NOPR 2006-2009 and the New Era of Comparative Effectiveness

1. NOPR 2006-2009 and the New Era of Comparative Effectiveness Bruce E. Hillner, M.D. Eminent University Scholar and Professor Virginia Commonwealth University Richmond, VA

2. Medicare (CMS) Coverage of New Technologies • Standard for reimbursement is “reasonable and necessary” • In 1990s, CMS adopted a new evidence-based approach for making coverage determinations • Requires peer-reviewed scientific evidence to document that new technology leads to changes in patient management and improved health outcome • CMS elected not to broadly consider oncologic indications for PET, but rather to evaluate the evidence on a cancer-specific and indication-specific basis

3. Medicare’s Coverage of PET • CMS initially covered PET on a cancer-specific and indication-specific basis • This approach rapidly became unwieldy • Decisions became, de facto, by cancer type • From 2006-2009, CMS used NOPR to provide access for PET to patients with not-previously-covered cancers • About 20% of CMS oncology PET scans (50,000/year) • In April 2009, CMS modestly expanded the “covered cancers,” while simplifying the plan for NOPR 2 • NOPR 2 will be about 10% of CMS oncology scans

4. NOPR’s Goals and Objectives • Assess the effect of PET on referring physicians’ plans of intended patient management • across a wide spectrum of cancer indications for PET that are currently not covered by the Medicare program, and • in relation to cancer-type, indication, performance status, physician’s role in management, and scan type • Provide access to the service • Minimize the burden to the patient, the PET center, and referring physicians • Generate evidence of reasonable quality to assist CMS in deciding whether to expand coverage of PET

5. NOPR Workflow PET interpreted & reported Ongoingpatientmanagement Referring MD requests PET PET done Ask patient for consent Pre-PET Form Post-PET Form sent, including question for referring MD consent Post-PET Form completed. Claim submitted

6. Timing of PET in Cancer Natural History Later Suspected Recurrences Suspected Cancer (Diagnosis) Initial Staging Restaging Suspected Recurrence TreatmentMonitoring TreatmentMonitoring

7. Pre-PET Form – 5 Questions • Reason for the PET Scan • Cancer Site/Type • Summary of Disease Stage • NED, Localized, Regional, Metastatic, Unknown • Performance Status • Asymptomatic, Symptomatic, Bedridden • Intended Patient Management Plan

8. Example of Question Detail:Intended Patient Management Plan • Observation (with close follow-up) • Additional imaging (CT, MRI) or other non-invasive diagnostic tests • Tissue biopsy (surgical, percutaneous, or endoscopic). • Treatment (if treatment is selected, then also complete the following) Treatment Goal: (check one) Curative  Palliative Type(s): (check all that apply) •  Surgical  Chemotherapy (including biologic modifiers) •  Radiation  Other  Supportive care 5. If PET were not available, your current management strategy would be (select one)?

9. Strengths of the NOPR Data • “Real world” data • Timely data • Very large patient cohorts • Current technology (≥ 85% PET/CT) • Good observational studies usually match controlled studies in magnitude and direction of effect (Concato NEJM 2000; Benson NEJM 2000; Ionnanidis JAMA 2001) • Results similar to more tightly managed single-institution studies (e.g., Hillner 2004) and to new Australian studies with outcome validation

10. Limitations of the NOPR Data • Collected change in “intended” management, not actual management • Unknown if management changes are in the correctdirection or improve long-term outcomes • Defining the relevant long-term “outcomes” for a diagnostic (instead of therapeutic) procedure is controversial • Potential that physicians may have been influenced by the knowledge that future Medicare reimbursement might be influenced by their responses

11. Limitations (2) • NOPR does not address: • Whether PET should be used in lieu of or as a complement to other imaging techniques • The optimal sequencing of CT, MRI and PET. • How much ‘better’ PET is than next best method

12. NOPR Results Overall Impact on Patient Management • Diagnosis, Staging, Restaging, Recurrence • Data on 22,975 scans from May 8, 2006 – May 7, 2007 • J Clin Oncol 2008; 26:2155-61 Impact on Patient Management by Cancer Type • Confirmed Cancers • Staging, Restaging, Recurrence • Data on 40,863 scans from May 8, 2006 – May 7, 2008 • J Nucl Med 2008; 49:1928-35 Treatment Monitoring • Data on 10,447 scans from May 8, 2006 – Dec 31, 2007 • Cancer 2009:115:410-18

13. Top Ten NOPR Cancer Sites/Indications • Ovary / Uterine Adnexa – Recurrence (Covered) • Ovary / Uterine Adnexa – Treatment Monitoring (Covered) • Ovary / Uterine Adnexa – Restaging (Covered) • Prostate – Initial Staging (Non-covered) • Prostate – Recurrence (CED) • Pancreas – Initial Staging (Covered) • Stomach – Initial Staging (CED) • Bladder – Initial Staging (CED) • Prostate – Restaging (CED) • Small Cell Lung – Restaging (CED)

14. Cohort Profile • First year of NOPR (5/8/06 to 5/7/07) • 22,975 “consented” cases from 1,519 facilities • Technology profile • 84% PET/CT • 71% non-hospital • 76% fixed sites Hillner et al., J Clin Oncol 2008

15. PET Changed Intended Management in 36.5% of Cases Hillner et al., J Clin Oncol 2008

16. Changes in Intended Management (%) Stratified by Pre-PET Plan Pre-PET Plan Hillner et al., J Clin Oncol 2008

17. Change in Management by Cancer Type % (patients) Hillner et al., J Nucl Med 2008

18. Change in Management by Cancer Type Hillner et al., J Nucl Med 2008

19. PET for Treatment Monitoring • PET during a planned course of cancer treatment • NOPR did not dictate or collect data on when during treatment PET was done • 82% Chemotherapy, 12% chemoXRT, 6% XRT • Ovarian, pancreas, NSCLC, SCLC most frequent • Metastatic disease in 54% Hillner et al., Cancer 2008

20. PET Used for Treatment Monitoring Switching to Another Therapy Effect of Year and Assessment of Prognosis No evidence supporting learning curve Hillner et al., J Clin Oncol 2008

21. Summary of NOPR Results Change in intended management associated with PET in previously non-covered cancers similar to that reported in single-institution studies of covered cancers ~1/3 of older patients undergoing PET for cancer types covered under Medicare’s CED policy had a major change in intended management, including type of treatment Examination of individual cancers did not find a significant difference in treatment changes between cancer NOPR has not yet examined if PET actually changed patient management or if PET improved outcome

23. CMS Coverage with Evidence Development Goals for NOPR 2 • Determine whether oncology care that is supported by PET improves health outcomes, as demonstrated by: • Improved survival, • Improved quality of life, or • Improved palliative care • NOPR data show both strengths and limitations when evaluated against CMS goals

24. Institute of Medicine Top 100 Priorities for Comparative Effectiveness Research • #17 “Compare the effectiveness of imaging technologies in diagnosing, staging, and monitoring positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT).”

25. The 2009 Challenge • Such ‘comparative effectiveness’ evaluations must move beyond the "if" to the “how" by addressing the relative value of • Sequencing • Frequency • Timing (during treatment monitoring) • Combinations of PET, MRI and CT • Measure actual (vs. intended management) • Complementary prospective and retrospective studies

26. The Challenge to Registry-based Studies:Defining appropriate comparison control groups Options a) Historical controls to Non-PET care when PET not available b) Contemporary controls to Non-PET when PET was available Both face: • Indication Bias • Differ in presentation • Differ in probability of metastasis • Differ in potential extent of metastasis • Provider Bias (MDs and hospital) • Patterns of care by referring MDs and hospitals using PET likely to differ from non-PET users • Spectrum Bias: For non-PET imaging, clinical indication not available

27. Could there be a patient selection bias in NOPR? Penetration of NOPR PET Scans for Advanced Disease

28. Grand Opportunity (GO) Grant • Collaboration of Dartmouth, Brown, ACRIN and NOPR • Starts 10/1/2009 (2 years) • Proposed Projects • Validation of Intended vs. Actual Management • End-of-Life Care associated with PET vs. Non-PET • Regional associations between PET use and intensity of non-PET advanced imaging

29. GO Study 2: End-of-Life care in 12 to 18 months before death, ± PET (CMS claims) Stratify by Comparator (Usual) Care Group -- NOPR years (no PET) -- 2004-2005 (Historical)Control for Cancer Type Initial Stage Known metastatic disease at DX NOPR PET Deaths from Pancreas Bladder Kidney Prostate (Metastatic dis. Pre-PET) - 2 years Comparator Imaging Specific cancer + ICD-9 for metastatic disease Usual Care Frequency & accuracy?

30. GO Study 3:Evaluate Geographic and Temporal Variation

31. Treatment Monitoring Revisions for NOPR 2 • Updated NOPR data collection forms: • Continue collecting data on palliative v. curative goal • New questions to assess: • timing during the planned course of treatment • planned duration of therapy • Further clarify the referring physician’s impression of response • More clearly ask what the alternative management plan during treatment would be if PET were not available

32. Final Comments • It has taken 20-30 years for one “knowledge turn” to show that PET has unique value in cancer management • NOPR has shown the feasibility of performing large-scale, policy-relevant imaging research that is minimally intrusive to patients and imagers • For current advanced imaging, the policy and economic questions going forward are when, how often, and in what sequence should advanced imaging be used in patients with suspected and confirmed cancer • Prospective multi-center investigator-initiated evaluations are needed to confirm ‘relative’ comparative value