Currently Viewing:
The American Journal of Managed Care August 2019
Late Diagnosis of Hepatitis C Virus Infection, 2014-2016: Continuing Missed Intervention Opportunities
Anne C. Moorman, MPH; Jian Xing, PhD; Loralee B. Rupp, MSE; Stuart C. Gordon, MD; Mei Lu, PhD; Philip R. Spradling, MD; Joseph A. Boscarino, PhD; Mark A. Schmidt, PhD; Yihe G. Daida, PhD; and Eyasu H. Teshale, MD; for the CHeCS Investigators
Current Evidence and Controversies: Advanced Practice Providers in Healthcare
Erin Sarzynski, MD, MS; and Henry Barry, MD, MS
From the Editorial Board: Elizabeth Mitchell
Elizabeth Mitchell
Passive Social Health Surveillance and Inpatient Readmissions
Nnadozie Emechebe, MPH; Pamme Lyons Taylor, MBA, MHCA; Oluyemisi Amoda, MHA, MPH; and Zachary Pruitt, PhD
The Adoption and Spread of Hospital Care Coordination Activities Under Value-Based Programs
Larry R. Hearld, PhD; Nathaniel Carroll, PhD; and Allyson Hall, PhD
Currently Reading
The Potential Impact of CAR T-Cell Treatment Delays on Society
Julia Thornton Snider, PhD; Michelle Brauer, BS; Rebecca Kee, BA; Katharine Batt, MD, MSc; Pinar Karaca-Mandic, PhD; Jie Zhang, PhD; and Dana P. Goldman, PhD
Access to Chiropractic Care and the Cost of Spine Conditions Among Older Adults
Matthew A. Davis, PhD, DC, MPH; Olga Yakusheva, PhD; Haiyin Liu, MA; Joshua Tootoo, MS; Marita G. Titler, PhD, RN; and Julie P.W. Bynum, MD, MPH
Tools to Improve Referrals From Primary Care to Specialty Care
Varsha G. Vimalananda, MD, MPH; Mark Meterko, PhD; Molly E. Waring, PhD; Shirley Qian, MS; Amanda Solch, MSW; Jolie B. Wormwood, PhD; and B. Graeme Fincke, MD
Influence of Out-of-Network Payment Standards on Insurer–Provider Bargaining: California’s Experience
Erin L. Duffy, PhD, MPH
Cost of Dementia in Medicare Managed Care: A Systematic Literature Review
Paul Fishman, PhD; Norma B. Coe, PhD; Lindsay White, PhD; Paul K. Crane, MD, MPH; Sungchul Park, PhD; Bailey Ingraham, MS; and Eric B. Larson, MD, MPH

The Potential Impact of CAR T-Cell Treatment Delays on Society

Julia Thornton Snider, PhD; Michelle Brauer, BS; Rebecca Kee, BA; Katharine Batt, MD, MSc; Pinar Karaca-Mandic, PhD; Jie Zhang, PhD; and Dana P. Goldman, PhD
Treatment delays limit the social value generated by chimeric antigen receptor (CAR) T-cell therapy for the treatment of pediatric acute lymphoblastic leukemia and diffuse large B-cell lymphoma.
Further, the development of formal policies to cover CAR T has been slow. Currently, reimbursement is frequently done on an individual basis,12 with hospitals facing high financial risk to treat patients with CAR T without a guarantee of payment from insurers.35 Although larger health plans are often better equipped than smaller regional plans to handle such requests, reviewing each case individually lengthens the authorization process.12 In some cases, waiting for CAR T reimbursement approval may take up to 90 days, which may be longer than a patient’s survival.11 Some payers, such as Medicare, have had success securing coverage of CAR T in the outpatient setting12; however, challenges remain to provide sufficient reimbursement to hospitals to administer the treatment in an inpatient setting. Even with the recent approval of the new technology add-on payment of up to $186,500 per patient,36 intended to mitigate the additional costs of treatment, the reimbursement promised may fall short of the additional costs. When faced with high financial risk in the event that the costs of treating patients with CAR T exceed this payment cap, hospitals face disincentives for CAR T adoption. Thus, such policies may limit access for patients.

Additionally, CAR T is produced through a complex and individualized process37 that may be challenging to scale quickly. Efforts are currently under way to minimize delays caused by inefficiencies in production.38-40 Timely administration also necessitates that treatment centers be equipped with the proper equipment and human capital. Educating community oncologists is especially important in maximizing the efficacy and safety of CAR T, as patients are usually referred to their local oncologists for follow-up care after receiving treatment at the specified transplant centers.41 Professional organizations, such as the American Society of Hematology and the Foundation for the Accreditation of Cellular Therapy, are in the process of developing guidelines on CAR T.41,42

Our social value analysis indicates that facilitating timely patient access is a key consideration in determining an optimal financing approach. For patients with rapidly progressing cancer and high mortality rates,13,28 delaying treatment comes at a high cost. The case of CAR T provides a lesson to payers, policy makers, and innovators for incentivizing innovation and providing access to other curative therapies. In particular, therapies providing large QALY gains, such as curative therapies, bring large social value to society. Allowing innovators to share in that value incentivizes the development of future cures. However, stakeholders must work together to facilitate prompt patient access to such therapies. Efficient payment mechanisms, sufficient technological capabilities, adequate capital and human capital, and payment policy reform are required to minimize treatment delays for patients. Others have also argued that the price of CAR T should be lowered.43 These considerations are particularly important given other new or curative therapies in the pipeline, such as voretigene neparvovec-rzyl for mutation-associated retinal dystrophy,44 SPK-9001 for hemophilia,45 and LentiGlobin BB305 for sickle cell disease and beta-thalassemia.46


Our study is based upon the overall experience of patients with pALL and DLBCL and does not account for heterogeneity in patient experiences. We excluded caregiver burden from this analysis, but a reduction could be expected using CAR T-cell therapies, as they may offer patients a possible remission with fewer treatments and adverse events. Additionally, our study examined the impact of treatment delays of various lengths in only the first cohort of patients. It is uncertain how treatment delays may change in the future. Because of a lack of clinical data, we were also unable to account in our analysis for potential reductions in CAR T efficacy due to treatment delays. To the extent that delayed treatment reduces CAR T efficacy, our estimates of the social value lost because of treatment delays are conservative.

Moreover, the total cost of treatment with CAR T is not yet clear20 and may change over time. The average total costs of tisagenlecleucel used in our analysis ($736,265; obtained from the ICER report10) included the average costs required by patients with pALL over the course of their treatment history (costs of CAR T, chemotherapy treatment, palliative chemotherapy, pretreatment, stem cell transplantation, adverse events, administration and monitoring, future healthcare, and end-of-life costs). This estimate substantially exceeded the average cost of treatment in the literature, which considered physician costs for leukapheresis and administration of lymphodepletion therapy, facilities, CAR T, drugs other than CAR T, facility fees for hospitalizations for cytokine release syndrome, and physician costs. These estimates ranged from $432,131 to $510,963 with the outcomes-based pricing arrangement.20

The average total cost of axicabtagene ciloleucel used in our analysis ($551,642) included costs accrued by patients over their treatment history (described above) and exceeded the $402,647 estimate reported by Hernandez et al in 2018.20


CAR T-cell therapies have the potential to provide significant benefit to patients with pALL and DLBCL and to society in the United States, particularly through gains in survival and productivity. However, the magnitude of benefit depends upon the ability of patients to access these treatments promptly.

Author Affiliations: Precision Health Economics (JTS, MB, RK, KB, DPG), Oakland, CA; Finance Department, Carlson School of Management, University of Minnesota (PK-M), Minneapolis, MN; Novartis Pharmaceuticals Corporation (JZ), East Hanover, NJ.

Source of Funding: Novartis.

Author Disclosures: Dr Thornton Snider is an employee of and holds equity in Precision Health Economics, which received payment from Novartis to conduct this research. Ms Brauer was employed by Precision Health Economics at the time that this research was conducted. Ms Kee is employed by Precision Health Economics. Dr Batt reports data interpretation for Novartis and consultancy for Precision Health Economics and has received honoraria from Novartis. Dr Karaca-Mandic provides consulting services to Precision Health Economics and received payment from Precision Health Economics for her involvement in the preparation of this manuscript. Dr Zhang is an employee of Novartis and owns Novartis stock. Dr Goldman served as a consultant to Precision Health Economics during the conduct of the study; owns equity (<1%) in Precision Health Economics’ parent company, Precision Medicine Group; has received payment from ACADIA Pharmaceuticals for service on a policy advisory board; was paid a fee for a lecture on cost-effectiveness at Amgen; and is the director of the Leonard D. Schaeffer Center for Health Policy & Economics, which is supported by gifts and grants from individuals, corporations, and associations; by government grants and contracts; and by private foundations (specific information about funding sources is available at

Authorship Information: Concept and design (JTS, PK-M, JZ, DPG); acquisition of data (JTS, MB, RK, JZ); analysis and interpretation of data (JTS, MB, RK, KB, PK-M, JZ, DPG); drafting of the manuscript (JTS, MB, RK, KB, PK-M, JZ); critical revision of the manuscript for important intellectual content (JTS, MB, RK, KB, PK-M, JZ, DPG); statistical analysis (JTS, MB, RK); obtaining funding (JTS, DPG); administrative, technical, or logistic support (MB, RK); and supervision (JTS, KB, DPG).

Address Correspondence to: Rebecca Kee, BA, Precision Health Economics, 1999 Harrison St, Ste 1420, Oakland, CA 94612. Email:

1. Cancer in children and adolescents. National Cancer Institute website. Updated October 8, 2018. Accessed October 12, 2018.

2. Pui CH, Evans WE. A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol. 2013;50(3):185-196. doi: 10.1053/j.seminhematol.2013.06.007.

3. Rovira J, Valera A, Colomo L, et al. Prognosis of patients with diffuse large B cell lymphoma not reaching complete response or relapsing after frontline chemotherapy or immunochemotherapy. Ann Hematol. 2015;94(5):803-812. doi: 10.1007/s00277-014-2271-1.

4. Fuster JL. Current approach to relapsed acute lymphoblastic leukemia in children. World J Hematol. 2014;3(3):49-70. doi: 10.5315/wjh.v3.i3.49.

5. Kymriah [prescribing information]. East Hanover, NJ: Novartis; 2018. Accessed June 6, 2018.

6. Yescarta [prescribing information]. Santa Monica, CA: Kite Pharma; 2017. Accessed June 6, 2018.

7. Levine BL, Maude S, Zheng Z, et al. Durable remissions with control of cytokine release syndrome (CRS) using T cells expressing CD19 targeted chimeric antigen receptor (CAR) CTL019 to treat relapsed/refractory (R/R) acute lymphoid leukemia (ALL). Cytotherapy. 2016;18(suppl 6):S14-S15. doi: 10.1016/j.jcyt.2016.03.039.

8. Lee DW III, Stetler-Stevenson M, Yuan CM, et al. Long-term outcomes following CD19 CAR T cell therapy for B-ALL are superior in patients receiving a fludarabine/cyclophosphamide preparative regimen and post-CAR hematopoietic stem cell transplantation. Blood. 2016;128(22):218.

9. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi: 10.1056/NEJMoa1707447.

10. Chimeric antigen receptor T-cell therapy for B-cell cancers: effectiveness and value: final evidence report. Institute for Clinical and Economic Review website. Published March 23, 2018. Accessed May 1, 2018.

11. Prevision Policy. CAR-T reimbursement: Medicare/Medicaid painted as biggest barriers at ICER forum; early launch difficulties? Washington, DC: Prevision Policy; March 12, 2018.

12. Andrews M. Staggering prices slow insurers’ coverage of CAR-T cancer therapy. Kaiser Health News website. Published July 17, 2018. Accessed September 4, 2018.

13. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study [erratum in Blood. 2018;131(5):587-588. doi: 10.1182/blood-2017-11-817775]. Blood. 2017;130(16):1800-1808. doi: 10.1182/blood-2017-03-769620.

14. Cortez M, Chen C, Rausch N. Months after approval, breakthrough cancer drug given to just five patients. Bloomberg website. Published December 14, 2017. Accessed January 8, 2018.

15. Weintraub A. Is Gilead’s new CAR-T overpriced or is payer bureaucracy to blame for slow pickup? FiercePharma website. Published December 15, 2017. Accessed June 5, 2018.

16. Weintraub A. Watch out, Gilead—Novartis got the FDA nod it needs to steal your CAR-T market. FiercePharma website. Published May 2, 2018. Accessed July 17, 2018.

17. Varian HR. Intermediate Microeconomics: A Modern Approach. 8th ed. New York, NY: W.W. Norton & Company; 2010.

18. Hirth RA, Chernew ME, Miller E, Fendrick AM, Weissert WG. Willingness to pay for a quality-adjusted life year: in search of a standard. Med Decis Making. 2000;20(3):332-342. doi: 10.1177/0272989X0002000310.

19. Mason H, Baker R, Donaldson C. Willingness to pay for a QALY: past, present and future. Expert Rev Pharmacoecon Outcomes Res. 2008;8(6):575-582. doi: 10.1586/14737167.8.6.575.

20. Hernandez I, Prasad V, Gellad WF. Total costs of chimeric antigen receptor T-cell immunotherapy. JAMA Oncol. 2018;4(7):994-996. doi: 10.1001/jamaoncol.2018.0977.

21. Labor force statistics from the current population survey. Bureau of Labor Statistics website. Published 2017. Accessed June 6, 2018.

22. Historical income tables: people. United States Census Bureau website. Published 2017. Accessed June 6, 2018.

23. Blackstone EA, Joseph PF. The economics of biosimilars. Am Health Drug Benefits. 2013;6(8):469-478.

24. Megerlin F, Lopert R, Taymor K, Trouvin JH. Biosimilars and the European experience: implications for the United States. Health Aff (Millwood). 2013;32(10):1803-1810. doi: 10.1377/hlthaff.2009.0196.

25. Grabowski H, Guha R, Salgado M. Biosimilar competition: lessons from Europe. Nat Rev Drug Discov. 2014;13(2):99-100. doi: 10.1038/nrd4210.

26. Ramsey S, Willke R, Briggs A, et al. Good research practices for cost-effectiveness analysis alongside clinical trials: the ISPOR RCT-CEA Task Force report. Value Health. 2005;8(5):521-533. doi: 10.1111/j.1524-4733.2005.00045.x.

27. Mulcahy AW, Predmore Z, Mattke S. The cost savings potential of biosimilar drugs in the United States. RAND Corporation website. Published 2014. Accessed June 6, 2018.

28. Jeha S, Gaynon PS, Razzouk BI, et al. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006;24(12):1917-1923. doi: 10.1200/JCO.2005.03.8554.

29. Ronson A, Tvito A, Rowe JM. Treatment of relapsed/refractory acute lymphoblastic leukemia in adults. Curr Oncol Rep. 2016;18(6):39. doi: 10.1007/s11912-016-0519-8.

30. Caffrey M. With approval of CAR T-cell therapy comes the next challenge: payer coverage. Am J Manag Care. 2018;24(spec no 2):SP35-SP36.

31. Weintraub A. How to cover Novartis’ $475K CAR-T drug Kymriah? a ‘new payment model’ is the only way, Express Scripts says. FiercePharma website. Published September 22, 2017. Accessed March 13, 2018.

32. Cunningham PJ, Kohn L. Health plan switching: choice or circumstance? Health Aff (Millwood). 2000;19(3):158-164. doi: 10.1377/hlthaff.19.3.158.

33. Basu A, Subedi P, Kamal-Bahl S. Financing a cure for diabetes in a multipayer environment. Value Health. 2016;19(6):861-868. doi: 10.1016/j.jval.2016.03.1859.

34. Basu A. Financing cures in the United States. Expert Rev Pharmacoecon Outcomes Res. 2015;15(1):1-4. doi: 10.1586/14737167.2015.990887.

35. Andrews M. Insurers and government are slow to cover expensive CAR-T cancer therapy. NPR website. Published July 17, 2018. Accessed August 8, 2018.

36. Inserro A. CMS approves extra payments for CAR T, increases other payments in final rule. The American Journal of Managed Care® website. Published August 3, 2018. Accessed September 12, 2018.

37. Wang X, Rivière I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics. 2016;3:16015. doi: 10.1038/mto.2016.15.

38. Palmer E. Gilead to build its EU CAR-T manufacturing facility at Amsterdam airport. FiercePharma website. Published May 15, 2018. Accessed July 17, 2018.

39. Palmer E. Novartis commits to CAR-T manufacturing in restructure of cell therapy work. FiercePharma website. Published August 31, 2016. Accessed July 17, 2018.

40. Pagliarulo N. Novartis partners with French CDMO to bolster CAR-T supply. BioPharmaDive website. Published July 12, 2018. Accessed July 17, 2018.

41. London S. Logistics of CAR T-cell therapy in real-world practice. The ASCO Post website. Published May 25, 2018. Accessed July 17, 2018.

42. Maus MV, Nikiforow S. The why, what, and how of the new FACT standards for immune effector cells. J Immunother Cancer. 2017;5:36. doi: 10.1186/s40425-017-0239-0.

43. Kleutghen P, Mitchell D, Kesselheim AS, Najafzadeh M, Sarpatwari A. Drugs don’t work if people can’t afford them: the high price of tisagenlecleucel. Health Affairs Blog website. Published February 8, 2018. Accessed March 7, 2019.

44. FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss [news release]. Silver Spring, MD: FDA; December 19, 2017. Accessed August 1, 2018.

45. Taylor NP. Spark hemophilia B gene therapy clears test en route to Pfizer-sponsored phase 3. FierceBiotech website. Published May 22, 2018. Accessed August 1, 2018.

46. Herper M. Bluebird bio gene therapies show promise against deadly anemias. Forbes website. Published June 15, 2018. Accessed August 1, 2018.
Copyright AJMC 2006-2020 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
Welcome the the new and improved, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up