Cost-Effectiveness of Novel Agent Regimens for Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients in India.

BACKGROUND: Survival outcomes for multiple myeloma have improved dramatically since the introduction of novel therapeutic agents. While these drugs are highly effective in improving survival outcomes and quality of life in patients with multiple myeloma, they come at a significant cost. We assessed the cost-effectiveness of bortezomib-based triplet or quadruplet drug regimens in isolation and followed by autologous hematopoietic stem cell transplantation (AHSCT) for the treatment of newly diagnosed multiple myeloma (NDMM) in the Indian context. METHODS: A Markov model was developed to assess the health and economic outcomes of novel drug regimens with and without AHSCT for the treatment of NDMM in India. We estimated the lifetime quality-adjusted life-years (QALYs) and costs in each scenario. The incremental cost-effectiveness ratios (ICERs) were computed and compared against the current willingness-to-pay threshold of a one-time per capita gross domestic product of ₹146,890 (US$1,927.70) for India. Parameter uncertainty was assessed through Monte Carlo probabilistic sensitivity analysis. RESULTS: Among seven treatment sequences, the VCd (bortezomib, cyclophosphamide, dexamethasone) alone arm has the lowest cost and health benefits as compared to four treatment sequences, namely VTd (bortezomib, thalidomide, dexamethasone) alone, VRd (bortezomib, lenalidomide, dexamethasone) alone, VRd plus AHSCT and DVRd (Daratumumab, bortezomib, lenalidomide, dexamethasone) plus AHSCT. It was found that VTd plus AHSCT and VCd plus AHSCT arms were extendedly dominated (ED) by combination of two alternative treatments. Among the five non-dominated strategies, VRd has a lowest incremental cost of ₹ 2,20,093 (US$2,888) per QALY gained compared to VTd alone followed by VRd plus AHSCT [₹3,14,530 (US$4,128) per QALY gained] in comparison to VRd alone. None of the novel treatment sequences were found to be cost-effective at the current WTP threshold of ₹1,46,890 (US$1,927.7). CONCLUSION: At the current WTP threshold of one-time per capita GDP (₹ 146,890) of India, VRd alone and VRd plus AHSCT has 38.1% and 6.9% probability to be cost-effective, respectively. Reduction in current reimbursement rates of novel drugs, namely VRd, lenalidomide, and pomalidomide plus dexamethasone under national insurance program and societal cost of transplant by 50%, would make VRd plus AHSCT and VTd plus AHSCT cost-effective at an incremental cost of ₹40,671 (US$34) and ₹97,639 (US$1,281) per QALY gained, respectively.

Cost-Effectiveness Analysis of Denosumab in the Prevention of Skeletal-Related Events Among Patients With Breast Cancer With Bone Metastasis in India.

PURPOSE: Denosumab is clinically superior to zoledronic acid (ZA) for preventing and delaying time to first and subsequent skeletal-related events (SREs) among patients with breast cancer (BC) with bone metastases. We evaluated the cost and health benefits of denosumab and ZA (once every 4 weeks and once every 12 weeks) among four different molecular subtypes of BC with bone metastases in India. MATERIALS AND METHODS: A Markov model was developed in Microsoft Excel to estimate lifetime health consequences and resulting costs among cohort of 1,000 patients with BC with bone metastasis, for three intervention scenarios, namely denosumab (once every 4 weeks), ZA (once every 4 weeks), and ZA (once every 12 weeks). The health outcomes were measured in terms of SREs averted and quality-adjusted life-years (QALYs) gained. The cost of each intervention scenario was measured using both the health system and the patient's perspectives. Indirect costs because of lost productivity were not included. The future costs and outcomes were discounted at the standard rate of 3%. RESULTS: Over a lifetime, the incremental number of SREs averted with use of denosumab once every 4 weeks (compared with ZA once every 4 weeks and once every 12 weeks) among patients with luminal A, luminal B, human epidermal growth factor receptor 2-enriched, and triple negative breast cancer were estimated as 0.39, 0.26, 0.25, and 0.19, respectively. The number of QALYs lived were slightly higher in the denosumab arm (1.45-2.80) compared with ZA once every 4 weeks and once every 12 weeks arms (1.44-2.78). However, denosumab once every 4 weeks was not found to be a cost-effective alternative for either of the four molecular subtypes of breast cancer. ZA once every 12 weeks was found to be a cost-effective option with an average cost-effectiveness ratio ranging between ₹68,254 and ₹73,636. CONCLUSION: ZA once every 12 weeks is the cost-effective treatment option for BC with bone metastases in India. The present study findings hold significance for standard treatment guidelines under India's government-funded health insurance program.

Health-related quality of life and its determinants among cancer patients: evidence from 12,148 patients of Indian database.

BACKGROUND: Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants. METHODS: Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics. RESULTS: Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45-60 years and females (49.3-58.3%). Most patients were found to be in stage III (40-40.6%) or stage IV (29.4-37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771). CONCLUSION: Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.

Financial toxicity of cancer treatment in India: towards closing the cancer care gap.

Background: The rising economic burden of cancer on patients is an important determinant of access to treatment initiation and adherence in India. Several publicly financed health insurance (PFHI) schemes have been launched in India, with treatment for cancer as an explicit inclusion in the health benefit packages (HBPs). Although, financial toxicity is widely acknowledged to be a potential consequence of costly cancer treatment, little is known about its prevalence and determinants among the Indian population. There is a need to determine the optimal strategy for clinicians and cancer care centers to address the issue of high costs of care in order to minimize the financial toxicity, promote access to high value care and reduce health disparities. Methods: A total of 12,148 cancer patients were recruited at seven purposively selected cancer centres in India, to assess the out-of-pocket expenditure (OOPE) and financial toxicity among cancer patients. Mean OOPE incurred for outpatient treatment and hospitalization, was estimated by cancer site, stage, type of treatment and socio-demographic characteristics. Economic impact of cancer care on household financial risk protection was assessed using standard indicators of catastrophic health expenditures (CHE) and impoverishment, along with the determinants using logistic regression. Results: Mean direct OOPE per outpatient consultation and per episode of hospitalization was estimated as ₹8,053 (US$ 101) and ₹39,085 (US$ 492) respectively. Per patient annual direct OOPE incurred on cancer treatment was estimated as ₹331,177 (US$ 4,171). Diagnostics (36.4%) and medicines (45%) are major contributors of OOPE for outpatient treatment and hospitalization, respectively. The overall prevalence of CHE and impoverishment was higher among patients seeking outpatient treatment (80.4% and 67%, respectively) than hospitalization (29.8% and 17.2%, respectively). The odds of incurring CHE was 7.4 times higher among poorer patients [Adjusted Odds Ratio (AOR): 7.414] than richest. Enrolment in PM-JAY (CHE AOR = 0.426, and impoverishment AOR = 0.395) or a state sponsored scheme (CHE AOR = 0.304 and impoverishment AOR = 0.371) resulted in a significant reduction in CHE and impoverishment for an episode of hospitalization. The prevalence of CHE and impoverishment was significantly higher with hospitalization in private hospitals and longer duration of hospital stay (p < 0.001). The extent of CHE and impoverishment due to direct costs incurred on outpatient treatment increased from 83% to 99.7% and, 63.9% to 97.1% after considering both direct and indirect costs borne by the patient and caregivers, respectively. In case of hospitalization, the extent of CHE increased from 23.6% (direct cost) to 59.4% (direct+ indirect costs) and impoverishment increased from 14.1% (direct cost) to 27% due to both direct and indirect cost of cancer treatment. Conclusion: There is high economic burden on patients and their families due to cancer treatment. The increase in population and cancer services coverage of PFHI schemes, creating prepayment mechanisms like E-RUPI for outpatient diagnostic and staging services, and strengthening public hospitals can potentially reduce the financial burden among cancer patients in India. The disaggregated OOPE estimates could be useful input for future health technology analyses to determine cost-effective treatment strategies.

Diagnostic Accuracy of Screening of Lip and Oral Cavity Cancers or Potentially Malignant Disorders (PMD) by Frontline Workers: A Systematic Review and Meta-Analysis.

BACKGROUND: Oral cancer screening strategies help reduce associated mortality and could be performed by a trained frontline health worker (FHW). The present review aims to assess the diagnostic accuracy of commonly used screening modalities for oral cancer performed by FHW in apparently healthy individuals. METHODS: Electronic databases PubMed, Scopus, Embase, Cochrane Library, and Google Scholar, were searched. The review included studies conducted where apparently healthy adult individuals were screened by the FHW for cancer or PMD of the lip and oral cavity by any of the four commonly used techniques - Conventional Oral Examination (COE), toluidine blue staining (TBS), Oral Cytology (OC), and Chemiluminescent Illumination (CLI). FINDINGS: A total of 2,413 potentially relevant articles were retrieved from the search, among which five studies for COE were included in the review. Four out of those five studies were done before the year 2000. None of the studies fitted the inclusion criteria for TBS, OC, and CLI. Pooled sensitivity of oral screening by COE performed by an FHW (n=5) was 88.8% (95% CI: 71.6-96.1), whereas pooled specificity was 91.9% (95% CI: 78.3-97.3). On subgroup analysis, the pooled sensitivity and specificity of studies where the prevalence of disease was <50% (n=4) was 84.5% (95% CI: 62.6 - 94.7) and 94.1% (95% CI: 82.2 - 98.2), respectively. INTERPRETATION: COE by trained FHW had high pooled sensitivity and specificity for screening of oral cancer and PMDs. The screening techniques TBS, OC, and CLI, were not studied for mass screening by trained FHW. COE by trained FHW could be utilized for oral screening in limited-resource settings. However, the FHW should be sufficiently trained to get the desired benefits of early detection. FUNDING: Department of Health Research, Ministry of Health & Family Welfare, Government of India.

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 Bevacizumab Plus Chemotherapy for the Treatment of Advanced and Metastatic Cervical Cancer in India-A Model-Based Economic Analysis.

PURPOSE: Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India. METHODS: Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty. RESULTS: Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy. CONCLUSION: Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.

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.

Development of National Cancer Database for Cost and Quality of Life (CaDCQoL) in India: a protocol.

INTRODUCTION: The rising economic burden of cancer on healthcare system and patients in India has led to the increased demand for evidence in order to inform policy decisions such as drug price regulation, setting reimbursement package rates under publicly financed health insurance schemes and prioritising available resources to maximise value of investments in health. Economic evaluations are an integral component of this important evidence. Lack of existing evidence on healthcare costs and health-related quality of life (HRQOL) makes conducting economic evaluations a very challenging task. Therefore, it is imperative to develop a national database for health expenditure and HRQOL for cancer. METHODS AND ANALYSIS: The present study proposes to develop a National Cancer Database for Cost and Quality of Life (CaDCQoL) in India. The healthcare costs will be estimated using a patient perspective. A cross-sectional study will be conducted to assess the direct out-of-pocket expenditure (OOPE), indirect cost and HRQOL among cancer patients who will be recruited at seven leading cancer centres from six states in India. Mean OOPE and HRQOL scores will be estimated by cancer site, stage of disease and type of treatment. Economic impact of cancer care on household financial risk protection will be assessed by estimating prevalence of catastrophic health expenditures and impoverishment. The national database would serve as a unique open access data repository to derive estimates of cancer-related OOPE and HRQOL. These estimates would be useful in conducting future cost-effectiveness analyses of management strategies for value-based cancer care. ETHICS AND DISSEMINATION: Approval was granted by Institutional Ethics Committee vide letter no. PGI/IEC-03/2020-1565 of Post Graduate Institute of Medical Education and Research, Chandigarh, India. The study results will be published in peer-reviewed journals and presented to the policymakers at national level.

Toxicity profiling and antioxidant activity of ethyl acetate extract of leaves of Premna integrifolia L. for its application as protective agent against xenobiotics.

Premna integrifoliaL. (Lamiaceae) is widely used in herbal formulation "Dashmoolarishta" which is useful in postnatal care. Ethyl acetate extract obtained from the leaves was evaluated for phenolic content and its antioxidant activity. Acute and subacute toxicity of the extract was studied in mice of both sexes to get an idea about LD50 value and assessed its safety profile before its application as a protective agent against different toxicities induced by xenobiotics. Phenol enriched extract (phenol content is 63.10 ± 1.26 mg/g of gallic acid equivalent and flavonoid content 75.33 ± 0.23 mg/g of rutin equivalent) showed good antioxidant activity. In acute toxicity studies it was observed that single different doses (300-5000 mg/kg b.wt.) of extract did not show any mortality of mice. Thus the LD50 of the extract was determined, and it was higher than 5000 mg/kg. There was no major change in behavioral and general appearance of mice. External morphology of liver, kidneys, lungs, spleen and heart did not show any effect of treatment. In subacute toxicity no statistically significant change in body weight, relative organ weight, food intake and water uptake, hematological, biochemical parameters were reported after comparison with control. Extract did not show significant effect in the level of antioxidant enzymes in the liver of mice of treated groups. No histopathological changes were observed in liver and kidney tissues. Thus, extract did not show any sign of toxic effects, when administered orally to male and female mice at dose level up to 1000 mg/kg. So, it can be utilized as protective agent against toxicity produced by different xenobiotics.

Cost of Treatment of Valvular Heart Disease at a Tertiary Hospital in North India: Policy Implications.

BACKGROUND: Lack of data on the cost of cardiac care is an impediment to evidence-based planning, especially for determining provider payment rates under publically financed health insurance schemes. OBJECTIVE: This study estimates the unit costs of outpatient consultation, hospitalization, intensive care, selected surgical procedures and diagnostics for providing cardiac care for valvular heart disease at a tertiary hospital in India. METHODS: We undertook an economic costing of cardiac care using both patient and health system perspectives. For the health system costs, a bottom-up costing methodology was used. Data on all resources (capital and recurrent) utilized for the delivery of cardiac care services for valvular heart disease for 1 year were collected. Data on out-of-pocket expenditures was collected from 100 cardiac patients who underwent valve replacement and balloon valvotomy procedures. All estimated costs represent the year 2016-2017. RESULTS: The health system cost of an outpatient cardiac consultation was estimated as 182.4 Indian rupees (INR) (US$2.8) and INR334.8 (US$5.2) in the cardiology, and cardio-thoracic and vascular surgery (CTVS) departments, respectively. The cost of hospitalization per bed-day in cardiology, CTVS and the intensive care unit (ICU) was INR1040 (US$16), INR3853 (US$60) and INR12,635 (US$197), respectively. The median out-of-pocket expenditure for valve replacement surgery using mechanical and bio-prosthetic valves was estimated to be INR107,800 (US$1684) and INR154,000 (US$2406), respectively, and for balloon valvotomy was estimated to be INR14,456 (US$367). Overall package cost per mechanical and bio-prosthetic single valve replacement surgery and balloon valvotomy procedure was estimated as INR127,919 (US$1999), INR148,919 (US$2372) and INR14,456 (US$226), respectively. CONCLUSION: Our findings are useful for planning expansion of public sector cardiac care services, developing package rates for publically financed insurance schemes in India and for undertaking research on cost effectiveness of various models of cardiac care.