Cost minimization analysis of subcutaneous trastuzumab versus intravenous biosimilar trastuzumab: policy recommendations for breast cancer treatment in Malaysia

Abstract

Purpose

Current clinical practice recommends switching innovator intravenous trastuzumab (IV-TZM_i) to subcutaneous trastuzumab (SC-TZM) to save healthcare resources. However, with the availability of biosimilar intravenous trastuzumab (IV-TZM_b), there is a need to re-evaluate the recommendation. Hence, this study aims to compare the cost and resource use of SC-TZM and IV-TZM_b in a Malaysian public healthcare facility.

Methods

This activity-based costing study consists of (1) a retrospective medical record abstraction to determine patient details to estimate drug costs and (2) a time-motion study to quantify personnel time, patient time, and consumables used. The total cost of both SC-TZM and IV-TZM_b were then compared using a cost-minimization approach, while differences were explored using an independent t-test. A sensitivity analysis was also conducted to determine the impact of uncertainties in the analysis.

Results

The mean total cost of SC-TZM and IV-TZM_b was USD 13,693 and USD 5,624 per patient respectively. The cost difference was primarily contributed by savings in drug cost of IV-TZM_b, a reduction of USD 8,546 (SD = 134), p < 0.001 compared to SC-TZM. Interestingly, SC-TZM had a significantly lower cost than IV-TZM_b for both the consumable and personnel cost, a reduction by USD 300 (SD = 17.6); p < 0.001 and USD 176 (SD = 7.3); p < 0.001 respectively. The sensitivity analysis demonstrated that the total cost difference between the formulation was mainly driven by drug costs.

Conclusion

The study evidenced that IV-TZM_b was a more economically viable option in Malaysian public healthcare currently compared to SC-TZM.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40199-023-00485-9.

Introduction

Breast cancer is the most common cancer among females worldwide [1]. It accounts for one in four cancer cases and one in six cancer deaths in women [2]. It is also ranked as the first highest contributor to cancer mortality in 110 countries [2]. Intriguingly, one in five of these breast cancer incidences is estimated to be Human Epidermal Growth Factor Receptor 2 (HER2) positive [3]. The HER2 receptor is a type of oncoprotein involved in cell proliferation pathways that protect abnormal cancer cells from apoptosis or better known as programmed cell death [4]. The over-expression of HER2 has been associated with a high recurrence rate, high metastases rate, and death, leading to poorer prognosis [5]. As HER2-positive breast cancer has a genetic predisposition, the prevalence may differ accordingly. Locally in Malaysia for example, HER2-positive cases were reported in 23% to 37% of breast cancer patients and continue to form a significant disease and financial burden [5–7].

The introduction of Trastuzumab (TZM), a monoclonal antibody that inhibits the growth of cancer cells by interfering with the HER2 receptor has in recent years improved the treatment outcome of breast cancer patients. It is now an essential part of the standard treatment as adjuvant therapy in early breast cancer. This is because TZM evidenced a significant and extended improvement in survival from a sustained marked reduction in cancer recurrence [8, 9]. TZM can also be used in metastatic HER2-positive breast cancer, to further increase patient survival rate [1, 8, 10, 11]. Albeit clinically effective, the use and accessibility of this life-saving drug are still very much dependent on its price. Lammers et al., for example, stated that a lack of funding was the major barrier to the use of TZM in breast cancer treatment. This was reported by 37% to 49% of oncologists in various countries, including the United States, Mexico, Turkey, Russia, and Brazil [12]. They further described that these challenges were closely related to the health system, funding mechanisms, and availability of cheaper biosimilars in respective countries [12].

Malaysia forms an interesting case study on the impact of such expensive therapies, as cancer care is predominantly provided by the highly-subsidized public healthcare sector [5]. The public healthcare system here is funded by taxation and national revenues, with minimal fees for service from patients [13]. For example, excluding other supplementary care, TZM treatment in 2016 was estimated to cost public hospitals around MYR 79,593 to MYR 87,154 (USD 19,238 to USD 21,065) [5]. However, Malaysian citizens treated in public hospitals only spent an average of MYR 6,029 (USD 1,457) per year due to the subsidies and inpatient cost-capping mechanism for cancer patients [14]. Thus, while the universal health coverage in Malaysia is exemplary, the introduction of TZM treatment in HER2-positive breast cancer has significantly increased the current financial burden in the public healthcare system [5].

Aside from requesting additional budgets, one of the cost-saving recommendations from recent studies was substituting the conventional innovator TZM delivered intravenously (IV-TZM_i) for a subcutaneous (SC-TZM) formulation. Even though the cost of SC-TZM was more expensive, it was associated with better use of resources [3, 15]. Many studies evidenced that the switch generated overall savings from lower consumable and personnel use [4, 5, 16]. SC-TZM for example required a shorter preparation and administration time [5, 17]. The administration of SC-TZM was reported to be as short as five minutes compared to the IV-TZM_i infusions, which ranged from 60 to 90 min [5, 17, 18]. The reduction in time not only allows for optimal use of healthcare personnel but also reduced patients' productivity loss by requiring less chair time [1]. These cost-saving impacts were also echoed by Lee et al., in their study conducted in four Malaysian tertiary hospitals in 2016. They reported the switch brings about a cost savings of MYR 7,561 (USD 1,827) for the completion of the treatment regimen [5].

However, the introduction of intravenous biosimilar trastuzumab (IV-TZM_b) led to a drastic price reduction in conventional IV-TZM_i treatment. Biosimilar trastuzumab is similar to the reference biologics of the innovator, conferring similar clinical safety and efficacy. The cost on the contrary is often lower, contributed by the lack of an expensive drug discovery process and avoidance of clinical trial repetitions via extrapolation of the innovator drug’s safety and efficacy for indication approvals [19, 20]. There are currently three brands available in Malaysia – namely Hertraz and Zuhera which were registered back in 2018 and Herzuma which was registered in 2019 [21]. The introduction of these agents not only provided a cheaper option but also pressured further reductions of the prices of its counterparts in the market. The IV-TZM_b nevertheless, similar to IV-TZM_i, still requires more complex handling and a longer administration period, relative to the SC-TZM.

These dynamic changes in drug prices in addition to differing resource consumption of both SC-TZM and the newly formulary-listed IV-TZM_b raise the question of whether the previous clinical practice recommendations of switching IV-TZM_i to SC-TZM remain cost-saving, given the lower cost of IV-TZM_b. Although local evidence is available, it was mainly focused on the costs of SC-TZM and IV-TZM_i, instead of the biosimilar formulation [5]. Additionally, these data did not also capture the resource use in terms of consumables and personnel time, which are critical for selection and guiding local practice in public healthcare facilities. This study thus aims to estimate the cost of SC-TZM and IV-TZM_b in HER2-positive breast cancer, from the perspective of the Malaysian Ministry of Health.

Materials and methods

The current investigation was conducted as an activity-based costing study, incorporating a retrospective medical record abstraction and a prospective time motion study. The data collection was carried out in Hospital Pulau Pinang, Malaysia from December 2020 to Jun 2021. This is a publicly funded tertiary hospital that functions as the main cancer referral center for the Northern zone of Malaysia. The 2,130 bedded hospital was selected to ensure a diverse range of patient characteristics and a sufficient number of samples was obtained. The study was registered and approved by the Ministry of Health Medical Research Ethics Committee (NMRR-20–2364-54879).

Study design

Activity-based costing methodology assumes that while similar activities are required to provide the outputs, each activity would differ in terms of the proportion of resources required. This costing approach allows for variation between patients to be taken into account during the cost estimations [22]. In activity-based costing, the first step involves the identification of the practice pathway and the resources consumed for the provision of TZM treatment. In the study, the pathway was established via discussion with clinicians, oncology pharmacists, and nurses. Two main activities were identified following the discussion – drug preparation and administration. Based on these activities, three major cost components were included in the cost analysis—drugs, personnel, and consumables. Personnel involved can be further categorized based on the activities involved. As the study is based on a public healthcare provider perspective, there was no inclusion of patient out-of-pocket expenditures and productivity losses. Nevertheless, the total patient time for treatment with TZM was still obtained. This was based on discussions with stakeholders, where the value was used as a proxy for public healthcare facilities' resource use instead. This was important for policy planning in terms of resource allocations and possibilities for congestion if cost-saving but resource-intensive options are adopted. The cost components and data collection process are summarised in Fig. 1.

Fig. 1.

Study framework of activity-based costing

Medical Record Abstraction

A retrospective medical record abstraction was first conducted to obtain patient cohorts on SC-TZM and IV-TZM_b. As there was no published study in cost comparison between SC-TZM and IV-TZM_b, the sample size was estimated using available data on cost assessment of comparing SC-TZM with IV-TZM_i. Additionally, while the local study reported the mean difference between the formulation, there was no data on the standard deviation, which was required for sample size calculations. Thus, reported values from a similar study conducted in Greece were used based on the assumption that the mean cost differences would be consistent. A sample of 22 patients per group was required to detect a cost difference of EUR 1,248 (SD ± EUR 1,500), with a confidence level of 95% and power of 80%, [16].

As IV-TZM_b was just recently introduced in Hospital Pulau Pinang, there was an inadequate sample to fulfill the sample size criteria. The study thus opted to estimate the usage of IV-TZM_b based on existing patients on IV-TZM_i. The rationale for this was the dosing for IV-TZM_i and IV-TZM_b is the same and interchangeable. The sampling frame consisted of all HER2-positive breast cancer patients treated with TZM either in IV or SC formulation. Patients were identified from the registration list obtained from the Cytotoxic Drug Reconstitution Unit and Oncology Day Care. Only patients who had completed chemotherapy and were on single-agent adjuvant TZM therapy were included in the study. Metastasis breast cancer patients and patients on TZM as part of a combinational therapy were excluded. The initial data obtained from the patient records were age (in years), body weight (in kg), treatment cycles, route of administration, and prescribed doses (in mg). These data were used to estimate the drug cost and to characterize the patient group.

Time motion study

The time-motion study was conducted prospectively to quantify the time, consumables, and personnel involved in the preparation and administration of TZM. Upon identification of newly eligible patients, their drug preparation and administration were observed by an investigator. The investigator observed the process of pharmaceutical preparation and administration of one cycle of TZM. In pharmaceutical preparation, the tasks consisted of drug regimen worksheet preparation, preparation of materials, reconstitution, checking, and dispensing of the final product to the Oncology Day Care unit. The team involved in this task consists of pharmacists, pharmacist assistants, and general technicians. As for administration, the tasks involved patient preparation and initiation of IV or SC injection followed by post-administration management by the nurse or medical assistant. An electronic timer was used to capture the time interval from the beginning to the completion of each task by every personnel involved. Additionally, all consumables used in both processes were itemized and quantified.

Although patient cost was not included in the costing exercise, their time was captured to reflect the resource use in terms of the bed and facilities. Thus, investigators also observed and recorded patients’ time spent in the Oncology Day Care unit. The time was started at the point of patient registration and stopped only after the patient is successfully discharged. The time interval definitions are summarised in Table 1.

Table 1.

Summary of personnel and patient time interval by task

Task		Activity
Patient Waiting Time	:	From patient registration for TZM treatment to patient being discharged from the clinic
Pharmaceutical Preparation	:	From worksheet preparation (prescription screening and label preparation), component preparation (drug vial and consumables preparation), reconstitution (preparation in isolator and product labeling), and checking to the dispensing in the pharmacy department
Patient Preparation	IV	: From checking the patient's details, dose, regimen, and informing patients to the preparation of medication tray
	SC	: From checking the patient's details, dose, and regimen to informing patients
Administration	IV	: From giving pre-medications and initiating infusion to monitoring infusion
	SC	: From initiating subcutaneous injection and monitoring patients to applying plaster
Post-administration	IV	: From clamping the regulator, disconnecting brannula, applying plaster, and documentation to the patient being discharged from the clinic
	SC	: From documentation to the patient being discharged from the clinic

Valuation

The drug costs for SC-TZM and IV-TZM_b were obtained from the national public hospital tender price list, which was last updated on September 2021. The cost for a vial of 440 mg IV-TZM_b (Herzuma) was MYR 1,398.75 (USD 299.42) whereas 600 mg SC-TZM (Herceptin®) was MYR 3,492.50 (USD 747.62). According to the hospital TZM treatment protocol, IV-TZM_b required an initial loading dose of 8 mg/kg for the first treatment cycle, followed by a maintenance dose of 6 mg/kg for the next 16 cycles[23]. SC-TZM on the other hand was administered at a fixed dose of 600 mg to all patients, regardless of body weight [17]. Both TZM formulations had the same treatment interval of three weeks between cycles. Thus, to calculate drug costs, patients' cumulative doses over the course of treatment were multiplied by the respective cost per 1 mg of SC-TZM and IV-TZM_b.

Generally, patients with HER2-positive breast cancer who are on adjuvant TZM therapy would require 17 cycles of therapy [23]. Thus the observations of a single treatment cycle from the previous time motion study were multiplied by 17 to obtain the total time and consumable use. The total time by task type was multiplied by their respective personnel's hourly remuneration rate obtained from the finance department. This rate was dependent on the personnel type, grade, and whether the tasks involved team operations. For consumables, the total quantity of consumption was multiplied by prices obtained from the hospital procurement unit.

Analysis

A cost-minimization approach was adopted in this study, where only cost components were compared to provide evidence of the cost-effective treatment. This was based on the similar clinical efficacy and comparable side effect profile of both SC-TZM and IV-TZM_b [15, 24]. Thus, the findings reflect treatment with a lower cost that generates the same outcomes. The total cost of SC-TZM and IV-TZM_b was estimated by summing all three cost components (drugs, consumables, and personnel). An Independent t-test was applied to investigate whether there was a significant difference between the total cost. Additionally, both the cost parameters and time factor were also explored using an Independent t-test. All cost and time data were reported in mean, standard deviation (SD), and 95% confidence interval. The cost value was reported in Malaysian Ringgit (MYR) and United States Dollars (USD), following an exchange rate of MYR 1.00 = USD 0.2141.

A one-way sensitivity analysis was also conducted to explore the impact of uncertainties on the cost difference between SC-TZM and IV-TZM_b. The influence of numerous variables on the overall treatment cost of both TZM formulations was determined by sensitivity analysis. This was performed by varying cost input parameters using possible minimum and maximum values reported in the literature or based on expert opinions.

Result

A total of 36 IV-TZM_b and 32 SC-TZM samples were included in the study. Table 2 shows the characteristics of the subjects. The difference in the mean cumulative dose of IV-TZM_b and SC-TZM was mainly contributed by the dosing regimen. For every cycle, IV-TZM_b was dosed according to the patient’s body weight whereas SC-TZM was given at a fixed dose of 600 mg. Hence, the cumulative dose and drug cost for 17 cycles of SC-TZM appeared to be constant.

Table 2.

Characteristics of patients treated with IV-TZM_b and SC-TZM

Characteristics	IV-TZMb (n = 36)	SC-TZM (n = 32)
	Mean (SD)	95% CI	Mean (SD)	95% CI
Age (years)	47.2 (7.4)	44.7-49.7	47.8 (8.8)	44.6-51.0
Weight (kg)	59.0 (10.7)	55.3-62.6	66.6 (13.2)	61.9-71.4
Cumulative dose (mg)	6,120.0 (1112.6)	5,743.6-6,496.4	10,200.0a	N/Aa

N/A: not applicable

^aStandard deviation and 95% CI was not available as the value of the cumulative dose for SC-TZM remains constant due to the fixed dosing regimen

Figure 2 further shows the time interval by task for 17 cycles of treatment. Personnel time was evidenced to be significantly higher for IV-TZM_b at every task compared to SC-TZM cost (p < 0.05). Overall, the personnel time for IV-TZM_b was 27.29 h longer than SC-TZM. This was predominantly contributed by the higher personnel time for drug administration, which formed 82.4% of the total time for IV-TZM_b. The biggest time differences were also seen in drug administration, with a reduction of 92.7% when switching from IV-TZM_b to SC-TZM. Correspondingly, the patient time for IV-TZM_b was longer by 24.76 h per patient compared to SC-TZM.

Fig. 2.

Time interval by task for 17 cycles of TZM treatment

Table 3 shows the total cost and breakdown by its components over 17 treatment cycles. IV-TZM_b had a constant cost for the consumables because the preparation task was not dose-dependent. The pharmaceutical preparation requires a similar number of consumables regardless of the dose required. As for SC-TZM, it had a constant cost for both the drug and consumable components. This was because SC-TZM had a fixed cumulative dose of 10,200 mg. Overall, significant differences were seen in all of the cost components. The total cost for IV-TZM_b was significantly lower than SC-TZM by MYR 37,686 (SD = 641), p < 0.0001 (USD 8,068). The switch to IV-TZM_b will bring about a net saving of 58.9% from the total SC-TZM cost. This was predominantly contributed by a large reduction in the drug cost of IV-TZM_b compared to SC-TZM, by about 67.2% [MYR 19,455 (USD 4,165) versus MYR 59,372 (USD 12,711)]. However, IV-TZM_b generated significantly higher consumable and personnel costs, an increase of 32.3% and 344% respectively when compared with SC-TZM.

Table 3.

Total treatment cost (in MYR) per patient for 17 cycles of TZM

	IV-TZMb (X)		SC-TZM (Y)		Mean difference, [Y-X](SD)		P-value*
	Mean (SD)	[95% CI]	Mean (SD)	[95% CI]		[95% CI]
(i) Drug
Trastuzumab	19,455 (3,537)	18,258—20,652	59,372a	N/Aa	39,917 (626)	38,668—41,167	< 0.001
(ii) Consumable items	5,750 (462)	5,594—5,906	4,345b	N/Ab	-1,405 (82)	-1,568 – (-1,242)	< 0.001
a. Preparation task	3,911b	N/Ab	3,885b	N/Ab	-26.0a	N/Ab	N/Ab
b. Administration task	1,831 (462)	1,683—1,996	461b	N/Ab	-1,379 (82)	-1,542 – (-1,216)	< 0.001
(iii) Personnel	1,067 (180)	1,006—1,127	240 (67)	216—265	-826 (34)	-894 – (-759)	< 0.001
a. Preparation task	258 (76)	233—284	157 (62)	135—179	-101 (17)	-135 – (-67)	< 0.001
b. Administration task	808 (162)	753—863	83 (39)	69—97	-725 (29)	-784 – (-782)	< 0.001
Total Cost	26,272 (3,620)	25,047—27,497	63,958 (67)	63,934—63,983	37,686 (641)	36,407—38,965	< 0.001

N/A: not applicable, MYR: Malaysian Ringgit

*Difference between IV- TZM_b and SC-TZM based on independent t-test, with significance set at p < 0.05

^aStandard deviation and 95% CI was not available as the value over the 17 cycles of TZM treatment for SC-TZM was estimated from a fixed cumulative dose of 10,200 mg

^bStandard deviation and 95% CI was not available as the value over the 17 cycles of TZM treatment for IV- TZM_b and SC-TZM was estimated from same items used per cycle

According to the one-way sensitivity analysis in Table 4, drug costs were the primary driver of total treatment costs for both formulations. Whereas administration costs, consumable costs and personnel time had only minor effects, as evidenced by the smaller range of difference between the minimum and maximum total values.

Table 4.

One-way sensitivity analysis

Input Parameter		Base Case Value	Minimum	Maximum	Cost difference from base-case scenario ( MYR 37,686 – newly calculated estimate)
					Cost-difference at minimum value (MYR)	Cost- difference at maximum value (MYR)
Drug cost for IV-TZMb		MYR 1,399	MYR 1,200	MYR 2,500	− 2,773	15,309
Drug cost for SC-TZM		MYR 3,493	MYR 3,000	MYR 4,300	8,363	− 13,737
Consumable cost (preparation and administration)	IV:	MYR 5,741	MYR 4,593	MYR 6,889	− 288	270
	SC:	MYR 4,346	MYR 3,746	MYR 5,215
Administration cost per dose		MYR 29.52	MYR 12.60	MYR 43.20	− 415	359
IV-TZMb administration time per dose		1.62 h	1.3 h	1.94 h	− 168	156
IV-TZMb preparation time per dose		0.34 h	0.18 h	0.51 h	− 134	116

Discussion

The results of this study suggest that overall IV-TZM_b was more cost-saving compared to SC-TZM. The availability of IV-TZM_b generated a large margin of drug cost reduction, which was able to compensate for the slight increase in consumable and personnel costs. These findings were contrary to many studies published internationally and locally using the innovator formulation cost (IV-TZM_i). The study by Mylonas et al., for example, reported the total cost of treatment for SC-TZM was lower by EUR 1,248 compared to IV-TZM_i [16]. Consistently Rojas et al., who conducted a similar study in a Chile private hospital reported a cost savings of USD 6,241 per patient in favor of SC-TZM when compared with IV-TZM_i [4]. These findings were consistent with the currently available local cost analysis by Lee et al., where SC-TZM saved up to MYR 7,561 (USD 1,619) compared to IV-TZM_i [5]. The primary reason for this disparity is the higher-priced innovator IV-TZM_i formulation used. When compared to biosimilars, the price of the innovator drugs was approximately 20.0% to 75.0% higher [25].

Although our study used the cheaper biosimilar as the comparator, drug cost remained the main cost driver. However, when compared to other studies, the contribution of IV-TZM_b was lower at 74.0%. Mylonas et al., reported that drug costs accounted for 96.0% and 99.0% of total treatment costs for IV-TZM_i and SC-TZM [16]. A similar contribution was also seen in the Malaysian study by Lee et al., where drug costs accounted for 98.2% and 99.3% of total treatment costs for IV-TZM_i and SC-TZM [5]. The lower drug cost contribution in our study was primarily due to the reduction in overall drug price rather than an increment in other cost components. Based on the price guide in 2019, the drug cost of IV-TZM_b was lesser by 53.0% compared to the innovator price [MYR 1,399 (USD 300) versus MYR 2,990 (USD 640)].

One of the interesting findings observed was the impact of body weight on the cost-saving of TZM therapies. Heavier patients and patients showing an increment in body weight over time will require higher doses of IV-TZM (both biosimilars and innovators) because it is dosed according to the patient’s body weight [18]. This means the cost of IV formulation will increase more rapidly relative to the constant dosing of SC-TZM as more drugs are required. [4, 5, 18]. Previous studies evidenced that SC-TZM was more cost savings than IV-TZM_i, especially when the patient’s body weight increased over the course of treatment [16, 17]. Our study on the contrary evidenced that SC-TZM will only be more cost-saving than IV-TZM_b for patients above 143.6 kg. This was because albeit being dosed by body weight, the cost per mg of TZM for the biosimilar was still very much cheaper than the SC-TZM.

It is worth highlighting that even though the switch from SC-TZM to IV-TZM_b will bring about a net cost saving of 58.9%, it unfortunately also led to a small increment in the consumable and healthcare personnel cost. In the setting of Malaysian public hospitals, both components contributed to only a 3.5% increment from the total SC-TZM treatment. This was relatively small compared to the 62.4% saved on drug costs. However, in high-income countries with higher consumable costs and personnel wages, the net margin of cost savings might be further reduced [4, 16, 26].

Benefits of SC-TZM

SC-TZM confers three main advantages over IV-TZM (biosimilar or innovator) – personnel time, resource use, and patient preference. For healthcare personnel, for example, the time spent in the pharmacy preparing and dispensing IV-TZM_b was 1.6 times more than that of SC-TZM. IV-TZM_b vial preparation requires different dose calculations based on the patient’s body weight. Additionally, the reconstitution process must be handled carefully to avoid foaming before transferring an appropriate amount of solution into the infusion bottle [18]. SC-TZM on the other hand is administered at a fixed dose and is packaged in a 600 mg/5 mL ready-to-use solution vial [17]. Similarly, nurses also spent more time on IV-TZM_b infusion-related tasks, such as catheter installation, central venous access device checking, infusion pump setting, line flushing, hydration, and infusion. The findings were consistent with the time-motion study conducted concurrently with the PrefHer trial, in which a 29% reduction in drug preparation time and 56% in administration time was reported for SC-TZM [27].

As patient time was also used as a proxy for healthcare resource use, it can be postulated that the switch to IV-TZM_b may lead to higher consumption of other resources. These can be in the form of overhead costs such as utilities, in addition to inpatient and bedside care. While this was not accounted for in this costing exercise, a study by Azzani et al., among colorectal cancer patients in Malaysia evidenced that resources used in the daycare can still be significant. This can arise from labor costs aside from the preparation and administration of chemotherapy, equipment, medical supplies, and general overheads [28]. Thus, although being more expensive, SC-TZM may save costs in terms of shared resources.

SC-TZM is also the preferred treatment option based on the patient’s perspective. This is because SC-TZM requires lesser time spent in healthcare facilities. The patient out-of-pocket expenditures might not show large savings due to the highly subsidized public healthcare in Malaysia. However, the patient’s and carers’ loss of productivity due to absenteeism may be significant [14, 29]. Furthermore, besides cost, studies have also shown that patients, in general, prefer SC-TZM in outpatient settings compared to IV-TZM in inpatient wards. Patients reported that the process was more efficient and comfortable [30]. A multi-centered study in the United Kingdom by Pivot et al., also reported that 88.9% out of 467 patients surveyed preferred SC-TZM administration, with 80.3% of them attributing the preference due to the time saved [24, 31].

Financial Implications and Policy Recommendations

With the increasing health budget constraints and ever-growing medical inflations, the current public health service aims to improve cancer care efficiency to better use available resources without compromising the quality of care [32]. Initiatives such as switching from SC-TZM to IV-TZM_b may benefit the population while awaiting increased financial allocations [33]. This can be best illustrated by the projected financial impact of the introduction of IV-TZM_b in Croatia. The study expected savings of EUR 0.26 million to EUR 0.69 million in just after one year of IV-TZM_b uptake for treating patients with metastatic breast cancer or early breast cancer [34]. On the other hand, a study involving 28 European countries demonstrated switching to IV-TZM_b could allow 55,000 to 116,000 additional patients to be treated with TZM [35]. From the perspective of a tertiary public hospital in Malaysia, treating 100 patients over a year in our facility could result in a budget savings of MYR 3,768,617 (USD 806,860).

A potential benefit of SC-TZM over IV-TZM_b that can be taken into consideration is the healthcare personnel and patient time saved. For a full treatment course of SC-TZM, approximately 26.14 h were saved during the administration period. Time saved from SC-TZM treatment can be utilized efficiently by relocating the existing staff to serve in other critical areas and improve patient monitoring [1, 36]. From the hospital perspective, drug formulation that results in shorter patient time provides greater availability of beds to other patients who require IV treatment in the unit. This indirectly will further reduce congestion and patients’ waiting time for oncology treatment [4, 11, 31, 33, 37, 38]. Such an issue remains pertinent as delays in treatment were identified as one of the reasons for treatment failures in public healthcare settings [39].

Furthermore, breast cancer treatment demands substantial time commitment from patients and their family members [38]. Patients who received SC-TZM found greater flexibility in making appointments which enable them to integrate breast cancer treatment into their daily activities [27]. Such a factor is also important in ensuring compliance [1, 24]. Thus, both the time and availability of carers should also be taken into consideration in selecting the type of formulation. Nevertheless, it is worth pointing out that although most patients preferred SC-TZM, these preferences were not reflected by a significant difference in health-related quality of life survey when compared with IV-TZM_i. Thus, in terms of patient-reported quality of life, both forms of TZM are still comparable [30].

Limitations

There are several limitations to our findings arising from the study design. Firstly the small sample size and single-center data may reduce the generalization of the findings from this study to other settings. However, there is no regional variation in drug costs in public healthcare facilities because these are purchased under a national tender system. While there might be variation in the total number of personnel required, their unit costs are also constant and do vary only by their personnel wage grades. As a result, the findings are likely to be applicable across all public healthcare facilities in Malaysia. Secondly, the current method of cost estimation focusing on resources in the preparation and administration stages only may underestimate the actual burden. Such an approach was taken to simplify the cost estimation process. Thus, the inclusion of overhead costs and shared resources may show a higher financial burden than reported. Lastly, the study did not take into account societal perspectives, which also underestimates the true difference in terms of the impact of the switch. Thus it is recommended for future studies to include patients' time spent in the clinic, preferences, utility, and quality of life for both formulations.

Conclusion

Given the similar pharmacokinetic and clinical profiles of SC-TZM and IV-TZM_b formulations, there are several factors such as cost, personnel time and patient preference that need to be considered when selecting the type of TZM formulation. From the public hospital perspective, the cost-saving from IV-TZM_b allows for an additional budget for expanding the treated population or providing other treatment options for patients [12]. On the other hand, SC-TZM benefits facilities that may face challenges in terms of availability of personnel and congestion. However, from an economic standpoint and accessibility of treatments, the IV-TZM_b at a lower drug cost outweighed the modest benefits of SC-TZM. Hence, based on our study findings, we encourage the clinical practice to be revised to prioritize the use of IV-TZM_b instead of SC-TZM for the treatment of patients with HER2-positive breast cancer. The savings can then be reallocated to improve the human resources required to manage the therapy. It is also hoped that the cost data may aid in further exploration of future breast cancer treatment cost-effectiveness and efficiency.

Supplementary Information

Below is the link to the electronic supplementary material.

Data Availability

The data supporting the study’s conclusions are available upon request from the corresponding author. 

Declarations

Conflict of Interest

There are no declared competing interests of the authors that are pertinent to the subject matter of this study.