Impact of Clinical Pharmacists’ Interventions on Medication Use and Direct Cost Savings in an Inpatient Medical Oncology Setting

Abstract

Introduction:

There are limited studies evaluating the impact of clinical pharmacists’ interventions (CPIs) and pharmacist-driven cost savings in the inpatient oncology settings. This study aimed to assess the clinical impact of CPIs and direct cost savings from deprescribing-related interventions in an inpatient oncology service.

Methods:

A retrospective study was conducted by assessing CPIs extracted from the pharmacy documentation system in the medical oncology service between January 2022 and December 2023. The clinical impact of these CPIs was evaluated through including interventions accepted by physicians and resulted in therapy changes, along with their significance levels. Direct cost savings were calculated for deprescribing interventions, including drug discontinuation and intravenous-to-oral (IV-PO) conversions, based on the cost saved per intervention over a 24-hour period.

Results:

During the study period, 9995 CPIs were identified, of which, 99.0% (n = 9887) were accepted by physicians and included in the analysis. The most frequent interventions were recommendations for drug additions/dose change (n = 3603, 36.4%), followed by drug discontinuations (n = 2886, 29.0%). Antimicrobials were the most frequently involved drug class (n = 4017, 40.7%). Significant CPIs that improved standard of care accounted for 7274 (73.6%) interventions, while very significant and extremely significant interventions were 2595 (26.3%) and 14 (0.14%), respectively. The overall direct cost savings from deprescribing were $102 710, with drug therapy discontinuations and IV-PO conversions contributing $99 305 and $3405, respectively.

Conclusion:

CPIs showed significant clinical and financial impact, with a high rate of accepted interventions resulting in therapy changes. Further prospective studies are required to analyze the clinical outcomes and indirect cost savings.

Introduction

During the past 50 years, the pharmacy profession has transformed from the focus on manufacturing pharmaceutical products to targeting patient-centered care, with the goal of providing the best pharmaceutical care, optimizing patient management, and reducing drug-related problems. Clinical pharmacists play an important role in the interdisciplinary team, guiding healthcare professionals in the selection of medication.^1-5 Clinical pharmacists provide patient care that directly impacts medication safety, patient knowledge and education, medication adherence, and quality of life.^4,6-9

The role of clinical pharmacists is critical in the care of cancer patients, due to complexities associated with the malignancy and antineoplastic treatments, such as impaired organ function, polypharmacy, and prolonged hospitalization. ¹⁰ Addressing these issues is essential to optimize medication safety and reduce drug-related problems, which are considered a major concern for patient’s safety.^10-16 Clinical pharmacists actively contribute to the healthcare team by performing comprehensive medication reviews, reporting adverse drug reactions and medication errors, and providing detailed pharmaceutical plans. One important role of the clinical pharmacist is deprescribing, which involves the discontinuation of unnecessary or harmful medications to reduce the risk of drug-related problems, enhance medication safety, optimize resource allocation, and consequently improve the quality of care for patients with cancer.^17,18

There are limited studies about the impact of the clinical pharmacist in the management of hospitalized patients with cancer.^18-22 The majority of the studies focused on their role in the outpatient settings, where clinical pharmacists are actively involved in medication management, patient education, and reporting of adverse drug reactions.^10,23-30 On the other hand, few studies have evaluated their contributions in the inpatient settings, where complexity of the patients and their conditions should be considered. These can include acute complications, the use of high-risk medications with narrow therapeutic index, polypharmacy, abnormal organ function, and the need for close monitoring.^18-22,31-34 In addition, there have been limited studies reporting pharmacist-driven cost-savings as a result of clinical pharmacists’ interventions (CPIs) in the inpatient oncology settings.^31,33-35 These gaps highlight the need for further research to evaluate the characteristics and clinical and economic impact of CPIs in these settings. This study aimed to assess the overall clinical impact of all types of CPIs, as well as direct cost savings associated with deprescribing of medications by clinical pharmacists, in the inpatient oncology setting at a comprehensive cancer center.

Methods

A retrospective, single-center study was conducted at King Hussein Cancer Center (KHCC), a 350-bed cancer center in Amman, Jordan. KHCC provides comprehensive care to adult and pediatric patients for the treatment of all types of cancer in Jordan and the Middle East region. The clinical pharmacists at KHCC are part of the interdisciplinary healthcare team, where they are involved in optimization of drug therapy, ensuring safe and effective use of medications. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by KHCC Institutional Review Board (IRB) on April 17th, 2024, with approval number 24 KHCC 65.

CPIs reports for adult cancer patients admitted to the medical oncology service were extracted, as documented by clinical pharmacists in the pharmacy documentation database (Quantifi^®) between January 2022 and December 2023. Interventions with incomplete information were excluded. Quantifi^® is an electronic documentation database used by clinical pharmacists to report daily clinical interventions, detected medications errors, and adverse drug reactions. The medical oncology service includes adult patients with solid tumors, multiple myeloma, and lymphoma. Clinical pharmacists covering this service are licensed pharmacists with a minimum of Doctor of Pharmacy (PharmD) degree. The majority have additional postgraduate certificates, including a board certification in oncology pharmacy (BCOP) or pharmacotherapy (BCPS). They are involved in direct patient care and follow the institutional standards for reporting and documentation of interventions. The generated CPIs reports from Quantifi^® were analyzed by the investigators to extract data related to the study. The clinical impact of CPIs was assessed by identifying interventions that were accepted by physicians, and resulted in direct changes to patient’s medication.

The CPIs reports included the drug involved in each intervention, the type and clinical significance of the intervention, and physicians’ acceptance of these CPIs. The interventions included drug therapy recommendations to add medications or adjust dosing, hepatic dose adjustments, modifications of chemotherapy protocol or dosing, pharmacokinetic evaluations, renal dose adjustments, antibiotics recommendation/de-escalation, avoidance of therapeutic duplication, intravenous (IV) to oral (PO) conversions, avoidance of drug level, and drug therapy discontinuations. The clinical significance of the CPIs was categorized as follows: significant, indicating improved standard of care/optimized therapy; whereby the intervention brought care to a more appropriate level; very significant, indicating the prevention of major toxicity and/or organ damage; and extremely significant indicating lifesaving intervention. Physicians’ acceptance was considered as whether the intervention was implemented.

For the calculation of direct cost savings, the study only included deprescribing-related interventions in the economic analysis, which consisted of IV to PO conversions and drug therapy discontinuations. The co-investigators collected the public pricing for the medications involved in these interventions from the Jordan Food and Drug Administration (JFDA) website. ³⁶ A co-investigator from the research team verified a random sample of the collected cost data to ensure accuracy.

Daily cost of each medication was calculated by multiplying the price of a single dose by the corresponding daily defined dose, retrieved from the World Health Organization (WHO) website. ³⁷ The cost savings from drug therapy discontinuation was determined by calculating the cost of what would have been dispensed if no intervention had occurred for 24 hours. For IV to PO conversion interventions, the cost savings were calculated as the difference between the cost of the IV and PO dosage forms for each medication for 24 hours. The total cost savings for each type of intervention was calculated by multiplying the cost saved per medication for 24 hours by the total number of interventions recorded. Finally, the results for all medications were summed to determine the overall cost saved for each intervention.

Statistical Analysis

Statistical analysis was performed using Microsoft Excel (version 365). Continuous data were presented as means with standard deviations (SD), while nominal data were presented as numbers and percentages.

Results

During the predefined study period, 10 872 CPIs were extracted, of which, 9995 were included for 3800 patients and 877 were excluded due to missing data. The mean age of patients was 56 years old (±14.4 SD), with 49.0% being female. Among the included CPIs, 9887 (99.0%) were accepted by physicians, led to change in therapy, and included in the final analysis. The most common interventions were drug recommendations for initiation of drug/dose adjustments (n = 3603, 36.4%), followed by drug therapy discontinuations (n = 2886, 29.0%), and renal dose adjustments (n = 682, 6.9%). The included CPIs are summarized in Table 1. The drug class most commonly associated with CPIs were antimicrobials (n = 4017, 40.7%), followed by drugs for cardiovascular system, including antiplatelets (n = 1385, 14.0%), and drugs for gastrointestinal system (n = 1152, 11.7%) (Table 2).

Table 1.

Clinical Pharmacists’ Interventions (CPIs) by Clinical Pharmacists.

Intervention	Number (%)
Initiation of drug/dose adjustments	3603 (36.4)
Drug discontinuation	2886 (29.1)
Renal dose adjustments	682 (6.9)
Antibiotic recommendations/addition	550 (5.6)
PK evaluations	538 (5.4)
De-escalation of antimicrobial therapy	445 (4.5)
IV-to-PO conversions	393 (3.9)
Hepatic dose adjustments	304 (3.1)
Therapeutic interchange done	206 (2.1)
Drug/drug interaction	98 (1.0)
Avoidance of therapeutic duplication	80 (0.8)
Modifications of chemotherapy protocol or dosing	76 (0.8)
Avoidance of drug levels	26 (0.3)

Abbreviations: IV-to-PO, intravenous to oral; PK, pharmacokinetics.

Table 2.

Drug Classes Involved in Clinical Pharmacists’ Interventions (CPIs).

Drug class	Number (%)
Antimicrobials	4017 (40.7)
Cardiovascular (including anticoagulants and antiplatelets)	1385 (14.0)
GI	1152 (11.7)
Metabolic	845 (8.6)
Pain medications	788 (7.9)
Endocrine	352 (3.6)
Antineoplastic	313 (3.2)
Corticosteroids	288 (2.9)
CNS	272 (2.8)
Blood disorders	235 (2.4)
Chemoprotective	28 (0.3)
GU	21 (0.2)
Skin	16 (0.2)
Others	63 (0.7)

Abbreviations: CNS, central nervous system; GI, gastrointestinal; GU, genitourinary.

Regarding clinical significance, 7274 (73.6%) interventions were classified as significant. Very significant interventions accounted for 2595 (26.3%), while extremely significant interventions represented 14 (0.14%) of the total CPIs.

A total of 3317 interventions were included in the direct cost-savings analysis from deprescribing over a period of 24 hours. These interventions resulted in total direct cost savings of $102 710. Cost savings were primarily attributed to drug therapy discontinuations, which accounted for $99 305. IV to PO conversions contributed for $3405. Table 3 summarizes the total and the average cost savings for each type of intervention.

Table 3.

Direct Cost Saving from Deprescribing Interventions.

Intervention	Average cost saved over 24 h (±SD)	Total cost savings
Drug therapy discontinuation	$34.4 (±267)	$99 305
IV to PO conversions	$8.6 (±20.3)	$3405
Total		$102 710

Abbreviations: IV to PO, intravenous to oral; SD: standard deviation.

In a subgroup analysis for drug therapy discontinuations, cost savings related to antimicrobials (n = 1287, 44.6%) and antineoplastic agents (n = 15, 0.5%) were evaluated. The total cost savings for these groups were $44 664 and $22 795, respectively.

Discussion

This study highlights the significant clinical and economic impact of CPIs in optimizing patients’ medications in the inpatient medical oncology setting. During the study period, nearly all CPIs were accepted by physicians leading to drug therapy adjustments. This reflects strong collaboration between clinical pharmacists and physicians, and underscores the importance of integrating clinical pharmacists into the healthcare teams to enhance patient management and outcomes. Similar high acceptance rates have been reported in other studies.^{7,19,20,24,28} For example, a retrospective study by Han et al, ⁷ reported a 71% acceptance rate, while a prospective study by Delpeuch et al ²⁰ in a hematology and oncology inpatient setting showed 96% acceptance rate. Our study showed a high acceptance rate of CPIs among physicians, compared to other non-oncologic inpatients settings. For instance, a study conducted in the intensive and cariology care units in Brazil, reported a 76.3% acceptance rate of interventions, with the majority related to dosing adjustments. ⁴ In another study conducted in an internal medicine service in Italy, where they used a structured communication strategy between pharmacists and physicians, reported a 93.2% acceptance rate. ³ These findings highlight the differences in accepting CPIs across various inpatient services, including oncology. Future research should assess the attitude of physicians toward pharmacist’s involvement in the inpatient setting and the reasons behind the variation in the acceptance of CPIs.

In this study, the most frequent interventions were drug therapy recommendations for drug additions/dose adjustments, which accounted for one third of all CPIs. This reflects the critical role of clinical pharmacists in ensuring appropriate drug choice and dosing regimens. Additionally, drug therapy discontinuations constituted almost one third of the total interventions, which aligns with the importance of deprescribing to minimize unnecessary medications, reduce adverse drug reactions and polypharmacy, and help in cost savings. Similar findings were reported by Delpeuch et al, ²⁰ who found that treatment discontinuation was among the most common types of interventions. Renal dose adjustments were the third most common interventions in the present study, as they are essential in preventing supratherapeutic drug levels and toxicity in this vulnerable populations. These findings align with previous studies that have shown clinical pharmacists’ involvement in optimizing drug therapy to provide patient care in areas such as antimicrobial stewardship, renal dosing, and drug safety management. Since this study was conducted in an inpatient medical oncology service, the focus was not limited to chemotherapeutic management. Instead, it aimed to assess a broad spectrum of CPIs including, but not limited to, deprescribing, dose modifications, renal dose adjustments, drug recommendations, and pharmacokinetic evaluation. This approach reflects the critical role of clinical pharmacist in providing comprehensive management in the inpatient oncology settings, beyond specific type of intervention.

Notably, antimicrobials emerged as the most common drug class associated with CPIs, accounting for about one-third of the interventions. This highlights the critical role of pharmacists in managing infections through the appropriate selection of antimicrobials, doses adjustment, and monitoring of response, especially in immunocompromised patients who are more prone to different types of infections. Drugs for cardiovascular and gastrointestinal systems also constituted significant proportions, reflecting their prevalence among the cohort of medical patients and the common complications associated with malignancy and cancer treatment, such as nausea, vomiting, and diarrhea. Delpeuch et al ²⁰ reported a similar finding. In our study, a small percentage of interventions were related to antineoplastic agents, as the majority of antineoplastic agents at KHCC are administered in the ambulatory chemotherapy clinic, with only specific protocols requiring hospital admissions due to feasibility and the need for specialized administration protocols with extended infusion durations. Although the number of interventions directly related to antineoplastic agents in the inpatient setting was limited, oncology clinical pharmacists play an essential role in the interdisciplinary team. Their expertise and responsibilities extend beyond direct antineoplastic therapy modifications, to include optimizing supportive care regimens for all types of cancer, managing complex drug-related problems associated with antineoplastic agents, monitoring and preventing adverse drug reactions, adjusting doses in patients with organ dysfunction, and facilitating transitions of care to the outpatient chemotherapy clinic. These contributions are important to ensure patient safety, maintain treatment effectiveness, and improve overall clinical outcomes in hospitalized oncology patients.

The majority of CPIs were classified as significant, with approximately one-third categorized as very significant, and less than 1.0% deemed lifesaving recommendations. These findings demonstrate the importance of CPIs in optimizing therapy, preventing adverse events, and improving patient outcomes. Consistent with the results of this study, Daupin et al ³⁸ reported that two-thirds of interventions were scored as having at least a significant impact on patient safety, while Han et al ⁷ showed that half of their interventions were classified as having significant or greater impact. Similarly, a study in Singapore found that approximately half of the interventions were rated as clinically significant or very significant. ²⁸

The direct cost-savings analysis showed financial benefits of deprescribing-related interventions. CPIs of drug therapy discontinuations accounted for the majority of total cost savings, highlighting their advantages of reducing unnecessary medications, improving patient safety, and lowering medications costs. Drug therapy discontinuations may also result in indirect cost savings, such as prevention of adverse events or hospital admission; however, these potential savings were not evaluated in this study. Further research is needed to explore these indirect savings. Though IV-to-PO conversions contributed a smaller proportion of direct cost savings, they remain an essential intervention for reducing medications costs, pharmacy preparation time, and the need for venous access. Notably, the analysis of this study only accounted for medication costs in these interventions. The potential cost savings would be greater if factors such as pharmacy preparation time and venous access requirements were included. Further research could provide more comprehensive analysis into the long-term outcomes of CPIs on overall patient health and indirect cost savings.

A study conducted by Herledan et al ³⁴ in France found that pharmaceutical interventions at admission and discharge helped with identification and resolution of drug-related problems in geriatric patients aged above 75 years and older. The study concluded that the potential cost savings outweighed the cost of pharmacist-time invested. In our study, the time required to perform the interventions was not compared with the associated cost savings. Similarly, Abushanab et al ³³ studied the overall economic impact of clinical pharmacist interventions in inpatient setting in Qatar, focusing on the preventions of adverse drug events and the cost savings associated with use of therapeutic-based resources. In the present study, the total direct cost savings from two types of CPIs were calculated, without evaluating the long-term outcomes of these interventions, such as avoidance of adverse drug reactions or prevention of hospital admission. A study by Chen et al, ³⁵ which evaluated the clinical and economic impact of CPIs in hematology unit in Taiwan, demonstrated that clinical pharmacists reduced the costs of medications and potential adverse drug events, as a result of decreasing medication errors and preventable adverse drug events. Our study highlights the need for efforts to expand pharmacist’s involvement in decision-making and treatment protocol in other hospitals across Jordan and the region. On the other hand, the contribution of clinical pharmacists can be supported through the use of innovative new technologies. For instance, a study conducted at Good Shepherd Medical Center in Texas evaluated the impact of implementing a clinical decision support system (CDSS) known as TheraDoc. The number of monthly clinical interventions increased by 105%, and the estimated annual cost savings reached around $3 million, following the implementation of CDSS. ³⁹ This example highlights the benefits of having structured systems, and new tools and resources such as CDSS, to enhance the efficiency and impact of CPIs, and could be specifically essential for high-risk patients in the acute settings, including oncology.

The strengths of this study were the inclusion of large number of interventions that led to changes in therapy and over extended duration, which include different periods throughout the year, providing a more comprehensive perspective. However, the study has several limitations that must be acknowledged. First, its retrospective design, including the limitations of retrospective data set. Secondly, clinical pharmacists carried out numerous interventions without consistently reporting and documenting them, potentially leading to an underreporting and underestimation of their frequency. As a result, higher numbers of interventions might be anticipated if documentation was more comprehensive and consistent. Moreover, a significant proportion of CPIs lacked data, such as medications names, so they were excluded, preventing a vigorous analysis of such data. Additionally, because we only relied on the available, structured pharmacy documentation system, and due to limitations in the data reported in this system, we were unable to extract additional clinical data, such as malignancy type, number of medications, reason for admission, or length of stay. This lack of data limited the ability to fully assess the patients’ overall clinical condition retrospectively. Although the role of clinical pharmacists in chemotherapy management is well-recognized, this study was unable to conduct a focused subgroup analysis for CPIs specifically related to chemotherapy, since these interventions were not consistently recorded with all the details within the Quantifi^® database. Lastly, the impact of the interventions on specific outcomes, such as length of stay and prevention of adverse drug reaction, was not evaluated.

Conclusion

This study identified a high proportion of CPIs classified as at least significant that resulted in changes in patients’ therapy, showing the critical role of clinical pharmacists in the interdisciplinary team in the inpatient medical oncology setting. Clinical pharmacists should be considered essential members of the medical team, where their interventions directly improve patient care and contribute to cost savings. Deprescribing-related interventions, primarily drug therapy discontinuations, resulted in substantial direct cost savings. These findings reinforce the essential role of clinical pharmacists in optimizing resource utilization and support cost-saving strategies in oncology care. Studies should be conducted to explore these findings with respect to long-term outcomes on patient care and the resulted indirect cost savings.