NOPR 20062009 and the New Era of Comparative Effectiveness

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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
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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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Medicares 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

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NOPRs 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, physicians 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

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

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Example of Question DetailIntended Patient
Management Plan
5. If PET were not available, your current
management strategy would be (select one)?

• 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

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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

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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

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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

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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 262155-61
• 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 491928-35
• Treatment Monitoring
• Data on 10,447 scans from May 8, 2006 Dec 31,
  2007
• Cancer 2009115410-18

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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)

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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
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PET Changed Intended Management in 36.5 of Cases
Hillner et al., J Clin Oncol 2008
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Changes in Intended Management () Stratified by
Pre-PET Plan
Pre-PET Plan
Hillner et al., J Clin Oncol 2008
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Change in Management by Cancer Type
(patients)
Hillner et al., J Nucl Med 2008
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Change in Management by Cancer Type
Hillner et al., J Nucl Med 2008
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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
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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
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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 Medicares 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

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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

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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).

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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

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The Challenge to Registry-based StudiesDefining
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

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

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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
Deaths from Pancreas Bladder Kidney Prostate
PET
(Metastatic dis. Pre-PET)
- 2 years
Comparator Imaging
Specific cancer ICD-9 for metastatic disease
Usual Care
Frequency accuracy?
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GO Study 3Evaluate Geographic and Temporal
Variation
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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 physicians
  impression of response
• More clearly ask what the alternative management
  plan during treatment would be if PET were not
  available

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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