Modeling Cancer Outcomes and Economic Impact of the Anti-PD-1/PD-L1 Immunotherapy in the Gulf: United Arab Emirates, Oman, and Kuwait

Abstract

Background and Objectives

Cancer has a substantial health and economic impact on the populations of the Gulf countries—the United Arab Emirates (UAE), Kuwait, and Oman; however, uncertainty remains among decision-makers, payers, and stakeholders regarding their clinical and economic advantages. Hence, this study aims to evaluate the potential health and economic impact of programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitor immunotherapies to reduce uncertainty and inform coverage, reimbursement, and treatment decisions across the Gulf region.

Methods

The Health Impact Projection (HIP) model, a partitioned survival model, was adapted from a payer perspective for the UAE, Oman, and Kuwait to explore the health and economic impact of the anti-PD-1/PD-L1 class over 2022–2026 among key indications, including: first line non-squamous non-small cell lung cancer (1LNSCLC), neo-adjuvant triple-negative breast cancer (TNBC), metastatic TNBC, head and neck cancer, 1L metastatic urothelial carcinoma, metastatic renal cell carcinoma (RCC), second line endometrial cancer, 1L cervical cancer, and colorectal cancer. The model adopted a 1-to-5-year time horizon, structured in weekly cycles, with a new cohort joining yearly. Model inputs were based on publicly available data, literature, and expert advice.

Results

The model estimated that, over 5 years, 3763 patients across the UAE, Kuwait, and Oman would receive anti-PD-1/PD-L1s treatments, resulting in total gains of 1745 life years, 2791 progression-free survival (PFS) years, and 1625 quality adjusted life-years (QALYs). The introduction of anti-PD-1/PD-L1s would have an average annual impact of $149 million and a 0.17% share of healthcare expenditure in 2022. While disease management and drug acquisition costs are significant, they are partly offset by reductions in end-of-life costs ($1,011,773/year) and cancer-related productivity losses ($3,111,454/year).

Conclusions

The HIP model aids horizon scanning by providing a framework for stakeholder discussions on equitable access to anti-PD-1/PD-L1 treatments. It highlights the notable survival and QoL benefits of this novel class in Gulf countries, achievable with a modest 0.17% increase in healthcare expenditure.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1007/s40261-026-01577-5.

Key Points

Cancer imposes a growing health and economic burden in Gulf countries, and anti-PD-1/PD-L1 immunotherapies have demonstrated clinical benefit across several tumor types.

Gulf region-specific Health Impact Projection (HIP) model estimating the clinical and economic value of anti-PD-1/PD-L1 therapies in the UAE, Kuwait, and Oman demonstrated consistent survival gains across all three countries, including a 20% increase in life-years gained, a 24%–25% increase in QALYs, and a 68% increase in progression-free life-years.

These health gains can be achieved with minimal impact on total healthcare expenditure, as drug acquisition costs are partially offset by reductions in indirect costs and end-of-life care, supporting Gulf policymakers in budget planning and resource allocation for immunotherapy.

Introduction

Cancer is a significant health issue in the United Arab Emirates (UAE), Kuwait, and Oman. In 2021, UAE experienced 5830 new cases and 975 deaths, making it the fifth leading cause of death [1]. Kuwait experienced 4347 new cases and 1968 deaths in 2022 [2]—making it the second leading cause of death [3]. Oman had 4045 new cases in 2022, with an age standardized incidence rate of 105.3 per 100,000 [4]. There were 2261 deaths attributed to cancer in Oman [4]. Despite the young demographics in Kuwait and Oman, and the growing and urbanizing population of UAE, there is an increase in cancer morbidity and mortality among these selected Gulf citizens [5–7].

These Gulf countries have government-funded public healthcare systems for their nationals, with significant and growing investment in their healthcare sectors, including expansion of the private healthcare sector in the UAE [8–14]. Kuwait’s Vision 2035 and Oman’s Vision 2050 aim to reduce the socio-economic burden of cancer by improving the availability and accessibility of high quality infrastructure and expertise [14–16]. In the UAE, many public and private facilities are now integrated for oncology care [17], the Ministry of Health and Prevention (MoHAP) has developed a cancer control plan for 2022–2026 that aims to reduce the incidence of cancer, reduce the number of cancer deaths by 25%, and improve patient quality of life [18]. These efforts demonstrate the ongoing dedication of Gulf countries to provide high quality, accessible, and efficient cancer care, ultimately improving patients’ quality and longevity of life.

Each type, location, and disease stage of cancer has extensive treatment options including chemotherapy, radiotherapy, immunotherapies, and targeted therapies. Chemotherapy remains the most used modality and is considered standard of care (SOC) in various oncology cases, despite being associated with very high levels of toxicity and significant declines in patient quality of life, especially during advanced disease stages [19, 20]. Some patients might discontinue or refuse treatment due to the severity of high-grade adverse events (AEs) experienced; thus, forgoing survival benefit that might have been gained [21]. Consequently, there is a need to increase access to treatments that can prolong survival while still having a reduced toxicity.

The approval of novel immunotherapy treatments across various cancer indications in the last 5 years has significantly improved cancer care [22]. Globally, immuno-oncology breakthroughs and precision biomarkers have become SOC in a wide range of malignancies due to their significant clinical efficacy, prolonging survival, and helping patients achieve remission [23, 24].

This is particular for the programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitor class of immunotherapies that includes agents such as: atezolizumab, avelumab, cemiplimab, durvalumab, nivolumab, and pembrolizumab. Programmed cell death protein-1 and PD-L1 play a crucial role in regulating the immune system and maintaining immune homeostasis by preventing autoimmune responses. However, cancer cells can manipulate this regulatory pathway, overexpressing PD-L1 to suppress immune surveillance and evade destruction, thereby promoting unchecked tumor growth. Therapies targeting the PD-1/PD-L1 pathway have transformed cancer treatment by restoring the immune system's ability to recognize and eliminate tumor cells, demonstrating significant effectiveness across a broad range of cancer types [25]. A systematic review and meta-analysis of 35 randomized controlled trials encompassing over 21,000 patients demonstrated that anti-PD-1/PD-L1 inhibitors confer a significant survival advantage over conventional therapies, establishing them as a preferable treatment option for advanced or metastatic cancer [26]. Beyond efficacy, the therapeutic class also demonstrated a more favorable tolerability profile compared to SOC treatments. A meta-analysis of seven randomized controlled trials involving 3450 patients found that PD-1/PD-L1 inhibitors carried a significantly lower risk of fatigue, sensory neuropathy, hematologic toxicities, anorexia, nausea, and constipation. Treatment discontinuation also showed lower risks [27].

Recent advances in combining PD-1/PD-L1 inhibitors with chemotherapy, radiotherapy, and other treatment modalities have further enhanced patient outcomes, and additional combination regimens are expected to continue reshaping the immuno-oncology landscape [28, 29].

The rapid expansion of PD-1/PD-L1 therapies across multiple cancer indications has raised concerns around long-term affordability. The global oncology drug market, valued at USD193.04 billion in 2024, is expected to more than double to USD503.13 billion by 2033, with immunotherapies representing a key driver of this growth [30]. This escalating financial burden places a strain on healthcare systems, compelling ministries, payers, and budget planners to make increasingly complex reimbursement decisions, a challenge that is pronounced in government-funded systems such as those across the Gulf countries, where the acquisition costs of these agents weigh heavily on national healthcare budgets. Therefore, there is a critical need for comprehensive, region-specific analyses of the potential health and economic impact of PD-1 and PD-L1 inhibitor immunotherapies in the UAE, Kuwait, and Oman to support evidence-based decision making and ensure equitable patient access to these innovative therapies.

The HIP Model

The Health Impact Projection (HIP) model forecasts the key health and economic outcomes of anti-PD-1/PD-L1 across indications (compared to SOC) over a 5-year period. It is based on a set of assumptions and gathers country-level data on health-related factors. The model draws on budget impact analysis, and scenario inputs are incorporated. It aids decision making in public health and policy.

Study Objectives

Evidence on the impact of the anti-PD-1/PD-L1 class on the three Gulf healthcare systems is scarce and focuses on individual tumor locations or medicines. With the aim of reducing uncertainty and informing decision makers, payers, and stakeholders, the HIP model was adapted to UAE, Kuwait, and Oman to explore the health and economic impact of the anti-PD-1/PD-L1 class—the first systematic effort of this kind in the region.

Material and Methods

This HIP model evaluation explored the health and economic impact of the anti-PD-1/PD-L1 class compared to SOC treatments over a 5-year period (2022–2026) for the following 11 key indications: first-line non-squamous non-small cell lung cancer (1L NSCLC), neo-adjuvant triple-negative breast cancer (TNBC), metastatic TNBC, head and neck cancer, 1L metastatic urothelial carcinoma, metastatic renal cell carcinoma (RCC), second line endometrial cancer, 1L cervical cancer, and colorectal cancer. These indications were selected due to the high disease burden in the Gulf Cooperation Council (GCC), and the high number of patients receiving immune-oncology therapy for these indications. The model estimated the number of patients treated, health impacts gained, and healthcare costs accrued in the context of the three selected Gulf countries and their specific healthcare systems. The HIP model takes the payer perspective, including productivity losses.

Model Structure

The model compared healthcare outcomes and costs between a reference scenario where all patients received SOC and an intervention scenario where patients received a mix of SOC and anti-PD-1/PD-L1 treatment, with the difference between scenarios representing the full health and economic impact of introducing this therapeutic class (Fig. 1).

Fig. 1.

Diagram of the model structure. PD-1 programmed cell death protein 1, PD-L1 programmed cell death-ligand 1

Health outcomes included life-years (LYs) gained, quality-adjusted life-years (QALYs) gained, progression-free life-years (PFLYs) gained, and adverse events (AEs) experienced, while economic outcomes encompassed treatment and indirect costs. Both were compared over a 5-year time horizon.

Partitioned survival modelling was used to estimate survival outcomes and budget impact, preferred over Markov modelling for its alignment with published literature and lower data requirements [31–33]. Survival outcomes were modelled at the class level, with a conservative approach applied to trial selection to avoid overestimation of treatment benefits [31–33]. Hazard ratios (HRs) derived from pivotal clinical trials were applied to SOC survival curves to generate anti-PD-1/PD-L1 survival curves for each indication, with goodness of fit assessed through visual inspection [31–33]. Utility weights applied to each health state informed QALY generation, while costs were assigned according to patients' health state and treatment status at each cycle. A detailed overview of the indications, corresponding anti PD-1/PD-L1 treatments, SOC comparators, and clinical trials used in the model can be found in Tables 1 and 2 of Rachev et al (2020) [31].

Table 1.

Health gains due to the introduction of anti-PD-1/PD-L1s by the whole patient population in UAE, Kuwait and Oman

Health outcome	Across the three countries: over 2022–2027 +
	Total absolute change	Relative change
Life-years gained	1745	+ 20%
QALYs gained	1625	+ 25%
Progression-free life-years gained	2791	+ 68%
AEs experienced	54	+ 3%
UAE
Life-years gained	796	+ 20%
QALYs gained	734	+ 24%
Progression-free life-years gained	1287	+ 68%
AEs experienced	32	+ 4%
Kuwait
Life-years gained	507	+ 20%
QALYs gained	470	+ 24%
Progression-free life-years gained	804	+ 68%
AEs experienced	13	+ 2%
Oman
Life-years gained	442	+ 20%
QALYs gained	421	+ 25%
Progression-free life-years gained	700	+ 68%
AEs experienced	9	+ 2%

AEs adverse events, PD-1 programmed cell death protein 1, PD-L1 programmed cell death-ligand 1, QALY quality-adjusted life year, UAE United Arab Emirates

Table 2.

Yearly breakdown of the health care economic impact of the anti-PD-1/PD-L1 class in UAE, Kuwait and Oman (in million USD)

Country	2022	2023	2024	2025	2026	2027+	Average	Total
UAE	33.21	42.42	43.25	43.92	43.98	11.66	41.13	206.53
Kuwait	30.45	58.31	66.92	72.22	79.09	36.41	61.87	309.35
Oman	33.54	46.80	49.66	53.04	56.42	25.74	47.92	239.61

PD-1 programmed cell death protein 1, PD-L1 programmed cell death-ligand 1, UAE United Arab Emirates

Model Inputs

This study used a combination of existing inputs from the HIP with inputs locally sourced and adapted specifically for the three selected Gulf countries (Fig. 2).

Fig. 2.

Non-adapted and adapted inputs. AEs adverse events, PD-1 programmed cell death protein 1, PD-L1 programmed cell death-ligand 1

The existing HIP offers the flexibility to choose different trials for each treatment. The selection of clinical trials for a treatment within an indication was based on identifying the most pivotal trial. In cases where appropriate clinical trials were unavailable for a specific treatment within an indication, clinical data from similar anti-PD-1/PD-L1 treatments or indications were assumed to be transferable. Clinical inputs within HIP outline the evidence pertaining to each treatment's health outcomes, including progression-free survival (PFS) and overall survival (OS), drawing from key clinical trials involving anti-PD-1/PD-L1 treatments for the diseases covered in HIP. These parameters were not adapted to the selected Gulf markets and were kept unchanged [29]. In addition, clinical data, high-grade AE rates, country-specific utility inputs, and maximum treatment duration for each product remained unchanged and were not adapted to the selected Gulf markets, using the original inputs instead [29].

Model Inputs Adaptation Methodology

The parameters adapted encompassed a wide range of model inputs and settings. Inputs included country setting data (population size, annual growth rate, inflation rate), drug wastage, and direct and indirect costs.

Direct costs include drug acquisition, administration, PD-L1 testing, treatment-associated AEs, hospitalization, and palliative care, in addition to weekly disease management costs, which included monitoring costs (laboratory tests, diagnostics, follow-up visits/monitoring).

The weekly costs for disease management represent the expected expenses for a patient based on their treatment and disease condition. Each disease incurs a cost for patients treated with an anti-PD-1/PD-L1 in both progression-free (PF) and progressed disease (PD) states, as well as the weekly cost for a patient on SOC in PF and PD. These figures exclude the costs related to each treatment dose, including administration and drug acquisition costs.

Indirect costs included the costs to society due to loss of productivity, estimated as hours of work lost using the human capital approach. Hours of work lost per week were estimated across four health states: progression-free on treatment, progression-free off treatment, progressed disease state, and dead, and varied by country. These hours were monetized using country-specific national average hourly wage rates.

All cost inputs are collected in local currencies (Emirati Dirham, Omani Rial, and Kuwaiti Dinar, for the UAE, Oman, and Kuwait, respectively) and subsequently converted and reported to United States Dollars (USD) using 2025 annual average exchange rates.

The adapted inputs used in HIP were sourced from published literature (see Sect. 2.3.1) and insurance data claims (see Sect. 2.3.2) then validated through interviews with Key Opinion Leaders (KOLs) (see Section 2.3.3) and are detailed in the Supplementary file.

Literature Review

A targeted literature review was conducted on PD-1/PD-L1 class to gather information about the treatment patterns and costs, total drug expenditure, monitoring tests (laboratory, imaging) frequency, and high-grade AE management.

The review involved a targeted (non-systematic) search of the PubMed and Cochrane Library, in addition to National Comprehensive Cancer Network (NCCN) guidelines, American Society of Clinical Oncology (ASCO) guidelines, the MSD Manual (a comprehensive medical reference book) and peer-reviewed journals.

Insurance Data Claims

Data from 2022 were collected from Globemed—a third-party administrative patient data claims database encompassing over 25 million insured members in the Middle East and North Africa (MENA) region. Unit costs for laboratory tests, imaging, physician consultations, procedures, hospitalization and drug administration were generated using International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes, as well as a micro-costing cost component method.

Laboratory tests included: liver function test, renal function test, complete blood count (CBC), carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, CA 19.9, electrolyte panel, glucose, and thyroid tests.

Imaging tests included: computed tomography (CT-scan) with-contrast, abdomen/pelvis CT-scan with-contrast, bone scan, positron emission tomography (PET), mammography, colonoscopy, and electrocardiogram.

Interviews with Key Opinion Leaders (KOLs)

Treatment-related AE costs, end-of-life costs, drug wastage rates, and hours of work missed due to cancer across disease stages were estimated through expert estimations, as such data are not readily available in the published literature for this setting. All remaining cost and epidemiological parameters were sourced from a structured literature review and insurance claims data and subsequently validated by KOLs to ensure alignment with local clinical practice. Nine KOLs, including oncologists and health economists, representing the Ministry of Health (MOH) as well as both governmental and private hospitals, were interviewed across the selected Gulf countries. In the UAE, representatives from institutions such as Dubai Health Insurance Corporation, Sheikh Shakhbout Medical City, and Burjeel Cancer Institute in Abu Dhabi were interviewed. Similarly, in Kuwait, experts were consulted from the MOH and Kuwait Cancer Control Center. Meanwhile, in Oman, representatives were interviewed from Oman Royal Hospital and Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCC).

Adapted Input Value Determination

The data retrieved for each adapted parameter from the literature review (2.3.1), insurance data claims (2.3.2), and interviews from KOLs (2.3.3), were reviewed and analyzed to determine the adapted model input values. The estimations provided by KOLs were used as the final model inputs. To ensure representativeness, averages were calculated, and any outliers were identified and excluded to preserve the integrity of the dataset.

Drug acquisition costs were adapted based on the UAE, Kuwait and Oman public drug list. For unavailable prices assumptions were obtained from the interviews with the KOLs. As such, the economic impact of the anti-PD-1/PD-L1 class was likely to be an upper-estimate.

Analysis

The model incorporates a budget impact analysis (the total economic impact of introducing anti-PD-1/PD-L1’s for the years between 2022 and 2026), alongside an evaluation of the comparative health advantages, including gains in LYs and QALYs. Partitioned survival model was used to estimate survival outcomes in each scenario.

The model adopted a 1-to-5-year time horizon, structured in weekly cycles, with a new cohort joining yearly. Costs and health outcomes were discounted at an annual rate of 5% for all Gulf countries evaluated. This time horizon was later extended to show the results of year six onwards as a single set of results “2027 +”, that captures the outcomes for all cohorts for a full 5 years after treatment commencement. “2027 +” is not to be compared to other years in the model as it is modelled differently and is not included in any of the calculated averages. Total costs of the anti-PD-1/PD-L1 class were also estimated via combining costs of individual products and estimating a weighted average using the market share of each product in each selected Gulf country. All costs are reported in USD.

One-way deterministic sensitivity analysis was included in the model to determine the impact of uncertainty on a specific parameter, increase confidence in the model estimations and inferences, and identify key drivers of the model’s results [34]. A variation range of ±25% was applied to incidence rates, market shares, treatment rates, utility values, and maximum treatment duration to capture the extreme bounds of uncertainty across these parameters and ensure a consistent relative change in input values. Cost inputs, including management, treatment, and AE costs, were varied by a narrower range of ±10%, reflecting their derivation from real-world observed expenditures and consequently lower uncertainty.

Results

The model estimated that a total of 3763 patients would be treated with anti-PD-1/PD-L1, across the 11 indications over a 5-year time horizon with 956 patients in Oman, 1089 patients in Kuwait, and 1718 patients in the UAE.

After 5 years of anti-PD-1/PD-L1 drug implementation across all indications and all patients in all countries, the HIP model projected additional gains in LY, with a total of 1745 LYs (+ 20%) expected. This projection includes anticipated increases in LYs for each respective country: UAE is expected to gain 796 LYs (+ 20%), Kuwait 507 LYs (+ 20%), and Oman 442 LYs (+ 20%).

Once quality adjusted, an increase of approximately 1625 QALYs is projected, with 734 (+ 24%) for the UAE, 470 (+ 24%) for Kuwait and, 421 (+ 25%) for Oman—an average of 25% rise compared to SOC outcomes. Additionally, a total of 2791(+ 68%) progression-free life years (PFLYs) gained are expected, with 1287 (+ 68%) for the UAE, 804 (+ 68%) for Kuwait and, 700 (+ 68%) for Oman. The model also predicts a 3% relative increase in the number of high-grade AEs, totaling + 54 events, with 32 (+ 4%) for the UAE, 13 (+ 2%) for Kuwait, and 9 (+ 2%) for Oman.

Table 1 summarizes the absolute and relative results per health outcome incurred by introducing anti-PD-1/PD-L1 class. It shows the difference in outcomes between the scenario with anti-PD-1/PD-L1s and the reference case scenario without.

In terms of budget impact, the total economic costs are expected to increase by 313% in the base-case scenario compared to the reference scenario in the UAE, with an average cost of USD41.13 million over the 5 years and a total cost of USD206.53 million. In Kuwait, total economic costs are expected to increase by 321% compared to the reference scenario, reaching an average cost of USD61.87 million and a total cost of USD309.35 million. In Oman, total economic costs are expected to increase by 404%, reaching an average cost of USD47.92 million and a total cost of USD239.61 million (details in Table 2).

Figure 3 illustrates the health and economic impact of the anti-PD-1/PD-L1 class over 5 years.

Fig. 3.

Health and economic impact of anti-programmed cell death protein 1/programmed cell death-ligand 1 (Over 2022–2026). LYs life years

Table 3 provides a breakdown of the various cost components contributing to the overall economic impact from 2022 to 2026. Among these components, drug acquisition costs stand out as the primary contributor to the total economic impact during this 5-year period. Additionally, the introduction of anti-PD-1/PD-L1s is projected to lead to a decrease in indirect costs. Specifically, over a span of 5 years, this implementation is anticipated to result in a reduction of over USD780 thousand in the UAE. Moreover, the implementation of anti-PD-1/PD-L1s is expected to bring about a decrease in indirect costs totaling approximately USD1.5 million in Oman and around USD809 thousand in Kuwait over a 5-year period.

Table 3.

Cost category breakdown of the economic impact in UAE, Kuwait and Oman (in USD)

Cost category	Average economic impact for all indications (2022–2026) (USD)
	UAE	Kuwait	Oman
Disease management costs	429,960.72	517,488.06	254,298.07
Administration costs	1,067,138.17	706,166.44	167,425.69
Drug acquisition costs	41,286,126.58	60,840,601.89	49,127,288.68
PD-1/PD-L1 testing costs	38,716.91	0	0
Indirect costs	− 780,798.56	− 809,528.31	− 1,528,127.46
Adverse events costs	36,248.14	14,083.77	10,703.17
Wastage costs	8,933.34	31,651.11	12,232.94
End-of-life costs	− 431,048.67	− 319,359.08	− 261,365.47
Total	41,641,541.28	61,028,797.70	47,786,017.31

PD-1 programmed cell death protein 1, PD-L1 programmed cell death-ligand 1, UAE United Arab Emirates

Figure 4 shows a detailed breakdown of the estimated expenditure of anti-PD-1/PD-L1s as a proportion of the predicted total healthcare and total pharmaceutical expenditure in 2022.

Fig. 4.

The estimated budget expenditure, total healthcare budget and total pharmaceutical expenditure on PD-1/PD-L1s in 2022 in UAE, Kuwait and Oman. PD-1 programmed cell death protein 1, PD-L1 programmed cell death-ligand 1, UAE United Arab Emirates

In 2022, out of the total healthcare expenditure in the UAE, Kuwait, and Oman—81.399 AED bn [35], 2.943 KWD bn [36], and 1.596 OMR bn [37], respectively (equivalent to 22.16 bn USD, 9.60 bn USD, and 4.15 bn USD), the HIP model estimated that an investment equivalent to 0.15%, 0.31%, and 0.81% of these expenditures was required to support the funding of anti-PD-1/PD-L1. This corresponds to a respective projected share of 0.85%, 1.35%, and 5.64% of the pharmaceutical expenditures—14.400 AED bn [35], 0.67 KWD bn [36], and 0.23 OMR bn [37] (equivalent to 3.92 bn USD, 2.19 bn USD, and 0.598 bn USD).

Sensitivity Analysis Results

Deterministic sensitivity analysis was performed for every indication included in the HIP model to identify changes in the economic impact and LYs gained from the introduction of the anti-PD-1/PD-L1s.

Drug acquisition costs and incidence rates were the leading causes of changes in economic results. Market shares and treatment rates also influence the LYs gained results, thus impacting the number of treated patients as well as health outcomes. The sensitivity analysis confirmed the increase of LYs obtained by the increasing availability of anti-PD-1/PD-L1 therapies in the markets.

Upon varying the average economic impact and LY gains by 25%, sensitivity analysis exhibited stable results.

Discussion

The HIP model provides insight into the therapeutic benefits and budget impact of the anti-PD-1/PD-L1s. To our knowledge, this is the first study using the HIP model to estimate the potential health and economic impact of introducing PD-1/PD-L1 inhibitors in the Gulf region. Given the rapid and continuous innovation in immuno-oncology, the model facilitates the incorporation of new data. This flexibility enables its adaptation to evolving market dynamics, such as the rise of new combination therapies or the potential effects of price negotiations. Study results have demonstrated that health gains in OS, QALYs, and LYs in PFS across the three Gulf countries are expected to occur with the introduction of the PD-1/PD-L1 drug class. However, health gains need to be analyzed alongside the budget impact to assess the overall value of this intervention.

These general results could help inform health policy decisions on the adoption of any new therapeutic class for cancer care. By forecasting the number of patients expected to be treated with this novel class of therapy, the HIP model aids budget planning for the associated cancer care costs. These class-level projections complement the medicine-specific cost-effectiveness evidence that reimbursement bodies require. The HIP model allows to explore the option of increasing cancer budgets with additional funds dedicated for immunotherapy and can serve as a tool for policymakers to weigh the opportunity costs of redirecting funds from other healthcare priorities.

When comparing the health outcomes of introducing the anti-PD-1/PD-L1 class over the period of 2022–2026 across the UAE, Kuwait, and Oman, certain patterns appear. In terms of LYs gained, all three countries have seen considerable increases, with the UAE leading with 796 LYs gained, followed by Kuwait with 507, and Oman with 442. However, when studying the relative change, all three countries show the same 20% increase, suggesting a constant encouraging impact on life expectancy. Likewise, when comparing QALYs gained, there is an evident increase for all three Gulf countries, with the UAE at the front position with 734 QALYs gained, followed by Kuwait with 470, and Oman with 421. However, the relative change in QALYs gained is also consistent at 24% for UAE and Kuwait and at 25% for Oman, indicating an equal improvement in the quality of life. Furthermore, the PFLYs gained exhibit identical patterns across the nations with a 68% increase. This suggests a considerable enhancement in the duration of disease control. Lastly, when observing AEs experienced, while the absolute numbers vary, the relative change remains relatively consistent, ranging from 2% (Kuwait and Oman) to 4% (UAE), indicating a comparable increase in AEs relative to the baseline. The introduction of anti-PD-1/PD-L1s has led to an increase in AEs, primarily because of combination treatments and extended treatment durations compared to scenarios without the anti-PD-1/PD-L1s, as patients live longer with the introduction of immunotherapy agents.

Several factors come to play with the increased uptake of anti-PD-1/PD-L1s, such as the increased incidence and burden of cancer, as well as the increased life expectancy of the three Gulf populations. The major contributors to the economic impact of anti-PD-1/PD-L1s are the drug acquisition costs projected over 5 years. On the other hand, indirect costs are estimated to decrease over the 5-year period as a result of a reduction in patient productivity lost to cancer associated with anti-PD-1/PD-L1s. Disease management costs and drug acquisition costs are partially balanced by end-of-life costs and indirect costs.

The results for the selected Gulf countries confirm the model stability across different markets, as HIP studies in European markets (Belgium, Slovenia, Austria, and Italy) [31] in 2021, as well as in France [32] in 2022 and Portugal [33] in 2023, showed that the PD-1/PD-L1 inhibitor class provided improvements in all health outcomes (LY gained, QALY gained, and PFLY gained) with a substantial increase in budget impact. In Turkey [38], a HIP model analysis demonstrated that PD-1/PD-L1 inhibitors can deliver considerable survival and LY benefits to the population, with the 5-year economic burden of these agents representing approximately 1.67% of projected total healthcare expenditure. A direct comparison between these countries cannot be applied due to differences in study period durations, incidence of cancer, and specific oncology indications studied in each market, e.g., esophageal cancer was not included in the model adaptation of the Gulf model. Nevertheless, trends across the countries could be compared and consistently showed an increase in absolute numbers for health outcomes and AE rates.

Limitations

The HIP model relies on several assumptions from available data or resources despite efforts to involve experts from various countries for validation. Stronger data, like cancer registries following patient experiences over 5 years, could enhance data maturity and better predict outcomes.

The analysis assumes public list prices for anti-PD-1/PD-L1 treatments, likely overestimating actual costs, as it doesn't consider tender prices or confidential agreements between companies and healthcare providers.

The impact of biosimilars on the market share of originator anti-PD-1/PD-L1 products is not accounted for, as their introduction is not expected soon. The optimal treatment duration for the anti-PD-1/PD-L1 class remains uncertain, and the model's fixed stopping rule (maximum of 2 years or until treatment progression, whichever is sooner) may not capture individual patient variations accurately.

Depending on patient entry into the HIP model, treatment costs may also vary. Costs may be slightly lower in 2022 due to the exclusion of patients diagnosed and treated before the start of the model.

An activity costing study focusing on various treatment costs could improve the accuracy of the model by addressing underlying assumptions and providing a more realistic representation of real-world costs.

A limitation of this approach lies in the assumption that the outcomes in early-stage indications (recurrence/event/disease-free survival) are equivalent to the outcomes in metastatic indications (progression-free survival, or PFS), applying them uniformly within the model for simplification. A more appropriate strategy would involve accurately modeling the relevant outcomes specific to early-stage indications rather than approximating early clinical endpoints to PFS, as this would more effectively capture the distinct clinical differences between early-stage and advanced diseases and avoid underestimating the health outcomes within the model.

Where model inputs were not available from Gulf-specific sources, data were drawn from international literature or global databases, which may introduce bias into the estimates and should be considered when interpreting the results.

While the model allows for showcasing results beyond the initial 5 years, its deterministic structure limits its ability to capture uncertainty associated with input parameters. Furthermore, the absence of probabilistic sensitivity analysis to assess the impact of multiple random samplings of input parameters might restrict the ability to fully capture uncertainty and variability in the model’s outcomes.

Finally, the analysis was conducted exclusively from a payer perspective, capturing direct healthcare costs and productivity losses. Indirect costs such as informal caregiving was not captured, and therefore the full economic burden of cancer on patients and society may be underestimated. This is particularly relevant in the Gulf context, where evidence suggests that the total economic impact of cancer extends well beyond direct healthcare expenditure [39].

Conclusions

The HIP model helps with horizon scanning, as it provides a blueprint for future discussions and collaborations between stakeholders on the anti-PD-1/PD-L1 class, ensuring equitable access to innovative treatments. Study results demonstrated survival gains across all three Gulf countries, particularly in terms of OS, QALYs, and LYs in PFS. Overall, while there are variations in absolute numbers across the three Gulf countries, the relative changes paint a picture of similar proportional improvements in health outcomes across the UAE, Kuwait, and Oman due to the introduction of the anti-PD-1/PD-L1 class. These gains can be accomplished with a minimal impact on the total healthcare expenditure. Factors like rising cancer incidence and extended life expectancy of the selected Gulf population have influenced the increased uptake of the anti-PD-1/PD-L1s within the HIP model.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

The study was funded by MSD IDEA Middle East, a division of Merck Sharp & Dohme. Authors G.B., R.N., R.A., M.N., and O.B. are employed by MSD IDEA Middle East and were involved in the design, methodology, conceptualization, formal analysis, review, and approval of the manuscript. Funding was supported by Kentucky IDeA Networks of Biomedical Research Excellence.

Declarations

Conflicts of Interest

Authors G.B., R.N., R.A., M.N., and O.B. are employees of MSD IDEA Middle East, a division of Merck Sharp & Dohme. H.S., M.F., A.A., A.A., C.S., and Y.B. declare that they have no conflicts of interest relevant to the contents of this manuscript.

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Data Availability Statement

Clinical trial data supporting efficacy are publicly available (CheckMate and KEYNOTE and IMPOWER trials). Cost data and other inputs are provided by the KOLs and are included in the Supplementary file. Market share assumptions remain proprietary to MSD.

Authors' Contributions

All authors read and approved the final version of the manuscript and agree to be accountable for all aspects of the work. Conceptualization: Humaid O. Al-Shamsi, Mohamed Farghaly, Ammar Abdaljalil, Abdulwahab Altourah, Omar El-Badry, Rony Akel; methodology: Ghadah Albassam, Rami Nimer, Monika Naroz, Chana Saad, Youmna Bassil; formal analysis: Ghadah Albassam, Rami Nimer, Monika Naroz; data curation: Chana Saad, Youmna Bassil; writing—original draft: Chana Saad, Youmna Bassil; writing—review and editing: all authors; supervision: Ghadah Albassam, Rami Nimer, Monika Naroz