Biological and Pharmaceutical Bulletin
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Medical Economic Benefit Derived from the Use of Tracing Reports by Pharmacy-Based Pharmacists for Pharmaceutical Intervention and Reduction of Leftover Medicines
Yuki Koshino Hiroaki TanakaTakakiyo TatsumichiYuuri HouchiJun NishimuraShinji Kosaka
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2022 Volume 45 Issue 10 Pages 1482-1488

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Abstract

This study aimed to evaluate the effects on the medical economy of the use of tracing reports by pharmacy-based pharmacists for pharmaceutical interventions, including to reduce leftover medicines. These effects were estimated by analyzing 267 tracing reports issued by pharmacy pharmacists over a period of 1 year, 2020–2021. We estimate that these interventions created cost savings of USD108170.02/year (USD104800 via pharmaceutical interventions, USD3370.02 via interventions to reduce leftover medicines). The cost savings from pharmaceutical interventions prompted by patient follow-up was estimated to be USD47650. The medical economic effect per tracing report was estimated to be USD392.51 from pharmaceutical interventions, USD12.62 from reducing leftover medicines, and USD445.33 from pharmaceutical intervention prompted by patient follow-up. Overall, therefore, pharmaceutical interventions by pharmacy pharmacists using tracing reports, including those designed to reduce leftover medicines, may benefit the medical economy.

INTRODUCTION

Tracing reports (TR) are documents used by many medical facilities and health insurance pharmacies in Japan. They are prepared by pharmacists for physicians, to communicate medication information that is not urgent but is important for efficacy and patient safety.1) TRs are therefore different from inquiries, which are urgent requests sent by pharmacists to physicians, asking them to confirm a prescription. Similar information-sharing systems have been reported in other countries, such as Open Zorg Informatie Systeem (OZIS, Open Care Information System), a medication history-sharing system used by hospitals and health insurance pharmacies in the Netherlands.2) The Statistics of Medical Care Activities in Public Health Insurance, 2020 stated that 77.3% of prescriptions were filled at out-of-hospital pharmacies.3) The sharing of information between hospital physicians and pharmacy-based pharmacists is therefore important for improving the safety and therapeutic effect of outpatient treatments. Information sharing between pharmacists based in pharmacies and hospitals using TRs has been reported to contribute to the consistency of drug therapy and improvements in safety.4) TRs among physicians, pharmacy pharmacists, and hospital pharmacists therefore play an important role in improving the safety of drug therapy and effectiveness of treatments. Studies that have analyzed cases of pharmaceutical intervention by pharmacists have reported that pharmaceutical intervention was most often used to avoid drug-related adverse events at both health insurance pharmacies and hospitals, and that pharmaceutical intervention by pharmacists helps to prevent adverse events.57) Hamblin et al. reported that the cost savings generated by continuous pharmaceutical intervention by pharmacists in a single 31-bed emergency medical care unit in the United States amounted to USD565664 annually through the prevention of adverse drug reactions and exacerbation of the condition.8) Pharmaceutical intervention by pharmacists is considered to be beneficial for improving patient safety, and for reducing medical costs by preventing adverse drug reactions and exacerbation of conditions. Pharmaceutical intervention associated with inquiries by pharmacy pharmacists has been reported to have an average medical cost saving of USD630 (using an exchange rate of USD1 = JPY100) per prevention/avoidance case in Japanese health insurance pharmacies.9) However, few studies have examined the effects on the medical economy of pharmaceutical interventions by pharmacists at health insurance pharmacies using TRs. In this study, therefore, we examined cases of pharmaceutical intervention initiated at our hospital by information and prescription proposals through TRs sent from pharmacy-based pharmacists. These were analyzed to evaluate their medical economic effects from avoiding adverse drug reactions. The Basic Policy on Economic and Fiscal Management and Reform 2017 also emphasized proactive intervention by pharmacy pharmacists for the reduction of leftover medicines.10) We therefore also evaluated their medical economic effects through reducing leftover medicines.

MATERIALS AND METHODS

Investigation Period

The investigation period was 1 year, from November 1, 2020, to October 31, 2021. We analyzed all 267 TRs received by fax in the pharmacy department of Kagawa University Hospital during that period. Overall, 23 pharmacies sent TRs. Of these, 6 were pharmacies near the hospital and 17 were other pharmacies. If there were two or more TRs about the same patient, each one was counted separately. TRs developed by the hospital are available on our website and can be used by all pharmacy pharmacists. However, pharmacies may also create and use their own format for TRs. We have therefore not standardized the format of the TRs included in the survey.

Patient Characteristics

Data on the patients’ age, sex, presence or absence of consent by them or their family to the issuing of TRs, and the department that treated them were evaluated. If the presence or absence of consent to TRs was not specified, consent was considered to have been absent.

Collection of Cases of Pharmaceutical Intervention

In this study, a pharmaceutical intervention was defined as a case when a pharmacy pharmacist used a TR to provide information or proposed a prescription that resulted in a physician changing a prescription or patient instructions. The contents of the prescription change or instruction as a result of pharmaceutical intervention were investigated by collecting information from the patients’ clinical records. These interventions were classified into seven categories drawing on a previous study.9) The categories were: 1) avoidance of serious adverse drug reactions or exacerbation of the condition; 2) intervention in cancer chemotherapy; 3) avoidance of drug interactions; 4) dose recommendations depending on renal function; 5) checking of medication history; 6) proposal of other drug therapies; and 7) reduction of leftover medicines. Interventions in the first six categories were tallied as “pharmaceutical interventions” and those in the seventh category as interventions to reduce leftover medicines. Interventions in the second to sixth categories were also classified into avoidance of adverse drug reactions and improvement in therapeutic effects. Improvement in therapeutic effects was defined as avoiding any disadvantage to the patient, such as not receiving the best possible drug therapy. The TRs prompted by patient follow-up were counted separately.11) Patient follow-up is action taken by the pharmacist to provide optimal drug therapy when patients visit the pharmacy and throughout the period of drug use. It includes monitoring the medication status, side effects, and living environment, and analyzing and evaluating them based on pharmacological knowledge.11) Patients were judged to have been followed-up by pharmacy pharmacists when the TRs clearly indicated that the symptoms or the state of medication of the patients were checked using information and communication technology (ICT) such as telephone, fax, or text message during the period from the day after the delivery of the drugs to the next visit. Prescription changes after a pharmaceutical intervention were categorized as additions of drugs, discontinuation of medication, changes of drugs, dose decreases, dose increases, changes in the regimen, changes in the administration method, changes in the dosage form, changes in the duration or frequency of administration, changes in the dispensation method, addition/change of medication instructions, or other. Interventions were collected and classified by a single pharmacist to reduce the possibility of information bias. The collected and classified data were also checked by the co-authors to ensure reliability.

Method for Estimating the Medical Economic Effect for Classification of Interventions

The medical economic effects were estimated by estimating the cost of the individual category of intervention using the methods described by Tasaka et al.5) In the fiscal year 2019, the Pharmaceuticals and Medical Devices Agency (PMDA) issued 1285 cases of Adverse Drug Reaction Health Damage Relief Benefits with a total cost reduction of USD24610900 (using an exchange rate of USD1 = JPY100).12) This figure gave an estimate of the medical economic effect of avoidance of serious adverse drug reactions or exacerbation of the condition of USD19200 (USD24610900 divided by 1285 cases = USD19152.45) per case. In this study, serious adverse drug reactions were defined as those mentioned as serious adverse drug reactions or cautions in the package inserts. Hamblin et al. reported that 2.6–5.21% of the cases of various pharmaceutical interventions, such as avoidance of drug interactions and dose recommendations according to renal function, led to the avoidance of serious adverse drug reactions or exacerbation of the condition.8) We used the method described by Tasaka et al. to estimate the economic effect of each intervention in each of the second to sixth categories of pharmaceutical interventions (intervention in cancer chemotherapy: USD19152.45 × 5.21% = USD997.84, approx. USD1000/case; intervention in high-risk drugs: USD19152.45 × 3.91% (the intermediate value between 2.6 and 5.21%) = USD748.86, approx. USD750/case; intervention in other drugs: USD19152.45 × 2.6% = USD497.96, approx. USD500/case).5) High-risk drugs were defined as those mentioned in the Guidelines for Operations Related to High-Risk Drugs (Version 2.2) issued by the Japanese Society of Hospital Pharmacists.13) The economic effects of interventions to improve the therapeutic effects mentioned in the report by Yasunaga et al. vary depending on patient characteristics such as condition.9) We therefore did not evaluate them, and instead calculated the medical economic effects of the seventh intervention category (intervention for the reduction of leftover medicines) from the prices of the omitted drugs. The drug prices used for the calculations were those from November 1, 2021. Direct increases or decreases in the drug expenses caused by prescription changes resulting from pharmaceutical intervention were excluded from the evaluation (Table 1).

Table 1. Classification of Interventions and Method Used for Estimating the Medical Economic Effect
Classification of interventionEstimation formula for medical economic effect
1) Avoidance of serious adverse drug reactions or exacerbationAmount paid from the relief system for sufferers from adverse drug reactions, 2019USD24610900
Number of payments1285
Average amount of paymentUSD19152.45 (approx. USD19200)
2) Intervention in cancer chemotherapyAvoidance of adverse drug reactions: 
2.6–5.21% of pharmaceutical interventions lead to avoidance of serious adverse drug reactions. Interventions are classified into 3 levels (2.6, 3.91, or 5.21%) depending on the contents of drug therapy: 
•Cancer chemotherapy (category 2): 
USD19152.45 × 5.21% = USD997.84 (approx. USD1000) 
•High-risk drugs (high-risk drugs among categories 3–6): 
USD19152.45 × 3.91% = USD748.86 (approx. USD750) 
•Others (other drugs among categories 3–6): 
USD19152.45 × 2.6% = USD497.96 (approx. USD500) 
Improvement in therapeutic effect: Not evaluated
3) Avoidance of drug interactions
4) Dose recommendation according to renal function
5) Checking of medication history
6) Proposal of other drug therapies
7) Reduction of leftover medicinesCalculation of economic effect from the prices of reduced drugs

Ethical Considerations

This study was approved by the Kagawa University Ethical Research Committee (2021-133) and was conducted in accordance with the Declaration of Helsinki and Ethical Guidelines for Medical and Health Research involving Human Subjects by the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labour and Welfare of Japan. Japanese law does not require individual informed consent from participants in non-invasive observational trials such as this study. We therefore used our clinical research support center website as an opt-out method rather than acquiring written or verbal informed consent from patients. Consent to conduct the study was also obtained from all the pharmacies that sent TRs.

RESULTS

Patient Characteristics

Table 2 shows the characteristics of the 267 patients for whom TRs were sent.

Table 2. Patient Characteristics and Clinical Departments
Surveyed patients267
Median age, years [range]66 [0–94]
Sex (male/female)123/144
Consent (yes/no)237/30
DepartmentTRs (by follow-up)
All departments267 (107)
Internal medicine of endocrinology & metabolism30 (19)
Mammary gland & endocrine surgery29 (24)
Respiratory medicine24 (10)
Connective tissue disease/rheumatology24 (4)
Neurology20 (5)
Urinary/Adrenal gland/Kidney transplantation surgery18 (6)
Oncology17 (7)
Respiratory surgery12 (6)
Psychology/Neurology11 (2)
Nephrology11 (1)
Gastroenterology10 (1)
Perinatology/Gynecology9 (4)
Gastrointestinal Surgery9 (3)
Dental/Maxillary/Oral surgery7 (6)
Cardiology7 (2)
Pediatrics6 (1)
Anesthesiology/Pain clinic4 (1)
Dermatology3 (0)
Neurosurgery3 (1)
General internal medicine3 (0)
Plastic/Aesthetic surgery2 (1)
Orthopedic surgery2 (1)
Antiaging vascular medicine2 (0)
Hematology1 (0)
Pediatric surgery1 (1)
Otorhinolaryngology/Head and neck surgery1 (1)
Ophthalmology1 (0)

The numbers after each clinical department show the number of tracing reports (number of tracing reports prompted by patient follow-up).

Pharmaceutical Interventions and Interventions to Reduce Leftover Medicines

Of the 267 TRs evaluated, 81 were pharmaceutical interventions (52 (64.2%) to avoid adverse drug reactions and 29 (35.8%) to improve therapeutic effects), and 15 to interventions to reduce leftover medicines. Of these 81 TRs, 21 (25.9%) were prompted by patient follow-up (Table 3). Of the 81 pharmaceutical interventions, four resulted in avoidance of serious adverse drug reactions or exacerbation of the condition. There were seven cases of cancer chemotherapy interventions, of which five were to reduce adverse drug reactions and improve therapy, and two to improve adherence. There was one case of a precautionary intervention to avoid coadministration. None of the interventions were about dose recommendations according to renal function. There were 15 interventions related to checking medication history, with nine to improve adherence (including four requests for one-dose packaging), three for situations with difficulties taking medication, one case of polypharmacy, and two others. The interventions corresponding to proposals for other drug therapies included 33 interventions to control adverse drug reactions, nine to control symptoms, four about errors or inadequacies in prescriptions, two about duplicated administration of analogous drugs with similar effects, and six others. There were 15 interventions to reduce leftover medicines.

Table 3. Medical Economic Effects of Intervention by Pharmacy Pharmacists Using TRs
Classification of interventionNumber of cases*Cost savings (USD)
Per caseCategory total*
1) Avoidance of serious ADRs or exacerbation of disease4 (2)1920076800 (38400)
2) Intervention in cancer chemotherapyAvoidance of ADRs5 (4)10005000 (4000)
Improvement of therapeutic effect2 (1)
3) Avoidance of drug interactionsAvoidance of ADRsHigh-risk drugs07500
Others05000
Improvement of therapeutic effect1 (0)
4) Dose recommendation according to renal functionAvoidance of ADRsHigh-risk drugs07500
Others05000
Improvement of therapeutic effect0
5) Checking of medication historyAvoidance of ADRsHigh-risk drugs07500
Others5 (0)5002500 (0)
Improvement of therapeutic effect10 (0)
6) Proposal of other drug therapiesAvoidance of ADRsHigh-risk drugs6 (1)7504500 (750)
Others32 (9)50016000 (4500)
Improvement of therapeutic effect16 (4)
7) Reduction of leftover medicines15 (0)3370.02 (0)
Sum96 (21)108170.02 (47650)

*The number in parentheses is the number of interventions prompted by patient follow-up. ADR = adverse drug reaction, TR = tracing reports.

Interventions were made about 42 drugs in total (40 oral and two external drugs). These included 12 drugs for the cardiovascular system, nine for the digestive system, six related to metabolism, four related to blood/body fluids, two for nutrition and revitalization, two acting on the central nervous system, two hormonal preparations (including antihormone drugs), two vitamin preparations, one Chinese herbal medicine, one drug for external application, and one drug for the sensory organs.

The most common change in prescriptions after pharmaceutical intervention was discontinuation of administration (17 cases) (Fig. 1).

Fig. 1. Type and Reason for Prescription Changes after Pharmaceutical Intervention (n = 81)

ADR = adverse drug reaction.

Medical Economic Effects

We estimated the cost savings of pharmaceutical interventions, including interventions to reduce leftover medicines, using TRs during the 1-year investigation period as USD108170.02 in total (USD104800 via pharmaceutical interventions and USD3370.02 via interventions to reduce leftover medicines). The cost savings of pharmaceutical interventions using TRs prompted by patient follow-up were estimated to be USD47650 (Table 3). The cost savings achieved per TR for pharmaceutical interventions and interventions to reduce leftover medicines were estimated as USD392.51 and USD12.62 (267 TRs). The cost saving per TR achieved by interventions prompted by patient follow-up was estimated as USD445.33 (107 TRs).

DISCUSSION

Of the 81 pharmaceutical interventions, 52 (64.2%) were to avoid adverse drug reactions, and 29 (35.8%) to improve the therapeutic effect. These results were in line with previous analyses of pharmaceutical interventions by pharmacists, which found that the biggest group of interventions related to avoiding adverse events.57) In our study, four interventions to avoid serious adverse drug reactions or exacerbation of the patient’s condition were instances in which pharmacy pharmacists detected initial symptoms of serious adverse drug reactions after patients first began oral administration of newly prescribed drugs. These resulted in avoidance of exacerbation of the condition. Pharmacy pharmacists detected the initial symptoms of serious adverse drug reactions at the time of patient follow-up in two (50%) of these four cases, suggesting that patient follow-up by pharmacy pharmacists plays an important role in avoiding serious adverse drug reactions or exacerbation of the condition. In interventions in cancer chemotherapy, pharmacy pharmacists have been reported to be involved less frequently than hospital pharmacists.57) This study focused on pharmaceutical interventions using pharmacy pharmacists’ TRs, but a previous study of cases of pharmaceutical intervention prompted by inquiries by pharmacy pharmacists found that only two of the 287 interventions in cancer chemotherapy were made by pharmacy pharmacists.9) In our study, however, seven of the 81 interventions were made in cancer chemotherapy, indicating that pharmacy pharmacists intervened more frequently in cancer chemotherapy via TRs than via inquiries. This may be partly because our hospital began to calculate the additional payment to promote cooperation in November 2021. Pharmacy pharmacists therefore followed up drug adherence and adverse drug reactions with patients by telephone to obtain the additional payment for designated drug management and Guidance 2 at health insurance pharmacies.14) They also proactively provided information to our hospital using TRs. Five (71.4%) of the seven interventions in cancer chemotherapy were pharmaceutical interventions prompted by patient follow-up. The institutional criterion “At least one of the pharmacists working for the health insurance pharmacy must attend a workshop on chemotherapy using anticancer drugs implemented by the medical institution providing services covered by health insurance one or more times a year” is stipulated in the guidance on additional payment for designated drug management.14) Our hospital regularly provides workshops on cancer chemotherapy for pharmacy pharmacists in collaboration with the pharmacy departments of medical institutions in the prefecture. The reason why pharmacy pharmacists are more involved in cancer chemotherapy at our hospital may be because they have more knowledge about cancer chemotherapy following their attendance at the workshops. Ueda et al. reported that consolidating hospital clinic–pharmacy collaboration through the use of information-sharing tools such as TRs and team-based learning (TBL) training sessions improved the knowledge of health insurance pharmacists and hospital pharmacists about oral anticancer drugs. It also helped to improve the contents of TRs submitted from health insurance pharmacies, and contributed to qualitative improvements in TRs.15) We found 45 TRs related to cancer chemotherapy (including 30 prompted by patient follow-up) that did not lead to prescription changes and were not judged to have been pharmaceutical interventions. However, further promotion of workshops on cancer chemotherapy for hospital and pharmacy pharmacists is expected to result in additional improvements in the quality of intervention by pharmacy pharmacists in this area. This should also make these pharmacists more able to contribute to avoiding adverse drug reactions and enhancing the therapeutic effects of cancer chemotherapy.15) The only intervention that corresponded to the avoidance of drug interaction was about precaution for coadministration. There were no interventions related to contraindication for coadministration. This may be because there is a safety system to check contraindications for coadministration at the time of prescription input. However, Koguchi et al. conducted a study over a long survey period among many health insurance pharmacies, and found many interventions by pharmacy pharmacists for drug interactions.16) Our study only investigated pharmaceutical interventions for prescriptions at our hospital, which has a well-developed safety system. It would be desirable to collect data from multiple facilities for analysis. There were no interventions that corresponded to dose recommendations according to renal function. However, these interventions require prescription changes, such as emergency changes in the dosage regimen, and therefore any such cases may have been handled by inquiries rather than TRs. In our hospital, laboratory values are written on out-of-hospital prescriptions so that the pharmacy pharmacists can check these values. Noguchi et al. reported that including laboratory values on out-of-hospital prescriptions increased the number of inquiries about dosage based on renal function.17) Inquiries should be used when a prompt dose reduction or discontinuation is necessary, but we suggest that TRs may be useful to alert the patient to future dosage reductions and the occurrence of adverse effects based on renal function. In interventions corresponding to checking the medication history, requests for prescriptions of one-dose packaging, which are usually made by telephone inquiries, were made using TRs. Requesting prescriptions of one-dose packaging via telephone during busy times burdens both physicians and pharmacy pharmacists. The use of TRs for this purpose may therefore be useful. There were fewer interventions related to errors or inadequacies of prescriptions or the duplicated administration of analogous drugs than in other studies of pharmaceutical interventions prompted by inquiries by pharmacy pharmacists.9) This is probably because these interventions are often urgent, requiring rapid correction of the contents of prescriptions and discontinuation of administration, and are therefore more often transmitted as inquiries than TRs.

The endocrinology/metabolic department had the largest number of TRs (30), of which 15 (50%) were prompted by the need to check drug adherence and adverse drug reactions of insulin or sulfonyl urea preparations. This may be because patient follow-up and TR transmissions concerning insulin or sulfonyl urea preparations are made proactively because of the additional payment for medication management and guidance after dispensation implemented in the 2020 revision of medical service fees.14) All 15 TRs aiming to check drug adherence and adverse drug reactions of insulin or sulfonyl urea preparations were sent to our hospital after patient follow-up. There were also many interventions for departments such as Mammary Gland & Endocrine Surgery, Respiratory Medicine, Urinary/Adrenal Gland/Kidney Transplantation Surgery, and Oncology, where chemotherapy is administered. The medical expenses for diabetes and malignant neoplasms in Japan in FY2019 were USD12154000000 and USD41534000000.18) It is suggested that pharmaceutical intervention by pharmacy pharmacists using TRs will improve the efficacy and safety of drug therapy and contribute to the reduction of medical expenses for these diseases.

Of the 81 pharmaceutical interventions, 29 (35.8%) aimed to improve therapeutic effects. Seven of the prescription changes after these interventions involved the addition of drugs, and two involved dose increases. This would appear to increase the expense for the drugs necessary for treatment. However, improving the therapeutic effects by optimizing the drug therapy would probably prevent exacerbation of the disease, with a consequent reduction in medical cost.

Pharmaceutical interventions using TRs by pharmacy pharmacists were estimated to result in cost savings of USD392.51/TR. Pharmaceutical interventions prompted by patient follow-up saved an estimated USD445.33/TR. It has been reported that the mean medical economic effect of pharmaceutical intervention associated with inquiry by pharmacy pharmacists was USD630 per case.9) Our study suggests that pharmaceutical interventions by pharmacy pharmacists using TRs and those prompted by patient follow-up contribute to pre-avoidance of adverse drug reactions and avoidance of exacerbation in a similar way to those associated with inquiries by pharmacy pharmacists. They also yield comparable medical economic effects.

We estimated the medical economic effect of interventions to reduce leftover medicines as USD12.62 per TR. However, this effect was only estimated for drugs reduced as a result of interventions specifically for this purpose. Yasunaga et al. reported that intervention to reduce leftover medicines has a medical economic benefit of USD0.13 per prescription.9) This suggests that interventions to reduce leftover medicines through both inquiries and TRs can provide medical economic benefits. However, the reduction in drug costs may vary greatly depending on the department and the drugs used, and analysis of more facilities is needed. Nakamura et al. reported that shortening the duration of administration by reducing leftover medicines is effective for reducing both the cost of drugs and the cost of dispensation including the technical fee for the dispensing pharmacist.19) The true effect of intervention may therefore be higher than USD12.62 per TR if we included the reductions in technical fees for dispensing pharmacists. The median age of patients for whom there were interventions to reduce leftover medicines was 69 years, and the drugs targeted were predominantly those for chronic diseases such as cardiovascular and gastrointestinal disorders. This may therefore contribute to prolonged duration of administration and accumulation of leftover medicines. Proactive intervention to reduce leftover medicines by pharmacy pharmacists is specifically stated in the Basic Policy on Economic and Fiscal Management and Reform 2017.10) In addition to interventions to reduce leftover medicines using TRs, interventions that promote improvements in drug adherence are considered important to prevent older patients from stockpiling leftover medicines.

This study had some limitations. It was a single-center study, and TRs were exchanged with only 23 pharmacies. We also did not perform a sensitivity analysis of the medical economic effects of pharmaceutical interventions using TRs, including those to reduce leftover medicines, and did not confirm the reliability of the estimate of medical economic effects. We therefore cannot exclude the possibility of overestimation of the medical economic effects, and careful interpretation is necessary for generalization of our results. However, pharmacy pharmacists are currently being encouraged to move from object-targeted to human-targeted operations.20) Our results suggest that the human-targeted use of TRs may have medical economic value. It could also contribute to improved safety and efficacy of drug therapies and reduced leftover medicines, and therefore to the reduction of medical expenses throughout the national healthcare system. The results of this study may therefore serve as an important reference when considering coverage of pharmacy pharmacists’ human-targeted operations and transmission of TRs in medical service fees. In the future, we would like to disseminate the results of this study by presenting them at conferences on medical economics.

In conclusion, the cost savings generated by pharmaceutical intervention by pharmacy pharmacists using TRs were estimated to be USD392.51 per TR. The savings from interventions prompted by patient follow-up were estimated to be USD445.33 per TR. This suggests that pharmaceutical intervention using TRs contributes to the avoidance of adverse drug reactions and improvements in the effectiveness of drug therapy, and provides medical economic benefits similar to those from pharmaceutical interventions associated with inquiries. The medical economic effect of interventions to reduce leftover medicines using TRs by pharmacy pharmacists was estimated to be USD12.62 per TR. These interventions appear to contribute to the reduction of both leftover medicine and medication expenses in outpatient services.

Acknowledgments

We thank Melissa Leffler, MBA, for editing a draft of this manuscript.

Conflict of Interest

The authors declare no conflict of interest.

REFERENCES
 
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