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Value to Outcomes (V2O) in Oncology Drug Development Dr. John J. Doyle June 17, 2016 ™ © Copyright 2014 Quintiles Pharmaceutical companies are making remarkable investments in cancer research Number of pipeline products in R&D Source: Lloyd. Citeline Pharma R&D annual review 2015 - PharmaProject Jan 2015 2 For example, the PD-1/PD-L1 pipeline is intensely competitive across major oncology markets Phase I-III trials for PD-1 and PD-L1 Keytruda (43 trials) Opdivo (42 trials) Atezolizumab (28 trials) Launch 2017 MEDI-4736 (23 trials) Bl a dd er Bra in Bre as t Ce rvi cal Co l or ec tal Ga He str ic ad an dN eck He ma to l og He ic pa Ho t o dg c el lu k in l ar 's L ym ph om a Me l an om Me a so the M l iom ul t No ipl e a n-H My od gk elo in's ma Ly No m n-S ph om ma a ll C Ot he e ll r (S Lu ng oli d Tu mo rs) Ov ari an Pa nc rea ti c Pro s ta te Re na lC ell Sa r co Sm ma all Ce ll L un g Launch 2017 There are 143 oncology trials spanning 23 markets and 39 trials are phase III 5 trials 1 trial 3 Source: BioMedTracker September 2015, Quintiles Analysis These efforts are improving the prognosis for patients 5 Year Relative Survival, US 1990-2010 Source: SEER Survival Statistics, Period Analysis for 2010 – IMS Global Oncology Trend Report 2015 4 … but this innovation comes at a price that places a strain on health care budgets $ Billion Worldwide Prescription Drug & OTC Sales, by therapeutic area 1200 Oncology 1,029 Anti-diabetics 1000 153.1 CAGR + 11.6% Anti-rheumatics Anti-virals 781 Vaccines 79.2 Bronchodilators 800 Sensory Organs Anti-hypertensives 600 MS therapies Immunosuppressants 400 Anti-coagulants Dermatologicals Anti-hyperlipidaemics 200 Anti-fibrinolytics Anti-bacterials Other 0 2014 2020E 5 Especially in the US, cancer drug prices have been rising steadily Monthly and median costs of cancer drugs at the time of FDA approval, 1965-2015 Source: Peter B Bach, MD Memorial Sloan-Kettering Cancer Center – Available from: https://www.mskcc.org/research-areas/programs-centers/health-policy-outcomes/cost-drugs 6 There is a bright spotlight on value 7 Prices have been criticized not only by payers, but also by oncologists 8 How do we solve for value in cancer care? 9 The Value Cascade How do we define and measure unmet need? • No unmet need implies no value unless the aim is to drive cost reduction What is the consequence of addressing the unmet need? • Improved health outcomes, reduced mortality, reduced cost How good is this intervention at addressing the unmet need ? • Clinically meaningful improvement of outcomes in a defined patient population vs an appropriate comparator How good is our evidence of this? • Does uncertainty detract from the value How do we value the improved outcomes? • Does the value of this improved performance match the increased cost? (product price less cost offsets) • Different health systems take different approaches to value $ • How does the value translate into price? 10 Value-based assessment frameworks have emerged as a means to appraise oncology products to control costs US based Frameworks ASCO framework to assess the value of cancer treatment options NCCN Evidence Blocks Combines a long-term perspective on value through CE analyses with short-term affordability considerations Value-based pricing calculations based on 6 modifiable components using web-based tool DrugAbacus EU based Frameworks The European Society for Medical Oncology Magnitude of Clinical Benefit Scale ESMO-MCBS NHS Cancer Drug Fund (UK) NVMO PASKWIL Criteria (Netherlands) 11 Historical Evolution of Drug Evaluation in the US 1970 1980 1990 1972 1985 Congress establishes Office of Technology Assessment (OTA) 1968 ECRI Institute established OTA Health Policy staff focuses on need for HTA 1989 RAND call for health 1990 quality measures and clinical effectiveness guidelines AHRQ (Agency for Healthcare Research and Quality) established 1982 Begins HTA; WHO Collaboration Center 1985 Government Select Evidence Based Practice Center (EPC) Select Private 2000 Blue Cross Blue Shield Association establishes Technology Evaluation Center (BCBSA TEC) 1992 1995 Congress budget decision closes OTA 1997 Tech. DEcIDE AHRQ EvidenceAssessbased Practice ment Centers (EPCs) group established 1997 1993 2005 John M. Eisenberg Center established 2003 HTAIS HTA database Named AHRQ EPC Designated CMS advisor 1997 1993 Kaiser Permanente collaboration 1993 1994 ICSI Hayes Inc. Source: US Federation Scientists OTA Archive; Agency websites; Company websites; NPC report “Current Evidence Based Medicine Landscape Named AHRQ EPC 1997 Oregon EPC formed VA TAP 2003 Network of 14 states form DERP 2003 2004 United InHealth Biosource Consumer Reports Best Buy Drugs 12 12 Other countries struggle to determine how to value drugs • • • • UK undertook a process to redefine drug price methodology for PPRS • VBP (Pricing) • Renamed VBA (Assessment) Initiative failed last year due to debate over how to measure value Issues over differential value for different people Arbitrary “multiplier” for Burden of Illness and Wider Social Impacts not justifiable according to critics 13 Value framework implicaitons for drug manufacturers Clinical Trial Design Payer Access Pricing Strategy Provider Usage • Certain outcomes (e.g., OS) are valued more highly than others (e.g., Response Rate) • Major payers (e.g., Aetna) have acknowledged the potential utility of value-based frameworks for coverage decisions • Preliminary and interim clinical data will indicate outputs from value-based frameworks • Oncologists have expressed discomfort with discussing the cost or value of treatments with patients • NCCN and DrugAbacus have metrics for data quality and consistency (multiple trials are preferred over one larger trial) • Power shifts to Pharmacy Benefits Managers and Accountable Care Organizations have placed a premium on specialty drug value • Increased scrutiny on drug prices may lead to the use of value-based frameworks as guideposts for drug costs • Providers will rely on manufacturers to contextualize value outputs in a way that is useful for patients 14 The healthcare system is moving from volume to value …. to outcomes. 15 The Healthcare System is migrating from volume to value … to outcomes (V2O) Policymaker • Balance of quality and cost • Societal considerations • Health system statutes and guidelines Patient • Need to maintain health • Benefit/risk tradeoffs • Affordability of care Rx & Dx Manufacturer • Incentives to develop evidence • Reimbursement commensurate with value • Return on investment • Reward for innovation Laboratory • Better, faster, cheaper • Staff resource requirements and turn around • Managing with a budget V2O Healthcare System Payer & HTA • Balance of quality and cost • Evidence-based care • Provision of appropriate care to appropriate populations • Balancing care across the population Provider & Hospital • Provision of appropriate care • Provision of reimbursed services • Financial efficiency & viability • Managing with a budget 16 Different stakeholders have various views on risks, benefits and value Industry Regulators Payers Physicians Market / Patient Access Drug/Device Candidates • Improve patient outcomes • Prove value • Secure coverage and reimbursement • Enhance understanding of unmet patient needs • Explore new indications Patients • Delineate riskbenefit profile • Detect safety signals • Ensure long-term safety and effectiveness • Appraise value for coverage and reimbursement decisions • Monitor usage within criteria • Evaluate comparative- and cost-effectiveness • • • • Evaluate evidence Advance science Improve care Ensure continued reimbursement • Generate publications • My own health— what choices do I have? • What are the risks/benefits? • Which treatment will improve my quality of life? • Which treatment is safer, more convenient and affordable? 17 Risk-benefit analysis is also becoming personal PERSONALIZATION OF CARE RISING TIDE OF CONSUMERISM MINDING THE (SYSTEM) GAPS DEMOCRATIZATION OF CARE 18 How do we integrate RWE in cancer drug development development? 19 Real-world evidence plays an increasing role across the product lifecycle Incorporate real-world data needs earlier in the R&D process Development Growth Phase Post marketing commitments (safety, etc) Budget Impact Evidence Required Mature Phase Long-term clinical outcomes Utilization/ prescribing patterns Patient recruitment Effect of switching on outcomes Head to head comparative effectiveness Adherence Unmet need/ disease burden Differentiation in subpopulations Usage Difference Target populations Differentiate with or vs. protected formulation Understand standard of care Trial design Launch Now Pricing Review New Competition Past New Formulation/ Indication Competitor Goes Generic Source: Ref. modified from EMA Adaptive Pathways Pilot Presentation at STAMP http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2015/11/WC500196727.pdf - Confidential - 20 RWE can be generated through a variety of study designs Evidence Development Options Minimally interventional trials designed to include more representative populations, comparators and endpoints predicted for product use Enriched studies designed with experimental and observational elements to track real-time riskbenefit and spawn further research Retrospective Research Pragmatic RCTs Enriched Prospective Studies RWE databases evaluated to characterize treatment patterns and clinical disease patterns; also useful for informing prospective study design features Enriched Retrospective Observational Prospective Studies Enriched retrospective studies conducted to strengthen secondary data analyses with information from patients and clinicians Disease registries established early to investigate real-world practice patterns and outcomes 21 Cost/Time Sensitive Approaches Changing real world research evidentiary landscape Database & Hybrid Registries Pragmatic Pragmatic Ph IV trials • High external validity • Large sample size • Simple design • Diverse settings • Real world late phase operations • High internal validity • Smaller sample size • Sophisticated design • Controlled environment Explanatory trials (RCT) 22 Engage Early Early evidence for better outcomes REIMBURSEMENT APPROVAL PRODUCT DECISION Regulators BioPharma Preclinical Clinical Development Phase I Phase II Phase III Regulatory Submission Payers Providers Patients Healthcare Delivery Phase IIIB/IV Product Development Services Real World & Late Phase Research Services Evidence for Regulators, Providers, Payers, Patients 23 Healthcare System Goals Equity Economics Effectiveness Improve Enhance Population Patient Outcomes Experience Efficiency What Success Looks Like Reduce Costs System Levers 24