Drug utilization patterns and associated cost among cancer patients treated in the intensive care units at a comprehensive cancer center in Jordan: A retrospective study

Abstract

Introduction

Cancer patients often experience complications from their disease and treatment, frequently requiring intensive care units (ICU) admissions. Despite significant clinical and economic impacts, data are limited. This study evaluated medication utilization and associated costs in adult cancer patients admitted to the ICU.

Methods

This retrospective study included adult cancer patients treated in the ICU between August and November-2023, excluding post-surgical observation cases. Patients’ demographics, ICU medications, and related-costs were recorded. Medication data were obtained from the hospital pharmacy-database, and direct costs were calculated. Descriptive statistics were done to report the results, with subgroup analysis based on cancer treatment status.

Results

A total of 233 admissions were analyzed; 64.0% were males, 79.1% had solid tumors, and 58.6% were not on active cancer treatment. Sepsis and respiratory conditions were the most common admission reasons. Antibiotics and proton pump inhibitors were the most utilized medications. The mean medication cost per admission was $2363.7, with a median (IQR) of $1001.8 (423.9–1886.8). Human albumin had the highest median (IQR) cost at $1243.6 (932.7–1865.4), followed by antifungals at $316.4 (158.2–1048.8) and antibiotics at $166.5 (85.4–340.4). Median (IQR) ICU medication costs were $980.1 (364.2–1661.6) for patients on active treatment and $1116.2 (460.5–2127.0) for those not.

Conclusions

In a cohort of cancer cases admitted to the ICU, multiple medications were utilized and contributed substantially to overall treatment costs. While antibiotics and proton pump inhibitors were the most commonly used medications, human albumin and antifungals accounted for the greatest share of costs.

Keywords

Neoplasms critical illness drug utilization costs and cost analysis

Introduction

Cancer is a major public health problem that continues to rise globally, posing significant challenges for healthcare systems worldwide.¹ Patients with cancer are vulnerable to a wide range of complications arising from both the disease itself and the related treatments. Such complications may necessitate admission to intensive care units (ICUs).² According to the most recent global statistics, about 20 million new cancer cases were reported in 2022.³ This number is projected to reach 35 million by 2050, representing a 77% increase from 2022.³

Drug utilization studies are important tools for analyzing prescribing patterns and medication use within hospitals. This is particularly relevant in the management of critically ill patients, where medications account for 31% of total drug costs and is significantly higher than in other hospital departments.⁴ Despite this substantial use and cost, there is limited data on drug utilization specifically within cancer populations, underscoring the need for focused research in this area. One study from over a decade ago evaluated drug utilization in cancer patients focused primarily on severe sepsis and septic shock,⁵ leaving gaps in understanding medication use patterns in cancer patients with other diseases. While Suda KJ et al.⁶ reported higher hospital medications cost in cancer patients when compared to non-cancer patients, Zheng B et al.⁷ found that cancer did not lead to increased ICU costs, with daily expenses being nearly equivalent between cancer and non-cancer patients.

This conflicting evidence reflects the complexity of medication use in cancer care, particularly in critical illness, underscoring the need for institutions to identify opportunities for optimizing treatment strategies and resource allocation. Accordingly, this study was conducted to evaluate patterns of medication utilization and their associated costs among cancer patients admitted to intensive care units (ICUs).

Methods

This retrospective study was conducted at King Hussein Cancer Center, a 352-bed comprehensive cancer center in Jordan. The hospital has two adult medical-surgical ICUs, with a total of 21 beds that serve around 1350 cancer patients per year for both oncology and non-oncology-related critical illnesses. The ICUs operate under a closed-unit model where daily multidisciplinary rounds are conducted and include an ICU consultant, hospitalist, nursing team, pharmacist, and respiratory therapist.

We included all patients that were admitted to the adult ICU over a period of 4 months, between Aug 6^th and Nov 19^th, 2023. Patients who were admitted for observation following surgery were excluded. The electronic medical records were used to retrieve the following patient characteristics: patient demographics, type of malignancy, active cancer treatment (defined as receiving chemotherapy, immunotherapy, or hormonal therapy within the past 30 days prior to ICU admission), ICU admission diagnosis, the need for organ support (i.e., mechanical ventilation, dialysis), as well as the ICU length of stay and ICU mortality.

The pharmacy medication database was used to retrieve data related to the type and quantity of medications prescribed for each patient during the ICU stay. We recorded all medications that were received during the ICU stay, including both chronic and ICU-related medications. Medications were then classified based on the following classes: antibiotics, antifungals, antivirals, proton pump inhibitors, vasopressors, sedative agents, systemic corticosteroids, anticoagulants, analgesics, human albumin, diuretics, and cardiovascular medications.

The direct cost for each medication was determined based on the cost set by the Jordan Food and Drug Administration (JFDA). For medications that were not registered in Jordan, we referred to our hospital's supply chain section to obtain their prices. We recorded the total number of vials or ampoules that were needed for the medications to determine the final cost.

Statistical analysis

Descriptive statistics were used to summarize the data. Continuous variables were reported as mean ± standard deviation (SD) or median with interquartile range (IQR). Categorical variables were presented as frequencies and percentages. In addition, given that patients who had recently received cancer-related treatment may require different management approaches and treatment plans during their ICU stay, we performed a subgroup analysis of patients who received active cancer treatment within 30 days prior to their ICU admission and those who did not.

Results

During the study period, a total of 233 ICU admissions for 225 patients were included. The mean ± SD age was 58.7 ± 14.3 years, the majority of the population were males (n = 144, 64.0%), and most of them had solid tumors (n = 178, 79.1%). Among the admitted patients, 93 (41.3%) had received active cancer treatment within 30 days prior to their ICU admission; however, none received treatment during their ICU stay. The most common admission diagnosis was sepsis in 122 (52.4%) patients, followed by respiratory-related conditions in 57 (24.5%) patients. The median (IQR) ICU length of stay was 3 days (2–5) and ICU mortality rate was 25.8%. Table 1 outlines the baseline patient's characteristics.

Table 1.

Baseline patient characteristics.

Characteristic	Total cohort(N = 225 patient, 233 ICU admission)	On active cancer treatment(N = 93 patient, 95 ICU admission)	Not on active cancer treatment (N = 132 patient, 138 ICU admission)
Age, mean (SD) *	58.7 (14.3)	58.0 (13.9)	59.4 (14.5)
Gender, male n (%) *	144 (64.0%)	53 (57.0%)	91 (68.9%)
Type of malignancy, n (%)*
Solid	178 (79.1%)	71 (76.3%)	107 (81.1%)
Hematological	47 (20.9%)	22 (23.7%)	25 (18.9%)
Admission diagnosis, n (%)^
Sepsis	122 (52.4%)	51 (53.7%)	71 (51.4%)
Respiratory	57 (24.5%)	21 (22.1%)	36 (26.1%)
Gastrointestinal	11 (4.7%)	5 (5.3%)	6 (4.3%)
Neurological	19 (8.2%)	7 (7.4%)	12 (8.7%)
Cardiac	27 (11.6%)	13 (13.7%)	14 (10.1%)
Renal	12 (5.2%)	7 (7.4%)	5 (3.6%)
Hematological	4 (1.7%)	3 (3.2%)	1 (0.7%)
Others	17 (7.3%)	7 (7.4%)	10 (7.2%)
ICU mortality, n (%)	60 (25.8%)	27 (28.4%)	33 (23.9%)
Median Length of stay (LOS) in days (IQR)	3 (2–5)	2 (2–4)	3 (2–5)
Organ support during ICU stay, n (%)
Vasopressors	134 (58.0%)	59 (62.1%)	75 (54.3%)
Mechanical ventilation	57 (24.5%)	20 (21.1%)	37 (26.8%)
Dialysis	18 (7.7%)	8 (8.4%)	10 (7.2%)

^Some patients had more than one ICU diagnosis upon admission.

*Numbers were calculated based on the number of unique patients.

The most utilized medication classes were antibiotics (n = 207, 88.8%) followed by proton pump inhibitors (n = 185, 79.4%) and analgesics (n = 166, 71.2%). Table 2 outlines the medications prescribed and their utilization patterns. The total cost per ICU admission for all received medications was $2363.7, with a median (IQR) of $1001.8 (423.9–1886.8). Table 3 provides details about the costs per medication class. Human albumin, accounted for the highest cost per cohort, with a median (IQR) of $1243.6 (932.7–1865.4), followed by antifungals and antibiotics, with a median (IQR) cost of $316.4 (158.2–1048.8) and $166.5 (85.4–340.4), respectively. For patients on active cancer treatment, the median (IQR) cost per ICU admission was $980.1 (364.2–1661.6), compared to $1116.2 (460.5–2127.0) for those not on active cancer treatment.

Table 2.

Drug utilization pattern data.

Medications	All admissions(N = 233, 100%)	On active cancer treatment (n = 95, 40.8%)	Not on active cancer treatment(n = 138, 59.2%)
Antibiotics, n (%)	207 (88.8%)	82 (86.3%)	125 (90.6%)
Glycopeptides	168 (72.1%)	71 (74.7%)	97 (70.3%)
Beta-lactams	143 (61.4%)	59 (62.1%)	84 (60.9%)
Carbapenems	107 (45.9%)	43 (45.3%)	64 (46.4%)
Aminoglycosides	61 (26.2%)	29 (30.5%)	32 (23.2%)
Antifungals, n (%)	46 (19.7%)	18 (18.9%)	28 (20.3%)
Antivirals, n (%)	27 (11.6%)	11 (11.6%)	16 (11.6%)
Proton pump inhibitors, n (%)	185 (79.4%)	76 (80.0%)	109 (79.0%)
Anticoagulants, n (%)	145 (62.2%)	54 (56.8)	91 (65.9%)
Vasopressors, n (%)	134 (58.0%)	57 (60.0%)	77 (55.8%)
Systematic corticosteroids, n (%)	121 (51.9%)	50 (52.6%)	71 (51.4%)
Analgesics, n (%)	166 (71.2%)	67 (70.5%)	99 (71.7%)
Sedative agents, n (%)	69 (29.6%)	28 (29.4%)	41 (29.7)
Human albumin, n (%)	101 (43.3%)	43 (45.3%)	58 (42.0%)
Diuretics, n (%)	109 (46.8%)	42 (44.2%)	67 (48.5%)
Cardiovascular medications, n (%)	139 (59.7%)	56 (58.9%)	83 (60.1%)

*The above values were calculated per ICU admission, not for unique patients.

Table 3.

Medications cost data, median (IQR).

Medication class	All ICU admissions	On active cancer treatment	Not on active cancer treatment
Antibiotics	$166.5 (85.4–340.4)	$157.9 (75.2–305.7)	$171.9 (90.9–359.8)
Glycopeptides	$53.9 (26.9–80.8)	$40.3 (26.9–74.0)	$53.9 (40.4–80.8)
Beta-lactams	$50.6 (28.3–101.2)	$40.5 (30.3–86.1)	$60.7 (22.4–103.2)
Carbapenems	$151.3 (101.0–302.7)	$126.1 (101.0–227.0)	$164.0 (101.0–353.2)
Aminoglycosides	$11.3 (11.3–16.9)	$11.3 (11.3–11.3)	$11.3 (11.3–18.3)
Antifungals	$316.4 (158.2–1048.8)	$316.4 (158.2–1112.3)	$342.9 (108.7–990.4)
Antivirals	$34.1(13.4–76.6)	$43.7 (11.3–172.5)	$30.7 (13.8–62.0)
Proton pump inhibitors	$5.4 (1.1–15.1)	$5.0 (1.1–10.8)	$6.2 (1.5–15.1)
Anticoagulants	$12.5 (6.3–25.1)	$9.7 (6.3–25.1)	$12.5 (6.3–25.1)
Vasopressors	$1.8 (0.9–14.4)	$2.7 (0.9–36.9)	$0.9 (0.9–7.3)
Systematic corticosteroids	$8.2 (3.6–16.6)	$7.4 (3.6–13.5)	$7.9 (3.5–17.3)
Analgesics	$17.2 (6.1–42.9)	$14.1 (4.8–41.0)	$18.9 (8.3–48.8)
Sedative agents	$54.6 (13.0–109.8)	$43.1 (12.5–99.5)	$54.9 (23.1–138.6)
Human albumin	$1243.6 (932.7–1865.4)	$1243.6 (621.8–1803.2)	$1243.6 (932.7–1865.4)
Diuretics	$3.4 (1.5–6.9)	$3.6 (1.5–6.1)	$3.6 (1.5–8.3)
Cardiovascular medications	$11.9 (3.7–39.0)	$9.2 (2.7–42.3)	$14.8 (4.8–36.2)
Median (IQR) for all patients	$1412.5 (597.7–2660.4)	$1378.6 (513.5–2342.9)	$1573.8 (649.3–2998.9)

Discussion

In this retrospective study, we described the patterns of medication utilization and their associated costs among adult cancer patients admitted to the ICU. Notably, ICU cancer patients are often prescribed multiple medications during their stay, which are associated with substantial costs. To our knowledge, only a few other studies reported the drug utilization pattern and the drug cost in this patient population.^5,8 Among a wide range of prescribed medications in the ICU for this patient population, antibiotics emerged as the most frequently utilized medication class, which aligns with the high prevalence of sepsis, septic shock and respiratory conditions (including respiratory infections) as leading ICU diagnoses. Broad-spectrum antibiotics, such as glycopeptides, beta lactams and carbapenems were among the most commonly administered agents. These findings are consistent with prior studies conducted by Nazer et al. and Mittal et al.^5,8 The use of such broad-spectrum antibiotics is recommended for immunocompromised patients with severe infections, and their use is guided by our institutional pathogen profile and resistance patterns to further optimize antibiotic therapy.

Similarly, proton pump inhibitors were also among the most utilized medications class, which aligns with the current Society of Critical Care Medicine (SCCM) guidelines that recommend stress ulcer prophylaxis for patients with specific risk factors, including septic shock, which is commonly present as an ICU admission diagnosis in our population.⁹ Analgesics, including opioids, phenols and anticonvulsants that are used for neuropathic pain (gabapentin and pregabalin) were also among the most frequently used medications in our ICU. Opioids, particularly fentanyl, remain the cornerstone for non-neuropathic pain management in mechanically ventilated patients, in accordance with the current SCCM guidelines.¹⁰

In terms of cost, human albumin accounted for the highest medication-related cost among all drugs administered in our ICU. This is likely attributable to its use in patients with septic shock, despite the lack of clear evidence supporting its added benefit over crystalloids alone.¹¹ A recent retrospective study by Al-Kharabsheh et al.¹² conducted at our institution, evaluated the use of human albumin in adult cancer patients, including those in the ICU. The study found that ICU patients accounted for the largest proportion of albumin use (37%), primarily for the management of septic shock. These findings are consistent with our institutional guidelines, which aim to regulate albumin use in alignment with international recommendations, given its significant cost burden.

Antifungals represented the second highest medication cost after albumin in this patient population, a well-known drug class for its high expense. Although their use is generally restricted to specific approved indications, antifungals may be used empirically in critically ill cancer patients with septic shock and a high clinical suspicion of invasive fungal infections, including aspergillosis, invasive candidiasis, and mucormycosis, particularly in those with prolonged neutropenia.^13,14 At our institution, the incidence of such fungal infections among ICU patients admitted with septic shock was 13.1% between 2008 and 2019.¹⁵ Following antifungals, antibiotics, particularly meropenem, were identified as one of the most costly medications. Meropenem is one of the most commonly used broad-spectrum antibiotics in our ICU, reflecting the high prevalence of gram-negative bacterial infections, including ESBL-producing organisms that necessitate carbapenems according to our institutional antibiogram.¹⁶

Regarding cost, our data revealed a relatively high cost per patient for all medications administered during the ICU stay. However, there is limited literature available for direct comparison, particularly in similar settings and populations. One study by Suda et al.⁶ reported that oncology patients incurred significantly higher costs, primarily due to increased medication expenses, compared to non-oncology patients, including medications utilized during their ICU stays. Another study by Nazer et al.⁵ reported an average cost of medications per patient of $2935.30, exceeding the cost reported in our study. However, the difference may be attributed to variations in the spectrum of included ICU diagnoses between the two studies, as Nazer et al. only reported the cost for those who were admitted for septic shock, in addition to the time periods during which the data were collected, potentially reflecting changes in drug pricing, treatment protocols, or ICU practices over time. This scarcity of data highlights the need for further research focusing on cost and resource utilization among critically ill cancer patients.

We believe that our study has limitations. Firstly, this study is single centered which can limit the generalizability of our results. Secondly, we did not evaluate the goal of care and code status of the included patients during their ICU stay, which are factors that may impact the medications utilization and cost. Furthermore, only direct medication costs were included, as data on indirect costs that include medication preparation and administration costs were unavailable.

Conclusions

In a cohort of cancer patients admitted to the ICU, multiple medications were utilized and contributed substantially to overall treatment costs. Antibiotics and proton pump inhibitors were the most commonly prescribed agents, while albumin and antifungals accounted for a significant portion of the cost burden.

Footnotes

Acknowledgment

We extend our sincere gratitude to Navid Madani and Elizabeth Hamblin at the Science Health Education (SHE) Center at the Dana-Farber Cancer Institute for their exceptional editorial expertise and for conducting impactful scientific writing workshops. Their contributions have been invaluable in refining this work and strengthening our commitment to excellence in science communication.

ORCID iDs

Enas Alkurdi

Wedad Awad

Naheel Said

Asma'a Al-Kharabsheh

Ethical considerations

The study was approved by the institutional review board (IRB), with an IRB approval number: (24 KHCC 111).

Consent to participate

A waiver of consent was obtained due to the retrospective nature of the study.

Consent for publication

Not applicable.

Author contributions

EA, WA, and LN developed the research question. EA, NS, and WA contributed to data collection. All authors were involved in data analysis, interpretation of the results and manuscript writing, and all have reviewed and approved the final version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability

The data for this study is available upon request from the primary author.

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