Cost-Effectiveness of Ibrutinib for Chronic Lymphocytic Leukemia Treatment in India: Is Evidence Really at Crossroads?

In recent years, newer drugs, such as ibrutinib, have shown promising improvements in the survival of patients with chronic lymphocytic leukemia (CLL). Despite their effectiveness, concerns about their cost have arisen, prompting the need for an evaluation of their cost-effectiveness. However, recent assessments of ibrutinib's cost-effectiveness for treating CLL in India reveal divergent conclusions. The discord centers on divergent cost-effectiveness thresholds, comparator regimens, cost calculations, and outcome valuation approaches. Such discrepancies affect public health decisions and patient care. The recommendation calls for adherence to methodological guidelines by future studies, fostering consistent findings to empower policy makers and clinicians in leveraging economic evidence for informed decision making in CLL treatment strategies.

Health-related quality of life among breast cancer patients in India.

PURPOSE: This study evaluated the health-related quality of life (HRQoL) among breast cancer patients during various phases of treatment and with different treatment modalities, which helps in monitoring treatment outcomes, assessing the well-being of patients, and conducting health technology assessments. METHODS: A total of 534 interviews were conducted among the patients of breast cancer recruited at different stages of disease and with different treatment modalities. HRQoL was determined using EuroQoL five dimensions questionnaire with five levels (EQ-5D-5L), EuroQoL Visual Analogue Scale (EQ VAS), and the EORTC QLQ-BR23 instrument. The utility values were determined based on the Indian EQ-5D-5L value set. The socio-demographic and clinico-therapeutic determinants of HRQoL were evaluated using multiple linear regression. RESULTS: The mean utility value of breast cancer patients was 0.602 (SD = 0.311) and mean EQ VAS score was 75 (SD = 12.3). The mean utility value at diagnosis was 0.628, whereas utility value was 0.55, 0.595, and 0.64 for post-surgery, post-chemotherapy, and post-radiotherapy treatment groups, respectively. The most frequently reported problem was pain/discomfort (in 84.3% patients), followed by anxiety/depression (83.5%). On EORTC QLQ-BR23, the maximum symptom scale scores for systemic therapy side effects were reported in the post chemotherapy group. The body image score and future perspective score were better in patients undergoing breast conservative surgery (BCS) compared to patients undergoing modified radical mastectomy. Age, education, and employment status of the patient, type of treatment modality, and use of taxanes are the determinants of HRQoL in breast cancer patients. CONCLUSION: Clinical interventions should focus upon management of pain and anxiety. BCS should be offered to all eligible patients as it is associated with better HRQoL. Addressing the factors that independently affect the HRQoL will help in improving the treatment compliance and outcomes.

Cost Effectiveness of Ribociclib and Palbociclib in the Second-Line Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer in Post-Menopausal Indian Women.

BACKGROUND: In this study, we evaluate the cost and outcomes of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus fulvestrant, fulvestrant alone, and conventional chemotherapy as the second-line therapy for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in India. METHODS: Using a Markov model, the clinical effectiveness of managing HR+, HER2- MBC in postmenopausal women with either a CDK4/6i (either ribociclib or palbociclib) and fulvestrant, fulvestrant alone, and chemotherapy (single-agent paclitaxel or capecitabine) was measured in terms of quality-adjusted life-years (QALYs). The costs were estimated from two different points of view: scenario I, as per the prevailing market prices of the drugs; and scenario II, as per the reimbursement rates set up by the publicly financed national health insurance scheme. Incremental cost per QALY gained with a given treatment option was compared against the next best alternative and was assessed for cost effectiveness using a threshold of 1-time the per capita gross domestic product (GDP) in India from a societal perspective. RESULTS: In scenario I, an MBC patient was found to incur a lifetime cost of Indian Rupees (₹) 2.54 million ($34,644), ₹2.53 million ($34,496), ₹512,598 ($6,984), ₹326,026 ($4,442) and ₹237,115 ($3,230) for the ribociclib and palbociclib combination arms, fulvestrant monotherapy, single-agent paclitaxel and the single-agent capecitabine treatment arms, respectively. The lifetime cost for CDK4/6i (ribociclib and palbociclib) combination therapy, fulvestrant monotherapy, paclitaxel, and capecitabine arms was estimated to be ₹1.94 million ($26,459), ₹1.92 million ($26,220), ₹315,387 ($4,296), ₹187,392 ($2,553) and ₹153,263 ($2,088), respectively, in scenario II. The mean QALYs lived per MBC patient with CDK4/6i (either ribociclib or palbociclib) combination therapy, fulvestrant, paclitaxel and capecitabine were estimated to be 1.4, 1.0, 0.9 and 0.7, respectively. None of the treatment arms are cost effective at current prices and reimbursement rates at a threshold of 1-time the per capita GDP of India. However, a 78% reduction in the current market price or a 72% reduction in the reimbursement rate of fulvestrant in the government-funded insurance program will make it a cost-effective treatment option for HR+, HER2- MBC patients in India. CONCLUSION: CDK4/6i (ribociclib and palbociclib) therapy is not a cost-effective treatment option for MBC patients. A 72% reduction in the reimbursement rate for fulvestrant monotherapy will make it a cost-effective treatment option in the Indian context.

Cost-effectiveness of population-based screening for diabetes and hypertension in India: an economic modelling study.

BACKGROUND: India faces a high burden of diabetes and hypertension. Currently, there is a dearth of economic evidence about screening programmes, affected age groups, and frequency of screening for these diseases in Indian settings. We assessed the cost effectiveness of population-based screening for diabetes and hypertension compared with current practice in India for different scenarios, according to type of screening test, population age group, and pattern of health-care use. METHODS: We used a hybrid decision model (decision tree and Markov model) to estimate the lifetime costs and consequences from a societal perspective. A meta-analysis was done to assess the effectiveness of population-based screening. Primary data were collected from two Indian states (Haryana and Tamil Nadu) to assess the cost of screening. The data from the National Health System Cost Database and the Costing of Health Services in India study were used to determine the health system cost of diagnostic tests and cost of treating diabetes or hypertension and their complications. A total of 962 patients were recruited to assess out-of-pocket expenditure and quality of life. Parameter uncertainty was evaluated using univariate and multivariable probabilistic sensitivity analyses. Finally, we estimated the incremental cost per quality-adjusted life-year (QALY) gained with alternative scenarios of scaling up primary health care through a health and wellness centre programme for the treatment of diabetes and hypertension. FINDINGS: The incremental cost per QALY gained across various strategies for population-based screening for diabetes and hypertension ranged from US$0·02 million to $0·03 million. At the current pattern of health services use, none of the screening strategies of annual screening, screening every 3 years, and screening every 5 years was cost-effective at a threshold of 1-time per capita gross domestic product in India. In the scenario in which health and wellness centres provided primary care to 20% of patients who were newly diagnosed with uncomplicated diabetes or hypertension, screening the group aged between 30 and 65 years every 5 years or 3 years for either diabetes, hypertension, or a comorbid state (both diabetes and hypertension) became cost-effective. If the share of treatment for patients with newly diagnosed uncomplicated diabetes or hypertension at health and wellness centres increases to 70%, from the existing 4% at subcentres and primary health centres, annual population-based screening becomes a cost saving strategy. INTERPRETATION: Population-based screening for diabetes and hypertension in India could potentially reduce time to diagnosis and treatment and be cost-effective if it is linked to comprehensive primary health care through health and wellness centres for provision of treatment to patients who screen positive. FUNDING: Department of Health Research, Government of India.

Cost-effectiveness analysis of 'test and treat' policy for antiretroviral therapy among heterosexual HIV population in India.

Background & objectives: The World Health Organisation recommended immediate initiation of antiretroviral therapy (ART) in all adult human immunodeficiency virus (HIV) patients regardless of their CD4 cell count. This study was undertaken to ascertain the cost-effectiveness of implementation of these guidelines in India. Methods: A Markov model was developed to assess the lifetime costs and health outcomes of three scenarios for initiation of ART treatment at varying CD4 cell count <350/mm[3], <500/mm[3] and test and treat using health system perspective using life-time horizon. A few input parameters for this model namely, transition probabilities from one stage to another stage of HIV and incidence rates of TB were calculated from the data of Centre of Excellence for HIV treatment and care, Chandigarh; whereas, other parameters were obtained from the published literature. Total HIV-related deaths averted, HIV infections averted and incremental cost-effectiveness ratio per quality adjusted life years (QALYs) gained were calculated. Result: Test and treat intervention slowed down the progression of disease and averted 18,386 HIV-related deaths, over lifetime horizon. It also averted 16,105 new HIV infections and saved 343,172 QALYs as compared to the strategy of starting ART at CD4 cell count of 500/mm[3]. Incremental cost per QALY gained for the immediate initiation of ART as compared to ART at CD4 cell count of 500/mm[3] and 350/mm[3] was ₹ 46,599 and 80,050, respectively at reported rates of adherence to the therapy. Interpretation & conclusions: Immediate ART (test and treat) is highly cost-effective strategy over the past criteria of delayed therapy in India. Cost-effectiveness of this policy is largely because of reduction in the transmission of HIV.

Cost-effectiveness of Tamoxifen, Aromatase Inhibitor, and Switch Therapy (Adjuvant Endocrine Therapy) for Breast Cancer in Hormone Receptor Positive Postmenopausal Women in India.

BACKGROUND: Breast cancer is the leading cause of cancer among women in India. Treatment with hormone therapy reduces recurrence. We undertook this cost-effectiveness study to ascertain the treatment option offering the best value for money. METHODS: The lifetime costs and health outcomes of using tamoxifen, AI and switch therapy were measured in a cohort of 50-year-old women with HR-positive early stage breast cancer. A Markov model of disease was developed using a societal perspective with a lifetime study horizon. Local, contralateral, and distant recurrence were modelled along with treatment related adverse effects. Primary data collected to obtain estimates of out-of-pocket expenditure (OOPE) and utility weights. Both health system cost and OOPE were included. The future costs and consequences were discounted at 3%. A probabilistic sensitivity analysis was used. RESULTS: The lifetime cost of hormone therapy with tamoxifen, AI and switch therapy was to be ₹1,472,037 (I$ 68,947), ₹1,306,794 (I$ 61,208) and ₹1,281,811 (I$ 60,038). The QALYs lived per patient receiving tamoxifen, AI and switch were 13.12, 13.42 and 13.32. tamoxifen was found to be more expensive and less effective. As compared to switch therapy, AI for five years incurred an incremental cost of ₹259,792 (I$12,168) per QALY gained. At the willingness to pay equals to per capita GDP of India, there is 55% probability of AI therapy to be cost-effective compared to switch therapy. CONCLUSION: In postmenopausal women with HR-positive early-stage breast cancer, switch therapy is recommended for use on the basis of cost-effectiveness.

Health related quality of life among Rheumatic Fever and Rheumatic Heart Disease patients in India.

BACKGROUND: Measurement of health-related quality of life (HRQOL) of people with chronic illnesses has become extremely important as the mortality rates associated with such illnesses have decreased and survival rates have increased. Thereby, such measurements not only provide insights into physical, mental and social dimensions of patient's health, but also allow monitoring of the results of interventions, complementing the traditional methods based on morbidity and mortality. OBJECTIVE: The present study was conducted to describe the HRQOL of patients suffering from Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD), and to identify socio-demographic and clinical factors as predictors of HRQOL. METHODOLOGY: A cross-sectional study was conducted to assess the HRQOL among 702 RF and RHD patients using EuroQol 5-dimensions 5-levels instrument (EQ-5D-5L), EuroQol Visual Analogue Scale and Time Trade off method. Mean EQ-5D-5L quality of life scores were calculated using EQ5D index value calculator across different stages of RF and RHD. Proportions of patients reporting problems in different attributes of EQ-5D-5L were calculated. The impact of socio-economic determinants on HRQOL was assessed. RESULTS: The mean EQ-5D-5L utility scores among RF, RHD and RHD with Congestive heart failure patients (CHF) were estimated as 0.952 [95% Confidence Interval (CI): 0.929-0.975], 0.820 [95% CI: 0.799-0.842] and 0.800 [95% CI: 0.772-0.829] respectively. The most frequently reported problem among RF/RHD patients was pain/discomfort (33.8%) followed by difficulty in performing usual activities (23.9%) patients, mobility (22.7%) and anxiety/depression (22%). Patients with an annual income of less than 50,000 Indian National Rupees (INR) reported the highest EQ-5D-5L score of 0.872, followed by those in the income group of more than INR 200,000 (0.835), INR 50,000-100,000 (0.832) and INR 100,000-200,000 (0.828). Better HRQOL was reported by RHD patients (including RHD with CHF) who underwent balloon valvotomy (0.806) as compared to valve replacement surgery (0.645). CONCLUSION: RF and RHD significantly impact the HRQOL of patients. Interventions aiming to improve HRQOL of RF/RHD patients should focus upon ameliorating pain and implementation of secondary prevention strategies for reducing the progression from ARF to RHD and prevention of RHD-related complications.

Cost effectiveness of strategies for cervical cancer prevention in India.

The establishment of link between high-risk human papillomavirus (HPV) infection and occurrence of cervical cancer has resulted in development of various HPV related control strategies for the prevention of cervical cancer. The objective of the present study was to assess the cost effectiveness of various screening strategies for cervical cancer and human papilloma virus (HPV) vaccination in India. A Markov model based on societal perspective was designed to estimate the lifetime costs and consequences of screening (with either visual inspect with acetic acid (VIA), Papanicolaou test or HPV DNA test at various time intervals) in a hypothetical cohort of 30-65 years age women or vaccination among adolescent girls. Diagnostic accuracy of the screening strategies, efficacy of HPV vaccination and data on transition probabilities was based on the results of the existing meta-analyses. Primary data was collected for assessing per person cost of screening, cost of treating cervical cancer and quality of life. We found that introduction of different screening strategies leads to reduction in lifetime occurrence of cervical cancer cases caused by HPV 16/18 from 20% to 61%, and cervical cancer deaths from 28% to 70%, as compared to no screening. Among various screening strategies, screening with both VIA 5 yearly and VIA 10 yearly came out to be cost effective at 1-time per capita GDP, with VIA every 5 years providing greater health benefits as compared to VIA 10 years. Hence, screening with VIA 5 years at an incremental cost of US$ 829 (INR 54,881) per QALY gained is the recommended strategy for India. Further, with regards to HPV vaccination, it leads to 60% reduction in cancer cases and mortality caused by HPV 16/18 as compared to no vaccination. Moreover, when this vaccinated cohort of adolescent girls is also screened later in their life (with VIA every 10 years and VIA 5 years), it leads to 69%-76% reduction in cancer cases and 71%-81% reduction in cancer deaths. As compared to no vaccination and no screening, both HPV vaccination alone and vaccination plus screening (with VIA every 5 yearly and VIA 10 yearly) appears to be cost effective with ICERs in the range of US$ 86 (INR 5,693) to US$ 476 (INR 31,511) per QALY gained. In the long run, when the cohort of adolescent girls, who were immunized for HPV, reach the age of 30 years, the screening frequency using VIA should be determined based on the coverage of HPV vaccination in that cohort.

Health-related quality of life among cervical cancer patients in India.

INTRODUCTION: Estimation of health-related quality of life of cervical cancer patients in India is important in assessing the well-being of patients, monitor treatment outcomes, and conduct health technology assessments. However, health-related quality of life estimates for different stages of cervical cancer are not available for the Indian population. This study aims to generate stage-specific quality of life scores for cervical cancer patients in India. METHODS: A cross-sectional study using the EQ-5D (EuroQol 5-dimensions) instrument, that consists of the EQ-5D-5L descriptive system and the EuroQol Visual Analog Scale (EQ-VAS) was conducted. A total of 159 cervical cancer patients were interviewed. Mean EQ-5D-5L quality of life scores (utility scores) were calculated using the EQ-5D-5L index value calculator across different stages of cervical cancer. The proportion of patients reporting problems in different attributes of EQ-5D-5L was assessed. The impact of socio-economic determinants on health-related quality of life was evaluated using multiple linear regression. RESULTS: The mean EQ-5D-5L and EQ-VAS utility scores among patients of cervical cancer were 0.64 [95% CI=0.61-0.67] and 67.6 [95% CI=65.17-70.03], respectively. The most frequently reported problem among cervical cancer patients was pain/discomfort (61.88%), followed by difficulty in performing usual activities (53.81%), and anxiety/depression (41.26%). CONCLUSION: Cervical cancer significantly impacts the health-related quality of life of the patients in India. Clinical interventions should focus on the control of pain and relief of anxiety. The measurement of health-related quality of life should be an integral component of the effectiveness of interventions as well as health technology assessment.

Health impact and economic burden of alcohol consumption in India.

BACKGROUND: The health and economic consequences of alcohol consumption have been assessed mainly in developed countries. This study aims to estimate health impact and economic burden attributable to alcohol use in India. METHODS: A combination of decision tree and mathematical markov model was parameterized to assess the health effects and economic cost attributable to alcohol consumption. Health effect of alcohol was modelled for a time period of 2011 to 2050 on three sets of conditions - liver disease, cancers and road traffic accidents. Estimates of illness, death, life years lost and quality adjusted life years (QALYs) gained were estimated as a result of alcohol consumption. Both direct and indirect costs were estimated to determine economic burden. Future costs and consequences were discounted at 3% for time preferences of cost and utility. Uncertainties in parameters were assessed using probabilistic sensitivity analysis. RESULTS: Between 2011 and 2050, alcohol attributable deaths would lead to a loss of 258 million life years. In contrast, 552 million QALYs would be gained by eliminating alcohol consumption. Treatment of these conditions will impose an economic burden of INR 3127 billion (US$ 48.11 billion) on the health system. Societal burden of alcohol, inclusive of health system cost, out of pocket expenditure and productivity losses will be INR 121,364 billion (US$ 1867 billion). Even after adjusting for tax receipts from sale of alcohol, alcohol poses a net economic loss of INR 97,895 billion (US$ 1506 billion). This amounts to an average loss of 1.45% of the gross domestic product (GDP) per year to the Indian economy. CONCLUSION: Alcohol causes significant negative health impact and economic burden on Indian society and evidence informed policy interventions are needed to control alcohol attributable harm.

Cost Effectiveness of Hematopoietic Stem Cell Transplantation Compared with Transfusion Chelation for Treatment of Thalassemia Major.

Hematopoietic stem cell transplantation (HSCT) is the only cure for thalassemia major (TM), which inflicts a significant 1-time cost. Hence, it is important to explore the cost effectiveness of HSCT versus lifelong regular transfusion-chelation (TC) therapy. This study was undertaken to estimate incremental cost per quality-adjusted life-year (QALY) gained with the intervention group HSCT, and the comparator group TC, in TM patients. A combination of decision tree and Markov model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. Results are presented using societal perspective. Incremental cost per QALY gained with use of HSCT as compared with TC was 64,096 (US$986) in case of matched related donor (MRD) and 1,67,657 (US$2579) in case of a matched unrelated donor transplantation. The probability of MRD transplant to be cost effective at the willingness to pay threshold of Indian per capita gross domestic product is 94%. HSCT is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of TC.

Cost-effectiveness of human papillomavirus vaccination for adolescent girls in Punjab state: Implications for India's universal immunization program.

BACKGROUND: Introduction of human papillomavirus (HPV) vaccination for adolescent girls is being considered in the Punjab state of India. However, evidence regarding cost-effectiveness is sought by policy makers when making this decision. The current study was undertaken to evaluate the incremental cost per quality-adjusted life-years (QALYs) gained with introduction of the HPV vaccine compared with a no-vaccination scenario. METHODS: A static progression model, using a combination of decision tree and Markov models, was populated using epidemiological, cost, coverage, and effectiveness data to determine the cost-effectiveness of HPV vaccination. Using a societal perspective, lifetime costs and consequences (in terms of QALYs) among a cohort of 11-year-old adolescent girls in Punjab state were modeled in 2 alternate scenarios with and without vaccination. All costs and consequences were discounted at a rate of 3%. RESULTS: Although immunizing 1 year's cohort of 11-year-old girls in Punjab state costs Indian National Rupees (INR) 135 million (US dollars [USD] 2.08 million and International dollars [Int$] 6.25 million) on an absolute basis, its net cost after accounting for treatment savings is INR 38 million (USD 0.58 million and Int$ 1.76 million). Incremental cost per QALY gained for HPV vaccination was found to be INR 73 (USD 1.12 and Int$ 3.38). Given all the data uncertainties, there is a 90% probability for the vaccination strategy to be cost-effective in Punjab state at a willingness-to-pay threshold of INR 10,000, which is less than one-tenth of the per capita gross domestic product. CONCLUSIONS: HPV vaccination appears to be a very cost-effective strategy for Punjab state, and is likely to be cost-effective for other Indian states. Cancer 2017;123:3253-60. © 2017 American Cancer Society.

Cost-Effectiveness of Autologous Stem Cell Treatment as Compared to Conventional Chemotherapy for Treatment of Multiple Myeloma in India.

Recent innovations in treatment of multiple myeloma include autologous stem cell transplantation (ASCT) along with high dose chemotherapy (HDC). We undertook this study to estimate incremental cost per quality adjusted life year gained (QALY) with use of ASCT along with HDC as compared to conventional chemotherapy (CC) alone in treatment of multiple myeloma. A combination of decision tree and markov model was used to undertake the analysis. Incremental costs and effects of ASCT were compared against the baseline scenario of CC (based on Melphalan and Prednisolone regimen) in the patients of multiple myeloma. A lifetime study horizon was used and future costs and consequences were discounted at 5%. Consequences were valued in terms of QALYs. Incremental cost per QALY gained using ASCT as against CC for treatment of multiple myeloma was estimated using both a health system and societal perspective. The cost of providing ASCT (with HDC) for multiple myeloma patients was INR 500,631, while the cost of CC alone was INR 159,775. In the long run, cost per patient per year for ASCT and CC arms was estimated to be INR 119,740 and INR 111,565 respectively. The number of QALYs lived per patient in case of ASCT and HDC alone were found to be 4.1 and 3.5 years respectively. From a societal perspective, ASCT was found to incur an incremental cost of INR 334,433 per QALY gained. If the ASCT is initiated early to patients, the incremental cost for ASCT was found to be INR 180,434 per QALY gained. With current mix of patients, stem cell treatment for multiple myeloma is not cost effective at a threshold of GDP per capita. It becomes marginally cost-effective at 3-times the GDP per capita threshold. However, accounting for the model uncertainties, the probability of ASCT to be cost effective is 59%. Cost effectiveness of ASCT can be improved with early detection and initiation of treatment.