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Outcomes Research on Regenerative Medicine in the United States

Diana Brixner, RPh, PhD Professor and Chair Pharmacotherapy

Executive Director, Pharmacotherapy Outcomes Research Center L.S. Skaggs Pharmacy Institute

Director of Outcomes Personalized Health Care Program University of Utah, Salt Lake City, Utah

HTA Japan September 16, 2014

Presentation Overview •  Definition of Regenerative Medicine •  Regulatory and Reimbursement Issues •  Cost-effectiveness in Regenerative Medicine •  Applications of Regenerative Medicine •  Cost-effectiveness in Knee Cartilage and

Esophageal Cancer •  Future Outcomes Research needed for RM in

Knee Cartilage and Esophageal Cancer Application

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Definition of Regenerative Medicine (RM)

Goal: To cure or reduce disease burdens on patients

Hurdles of Regenerative Medicine

•  Regulatory Issues q  FDA approval can be challenging and complex

Ø  Therapies classified as device, biologic, or drug with each classification owning to its own regulation and review centers

Ø  RM therapies can fall under some or all classifications leading to the need to integrate regulations

•  Reimbursement Issues q  Currently no strong comparative cost-effective studies for

this therapy to justify coverage q  Standard of care for comparative effectiveness studies

not well defined

Alliance for Regenerative Medicine Reimbursement Portfolio www.alliancerm.org

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US Regulation Points •  September 2010 bill introduced:

q  “To provide for a Federal initiative to support regenerative medicine through increased funding for research and commercial development of regenerative medicine products and development of a regulatory environment that enables rapid approval of safe and effective products”

Ø  Bill Rejected Ø  Similar Bill Introduced again in April 2014

•  May 2014 under review by a subcommittee

US Reimbursement •  Must be FDA approved (assume this

challenge is overcome) •  Public Health Plans

q  Medicare Ø  65+ years of age

q  Medicaid Ø  Low income or disabilities

•  Private Insurance q  Blue Cross Blue Shield, Aetna, Cigna, etc.

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Reimbursement Challenges •  Clinical effectiveness and efficacy

q  US payers require clinical evidence that equals or exceeds that which is necessary for FDA approval

•  Cost effectiveness studies q  US payers want comparative studies to currently

approved standard care therapies representing all beneficial populations

•  Lack of sufficient CPT codes

CPT Codes •  Category I, II, and III

q  Category I: identify procedures and services q  Category II: identify health outcomes and quality patient

care q  Category III: tracking codes for new and emerging

technologies

•  Are current codes and payments adequate for the work and cost of RM?

•  Or is regenerative medicine conducted in the hospital and part of the combined hospital payment (DRG in the United States)

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Lessons from Organogenesis •  Tissue Engineering Company

q  Apligraf: bio-engineer cell based product Ø  Used for wound healing Ø  FDA approval in 1998

q  Filed for Chapter 11 bankruptcy in September 2002

Ø  Many issues but some claim reimbursement approval process was a leading factor

•  Lacked correct and sufficient CTP codes to cover the cost of manufacturing1

Ø  Target population was not realistically defined q  Company revamped and is now out of

bankruptcy and profitable

Cost-effectiveness analysis of early vs. late autologous stem cell transplantation (ASCT)

in multiple myeloma •  Background: Hematopoietic stem cell transplants are used

to treat multiple myeloma. Treatment costs total millions of US dollars per year for US payers.

•  Objective: Analyze the more cost-effective treatment for multiple myeloma: early (within 12 months of diagnosis) vs. delayed (after the first 12 months post diagnosis) ASCT

•  Results: q  Early ASCT cost $249,236 with a 2.06 QALY q  Delayed ASCT cost $262,610 with a 0.18 QALY

•  Conclusions: Early ASCT appears to be more cost effective

Pandya, C., et al., Cost-effectiveness analysis of early vs. late autologous stem cell transplantation in multiple myeloma. Clin Transplant, 2014.

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Prophylactic platelet transfusion in patients with blood malignancies: cost analysis of a

randomized trail •  Background: Prophylaxis with autologous hematopoietic

stem cell transplants led to lower rates of bleeding in patients with hematologic malignancies.

•  Objective: Assess the costs and consequences of alternative platelet transfusion treatments.

•  Results: No prophylaxis was more cost efficient than prophylaxis (∆$1760).

•  Conclusions: While no prophylaxis might be more cost efficient in different subgroups, additional studies are needed to value the benefit of lower bleeding rates.

Campbell, H.E., et al., Prophylactic platelet transfusions in patients with blood malignancies: cost analysis of a randomized trial. Transfusion, 2014.

Esophageal Cancer •  2013: 18,000 Americans were

predicted to be diagnosed with esophageal cancer q  12,000 with

Adenocarcinoma q  6,000 with Squamous Cell

Carcinoma •  Treatments

q  Surgery q  Radiation Therapy q  Chemotherapy q  Chemo-radiation Therapy q  Laser Therapy q  Electrocoagulation

http://www.cancer.gov/cancertopics/wyntk/esophagus/page2; www.cancer.gov

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Damaged Knee Cartilage •  Treatment Options

q  Non-surgical Ø  Physiotherapy Ø  Painkillers Ø  Supportive Devices Ø  Lifestyle Changes

q  Surgical Ø  Arthroscopic Lavage and

Debridement Ø  Marrow Stimulation Ø  Mosaicplasty Ø  Allograft Osteochondral

Transplantation Ø  Autologous Chondrocyte

Implantation

http://www.niams.nih.gov/Health_Info/Knee_Problems/knee_problems_ff.asp; http://www.nhs.uk/Conditions/Cartilage-damage/Pages/Treatment.aspx

Cost-Effectiveness of Minimally Invasive Versus Open Esophagectomy for

Esophageal Cancer •  Background: Esophagectomy for esophageal cancer can

result in high mortality rates 30-days post procedure. Minimally invasive esophagectomy (MIE) can yield improved outcomes, but is more expensive.

•  Objective: Compare the cost-effectiveness of MIE to open esophagectomy in esophageal cancer patients.

•  Results: MIE overall was less expensive (-$1641) and resulted in an increased of 0.022 QALYs as compared to open esophagectomy.

•  Conclusions: Even with the increased operative costs, MIE proved to be more cost-effective.

Lee, L., et al., Cost-effectiveness of minimally invasive versus open esophagectomy for esophageal cancer. Ann Surg Oncol, 2013. 20(12): p. 3732-9.

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Cost-Effectiveness Analysis of the Most Common Orthopaedic Surgery Procedures: Knee

Arthroscopy and Knee Anterior Cruciate Ligament Reconstruction

•  Background: Knee arthroscopy diagnosis is very common. Knee anterior cruciate ligament (ACL) surgery is the six most common surgery. A recent publication claimed ACL reconstruction has high cost-effectiveness in younger patients. The cost-effectiveness of knee arthroscopy was never investigated.

•  Objective: Investigate the cost-effectiveness of knee arthroscopy and ACL reconstruction in a patient population varying in age.

•  Results: For knee arthroscopy, cost per QALY was $5,783 and $10,326 for ACL reconstruction.

•  Conclusions: Both procedures are highly cost-effective in a wide age range of patients.

Lubowitz, J.H. and D. Appleby, Cost-effectiveness analysis of the most common orthopaedic surgery procedures: knee arthroscopy and knee anterior cruciate ligament reconstruction. Arthroscopy, 2011. 27(10): p. 1317-22.

How Outcomes Research will be used in US Reimbursement Decisions for RM

•  Methodologies from current surrogates of regenerative medicine will be modified towards specific applications such as knee cartilage replacement or esophageal cancer

•  Specific CE studies will be done of the use of RM in knee cartilage, esophageal cancer, or other therapeutic areas vs. current standards of care

•  This will lead to evidence to support the benefit in outcomes for patients at what cost to payers in the United States

•  These studies will hopefully provide a foundation to apply similar methods to CE analysis of RM in other countries

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Thank  you  and  Acknowledgments  

•  Amy  M.  Sainski,  PhD,  Pharmacotherapy  Outcomes  Research  Fellow  

•  Lindsey  M.  Smith,  PharmD  Candidate,  Pharmacy  Summer  Research  Program  Student  

•  Mimi  Egami  Tokyo  Women’s  Medical  University  •  Teruo  Okano,  PhD,  Tokyo  Women’s  Medical  University  •  David  Grainger,  PhD,  Chair  PharmaceuJcs  •  Margit  Janat-­‐Amsbury,  MD,  PhD,  Huntsman  

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