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Cost-Savings Using Patients’ Own Medication Supply of Letermovir for Allogeneic Hematopoietic Stem-Cell Transplant Recipients During Hospitalization

Web Exclusives - Original Research
Harrison S. Yoon, PharmD; Mallory Crain, PharmD, BCOP; Marissa Olson, PharmD, BCOP; Anupam Pande, MD, MPH; Jeff O. Klaus, PharmD, BCPS
Dr Yoon is Health Outcomes Research Fellow, St. Louis College of Pharmacy, Center for Outcomes Research and Education; Dr Crain and Dr Olson are Clinical Pharmacy Specialists, Hematologic Malignancies/Hematopoietic Cell Transplantation, Barnes-Jewish Hospital; Dr Pande is Assistant Professor, Division of Infectious Diseases and Hospital Medicine, Washington University School of Medicine; Dr Klaus is Clinical Pharmacy Specialist, Hematologic Malignancies/Hematopoietic Cell Transplantation, Barnes-Jewish Hospital, all at St. Louis, MO.
Abstract

OBJECTIVE: To evaluate the cost-effectiveness of de novo simvastatin plus standard therapy versus standard therapy alone in patients with sepsis during a 1-year period.

METHODS: A total of 145 critically ill patients were recruited in an open-label, randomized, controlled clinical trial. Of these, 80 patients received standard therapy according to Surviving Sepsis Campaign Guidelines 2012, and 65 received oral simvastatin plus standard therapy. The outcomes assessed include survival at the end of 1-year follow-up and intensive care unit (ICU) length of stay. Per protocol analysis was used.

RESULTS: The ICU length of stay was significantly decreased in the simvastatin group (P = .001). At 1 year, 46% of patients in the simvastatin group survived compared with 35% in the standard therapy group, although this was not significant (P = .173). However, a Kaplan-Meier curve showed a significant difference that favored the standard arm (P = .01). Simvastatin was the dominant treatment option based on lower total direct costs versus the standard group. Savings related to ICU length of stay was the main determinant of the cost-saving results of simvastatin. Incremental cost-effectiveness ratio was negative and thus was not calculated. Probabilistic sensitivity and one-way sensitivity analyses were done, and results were robust to change.

CONCLUSION: de novo simvastatin as an adjunct to standard therapy in ICU patients with sepsis lowered the overall cost by shortening ICU length of stay and its associated costs, but generalization to patients with different magnitudes of sepsis severity and to different ethnic groups requires further investigation.

Key Words: adjunctive simvastatin, ICU costs, ICU length of stay, sepsis, statins

Am Health Drug Benefits.
2022;15(4):118-126

Manuscript received August 3, 2020
Accepted in final form January 19, 2021

Disclosures are at end of text

Hematopoietic stem-cell transplants (HSCTs) are highly specialized procedures that require resource-intensive care and lengthy hospital admissions. The estimated total healthcare cost for patients undergoing an allogeneic HSCT in the United States is between $253,467 and $289,283 based on cost estimates from 2017.1 In addition to high healthcare costs, the number of HSCTs in the United States has increased in recent years, with more than 23,000 procedures reported in 2019,2 approximately 9400 of which were allogeneic HSCTs.3 In addition to the increasing cost and number of HSCT procedures, inpatient drug spending has drastically increased in recent years, making up a considerable portion of the total hospital costs and far outpacing payer reimbursement and prescription price inflation rates.4

Using a patient’s own medication supply involves inpatient administration of an oral medication that was procured by the patient at an outpatient pharmacy. According to a review of the available literature (mostly from Canada and the United Kingdom), in addition to reducing hospital costs, the use of patients’ own medication supply allows for the continuation of familiar medications after a hospital discharge and for better medication adherence by patients.5

Many hospitals allow the use of patients’ own medication supply today, but only a few studies describe its use and impact in the United States.5-7 In a 2002 US survey, Norstrom and Brown found that 91% of small hospitals in the United States allowed the use of patients’ own medication during hospitalization.6 And in 2022, Li and colleagues published a study in this journal, analyzing the use of patients’ own oral antineoplastic medication during hospitalization at their TriStar Centennial Medical Center in Nashville, TN, suggesting that such a strategy increases the safety of hazardous agents use.7

In other countries, the use of a patient’s own medication supply is more common and better described than in the United States.8-12 However, differences in hospital procedures and pharmacy operations in these studies from other countries8-12 can lead to difficulties in the application of this strategy and its interpretability in hospitals in the United States.

Letermovir is an antiviral medication indicated for the prophylaxis of cytomegalovirus (CMV) infection and disease in CMV-seropositive adults who have undergone allogeneic HSCT. According to letermovir’s prescribing information and publications related to allogeneic HSCT, letermovir prophylaxis after an allogeneic HSCT should start between day 0 and day 28 after the transplant and should continue daily through day 100.13-15

CMV seroprevalence increases with age; in the United States, the seroprevalence of CMV is approximately 60% in individuals older than 6 years and >80% in patients older than 60 years.16 Therefore, most adults undergoing allogeneic HSCT will be candidates for letermovir prophylaxis. Furthermore, letermovir prophylaxis after allogeneic HSCT reduces mortality, and, as such, the use of letermovir after allogeneic HSCT should be a goal for all CMV-seropositive recipients of allogeneic HSCT.14,16

The long duration of letermovir’s administration and its high per-tablet cost led to letermovir being a significant contributor to direct hospital costs associated with allogeneic HSCTs. The goal of this study was to evaluate the direct cost-savings to the hospital of using a patient’s own medication supply of oral letermovir at a large academic medical center.

Methods

This retrospective cohort study was conducted using electronic health record (EHR) data from patients admitted to the oncology units at Barnes-Jewish Hospital in St. Louis, a large tertiary academic medical center. The Institutional Review Board at Washington University in St. Louis and the University of Health Sciences and Pharmacy in St. Louis approved this study and waived consent for it.

To be eligible for inclusion in the study, patients had to be 18 years old or older and to have received at least 1 dose of letermovir during their index transplant admission or during readmission to the oncology department after having an allogeneic HSCT between June 1, 2018, and August 20, 2019. Patients who were readmitted after undergoing an allogeneic HSCT were included in a subgroup analysis. Because of the high number of post–allogeneic HSCT readmissions, only the first readmission to the oncology department after the allogeneic HSCT was included.

The patients’ clinical characteristics were identified through a data query of the EHR data during the index transplant admission and a manual chart review. Patients’ demographic variables (ie, age, race, and insurance status), in addition to the dosage, route of administration, and total number of doses of letermovir, were identified through a manual chart review of the patients’ notes and pharmacy administration records. Data were collected regarding CMV serostatus, cancer type, transplant donor source, and donor–recipient matching.

The process of using oral letermovir from the patient’s own medication supply during hospital admission was incorporated by our institution as part of the pretransplant care completed by the outpatient clinic team.

The procedures for procuring a patient’s own medication supply of oral letermovir for those who qualified for CMV prophylaxis were incorporated into the outpatient clinic team’s workflow. Before hospital admission for allogeneic HSCT, the outpatient clinic nurse coordinator generated a prescription for letermovir at the same time that the nurse made other routine allogeneic HSCT admission arrangements. The clinic’s physician or nurse practitioner then signed the prescription before submitting it to the patient’s preferred pharmacy for insurance consideration.

Most patients were directed by the outpatient nurse coordinator to pick up the letermovir prescription at the institution’s outpatient pharmacy, but they could request that their prescription be sent to another pharmacy of their choice. Patients were instructed to bring the medication with them when presenting for their allogeneic HSCT admission.

If prior authorization was needed for insurance approval, or if the patient required financial assistance to obtain the prescription, medical assistants in the outpatient clinic were available to facilitate this. If a patient’s own medication supply of letermovir was not obtained before hospitalization, the inpatient nurse coordinator contacted the outpatient nurse coordinator and/or medical assistants to identify what steps were needed to complete the patient’s own medication procurement process.

Once the patient’s own medication supply was brought to the hospital, the nursing staff notified the inpatient pharmacy. The inpatient pharmacy retrieved and reviewed the medication for appropriateness under the institutional patient’s own medication policy (eg, the medication was in the originally dispensed packaging from the outpatient pharmacy and was identifiable as letermovir), and was then returned to the nursing staff for secure storage.

After an appropriate inpatient order was placed by the provider, the nursing staff administered letermovir to the patient using his or her own medication supply, and the remaining patient’s own medication supply was returned to the patient at the time of discharge.

If the patient’s own medication supply was not obtained by day 10 after having an allogeneic HSCT, the hospital’s supply of letermovir was initiated and was then transitioned to the patient’s own medication supply, once it became available. Intravenous (IV) letermovir was always supplied by the hospital (ie, the patient’s own medication supply was never used) and was only used when the patient was unable to tolerate oral medications (eg, having severe mucositis) or if there were concerns related to poor oral drug absorption, and thus did not factor into the cost calculations.

The cost per dose of oral letermovir 480 mg was determined to be $225.73, based on the International Business Medicine Micromedex Redbook’s wholesale acquisition cost (WAC).17 Because our primary focus was direct cost-savings to the hospital, patients who used the hospital’s supply of oral letermovir 480 mg were calculated to incur a WAC of $225.73 per dose of letermovir that was received during their admission, whereas the use of the patient’s own medication supply of oral letermovir 480 mg incurred no direct cost to the hospital.

The total cost-savings were calculated by multiplying the total number of a patient’s own medication doses by the WAC during the study period, and the estimated annual cost-savings were calculated by dividing the total cost-savings by the number of months in the study, then multiplying this amount by 12 months. The mean cost-savings per admission was calculated by dividing the total savings by the number of HSCT-related admissions during the study period.

This method of assessing the cost-savings was influenced by cost-minimization analysis techniques described by Rascati in Essentials of Pharmacoeconomics and by Drummond and colleagues in Methods for the Economic Evaluation of Health Care Programmes.18,19 This type of analysis involves comparing the costs of 2 interventions when the outcomes are presumed to be equivalent in both groups.

Per our institutional guidelines, all patients, regardless of whether they received letermovir via the hospital’s supply or the patient’s own medication supply, began prophylaxis at day 10 after undergoing allogeneic HSCT if they were CMV-seropositive or if they were seronegative and had a seropositive haploidentical donor. Patients who did not meet the institutional guidelines could receive letermovir at their physician’s discretion (eg, CMV-seronegative recipients and a seropositive donor source other than haploidentical). Because the treatment received was identical in both groups, this method was determined to be appropriate to assess the cost-savings from the hospital’s perspective.

Descriptive statistics were used to characterize the patient population. The continuous variables are presented as median and interquartile range (IQR), or as mean and standard deviation where appropriate, and the categorical variables are presented as the number of patients and the percentage of the population. All statistical analyses were performed using R Version 4.0.2 (R Core Team, R Foundation for Statistical Computing; Vienna, Austria).

Results

A total of 142 patients met the inclusion criteria. Of those patients, 94 (66.2%) were in the allogeneic HSCT initial (index) admission cohort and 48 (33.8%) were in the post–allogeneic HSCT readmission cohort. In the initial admission cohort, the median age was 62 years (IQR, 54.5-67.5), 54 (57.4%) patients were male, and 79 (84%) patients were white (Table 1).

Table 1

The most common malignancies in the initial admission cohort were acute myeloid leukemia (N = 51; 54.3%), myelodysplastic syndrome (N = 20; 21.3%), and acute lymphocytic leukemia (N = 11; 11.7%). The majority (N = 67; 71.3%) of the allogeneic HSCT recipients were CMV-seropositive, although 27 (28.7%) of them were seronegative with seropositive donors.

A total of 33 (35.1%) patients had a matched unrelated donor, 28 (29.8%) had a haploidentical donor, 21 (22.3%) had a matched related donor, and 11 (11.7%) had a mismatched, unrelated donor; 1 patient received an umbilical cord blood transplant.

In the initial admission cohort, the median length of hospital stay was 27 days (IQR, 11.2-30.8), whereas the readmission cohort had considerably shorter hospital stays, at a median of 5.2 days (IQR, 3.1-11; Table 2). In all, 85 of the 94 (90.4%) patients in the initial admission cohort used their own supply of letermovir for 1001 of the 1100 (91%) oral letermovir doses administered, whereas 28 of the 48 (58.3%) patients in the readmission cohort used their own medication supply, for 194 of the total of 312 (62.2%) doses administered. Overall, 18 of the 94 (19.1%) patients in the initial admission cohort received a total of 152 doses of IV letermovir, and 5 of the 48 (10.4%) patients in the readmission cohort received 76 doses of IV letermovir on readmission.

Table 2

The cost-savings for each admission, for the total study duration, and the estimated annual savings resulting from the use of the patients’ own medication supply of oral letermovir are shown in Table 3. Although oral letermovir is available in 240-mg and 480-mg tablets, all patients in the study received 480-mg tablets; thus, the costs were calculated using the 480-mg tablets price. The mean cost-savings per initial admission was $2403.78, with a total savings of $225,955.73 for the initial admission cohort. An additional mean savings of $912.33 per patient and a total savings of $43,791.62 was calculated for the readmission cohort, yielding a combined cost-savings of $269,747.35 across the 14.6-month study period for all study participants (Table 3).

Table 3

Using a patient’s own medication supply of letermovir led to an estimated annual cost-savings of $185,717.04 and $35,993.11 in the initial admission cohort and the readmission cohort, respectively, yielding an estimated combined annual savings of $221,710.15 (Table 3).

Discussion

Our institution has been using a preferred patient’s own medication strategy for letermovir prophylaxis. This allowed us to initiate CMV prophylaxis with letermovir early after transplant in the inpatient setting, which minimizes the patient’s risk for CMV reactivation, while also minimizing the direct medical costs to the institution. Over the 14.6-month study period, 1195 of the 1412 (84.6%) doses of oral letermovir used came from the patient’s own medication supply, which resulted in an estimated annual cost-savings of more than $221,000 (Table 3).

In all, 91% of the inpatient oral doses of letermovir during the transplant admission were from the patient’s own medication supply, demonstrating that incorporating the procurement of a patient’s own medication supply into the outpatient clinic team’s workflow and engaging the inpatient healthcare team, as needed, successfully reduces the use of hospital-supplied letermovir.

In the readmission cohort, fewer, although still a majority (62%), of oral letermovir doses were from the patients’ own medication supplies; the increased use of hospital-supplied letermovir is reflective of the reliance on patients or their caregivers to bring the existing patient’s own medication supply to the hospital when the patient is readmitted.

One alternative to a patient’s own medication preferred approach would be to use only hospital-supplied letermovir, which would lead to higher direct hospital costs. Another alternative would be to delay the initiation of letermovir until the patient is discharged from the hospital, which would avoid incurring direct hospital costs but may increase the patient’s risk for CMV reactivation. Although the median time to CMV reactivation without prophylaxis is between 24 days and 47 days after an allogeneic HSCT, reactivation can occur earlier in a sizable percentage of patients, providing a rationale for the early provision of letermovir after allogeneic HSCT.20-24

CMV reactivation carries the potential for subsequent CMV disease, increased costs and adverse events from anti-CMV therapies (eg, myelosuppression from treatment with ganciclovir or valganciclovir, or nephrotoxicity from treatment with foscarnet), and increased costs associated with an increased length of hospital stay and/or readmissions because of CMV reactivation.25,26

Limitations

The limitations to this study include its single-center nature. The cost-savings seen in this study of using a similar patient’s own medication as a preferred approach are likely to vary at other institutions, based on the volume of allogeneic HSCTs performed and the institution’s ability to coordinate the procurement of a patient’s own medication supply before an admission for an allogeneic HSCT.

Furthermore, we limited our chart review in the readmission cohort to the first readmission after the admission for transplant. By not including subsequent readmissions during the study, it is likely that we have underestimated the cost-savings achieved with the patients’ own medication preferred strategy.

In addition, we did not account for the indirect costs incurred through a patient’s own medication strategy. Nevertheless, we believe that the indirect costs are likely negligible, because procuring an outpatient prescription would ultimately be required, whether a patient’s own medication supply of letermovir was started during the transplant admission or when the patient is being discharged.

Finally, steps were also taken by the inpatient pharmacy to verify and approve a patient’s own medication supply for inpatient use; however, we believe that these additional pharmacy personnel costs were minimal and were offset by not needing to dispense and deliver hospital-supplied letermovir.

Conclusion

Our findings showed that the use of a patient’s own medication letermovir prophylaxis strategy was effective in reducing the use of hospital-supplied letermovir. For institutions that currently exclusively use hospital-supplied letermovir, the use of a patient’s own medication as a preferred strategy may reduce hospital costs. For institutions that currently delay letermovir treatment initiation after an allogeneic HSCT, this may be an attractive alternative to reduce the patient’s risk for CMV reactivation early after a transplant and to reduce the resultant CMV reactivation–associated costs for the institution.

Author Disclosure Statement
Dr Klaus is on the Speaker’s Bureau of Merck, Jazz Pharmaceuticals, and Astellas Pharma; Dr Yoon, Dr Crain, Dr Olson, and Dr Pande have no conflicts of interest to report.

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