Impact of Allocation on Survival During Intermittent Chemotherapy Shortages: A Modeling Analysis

Authors:
Andrew Hantel Division of Population Sciences, and
Division of Inpatient Oncology, Dana-Farber Cancer Institute;

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Michael L. McManus Department of Anesthesiology, Boston Children’s Hospital;

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Martha Wadleigh Division of Hematologic Malignancies, Dana-Farber Cancer Institute; and

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Michael Cotugno Department of Pharmacy, Brigham and Women’s Hospital, Boston, Massachusetts.

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Gregory A. Abel Division of Population Sciences, and
Division of Hematologic Malignancies, Dana-Farber Cancer Institute; and

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Background: Intermittent shortages of chemotherapeutics used to treat curable malignancies are a worldwide problem that increases patient mortality. Although multiple strategies have been proposed for managing these shortages (eg, prioritizing patients by age, scarce treatment efficacy per volume, alternative treatment efficacy difference), critical clinical dilemmas arise when selecting a management strategy and understanding its impact. Patients and Methods: We developed a model to compare the impact of different allocation strategies on overall survival during intermittent chemotherapy shortages and tested it using vincristine, which was recently scarce for 9 months in the United States. Demographic and treatment data were abstracted from 1,689 previously treated patients in our tertiary-care system; alternatives were abstracted from NCCN Clinical Practice Guidelines in Oncology for each disease and survival probabilities from the studies cited therein. Modeled survival was validated using SEER data. Nine-month shortages were modeled for all possible supply levels. Pairwise differences in 3-year survival and risk reductions were calculated for each strategy compared with standard practice (first-come, first-served) for each 50-mg supply increment, as were supply thresholds above which each strategy maintained survival similar to scenarios without shortages. Results: A strategy prioritizing by higher vincristine efficacy per volume and greater alternative treatment efficacy difference performed best, improving survival significantly (P<.01) across 86.5% of possible shortages (relative risk reduction, 8.3%; 99% CI, 8.0–8.5) compared with standard practice. This strategy also maintained survival rates similar to a model without shortages until supply fell below 72.2% of the amount required to treat all patients, compared with 94.3% for standard practice. Conclusions: During modeled vincristine shortages, prioritizing patients by higher efficacy per volume and alternative treatment efficacy difference significantly improved survival over standard practice. This approach can help optimize allocation as intermittent chemotherapy shortages continue to arise.

Submitted January 14, 2021; final revision received April 19, 2021; accepted for publication April 20, 2021.

Author contributions: Study design: Hantel, McManus, Abel. Data acquisition: Hantel, Cotugno. Data analysis: Hantel, Cotugno, Abel. Data interpretation: Hantel, McManus, Wadleigh, Abel. Drafting of manuscript: Hantel. Revision of manuscript: McManus, Wadleigh, Cotugno, Abel.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this article was supported by the NCI of the NIH under award number T32 CA092203. Work for this study was also supported by the Dana-Farber Cancer Institute.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Gregory A. Abel, MD, MPH, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215. Email: gregory_abel@dfci.harvard.edu

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  • 1.

    Sruamsiri R, Ferrario A, Ross-Degnan D, et al. What are the volume and budget needs to provide chemotherapy to all children with acute lymphoblastic leukaemia in Thailand? Development and application of an estimation tool. BMJ Open 2020;10:e041901.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Martei YM, Chiyapo S, Grover S, et al. Availability of WHO essential medicines for cancer treatment in Botswana [published online January 23, 2018]. J Glob Oncol, doi: 10.1200/JGO.17.00063

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Faruqui N, Martiniuk A, Sharma A, et al. Evaluating access to essential medicines for treating childhood cancers: a medicines availability, price and affordability study in New Delhi, India. BMJ Glob Health 2019;4:e001379.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Hantel A, Siegler M, Hlubocky F, et al. Prevalence and severity of rationing during drug shortages: a national survey of health system pharmacists. JAMA Intern Med 2019;179:710711.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    American Society of Health-System Pharmacists. Drug shortages statistics. Accessed April 29, 2021. Available at: https://www.ashp.org/drug-shortages/shortage-resources/drug-shortages-statistics

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Miranda-Filho A, Piñeros M, Ferlay J, et al. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol 2018;5:e1424.

  • 7.

    U.S. Food & Drug Administration. Drug shortages: root causes and potential solutions. Accessed April 29, 2021. Available at: https://www.fda.gov/drugs/drug-shortages/report-drug-shortages-root-causes-and-potential-solutions

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Barr R, Robertson J. Access to cytotoxic medicines by children with cancer: a focus on low and middle income countries. Pediatr Blood Cancer 2016;63:287291.

  • 9.

    Becker DJ, Talwar S, Levy BP, et al. Impact of oncology drug shortages on patient therapy: unplanned treatment changes. J Oncol Pract 2013;9:e122128.

  • 10.

    Vail E, Gershengorn HB, Hua M, et al. Association between US norepinephrine shortage and mortality among patients with septic shock. JAMA 2017;317:14331442.

  • 11.

    Patel S, Liedtke M, Ngo D, et al. A single-center experience of the nationwide daunorubicin shortage: substitution with doxorubicin in adult acute lymphoblastic leukemia. Leuk Lymphoma 2013;54:22312235.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Metzger ML, Billett A, Link MP. The impact of drug shortages on children with cancer—the example of mechlorethamine. N Engl J Med 2012;367:24612463.

  • 13.

    Gupta S, Wang C, Raetz EA, et al. Impact of asparaginase discontinuation on outcome in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group. J Clin Oncol 2020;38:18971905.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Cohen P, Friedrich P, Lam C, et al. Global access to essential medicines for childhood cancer: a cross-sectional survey. J Glob Oncol 2018;4:111.

  • 15.

    Gogineni K, Shuman KL, Emanuel EJ. Survey of oncologists about shortages of cancer drugs. N Engl J Med 2013;369:24632464.

  • 16.

    Kehl KL, Gray SW, Kim B, et al. Oncologists’ experiences with drug shortages. J Oncol Pract 2015;11:e154162.

  • 17.

    Hantel A, Hlubocky FJ, Siegler M, et al. A qualitative analysis of oncology patient awareness of medication shortages and their preferences for how shortages should be managed. JCO Oncol Pract 2020;16:e10981111.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Kaakeh R, Sweet BV, Reilly C, et al. Impact of drug shortages on U.S. health systems. Am J Health Syst Pharm 2011;68:18111819.

  • 19.

    Unguru Y, Fernandez CV, Bernhardt B, et al. An ethical framework for allocating scarce life-saving chemotherapy and supportive care drugs for childhood cancer. J Natl Cancer Inst 2016;108:djv392.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Hantel A. A protocol and ethical framework for the distribution of rationed chemotherapy. J Clin Ethics 2014;25:102115.

  • 21.

    Decamp M, Joffe S, Fernandez CV, et al. Chemotherapy drug shortages in pediatric oncology: a consensus statement. Pediatrics 2014;133:e716724.

  • 22.

    Persad G, Wertheimer A, Emanuel EJ. Principles for allocation of scarce medical interventions. Lancet 2009;373:423431.

  • 23.

    Rosoff PM. Unpredictable drug shortages: an ethical framework for short-term rationing in hospitals. Am J Bioeth 2012;12:19.

  • 24.

    Salazar EG, Bernhardt MB, Li Y, et al. The impact of chemotherapy shortages on COG and local clinical trials: a report from the Children’s Oncology Group. Pediatr Blood Cancer 2015;62:940944.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Caruso C. Oncology drug shortages persist. Cancer Discov 2020;10:6.

  • 26.

    Toro-Díaz H, Mayorga ME, Barritt AS, et al. Predicting liver transplant capacity using discrete event simulation. Med Decis Making 2015;35:784796.

  • 27.

    Shechter SM, Bryce CL, Alagoz O, et al. A clinically based discrete-event simulation of end-stage liver disease and the organ allocation process. Med Decis Making 2005;25:199209.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Zhu Z, Hen BH, Teow KL. Estimating ICU bed capacity using discrete event simulation. Int J Health Care Qual Assur 2012;25:134144.

  • 29.

    Troy PM, Rosenberg L. Using simulation to determine the need for ICU beds for surgery patients. Surgery 2009;146:608617.

  • 30.

    McManus ML, Long MC, Cooper A, et al. Queuing theory accurately models the need for critical care resources. Anesthesiology 2004;100:12711276.

  • 31.

    Bonabeau E. Agent-based modeling: methods and techniques for simulating human systems. Proc Natl Acad Sci USA 2002;99(Suppl 3):72807287.

  • 32.

    Zhang X. Application of discrete event simulation in health care: a systematic review. BMC Health Serv Res 2018;18:687.

  • 33.

    Yancy CW, Fonarow GC. United Network for Organ Sharing 2018 heart transplant reallocation policy: aiming for evidence-based policy. JAMA Cardiol 2021;6:168.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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