniation and spondylosis. • The existing evidence is of insufficient quantity and quality.  The published evidence literature is limited to 3 small RCTs on two difference devices with less than 50 disc-patients with 24-month follow-up data reported. . KP INTC Discussion 12/07 What’s Different Now? • FDA approval and recommendation for approval • Access to new trial data (published & unpublished) • Additional perspectives on the evidence pending • Internal, BCBSA TEC, ECRI Target • Evolving PMG opinion and growing consumer interest

33. Thoughts for December Discussion • Studies suggest comparable adverse events, maintenance of ROM, patient satisfaction and decreased pain and disability levels. • Risks appear to be small, although number of patients examined is small • Protocols for the controls are not clear and may not represent current practice. • RCTs have not been blinded and are sponsored by device manufacturer • Significant variability in success rate by centers and many surgeons and most authors are financially tied to the manufacturers. • In the Prestige IDE trial, only 185 patients had completed outcome information including FSU. Inclusion of these patients without FSU into the overall success calculations was not consistent with the planned analysis. • In the Prestige IDE trial, 36 patients in the disc group and 48 in the control group declined surgery after randomization suggesting informed consent was not ideal. • In the Prestige IDE trial, the device used is not the device intended for market. Design modifications are being made in anticipation of FDA approval. • There are some reports regarding heterotopic ossification. • Marketing to physicians and consumers is increasing along with surgeon training programs. • The INTC’s previous recommendation regarding artificial lumbar discs may resurface.

34. Cervical Arthroplasty: The Strategy • Early Review • Iterative Reviews • Stay in touch with PMG practice and consumer interest • Monitor ongoing trials and unpublished data • Track FDA Advisory Panel meetings • Provide Spine Surgeons with evidence • Assists in early discussion of potential indications • Supports product discussions • Information regarding FDA recommendations and approvals, products in development, differences in design, tracking of literature and adverse events, etc. • Informs decision makers regarding potential deployment considerations including surgeon training and volume expectations

35. Cervical Disc Arthroplasty In July of 2007, the FDA approved the Prestige® Cervical Disc System. At the same time, the FDA's Orthopaedic and Rehabilitation Devices Panel recommended approval of Byran® Cervical Disc System. 10/07ECRI Target Expected TEC draft soon expected TBD + 7/07 9/07 10/07 11/07 12/07 TBD INTC Spine SST Meeting Immediately upon FDA approval, Medtronic approaches KP about training

36. What You Need To Make It Work • Evidence-based culture, or the makings of one • Supportive medical group leadership • Respected source of technology assessments • Effective physician/analyst partnerships • Resources and process that enable timely and relevant information and recommendations • Courageous physician opinion leaders • Realization that this is the grey-zone and uncertainty is the norm and decisions have to be made • Willingness to start somewhere and be persistent