Download - April 4, 2006
April 4, 2006
Reimbursement and Phase IV:
CRO Role In Clearing
The Fourth Hurdle
ObjectiveObjective
• Understand trends in payer use of Phase IV studies and registries
• Identify considerations for adapting Phase III and IV activities to accommodate those trends
• U.S. reimbursement planning and problem solving since 1998
• Former owner S&FA; Exec VP, PAREXEL
• Payer research; competitive analysis
• Strategic planning; reimbursement forecasting
• Advocacy with major payers
Tag Client MixTag Client Mix
Devices/ Diagnostics
15%
Ad/ PR/ PA Agencies
10%
Investors/ Advisors
15% Biotech/ Biologicals
40%
Pharmaceuti-cals20%
Current Assignment Current Assignment IncludeInclude
• Sepsis
• PDT
• HIV/AIDS
• Personalized cancer immunotherapy
• Immune globulins
• Osteoporosis
• Genetic testing
• Bleeding disorders
The Fourth HurdleThe Fourth Hurdle
1. Proof of efficacy
2. Acceptable safety
3. GMP
4. Reimbursement
4x4: 44x4: 4thth Hurdle’s Link to Hurdle’s Link to Phase IVPhase IV
• U.S. payers routinely require outcomes research to support coverage of high cost technologies
• High cost = “On my radar per case or in total”
Link Link – cont’d– cont’d
• Tech developers are often reluctant to include in Phase III more than what is needed for FDA. That’s OK because …
• Payers want to know how new tech affects real populations, not protocol-driven clinical trial subjects
• But Phase III design should anticipate Phase IV data collection
Payers Want Practical Payers Want Practical Clinical Trials (PCTs)Clinical Trials (PCTs)
• Evidence-based coverage policy will require PCTs– E.g. ICD
• Study design is formulated to enable treatment decision making– Distinguish from explanatory clinical
trials designed to maximize the chance that a biological effect of a new tx will be revealed
PCT CharacteristicsPCT Characteristics
• Compare clinically relevant interventions– E.g. Enroll based on presenting
symptoms rather than confirmed diagnosis
• Enroll a diverse population of study participants– E.g. Elderly not excluded
Characteristics – cont’dCharacteristics – cont’d
• Recruit from a variety of practice settings
• Collect data on a broad range of health outcomes beyond mortality and morbidity– E.g. QoL, symptom severity, cost,
patient satisfaction
MCO Views on Outcomes MCO Views on Outcomes Data Data
• Economic data Most persuasive
• Clinical data Sometimes useful
• Quality of life Interesting but seldom
compelling
Risks in Post Approval Risks in Post Approval TrialsTrials
• Failure
– Pfizer funded trial comparing its calcium channel blocker Norvasc to other antihypertensives
– Generic diuretic (chlorthalidone) was shown to be superior in preventing certain cardiovascular outcomes
Risks Risks – cont’d– cont’d
• Credibility
– Payers assume study lacks scientific rigor
Active Controlled TrialsActive Controlled Trials
• Payers want to know how the new tech compares to standard of care, not to absence of care
• Some manufacturers willing to risk active trials in Phase III because of payer, not FDA, pressure
Amgen Oncology and Amgen Oncology and OsteoporosisOsteoporosis
• Head-to-head trials of AMG-706 and Avastin
• Comparative trials of denosumab against Fosamax and Zometa
• “If not superior, we’d rather know now than later.”
AHRQ Payer Registry AHRQ Payer Registry GuideGuide
• Agency for Healthcare Research and Quality is developing “how to” guide for payers who create patient registries as part of coverage with evidence development
• On contract to Outcome Sciences, Inc.
Registry Guide Registry Guide – cont’d– cont’d
• National workshop to be scheduled – date TBD
• Monitor at ahrq.gov
Medicare Evolving to Be Medicare Evolving to Be National Treatment Policy National Treatment Policy ManagerManager
• CMS process for evaluating new technology is rigorous and evidence based
• Adverse Medicare coverage policy decision is routinely followed by private payers
• Part D benefit and Coverage With Evidence Development (CED) are accelerating the evolution
Part D Part D
• More difficult for manufacturers to differentiate products via detailing
• Part D benefit design drives utilization toward generics, forcing undifferentiated products to lower net selling price
Part D Part D – cont’d– cont’d
• Part D Plan P&T committees rely heavily on comparative effectiveness data
– Coverage decisions will likely migrate to Plans’ non-Medicare businesses
Medicare CED Medicare CED
• Coverage with evidence development for FDA approved drugs, biologicals, devices
• CMS can require evidence collection, including Phase IV trials and patient registries, as a condition for Medicare coverage
FeaturesFeatures
• Will be used only where Medicare coverage would otherwise be denied as not reasonable or necessary
• Systematic, protocol-driven data collection
• No reimbursement for data collection
Most Likely To Be Used For Most Likely To Be Used For ……
• Drugs in new classes with novel mechanisms
• Treatments that may be ineffective or unsafe in some patient subgroups
• Off label uses
Awaiting New Guidance Awaiting New Guidance DocumentDocument
• CMS intends to issue revised guidance by summer 2006
– Clarify Common Rule and IRB application to CED
One Current Use of CEDOne Current Use of CED
• Expand coverage of Eloxitin, Camptosar, Erbitux and Avastin off label for colorectal cancer
• Patient must be enrolled in NCI sponsored trial
• “Sufficient inference of benefit” + safeguards inherent in NCI sponsored trials
ICDs: Another Example of ICDs: Another Example of Evidence-Based Coverage Evidence-Based Coverage PolicyPolicy
Situation:
• Trials of implantable cardioverter defibrillator (ICD) showed it to be effective in some patients but not in others
• High cost, large population, unsettled medical evidence resulted in adverse coverage policies
ICD CoverageICD Coverage
Response:
• Manufacturer sponsored Phase IV trial: Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
• Medicare expanded coverage to include study population
Outcome Outcome
• Trial provided evidence on survival benefit with simple, single lead ICD
• Medicare issued new national coverage determination
How CRO Can Prepare How CRO Can Prepare Client for The Fourth Client for The Fourth HurdleHurdle• Design Phase III for beyond Phase III
• Conduct primary research to understand what important payer(s) want to see in that therapeutic class – E.g. What metrics are relevant?
• PMPM• Cost/savings • Drug budget impact; Overall budget
impact
How To Prepare – How To Prepare – cont’dcont’d
• Press to have Phase IV studies be at least as rigorous and credible as Phase III
• Identify new tools to address payer needs
– E.g. – validated biomarkers
Hypothetical CaseHypothetical Case
• New ADD/ADHD tx in development• Will universally be 3rd tier
– Inherent safety concerns – pediatric – complicated by conflicting, government sponsored class findings
– Not life saving– Many alternatives whose PMPM costs
are well understood– Competitor performance contracts in
place
Manufacturer Objective: Manufacturer Objective: Begin Moving To Tier 2 In Begin Moving To Tier 2 In Year 2Year 2
• How will drug move from 3rd to 2nd tier?
– Significant price concessions
– Outcomes research (OR)
• Which is the better choice for client? If OR, then need to identify– Endpoints that are relevant to payers
– Tools to accelerate conclusions
Example of Tool: Example of Tool: Validated Cognitive Validated Cognitive Biomarkers Biomarkers
• How can validated cognitive biomarkers:– Identify patients who are likely
responders to this drug?– Use response data to suggest cost
effectiveness?– Produce data that is credible to the
payer?
SummarySummary
• U.S. payers, led by Medicare, now require post-marketing outcomes data to grant or continue coverage of new, high cost technologies
• Many pharma companies do not yet– Recognize the extent of the trend– Prepare adequately pre-launch– Find out from payers what they
really need to see
Summary – Summary – cont’dcont’d
• Significant opportunity exists for CROs to fill the knowledge gap by– Determining payer data needs– Perfecting clinical trial tools to
address those needs (e.g. validated biomarkers)
– Helping clients understand that• Market access does not end with FDA
approval• Phase III planning is essential to
streamline the Phase IV work
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