Palliative care for cancer patients in resource-limited settings of Kazakhstan: implications for cost-effectiveness and health policy

ABSTRACT Introduction: About 60 million people need palliative care worldwide, and nearly 80% of them live in low-to middle- income countries (LMICs) where only 12% of patients who require palliative services have access to them. As a Central Asian LMIC with a transitional economy and a reforming healthcare system, Kazakhstan has recently taken on the task of integrating palliative care into the general healthcare system to meet its national needs and international standards. Although palliative care services in Kazakhstan have significantly improved care for persons nearing the end of life, patients needing these services still suffer from pain, lack of access, and high out-of-pocket expenditures. Palliative care in Kazakhstan is provided by hospices, cancer centers, general hospitals, and mobile teams. More than 100,000 people need palliative care in Kazakhstan; however, as one or more family members are usually involved in the care of a terminal patient, more than 200,000 people would benefit from high-quality palliative care services in this country. Considering that cancer is a primary illness necessitating palliative care, there is a need for a comprehensive understanding of how strategies aimed at preventing cancer could reshape the demand and delivery of the spectrum of cancer care services, including palliative care. Objectives of this study include: • Present a detailed analysis of palliative care in Kazakhstan, including funding, policy, workforce, education, infrastructure, etc., providing an evidence base for future assessments and research of palliative care in Kazakhstan and in other LMICs. • Assess the cost-effectiveness of hospice-based palliative care for cancer patients compared to the current standard of care provided in cancer centers across the country. • Explore the challenges faced by palliative care stakeholders in resource-limited settings, and to offer evidence-based recommendations for policymakers to facilitate the advancement of palliative care in Kazakhstan and other LMICs. • Asses the cost-effectiveness of genetic testing for Lynch syndrome provided to patients newly diagnosed with colorectal cancer, followed by cascade genetic screening of biological relatives from the perspective of the Swiss healthcare system. Methods: The authors assessed the nation's palliative care landscape using data from the Ministry of Health, regional healthcare centers, and NGOs (Study 1). This comprehensive evaluation involved soliciting information through official correspondence and engaging with key stakeholders. 6 For the cost-effectiveness analysis, a total of 182 family caregivers were recruited, 104 from three hospices and 78 from three palliative care units of cancer centers (Study 2). Patients’ state of health and family caregivers’ burden were assessed with the Palliative Outcome Scale (POS) and the Zarit Burden Inventory (ZBI). Direct medical and non-medical costs, and family caregivers’ out-of-pocket expenses associated with palliative care were collected. One-way and probabilistic sensitivity analysis was conducted by generating 1,000 resamples using bootstrapping with Monte-Carlo simulation. To assess challenges of palliative care stakeholders, we conducted 29 semi-structured interviews with palliative stakeholders (family caregivers n=12, healthcare professionals =12, administrators n= 5) across five regions (Study 3). Verbatim transcripts were analyzed using content analysis to identify challenges of palliative stakeholders in resource-limited settings. Recognizing that these findings mirror the well-documented challenges faced by palliative care stakeholders, we converted these insights into evidence-based recommendations, specifically designed for the resource-constrained contexts of LMICs, and in congruence with the latest body of literature on palliative care and family caregiving. Additionally, we used decision trees with Markov models to conduct a cost-effectiveness analysis of universal genetic testing for Lynch syndrome of all patients newly diagnosed with colorectal cancer, and compared it with the current tumour-based testing with immunohistochemistry techniques followed by DNA sequencing that examines for germline pathogenic variants associated with Lynch syndrome. Results: The authors obtained the necessary data through official responses from the Ministry of Health, regional centers of healthcare and NGOs. These responses were accompanied by supplementary materials that fulfilled the authors' requests. Overall, the findings of the assessment provide a thorough understanding of the current state of palliative care in Kazakhstan presented in this study along with areas that require attention for future development. Cost-effectiveness analysis revealed that after 14 days of inpatient palliative care, patients’ median POS score was 5 points better in the hospice group compared to the cancer center group. Family caregiver burden was also 2.5 points lower in favour of the hospice group. The median cost of palliative care per patient over 14 days was $31 lower for the hospice group. There was a statistically significant correlation between the cost of palliative care and patients’ 7 quality of life (r = 0.58). Probabilistic sensitivity analysis showed that hospice-based care has better outcomes and lower costs than care provided in cancer centers in 80% of tested scenarios. Discovering the challenges of palliative care stakeholders, our analysis identified seven main themes that were initially brought forward by different groups of stakeholders. The most common challenges highlighted by family caregivers were high out-of-pocket expenditures; the lack of mobile palliative care services; and shortages of opioids to prevent pain suffering. Health professionals highlighted poor palliative care education and lack of medication, especially opioids for pain relief as the major challenges they encounter in their daily practice. Major challenges for administrators included lack of societal awareness about palliative care, and lack of financial support from the State. Within the analysis of the universal genetinc testing for Lynch syndrome, the incremental cost- effectiveness ratio of this strategy was CHF65,058 per QALY saved, which is cost-effective in the Swiss context. Moreover, the universal testing correctly identifies all colorectal cancer patients with Lynch syndrome, prevents 17 deaths and prevents 19 colorectal cancer cases compared to the currently applied tumor-based testing. Conclusion: Despite recent progress, Kazakhstan faces ongoing challenges such as restricted opioid availability, insufficient education, and low public awareness about palliative care services. Hospice-based palliative care can be a cost-effective alternative in resource-limited settings of Kazakhstan. Implementation of further national palliative care strategies and policies require a large-scale coordinated involvement of all stakeholders. Family caregivers play a crucial role in providing palliative care, yet, they have been completely unsupported by they system in their tasks. Our recommendations are based on the idea that coordinated targeted and tailored stakeholder engagement is preferred to a one-size-fits-all strategy. In the Swiss healthcare context, universal genetic testing has demonstrated both cost- effectiveness and significant health advantages. However, the ICER of CHF 65,058 (USD 70,000) surpasses the cost-effectiveness threshold of most low-to middle-income countries, including Kazakhstan where the GDP per capita is USD 11,000. Hence, the authors underline the critical necessity for locally viable, low-cost cancer screening options in resource-restricted settings. The introduction of more affordable cancer preventive measures, such as mammography, Pap smear test, and fecal occult blood test, among others, could be considered as more financially viable options for population-based cancer screening

Health economics analysis of mammography screening program in the Republic of Kazakhstan

Breast cancer (hereinafter - BC) is the most frequent type of cancer among women in the Republic of Kazakhstan, accounting for almost 12% of all cases of cancers in the country [1]. Kazakhstan has the highest rates of breast cancer in the Central Asian region. Local physicians associate it with lack of breastfeeding, use of hormonal drugs, and poor ecological conditions [2]. There were 3,400 new cases of BC in Kazakhstan in 2016 [3], while number of deaths in the same year reached 1,022 [4]. The age-adjusted death rate from BC is 21.50 per 100,000, which ranks Kazakhstan 35th in the world [32]. The prevalence of BC reached 22.7 per 100,000 in 2013, and it has been increasing constantly, affecting younger population aged 25-40. It also takes the first place in mortality rates among all cancers in the 45-50-year age group. Between 1990 and 2010 the annual years of healthy life lost from breast cancer in Kazakhstan has increased by 44.0% [5]. In 1990, BC led to 38,000 years of life lost (hereinafter - YLL) in Kazakhstan. In 2010, the prevalence rate of BC has raised by 17% leading to 44,000 YLL [6]

Improving palliative care outcomes in remote and rural areas of LMICs through family caregivers: lessons from Kazakhstan

Approximately 60 million people require palliative care worldwide, and nearly 80% of them live in low- and middle-income countries (LMICs). Providing palliative care in remote and rural areas of LMICs requires special consideration to ensure equitable access to healthcare. This perspective aims to deliver pragmatic, context-oriented policy recommendations designed to improve palliative care outcomes in Kazakhstan by capitalizing on existing resources and considering its unique geopolitical and sociocultural context. With approximately half of the population in Kazakhstan residing in remote and rural regions, the provision of healthcare services – specifically palliative care – mandates particular attention to ensure equal access to high-quality care. To understand challenges of implementing palliative care in remote and rural regions of Kazakhstan and to propose tailored solutions, 29 key stakeholders, including family caregivers, health professionals, and palliative care administrators, were identified in five regions of Kazakhstan. The main challenges encountered by family caregivers include lack of palliative care skills, the need for home-based care from mobile services, and high out-of-pocket expenditures. The challenges highlighted by healthcare providers and administrators were the lack of formal education in palliative care, shortage of opioids, and limited societal awareness and state support. Based on challenges elaborated from stakeholders and existing literature in palliative care and family caregiving, this perspective advocates against replicating the strategies implemented in high-income countries. Family caregivers play a critical role in implementing affordable and efficient palliative care in resource-limited settings. Enhancing their competencies through digital training and increasing access to palliative care services through mobile teams are tailored and localized solutions that address specific challenges in Kazakhstan. It is postulated that these recommendations may find utility in other LMICs, potentially benefiting nearly 48 million individuals who require these services

Challenges for Developing Palliative Care Services in Resource- Limited Settings of Kazakhstan

Background: Approximately 40 million people in need of palliative care worldwide, while 80% of them live in low- and middle-income countries. Kazakhstan, a low-to middle-income country with a reforming healthcare system, is committed to improving quality and accessibility of care for its 100,000 terminal patients in need of palliative care.Policy Options and Recommendations: To join the group of countries where palliative care is available, accessible, and affordable, Kazakhstan must integrate palliative services into the mainstream healthcare system at all levels, from primary healthcare to hospices, and from major cities to remote villages. Based on the evidence thoroughly collected directly from the Ministry of Health, authors propose a feasible set of recommendations regarding palliative policy, paint relief, infrastructure, workforce, and education, which could be implemented in LMICs beyond Kazakhstan.Conclusion: This study presents an analysis of challenges, recent developments, and needs of palliative care in Kazakhstan, including funding, policy, workforce, education, and infrastructure, providing an evidence base and recommendations for future development of palliative care in Kazakhstan and in other LMICs

Health economics analysis of mammography screening program in the Republic of Kazakhstan

Breast cancer (hereinafter - BC) is the most frequent type of cancer among women in the Republic of Kazakhstan, accounting for almost 12% of all cases of cancers in the country [1]. Kazakhstan has the highest rates of breast cancer in the Central Asian region. Local physicians associate it with lack of breastfeeding, use of hormonal drugs, and poor ecological conditions [2]. There were 3,400 new cases of BC in Kazakhstan in 2016 [3], while number of deaths in the same year reached 1,022 [4]. The age-adjusted death rate from BC is 21.50 per 100,000, which ranks Kazakhstan 35th in the world [32]. The prevalence of BC reached 22.7 per 100,000 in 2013, and it has been increasing constantly, affecting younger population aged 25-40. It also takes the first place in mortality rates among all cancers in the 45-50-year age group. Between 1990 and 2010 the annual years of healthy life lost from breast cancer in Kazakhstan has increased by 44.0% [5]. In 1990, BC led to 38,000 years of life lost (hereinafter - YLL) in Kazakhstan. In 2010, the prevalence rate of BC has raised by 17% leading to 44,000 YLL [6]

Cost-effectiveness of DNA testing for Lynch syndrome for colorectal cancer patients in Switzerland

Purpose: To estimate the cost-effectiveness of genetic testing for Lynch syndrome among newly diagnosed patients with colorectal cancer and targeted testing for their relatives in Switzerland. Methods: We integrated decision tree and Markov model to calculate incremental costs per quality adjusted life-year saved for universal genetic testing for Lynch syndrome relative to using preliminary tumor tests (immunohistochemistry or microsatellite instability) followed by DNA sequencing test for patients with colorectal cancer. Results: The incremental cost-effectiveness ratio (ICER) of the proposed strategy using universal genetic testing for Lynch syndrome with systematic CASCADE testing of their relatives is CHF 65,058 per QALY saved, which is cost-effective in Swiss settings where cost-effectiveness threshold is CHF 100,000 per QALY saved. The gained utility is 361,358 QALYs saved. Sensitivity analysis demonstrated cost-effectiveness of the proposed strategies in most of the scenarios. Conclusions: The overall effectiveness of the universal genetic testing is greatly dependent on willingness of patients and relatives to be tested and compliance with the increased surveillance. Therefore, close cooperation across different stakeholders such as family doctors, oncologists, genetic clinicians, and laboratories is crucial to encourage and educate patients about the importance of the LS screening. Key messages: Universal genetic testing for Lynch syndrome for all patients with colorectal caner is cost-effective in Swiss settings. Close cooperation across all stakeholders such as family doctors, oncologists, genetic clinicians, and laboratories is crucial to encourage and educate patients about the importance of the LS testing

Cost- Effectiveness of Mammography Screening Program in a Resource-Limited Post-Soviet Country of Kazakhstan

Objectives: To conduct cost effectiveness and benefit-cost analyses of the organized mammography-screening program in the Republic of Kazakhstan comparing women who developed breast cancer in screened and unscreened scenario. Methods: 389,352 screened women were included in the study. Among these, 895 women were further diagnosed with breast cancer. Outcomes measures include life years saved, quality-adjusted life years, incremental cost-effectiveness ratio, and value of statistical life year. Sensitivity analyses were performed to assess uncertainty. Results: Compared to no screening scenario, an organized mammography yielded an additional 1,253 life years and 790 quality-adjusted life years in 2016. The incremental cost-effectiveness ratio was equal to 3,157 USD per one QALY saved, which is two times less than the GDP per capita in Kazakhstan in 2016. Sensitivity analysis showed that the mammography remains cost-effective in the majority of the scenarios. Conclusion: Mammography screening in Kazakhstan was found to be highly cost-effective, associated with treatment cost savings, and can be an efficient use of limited resources in Kazakhstan

Swiss cost-effectiveness analysis of universal screening for Lynch syndrome of patients with colorectal cancer followed by cascade genetic testing of relatives.

BACKGROUND We estimated the cost-effectiveness of universal DNA screening for Lynch syndrome (LS) among newly diagnosed patients with colorectal cancer (CRC) followed by cascade screening of relatives from the Swiss healthcare system perspective. METHODS We integrated decision trees with Markov models to calculate incremental cost per quality-adjusted life-year saved by screening all patients with CRC (alternative strategy) compared with CRC tumour-based testing followed by DNA sequencing (current strategy). RESULTS The alternative strategy has an incremental cost-effectiveness ratio of CHF65 058 compared with the current strategy, which is cost-effective according to Swiss standards. Based on annual incidence of CRC in Switzerland, universal DNA screening correctly identifies all 123 patients with CRC with LS, prevents 17 LS deaths and avoids 19 CRC cases, while the current strategy leads to 32 false negative results and 253 LS cases lost to follow-up. One way and probabilistic sensitivity analyses showed that universal DNA testing is cost-effective in around 80% of scenarios, and that the cost of DNA testing and the number of invited relatives per LS case determine the cost-effectiveness ratio. CONCLUSION Results can inform policymakers, healthcare providers and insurance companies about the costs and benefits associated with universal screening for LS and cascade genetic testing of relatives

Table2_Challenges for Developing Palliative Care Services in Resource- Limited Settings of Kazakhstan.pdf

Background: Approximately 40 million people in need of palliative care worldwide, while 80% of them live in low- and middle-income countries. Kazakhstan, a low-to middle-income country with a reforming healthcare system, is committed to improving quality and accessibility of care for its 100,000 terminal patients in need of palliative care.Policy Options and Recommendations: To join the group of countries where palliative care is available, accessible, and affordable, Kazakhstan must integrate palliative services into the mainstream healthcare system at all levels, from primary healthcare to hospices, and from major cities to remote villages. Based on the evidence thoroughly collected directly from the Ministry of Health, authors propose a feasible set of recommendations regarding palliative policy, paint relief, infrastructure, workforce, and education, which could be implemented in LMICs beyond Kazakhstan.Conclusion: This study presents an analysis of challenges, recent developments, and needs of palliative care in Kazakhstan, including funding, policy, workforce, education, and infrastructure, providing an evidence base and recommendations for future development of palliative care in Kazakhstan and in other LMICs.</p

Table3_Challenges for Developing Palliative Care Services in Resource- Limited Settings of Kazakhstan.xlsx

Background: Approximately 40 million people in need of palliative care worldwide, while 80% of them live in low- and middle-income countries. Kazakhstan, a low-to middle-income country with a reforming healthcare system, is committed to improving quality and accessibility of care for its 100,000 terminal patients in need of palliative care.Policy Options and Recommendations: To join the group of countries where palliative care is available, accessible, and affordable, Kazakhstan must integrate palliative services into the mainstream healthcare system at all levels, from primary healthcare to hospices, and from major cities to remote villages. Based on the evidence thoroughly collected directly from the Ministry of Health, authors propose a feasible set of recommendations regarding palliative policy, paint relief, infrastructure, workforce, and education, which could be implemented in LMICs beyond Kazakhstan.Conclusion: This study presents an analysis of challenges, recent developments, and needs of palliative care in Kazakhstan, including funding, policy, workforce, education, and infrastructure, providing an evidence base and recommendations for future development of palliative care in Kazakhstan and in other LMICs.</p