2025 年 11 巻 1 号 p. 12-18
Introduction: In some cases, anticancer drugs are wasted for various reasons after preparation, resulting in an economic burden. Therefore, the pharmacists in the study verified laboratory test values before dispensing the drug and determined the financial effect of reusing the wasted drug for other patients.
Methods: This study collected data from our electronic medical records of 46 of 17,042 cases prescribed with intravenous chemotherapy drugs between March 2021 and February 2023. The number, rate, and costs of wasted drugs were investigated between groups A (n = 18) and B (n = 28) for the year before and after the pharmacists' intervention.
Results: The wasted drug rate after preparation was 0.21% in group A and 0.33% in group B, with no significant difference between the two groups (p = 0.184). In group B, wasted drugs due to pharmacist-checked items were significantly lower (p < 0.001).
There was no significant difference in the cost of wasted drugs between the two groups (p = 0.628). However, the final wasted drug cost, excluding those avoided by using reused drugs, was lower in group B (p = 0.067).
Conclusions: If pharmacists verify laboratory test values and reuse drugs after discontinuation, it may decrease economic losses and ensure safe administration by reducing waste due to medical worker factors.
The increased number of patients due to the aging population, medical technology advances, and the introduction of new drugs could increase Japan's national healthcare expenditure in FY2021 to 45.359 trillion yen, a 4.8% increase from 42.966 trillion yen in the previous fiscal year.1) Goto reported that recent chemotherapy costs range from 1 million yen to a maximum of ～2 million yen when combined with molecular-targeted therapy drugs and immune checkpoint inhibitors, even though the average annual income of the Japanese population is 4.43 million yen (monthly income of approximately 370,000 yen) in 2021.2)
However, waste of drugs, including expired and used vials, has become a major problem.3) Anticancer drugs may have to be wasted because of dosage changes or discontinuation after preparation, which is a hospital management problem.4) Yamada revealed that pharmacist's intervention using chemotherapy criteria significantly reduced the number and cost of wasted drugs.5) However, there is a lack of reports on the economics surrounding the waste of drugs.
When administering anticancer drugs, physicians in our hospital place an order to confirm implementation in the electronic medical records, and the pharmaceutical department prepares the drugs accordingly. However, in some cases, drugs are wasted after preparation because the patient's physical condition deteriorates or abnormal laboratory test values. Therefore, in March 2022, the pharmacists in this study began verifying laboratory values before preparation to avoid waste of drugs due to the detection of abnormal laboratory values after preparation. Depending on their stability after dissolution, wasted drugs were reused for other patients. This study investigated the changes in waste factors and the economic effects of reusing the wasted drug for other patients.
From electronic medical records data, we identified 17,024 cases prescribed with intravenous chemotherapy drugs prepared in the pharmacy department from March 2021 to February 2023. Of these, 46 prescriptions were discontinued after preparation.
We excluded cases that used only oral anticancer drugs because this study investigated the discontinuation of dispensing in a chemotherapy center. Pediatric cancer cases were also excluded because chemotherapy centers do not prescribe drugs for pediatric cancers.
In March 2022, the pharmacists in this study began verifying patients' blood data before adjustment. They confirmed with the attending physician whether a drug could be administered if it met the criteria established based on grade 3 of the Common Terminology Criteria for Adverse Events version 5.06) (Table 1). In January 2021, we began reusing drugs based on their characteristics despite being subjected to waste once.
Laboratory measures in the pharmacist's checklist
| Checklist | Baseline value | |
|---|---|---|
| AST: aspartate aminotransferase ALT: alanine aminotransferase † When Immune checkpoint inhibitor is used |
||
| neutrophil cell | ＜1000 | /mm3 |
| hemoglobin | ＜8.0 | /dL |
| platelet | ＜50000 | /mm3 |
| AST/ALT | ＞100 | IU/L |
| total bilirubin | ＞2.0 | mg/dL |
| creatinine kinase† | ＞500 | IU/L |
| blood sugar† | ＞300 | mg/dL |
Based on the time we confirmed the patients' blood data, we classified them into groups A (n = 18, from March 2021 to February 2022) and B (n = 28, from March 2022 to February 2023). We compared the evaluation items, including the patient's age, sex, reason for discontinuation, cost of discontinuation, reuse rate, cost of reused drugs, and cost of wasted drugs, between the two groups.
Statistical analysisStudent's t-test determined the average monthly number of discontinued drugs and the discontinuation rate. The Mann-Whitney U test compared the cost of wasted drugs and patient age. The Fisher's exact test analyzed discontinuation rates, gender, and discontinuation factors. All statistical analyses were performed using EZR software (Version 1.63).7) Statistical significance was set at a p-value of <0.05.
The drug discontinuation rates in groups A and B were 0.21% (18/8436) and 0.33% (28/8588), respectively, with no significant difference between the two groups (p = 0.184). The median age was 66.0 (range: 25-80) years and 64.0 (range: 37-86) years in groups A and B, respectively, with no significant difference between the two groups (p = 0.597). Additionally, there was no significant difference in the proportions of males and females between the two groups (p = 0.769). The numbers of wasted drugs (cytotoxic anticancer drugs, molecular target drugs, and immune checkpoint inhibitors) were 24/7/0 in group A and 27/7/7 in group B, respectively. The reused drugs were 2/0/0 in group A and 2/3/6 in group B, respectively, with a higher proportion of immune checkpoint inhibitors in group B (Table 2).
Baseline characteristics of the patients
| Variables | Group A (n＝18) | Group B (n＝28) | P-value | |
|---|---|---|---|---|
|
§) One regimen contains several different drugs †) Fisher's exact test ‡) Mann Whitney U test |
||||
| Drug discontinuation rate | 0.21% (18/8436) | 0.33% (28/8588) | 0.184†) | |
| Median age (range) | 66 (25–80) | 64 (37–86) | 0.597‡) | |
| Gender (male/female) | 8/10 | 14/14 | 0.769†) | |
| Variables | Group A§) | Group B§) | ||
| Wasted Drugs | Cytotoxic anticancer drugs | 24 | 27 | |
| Molecular target drugs | 7 | 7 | ||
| Immune checkpoint inhibitors | 0 | 7 | ||
| Recycled Drugs | Cytotoxic anticancer drugs | 2 | 2 | |
| Molecular targeted drugs | 0 | 3 | ||
| Immune checkpoint inhibitors | 0 | 6 | ||
The average numbers of discontinuations per month were 1.500 (standard deviation [SD] = 1.168) and 2.333 (SD = 1.557) in groups A and B, respectively, with no significant difference between the two groups (p = 0.152) (Fig. 1a). Additionally, a comparison of the average monthly discontinuation rates revealed no significant difference between groups A and B (0.211 [SD = 0.163] vs. 0.324 [SD = 0.212]) (p = 0.156) (Fig. 1b).
Number of wasted drugs after preparation and discontinuation rate (monthly average). (a) Number of wasted drugs and (b) discontinuation rate.
The costs of wasted drugs were 3,574,860 and 5,526,292 yen in groups A and B, respectively. The total costs of wasted drugs (cytotoxic anticancer drugs, molecular target drugs, and immune checkpoint inhibitors) were 883,143 / 2,691,717 / 0 yen in group A and 462,567 / 1,570,486 / 3,493,239 yen in group B, respectively (Fig. 2a). There was no significant difference in the cost of wasted drugs between the two groups (p = 0.628) (Fig. 2b).
Comparison of total costs of wasted drugs and median cost of wasted drugs. (a) Comparison of total costs of wasted drugs. (b) Comparison of the median cost of wasted drugs.
The reasons for discontinuation after preparation were categorized into medical worker and patient factors (Table 3). In group B, the number of medical worker factors in which pharmacists intervened was 0. However, the most prominent reasons provided by the medical workers in group B were inadequate laboratory test confirmation, inadequate diagnostic imaging verification, tumor markers, incorrect dosage, administration date, and oversight-related discontinuation or request for discontinuation from other departments. There was a significant difference in medical worker factors (P < 0.001), but not in patient factors, between groups A and B (p = 0.736).
Reasons for discontinuation after preparation
| Medical worker factors | Group A (n＝7) |
Group B (n＝9) |
P-value | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| CV: central venous †) Fisher's exact test |
|||||
| Insufficient confirmation of laboratory values (Pharmacist confirmation items) | 6 | 85.7% | 0 | 0.0% | ＜0.001†) |
| Lack of confirmation of test values other than those listed above | 0 | 0.0% | 3 | 33.3% | |
| Lack of confirmation of results of imaging, tumor markers, etc. | 0 | 0.0% | 3 | 33.3% | |
| Incorrect dosage and date of administration | 0 | 0.0% | 2 | 22.2% | |
| Discontinuation of the program is missed or request for discontinuation from other departments. | 0 | 0.0% | 1 | 11.1% | |
| Other | 1 | 14.3% | 0 | 0.0% | |
| Patient factors | Group A (n＝11) |
Group B (n＝19) |
|||
| Physical condition prior to administration | 3 | 27.3% | 6 | 31.6% | 0.736†) |
| Allergies and other health problems during administration | 3 | 27.3% | 8 | 42.1% | |
| Difficulty in securing peripheral vein, CV port trouble | 4 | 36.4% | 4 | 21.1% | |
| Patient convenience (e.g., refusal of treatment) | 1 | 9.0% | 1 | 5.3% | |
We reused the wasted drugs in other patients based on information regarding their stability after dissolution. Through reuse, we saved total costs of 551,229 yen and 3,586,007 yen in groups A and B, respectively (Fig. 3a). Only cytotoxic drugs were reused in group A, whereas molecularly targeted drugs and immune checkpoint inhibitors were reused more frequently in group B. The final cost of wasted drugs, excluding reused drugs, was not significantly different between the two groups but showed a decreasing trend in group B (p = 0.067) (Fig. 3b).
Comparison of the cost of reused and wasted drugs, excluding reused drugs. (a) Comparison of total costs of reused drugs. (b) Comparison of the median cost of wasted drugs excluding reused drugs.
Our study determined if pharmacists' proactive verification of patient data could reduce the number of drug discontinuations caused by medical worker effects. We also investigated whether using reused wasted drugs in other patients could help reduce the loss of drugs in medical facilities. The results revealed that the pharmacist's intervention significantly reduced the number of discontinuations due to inadequate confirmation of laboratory values and reduced wasted drugs' costs when reused. This study showed a trend toward greater discontinuation of immune checkpoint inhibitors in group B than in group A. Due to the recent expansion of indications for immune checkpoint inhibitors, the frequency of using immune checkpoint inhibitors has increased.8)
The number and rate of wasted drugs after preparation were not significantly different between groups A and B. This study was conducted with few patients; therefore, the difference was not statistically significant.
Ueki et al. revealed that the reasons for drug discards were changes or discontinuation after dispensing and damage or contamination due to dropping.3) Fukuda et al. demonstrated that some drugs were discontinued because of a lack of confirmation of patient examination, vital laboratory data, and patient reasons such as the physical condition of dispensing.4) This study categorized these factors into medical worker and patient factors. Additionally, the reasons for discontinuation were categorized as medical worker and patient factors; however, the reasons for discontinuation appeared similar to those reported in previous studies.3,4)
Decreasing the number of medical worker factors is necessary to reduce the number of wasted drugs. Yamada et al. revealed a decrease in wasted drugs by introducing an initiative wherein laboratory values were verified before administration, and physicians were asked about prescriptions that did not meet the standards of practice.5) Owing to the short observation period in the current study, there were no significant differences in the number of wasted drugs or discontinuation rates. However, active pharmacist intervention is important from a safety perspective to avoid administering drugs to patients inappropriately. In our hospital, medical worker factors included discontinuation due to myelosuppression and liver dysfunction. Therefore, we selected these data as items to be checked in advance by pharmacists. Our study revealed no discontinuations due to pharmacist's intervention checkpoints in group B. Although there was a significant decrease in group B, there was no significant difference in the discontinuation rates between the two groups. This status may be due to new findings in group B, such as abnormal laboratory values (e.g., cortisol levels) other than pharmacist checkpoints, insufficient diagnostic imaging and tumor marker results, dosage and administration date errors, oversight discontinuation, and requests for discontinuation from other departments. It is difficult to overcome these problems simply by increasing the number of items pharmacists check. In particular, establishing criteria for cortisol levels is challenging because of diurnal fluctuations and subjective symptoms. Similarly, developing criteria for tumor markers is challenging. Thus, it is impossible to completely prevent the discarding of test results by checking them, and collaboration between physicians and pharmacists is essential in the future.
Additionally, many discontinuation cases are due to patient factors, including physical discomfort during administration, allergies, difficulty securing the peripheral route, and CV port trouble. Therefore, predicting these factors is difficult. However, some patients complained of physical discomfort after consultation and reported adverse events immediately before infusion administration because they forgot to inform their physician during the consultation. Confirming all examination items and physical symptoms within the limited time available for consultation is considered extremely difficult with the increasing complexity of drug therapy. Typically, a pharmacist conducts an interview in the outpatient chemotherapy room after the physician's consultation; however, detecting any physical problems before administration may be possible if a pharmacist conducts an interview during consultation. Developing such a system should be investigated in the future.
In recent years, expensive drugs, such as molecular-targeted drugs and immune checkpoint inhibitors, have increased. The comparison of wasted drugs after preparation by drug type has shown a high proportion of immune checkpoint inhibitors. Therefore, we reused the wasted drugs after preparation for other patients to decrease the number of wasted drugs. The drugs to be reused were those for which stability could be assured, based on the information in the package insert and interview form. Many immune checkpoint inhibitors are fixed-dose drugs; thus, they can be reused in other patients by standardizing infusion dilution, which facilitates reuse. Therefore, the reuse rate of immune checkpoint inhibitors was higher in group B, where immune checkpoint inhibitors have been increasing in recent years, indicating that the number of wasted drugs tends to decrease with the reuse of drugs but with no significant differences.
A limitation of this study is that some of the differences were not statistically significant because of the short study duration (2 years) and the small sample size. Additionally, the study was conducted in an outpatient setting and excluded pediatric patients with cancer. Therefore, this study did not include all anticancer drugs administered during hospitalization or pediatric cancer-specific discontinuation factors. Further validation of these factors is warranted.
In conclusion, pharmacists should verify laboratory test values and reuse drugs after discontinuation, decreasing economic losses and ensuring safe administration by reducing waste due to medical worker factors.
Funding source: MARUZEN-YUSHODO Co., Ltd. This study received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.
Authors' contribution: SY, YK, and HS drafted the manuscript. YA, KW, SM, HS, and MS were involved in the study design and data interpretation. TM was the supervisor. All authors have read and approved the final version of the manuscript.
Ethics statement: The Ethics Committee of Toho University Omori Medical Center (M22287) approved the study protocol. Information about the study was disclosed on the institutional website, and the potential participants were allowed to opt-out.
Conflicts of interest: None declared.
