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NOPR 2006-2009 NOPR 2006-2009 and the New Era of and the New Era of

Comparative EffectivenessComparative Effectiveness

Bruce E. Hillner, M.D.Eminent University Scholar and Professor

Virginia Commonwealth UniversityRichmond, VA

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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

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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

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

Referring MD requests PET

Pre-PET Form

PETdone

PET interpreted& reported

Post-PETForm sent,

including question for referring MD consent

Post-PET Form completed.

Claim submitted

Ongoingpatient

management

NOPR Workflow

Ask patient for consent

SuspectedCancer

(Diagnosis)Restaging Suspected

Recurrence

TreatmentMonitoring

LaterSuspected

Recurrences

Timing of PET in Cancer Natural History

TreatmentMonitoring

InitialStaging

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

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)?

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

Limitations of the NOPR Data• Collected change in “intended” management, not actual management• Unknown if management changes are in the correct direction 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

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

NOPR ResultsOverall 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

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)

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

PET Changed Intended Management in 36.5% of Cases

Non-Treat Treat 23.2 31.6 28.6 29.2 28.3

Treat Non-Treat 7.9 7.9 7.5 9.7 8.2

Patients with change post-PET (%) 31.1 39.5 36.1 39.0 36.5

Hillner et al., J Clin Oncol 2008

Clinical Indication for PET Study (Percent)

Pre-Pet Plan

Post-PET Plan

Dxn=5,616

Staging n=6,464

Restaging n=5,607

Recurrence n=5,388

Alln=22,975

Treat Same 16.0 46.5 15.8 20.4 25.5

Non-Treat Same 52.9 14.0 48.0 40.7 37.9

Changes in Intended Management (%) Stratified by Pre-PET Plan

Image n=9,518

Biopsy n=3,552

Watch n=2,199

Treatment n=7,706

Post-PET Plan

Image 5.8 6.0 4.6 3.0

Biopsy 9.5 24.0 9.0 6.8

Watch 37.2 33.6 62.3 15.6

Same Rx NA NA NA 42.4

New or Major Change in Rx

47.6 36.3 24.1 8.7

Minor change Rx NA NA NA 23.5

Pre-PET Plan

Hillner et al., J Clin Oncol 2008

Change in Management by Cancer Type

  Staging Restaging Suspected Recurrence

Bladder (CED) 39.9(1,461)

36.4(1,239)

36.7(878)

Brain (CED) -- -- 40.5(222)

Cervix (Covered) 36.1 (341)

26.9 (353)

35.9(290)

Kidney (CED) 41.1 (895)

34.4 (979)

32.4(1,003)

% (patients)

Hillner et al., J Nucl Med 2008

Change in Management by Cancer Type

  Staging Restaging Suspected Recurrence

Ovary (Covered) 43.2(378)

37.7 (1,971)

44.5(2,160)

Pancreas (CED) 39.2(1,491)

38.3 (1,021)

39.3(802)

Prostate (CED) 32.0(2042)

34.0 (1,477)

39.4(1,790)

Small Cell Lung(CED)

43.3(1,082)

40.8 (1,357)

38.1 (544)

Myeloma(CED)

52.2(402)

46.4(1009)

50.9 (373)

Hillner et al., J Nucl Med 2008

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

PET Used for Treatment MonitoringSwitching to Another Therapy

Effect of Year and Assessment of Prognosis

CancerType

Overall2006

Overall2007

Overall2008

2006If worse

2007If worse

2008If worse

Pancreas 30.9 28.7 25.0 66.3 58.1 55.6

Prostate 26.4 22.0 22.4 62.2 48.8 48.3

Kidney 21.9 24.0 23.1 53.7 56.6 54.2

Bladder 34.2 27.1 28.4 67.2 58.8 64.0

Stomach 20.6 25.2 24.4 46.9 59.4 59.3

Hillner et al., J Clin Oncol 2008No evidence supporting learning curve

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

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

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).”

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

The Challenge to Registry-based Studies:Defining appropriate comparison control groupsOptions a) Historical controls to Non-PET care when PET not available

b) Contemporary controls to Non-PET when PET was availableBoth 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

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

CancerCDC 65+

Incidence (2005)CDC 65+

Deaths (2005)

NOPR 65+ Restaging or

suspected recurrence 2007

NOPR PET for Restaging or

suspected recurrence (% of Annual Deaths)

Prostate 116,659 26,327 1,856 7.0%

Pancreas 22,252 23,397 1,035 4.4%

Kidney 21,571 8,147 1,126 13.8%

Bladder 32,800 7,627 1,202 15.7%

Stomach 12536 8,045 834 10.4%

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

Deaths from PancreasBladderKidney

Prostate

Specific cancer +ICD-9 for

metastatic disease

Comparator (Usual) Care Group-- NOPR years (no PET)-- 2004-2005 (Historical)Control forCancer TypeInitial StageKnown metastatic disease at DX

GO Study 2: End-of-Life care in 12 to 18 months before death, ± PET (CMS claims)

Stratify by

- 2 years

NOPR

Usual Care

PET(Metastatic dis. Pre-PET)

ComparatorImaging

Frequency & accuracy?

GO Study 3:Evaluate Geographic and Temporal Variation

1) Aggregate use for approved cancers (e.g. lung, colon, lymphomas)

Use Dartmouth Atlas Hospital Referral Regions (DA-HRR)

2) Compare pre-NOPR (04-05) and NOPR (07-08) utilization

Compare utilization by age strata, gender, cancer typeHRR specific means and rates

3) Examine rates of CT and MRI for these cancers for same periods

Study whether PET is predominantly an additive or a replacement relative to other advanced imaging

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

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