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

Abstract

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.

Which Drugs Should Be on the Essential Medicines List?

“…While current research is evaluating strategies to manage these drug shortages, 6 better, more enduring solutions are required to ensure that all patients have access to the medicines they need. In what follows, we examine differing policies and explore better ways to balance public health needs in times of uncertainty or crisis and to ensure an appropriate supply of critical medicines, as well as medicines with vulnerable supply chains, that are crucial to the everyday lives and well-being of patients.…”

Optimizing the doses of cancer drugs after usual dose finding

“…2 Postapproval dose optimization methodologies that illuminate a drug's true dose-response curve may be useful in the future to reduce the morbidity and mortality of drug scarcity, as well as individual and societal financial toxicity. [18][19][20] Most importantly, however, a more patient-centered approach to dosing is favored not only by patients but also by many oncologists. 21 Taken together, the motivation for postapproval dose optimization is clear but its priorities need defining.…”

Chemotherapeutic Shortages: How Do We Prioritize?

“…In this issue of JNCCN, Hantel et al 7 describe a hospital-level model constructed to compare effects of different chemotherapy allocation strategies on patient survival using vincristine as an example. Using an institutional database and survival probabilities from NCCN Guidelines, a model was constructed and validated to determine survival outcomes across varying levels of vincristine shortages, testing different prioritization strategies.…”

“…Using an institutional database and survival probabilities from NCCN Guidelines, a model was constructed and validated to determine survival outcomes across varying levels of vincristine shortages, testing different prioritization strategies. Hantel et al 7 found that an efficacy-per-volume prioritization strategy significantly improved projected survival. The model operates on the principle of maximizing survival and was successful in testing different allocation strategies and demonstrating that the choice of allocation strategy can impact patient survival based on real-world data.…”

“…Unpredictable and potentially devastating drug shortages will likely remain a problem in cancer care in the near future. Although paradigms such as the proposed vincristine model described by Hantel et al 7 are helpful in considering allocation schemas, we know that drug shortages are often sudden and unpredictable, leaving pharmacists and providers to make real-time allocation decisions without the benefit of an established model. In addition, the Hantel et al study is based on a projected 9-month shortage; another challenge with creating and interpreting these data is the uncertain duration of shortages, which may wax and wane.…”