Introduction

Women’s Health Day holds significant importance as it brings global attention to the unique health challenges faced by women. Consequently, this brings to light the necessity of implementing targeted treatments and enhancing access to healthcare for all women. This day not only raises awareness but also amplifies the importance of evaluating both the economic and clinical value of treatments tailored to women’s health issues, particularly economic evaluations in women’s health. Such evaluations are crucial for informing policy decisions and optimising resource allocation to improve health outcomes for women globally.

The Burden of Cervical Cancer in LMICs

Among these challenges, cervical cancer stands out as a major public health concern, particularly in Low-to-Middle-Income Countries (LMICs). In 2020, cervical cancer accounted for approximately 602,127 new cases and 341,831 deaths worldwide, with over 80% of these occurring in LMICs. [1] This high burden is exacerbated by limited screening programs, inadequate treatment facilities, and a high prevalence of further complications such as Human Immunodeficiency Virus (HIV). All of these serve as an obstacle in the management of cervical cancer in these regions. [1] Addressing this issue requires cost-effective treatment strategies that can improve outcomes without imposing significant financial strain on already resource-constrained healthcare systems.

Breast Cancer Treatment Challenges in High-Income Countries

In contrast, high-income countries face the challenge of managing diseases such as breast cancer, particularly the newly classified human epidermal growth factor receptor 2 (HER2)-low subgroup. Breast cancer remains a significant health concern, particularly for women with HER2-positive metastatic breast cancer. In the United States, the disease burden is substantial, with an estimated 281,550 new cases of invasive breast cancer diagnosed in women in 2021. Patients with HER2-positive metastatic breast cancer often face progression despite initial treatments, highlighting the need for effective and economically viable treatment options to improve outcomes and manage healthcare costs. [2]

Treatments like trastuzumab deruxtecan have shown promise in increasing survival rates and delaying disease progression for patients with HER2-low metastatic or unresectable breast cancer. [3] However, the high cost of such innovative treatments raises questions about their cost-effectiveness and sustainability within national healthcare systems in high income countries, such as the National Health Service (NHS) in the UK. In the United States, there is a focus on assessing the economic feasibility of innovative breast cancer treatments, which also leads to a demand for cost-effectiveness in breast cancer treatment. [2]

Innovative Treatments for Cervical Cancer in LMICs: The mEHT Approach

Given the socio-economic constraints in LMICs, there is an urgent need to enhance treatment outcomes for cervical cancer without significantly increasing costs. One promising approach is the integration of modulated electro-hyperthermia (mEHT) as an adjunct to standard chemoradiotherapy (CRT) for locally advanced cervical cancer (LACC). mEHT differs from classical hyperthermia (HT) techniques primarily in its approach and mechanisms. While classical HT relies on temperature-dependent dosing calculations and aims to achieve significant temperature increases to slow down DNA repair and induce tumour cell killing, mEHT uses a mild to moderate heating technology with amplitude modulation of 13.56 MHz radiofrequency (RF) waves.

This modulation enhances cell-killing effects through non-thermal field effects, which are not the primary goal in classical HT. More importantly, mEHT’s lower power output and non-thermal dosing parameters eliminate the need for thermal monitoring, making it safer and potentially more effective in targeting tumours, particularly in patients with thicker adipose layers, without causing significant damage to surrounding tissues. [1]

The Economic Viability of mEHT in LMICs: A South African Case Study

A study lead by South African doctor, Dr Carrie Minaar from Wits Donald Gordon Medical Centre University, [4] was conducted in South Africa to address the high burden of cervical cancer in a LMICs. The aim was to investigate the effects of adding mEHT to CRT protocols for managing LACC patients, with a focus on improving treatment efficacy without increasing costs. mEHT could serve as a useful treatment option in LMICS due to the following reasons: 1) it does not require sophisticated imaging and thermo-monitoring equipment, which are often scarce and expensive in these settings, and 2) the technology’s lower power output reduces the risk of significant side effects, leading to fewer complications and lower healthcare costs associated with managing treatment-related toxicity. This can reduce the overall economic burden on healthcare systems by decreasing the need for expensive screening tools and recurrent or prolonged treatments. [1]

Cost-Effectiveness Results: Markov Model Analysis

The cost-effectiveness analysis (CEA) was conducted using a Markov model with a three-year time horizon. The analysis compared the costs and outcomes from both government-funded public healthcare and privately-funded healthcare perspectives in South Africa. The results showed that mEHT combined with CRT was more cost-effective than CRT alone, driven primarily by the significant improvement in disease-free survival (DFS) rates. Specifically, the addition of mEHT led to lower overall treatment costs due to reduced recurrence rates and fewer hospitalisations for progressive disease. The incremental cost-effectiveness ratio (ICER) demonstrated that mEHT with CRT produced more health effects at a lower cost, with an 82.2% probability of being cost-effective in the public healthcare model and a 77.7% probability in the private healthcare model. These findings indicate that mEHT not only enhances clinical outcomes but also offers substantial economic benefits, making it a viable and cost-effective treatment option for LACC in resource-constrained settings. [1]

Table 1: Quality adjusted life year (QALY) data for private and government healthcare CEA models

Long-Term Clinical Benefits of mEHT: The ESTRO 2024 Conference Findings

The five-year results on the primary outcomes were presented at the ESTRO 2024 conference in Glasgow, United Kingdom, held in May 2024. The study demonstrated that mEHT significantly improved five-year disease-free survival (DFS) rates. Specifically, 32% of participants in the mEHT group achieved five-year DFS compared to only 14% in the control group. The five-year overall survival (OS) was 33% in the mEHT group versus 26% in the control group, with a significant increase in OS for participants with stage III disease (p=0.046). These findings suggest that mEHT not only enhances long-term DFS and OS but also has the potential to lower treatment costs and promote a sustained immune-mediated abscopal response, making it a valuable addition to standard LACC treatment protocols, particularly in LMICs. [5]

Challenges of Integrating New Treatments: Global Perspectives

Integrating new treatments into healthcare systems presents universal challenges, whether addressing cervical cancer in LMICs or breast cancer in high-income countries. The adoption of innovative therapies like mEHT for cervical cancer shows the need for thorough economic evaluations to ensure cost-effectiveness and accessibility. In LMICs, where resources are often limited and healthcare budgets are constrained, demonstrating the economic viability of new treatments is crucial for their inclusion in standard care protocols. Similarly, high-income countries face their own set of challenges, such as managing healthcare costs and ensuring equitable access to the latest advancements.

Economic evaluations in women’s health play an important role in both contexts, guiding policymakers and healthcare providers in making informed decisions that balance clinical efficacy with financial sustainability. Several health technology assessment (HTA) bodies play a crucial role in these countries to ensure the cost-effectiveness of treatment in their perspective settings. One of the most prominent HTA bodies, The National Institute for Health and Care Excellence (NICE), is a major player in these assessments in countries with higher incomes.

NICE’s Decision on Enhertu for Breast Cancer

NICE recently conducted an appraisal of Enhertu (trastuzumab deruxtecan) for treating HER2-low metastatic or unresectable breast cancer. The appraisal process involved a thorough evaluation of the drug’s clinical and economic benefits. NICE’s decision was heavily influenced by the ICER, which measures the cost per quality adjusted life year (QALY) gained. Despite recognising Enhertu’s innovative potential and its role as the first licensed HER2-low targeted treatment, the committee concluded that the ICERs were above the acceptable threshold in the UK. The committee considered an acceptable ICER to be around £30,000 per QALY gained, which sits at the higher end of what the NHS typically deems cost-effective (£20,000 per QALY gained). This decision was based on several economic concerns, including uncertainties in overall survival extrapolation and post-progression utility values. Consequently, NICE did not recommend trastuzumab for this indication, citing that it would not be a cost-effective use of NHS resources. [3]

Consideration of Additional Cost Factors in Treatment Administration

In assessing the additional cost factors for the administration of intravenous treatments such as trastuzumab deruxtecan, several critical considerations were incorporated. Firstly, the potential for vial sharing was acknowledged, with an assumption that this would eliminate wastage in 75% of administrations. Furthermore, administration costs were meticulously evaluated. The initial cost per administration was derived from the National Schedule of NHS Costs. A medical review cost of £144 for individuals undergoing chemotherapy was incorporated. Lastly, the severity of the condition was a crucial factor, with the committee considering the future health lost by patients receiving standard care. A severity modifier was applied to the QALYs, giving greater weight to the QALYs for conditions with high severity. [3]

Economic Assessment of Trastuzumab Deruxtecan in the USA

In the United States, a study evaluated the cost-effectiveness of trastuzumab deruxtecan (T-DXd) compared to trastuzumab emtansine (T-DM1) for treating HER2-positive metastatic breast cancer. The analysis showed that the total costs for T-DXd were significantly higher at $1,266,945, compared to $820,082 for T-DM1. More importantly, the QALYs gained were 5.09 for T-DXd and 3.15 for T-DM1. This resulted in a high ICER of $230,285 per QALY for T-DXd. The study concluded that, given a willingness-to-pay threshold of $100,000 per QALY, T-DXd would not be considered cost-effective. These findings highlight the financial challenges of adopting new cancer treatments in the US healthcare system. [2]

Comparing and Contrasting Economic Evaluations

Economic evaluations play a crucial role in determining the adoption of new treatments in different economic contexts. The economic challenges faced by trastuzumab in high-income countries like the UK and USA contrast sharply with the success of mEHT in LMICs. While Enhertu struggled to meet the stringent cost-effectiveness criteria set by the USA and by NICE, mEHT has shown promise in LMICs due to its relatively low cost and potential for significant clinical benefits. In the privately-funded healthcare model, mEHT demonstrated a high probability of cost savings and clinical benefits, which can be further explored given the newly signed National Health Insurance (NHI) act that will be rolling out in South Africa. This stark difference highlights how economic evaluations can vary dramatically based on the healthcare context and available resources.

Concluding Insights: Advancing Global Women’s Health through Economic Evaluations

The cases of trastuzumab and mEHT offer valuable insights into the importance of health economics and outcomes research (HEOR) in guiding global women’s health decisions. For high-income countries, HEOR ensures that new treatments are both clinically effective and economically viable, safeguarding the sustainability of healthcare systems. HEOR can help identify cost-effective treatments that maximise health benefits within limited budgets of LMICs. These insights once again indicates the need for tailored economic evaluations that consider the unique challenges and resources of different healthcare contexts. By leveraging HEOR, policymakers can make informed decisions that improve women’s health outcomes globally, ensuring that innovative treatments are accessible and affordable for all.

Takeaway Points

• Economic Evaluations are Crucial for Treatment Adoption: Economic evaluations, such as CEAs, play an important role in determining the adoption of new treatments in both high-income and LMICs. These evaluations ensure that new therapies provide value for money and are sustainable within healthcare systems.
• Context Matters in Health Economics: The success of treatments like mEHT in LMICs and the challenges faced by trastuzumab in high-income countries highlight the importance of context-specific economic evaluations. Different healthcare settings require tailored approaches to balance clinical efficacy with financial sustainability.
• HEOR Guides Policy Decisions: HEOR is essential for informing policy decisions and optimising resource allocation to improve women’s health outcomes globally. By leveraging HEOR, policymakers can make informed decisions that ensure innovative treatments are accessible and affordable for all women, regardless of their economic context.

References

1. Minnaar CA, Maposa I, Kotzen JA, Baeyens A. Effects of Modulated Electro-Hyperthermia (mEHT) on Two and Three Year Survival of Locally Advanced Cervical Cancer Patients. Cancers (Basel). 2022 Jan 27;14(3):656.
2. Mudumba R, Chan HH, Cheng YY, Wang CC, Correia L, Ballreich J, Levy J. Cost-Effectiveness Analysis of Trastuzumab Deruxtecan Versus Trastuzumab Emtansine for Patients With Human Epidermal Growth Factor Receptor 2 Positive Metastatic Breast Cancer in the United States. Value Health. 2024 Feb;27(2):153-163.
3. Trastuzumab deruxtecan for treating HER2-low metastatic or unresectable breast cancer after chemotherapy.pdf [Internet]. [cited 2024 May 22]. Available from: https://www.nice.org.uk/guidance/gid-ta10813/documents/674
4. Vivier TL. SA PhD Doc Unlocks Hope in Cancer Treatment – Findings Shared on World Stage [Internet]. Good Things Guy. 2024 [cited 2024 March 22]. Available from: https://www.goodthingsguy.com/people/dr-minnar-cervical-cancer/
5. ESTRO 2024 [Internet]. [cited 2024 May 22]. Available from: https://www.estro.org/Congresses/ESTRO-2024