- Email: [email protected]
Cost Effectiveness of Nivolumab Monotherapy for the Treatment of Advanced Melanoma Patients in the United Kingdom
A354
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
(CADTH). Results: All of the reviewed frameworks consider therapeutic benefit; however, few (ASCO, ESMO and CDF) employ detailed reviews and the hierarchy of clinical trial endpoints (overall survival, progression free survival and response rates) and in-depth evaluation of safety (toxicities’ rates). ICER and HTAs utilize Quality Adjusted Life Years (QALY) to measure effectiveness, while NCCN and MSKCC approaches lack transparency. Not all frameworks consider patients’ impact in terms of quality of life or treatment free period. Although many incorporate costs, these are mostly limited to price and do not consider other direct or indirect costs except for ICER and other HTA approaches. Application to MM will be presented. Conclusions: Heterogeneous methodologies, various data considerations and target audience may lead to potentially contradicting recommendations across frameworks. Further refinement of each valuation approach is ongoing; however, it is clear that these emerging frameworks will raise the objectivity and transparency of healthcare decisions.
Economic Evaluation Studies EE1 Economic Evaluation for the United Kingdom of Systemic Chemotherapies as First-Line Treatment for Metastatic Pancreatic Cancer Gharaibeh M1, McBride A2, Alberts D2, Slack M1, Erstad B1, Abraham I1 of Arizona, Tucson, AZ, USA, 2Arizona Cancer Center, Tucson, AZ, USA
1University
Objectives: Gemcitabine (GEM), oxaliplatin plus GEM (OX+GEM), cisplatin plus GEM (CIS+GEM), capecitabine plus GEM (CAP+GEM), FOLFIRINOX (FFX), and Nabpaclitaxel plus gemcitabine (NAB-P+GEM) are the most commonly used first-line treatment options for metastatic pancreatic cancer (MPC) in the UK. A comprehensive independent economic evaluation for these regimens has not been conducted for the UK. Methods: A state transition model with full time horizon was used to estimate the life years (LY) and quality-adjusted life years (QALY) gained and incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) for all regimens. Direct and indirect efficacy estimates were obtained from published clinical trials. Health-states utility values were adjusted from a US sample to represent sample of the UK population. Adverse events utility decrements were obtained from published clinical trials using EQ-5D questionnaire from British population. A 3.5%/year discount rate was used and all costs were presented in 2016 GB£. Results: NAB-P+GEM was dominated by FFX (NAB-P+GEM was more costly with incremental costs of £3,109, and less effective with incremental QALYs of –0.144). OX+GEM and CIS+GEM were dominated by CAP+GEM (OX+GEM was more costly with incremental costs of £3,109, and less effective with incremental QALYs of –0.144; and CIS+GEM was more costly with incremental costs of £1,947, and less effective with incremental QALYs of 0.07). The ICUR for CAP+GEM compared with GEM alone was £28,006 per QALY gained (incremental costs, £1,935; incremental QALYs, 0.07), and the ICER was £17,437 per LYG gained (incremental LYs, 0.11). The ICUR for FFX compared with GEM was £33,020 per QALY gained (incremental costs, £8,130; incremental QALYs, 0.247), and the ICER was £22,291 per LYG gained (incremental LYs, 0.365). Conclusions: The availability of less costly and more effective options such as FFX and CAP+GEM, make NABP+GEM, OX+GEM, and CIS+GEM less preferred regimens in the management of MPC in the UK.
EE2 Is it Really Cost-Effective to Risk-Assess all Hospitalized Patients for Pressure Ulcers Every Nursing-Shift? Padula WV1, Onyekwere U1, Makic MB2, Wald HL2, Epstein Z3, Meltzer DO4 Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2University of Colorado, Aurora, CO, USA, 3Pomona College, Claremont, CA, USA, 4University of Chicago, Chicago, IL, USA
1Johns
Objectives: Hospital-acquired pressure ulcers are localized skin injuries that cause significant morbidity and mortality, and are costly to treat. Following the International Guidelines for pressure ulcer prevention reduce rates over standard care, but require risk-assessment among all patients each nursing-shift using the Braden Scale. The relative value of only continually risk-assessing at-risk patients – about 7% of hospitalizations – is uncertain. Our objective was to analyze the cost-effectiveness of nursing resources to risk-assess all patients or select riskgroups identified by machine learning compared to standard care. Methods: We obtained patient-level data on 43,787 encounters from a university hospital EHR between 2011-2014, including daily Braden scores. Longitudinal arrays of adult inpatients with ≥ 10 Braden scores were classified into 5 risk-groups: very high-risk [6-9]; high-risk [10-11]; moderate-risk [12-14]; at-risk [15-18]; lowrisk [19-23]. We constructed a 10-state Markov model using supervised machine learning to calculate age-adjusted transition probabilities between risk-groups, pressure ulcer states and discharge states. Costs (2015 $US) and lifetime qualityadjusted life years (QALYs) related to pressure ulcer outcomes were added to the Markov model to compare the cost-utility of standard care, continual risk-assessment in all risk-groups or only follow-up risk-assessment in higher risk-groups. Probabilistic sensitivity analysis (PSA) tested model uncertainty at $100,000/QALY willingness-to-pay from the U.S. societal perspective. Results: Risk-assessing all patients every nursing-shift was cost-effective ($5,193, 15.43 QALYs) compared to standard care ($5,139, 14.00 QALYs) at an increment cost-effectiveness ratio of $37/ QALY. Follow-up risk-assessment only among patients with Braden scores < 19 dominated standard care ($1,745, 14.03 QALYs) in 50.89% of PSA simulations with small QALY gains. Follow-up among patients with lower Braden scores decreased costs at fewer QALYs. Conclusions: Our analysis using real-world data maintains that follow-up risk-assessment among all patients cost-effectively prevents pressure ulcers. Hospitals should encourage nurses’ adherence to International Guidelines on risk-assessment to prevent patient harm.
EE3 The Cost-Effectiveness of Bariatric Surgery in Germany, France, Italy and the United Kingdom Belarbi S1, Kusel J2, Thomas MG2 SAS, Issy-Les-Moulineaux, France, 2Costello Medical Consulting Ltd, Cambridge, UK
1Ethicon
Objectives: Obesity is a growing epidemic in Europe. The objective was to investigate the cost-effectiveness of bariatric surgery for obesity across four European countries. Methods: A Markov model was developed to compare the long-term (20 year) outcomes and costs for patients who receive bariatric surgery (gastric bypass, sleeve gastrectomy, adjustable gastric banding, duodenal switch) to those who receive diet and exercise programmes. The model was adapted for the German, French, Italian and UK healthcare systems. Body mass index (BMI) change, type II diabetes mellitus (T2DM), stroke, myocardial infarction, cancer, knee pain and sleep apnoea were included; inputs for these were taken from recent network metaanalyses. Utilities and costs were sourced from the literature and the healthcare system tariffs. The populations considered were patients with BMI≥ 40 or BMI≥ 35 with obesity-related comorbidities, and the subpopulation of T2DM patients. Results: Compared to those receiving conventional care, patients undergoing bariatric surgery were found to live longer and have fewer cases of stroke, myocardial infarction, cancer, knee pain and sleep apnoea. Bariatric surgery was associated with an incremental cost-effectiveness ratio (ICER) of € 125, € 88 and £859 per qualityadjusted life year (QALY) gained versus conventional care for France, Italy and the UK, respectively. Bariatric surgery dominated conventional care in Germany, with cost savings per patient of € 429 and QALY gains of 2.6. Bariatric surgery was associated with an ICER of less than € 10,000/QALY in 100% of probabilistic simulations, for all countries. Differences between countries were driven by differences in the cost of surgery and treatment of comorbidities. Results were similar in the T2DM population. Conclusions: Bariatric surgery is predicted to improve patient outcomes and be highly cost-effective compared to diet and exercise programmes in all four European countries investigated. Further updates to the model are planned. EE4 Cost Effectiveness of Nivolumab Monotherapy for the Treatment of Advanced Melanoma Patients in the United Kingdom Meng Y1, Hertel N2, Ellis J2, Johnson H3, Philips Z1, Roskell N1, Lee D1 Health Solutions, Sheffield, UK, 2Bristol-Myers Squibb Pharmaceuticals, Uxbridge, UK, 3Helen Johnson Consulting Ltd, Welwyn Garden City, UK
1BresMed
Objectives: Nivolumab was the first programmed death receptor 1 (PD1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients. We evaluated the cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Methods: A Markov state-transition model was developed in Excel®to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and ipilimumab, dabrafenib and vemurafenib for BRAF mutation-positive patients. Covariate-adjusted parametric curves for time-to-progression, pre-progression survival and post-progression survival were fitted based on patient-level data from two trials, including long-term ipilimumab survival data, and were used to populate the progression-free, progressed and death state for nivolumab, ipilimumab and dacarbazine. Indirect treatment comparisons between nivolumab, ipilimumab and dacarbazine were informed by these covariateadjusted parametric curves, allowing differences in patient characteristics to be accounted for. Due to the lack of patient-level data, Kaplan–Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib. Patient utilities and resource use data were based on trial data or sourced from the literature. Patients are assumed to receive nivolumab until there is no further clinical benefit, assumed to be the first of progressive disease by RECIST, unacceptable toxicity or two years of treatment. Results: Based on the nivolumab list price and assumed discounted comparator prices, nivolumab is the most cost-effective treatment option in both BRAF mutation-negative and mutation-positive patients, with incremental cost-effectiveness ratios of £24,483 and £17,362 per quality-adjusted life year, respectively. The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves. Conclusions: The analyses show that nivolumab is a cost-effective treatment for advanced melanoma patients in England and received a positive recommendation by NICE.
BREAKOUTS – SESSION VII
DATABASE USE IN OUTCOMES RESEARCH STUDIES DB1 Mortality Excess Due To Clostridium Difficile Infection - A National Database Analysis Bouee S1, Levy Bachelot L2, Ravonimbola H2, Longepierre L1, Godard C2, Gourmelen J3, Barbut F4 1CEMKA, Bourg La Reine, France, 2MSD France, Courbevoie, France, 3UMS 011 - Inserm - UVSQ, Villejuif, France, 4Laboratory for Clostridium Difficile, Paris, France
Objectives: Several researches have led to contradictory results on the question whether there was an excess mortality rate in CDI patients. The objective of this study was to estimate the increase of mortality attributable to Clostridium difficile infection (CDI). Methods: A French cohort of patients with a first episode of ICD hospitalized between 2007 and 2014 was extracted from a 1% representative sample of subjects covered by the general health insurance (EGB database, ≈600,000 patients). The one year incidence of deaths was estimated and compared to a control group with no CDI (2 controls per case) matched on a propensity score (PS). PS was calculated with the variables: age, gender, Charlson index, duration of stay, year of
VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
(CADTH). Results: All of the reviewed frameworks consider therapeutic benefit; however, few (ASCO, ESMO and CDF) employ detailed reviews and the hierarchy of clinical trial endpoints (overall survival, progression free survival and response rates) and in-depth evaluation of safety (toxicities’ rates). ICER and HTAs utilize Quality Adjusted Life Years (QALY) to measure effectiveness, while NCCN and MSKCC approaches lack transparency. Not all frameworks consider patients’ impact in terms of quality of life or treatment free period. Although many incorporate costs, these are mostly limited to price and do not consider other direct or indirect costs except for ICER and other HTA approaches. Application to MM will be presented. Conclusions: Heterogeneous methodologies, various data considerations and target audience may lead to potentially contradicting recommendations across frameworks. Further refinement of each valuation approach is ongoing; however, it is clear that these emerging frameworks will raise the objectivity and transparency of healthcare decisions.
Economic Evaluation Studies EE1 Economic Evaluation for the United Kingdom of Systemic Chemotherapies as First-Line Treatment for Metastatic Pancreatic Cancer Gharaibeh M1, McBride A2, Alberts D2, Slack M1, Erstad B1, Abraham I1 of Arizona, Tucson, AZ, USA, 2Arizona Cancer Center, Tucson, AZ, USA
1University
Objectives: Gemcitabine (GEM), oxaliplatin plus GEM (OX+GEM), cisplatin plus GEM (CIS+GEM), capecitabine plus GEM (CAP+GEM), FOLFIRINOX (FFX), and Nabpaclitaxel plus gemcitabine (NAB-P+GEM) are the most commonly used first-line treatment options for metastatic pancreatic cancer (MPC) in the UK. A comprehensive independent economic evaluation for these regimens has not been conducted for the UK. Methods: A state transition model with full time horizon was used to estimate the life years (LY) and quality-adjusted life years (QALY) gained and incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) for all regimens. Direct and indirect efficacy estimates were obtained from published clinical trials. Health-states utility values were adjusted from a US sample to represent sample of the UK population. Adverse events utility decrements were obtained from published clinical trials using EQ-5D questionnaire from British population. A 3.5%/year discount rate was used and all costs were presented in 2016 GB£. Results: NAB-P+GEM was dominated by FFX (NAB-P+GEM was more costly with incremental costs of £3,109, and less effective with incremental QALYs of –0.144). OX+GEM and CIS+GEM were dominated by CAP+GEM (OX+GEM was more costly with incremental costs of £3,109, and less effective with incremental QALYs of –0.144; and CIS+GEM was more costly with incremental costs of £1,947, and less effective with incremental QALYs of 0.07). The ICUR for CAP+GEM compared with GEM alone was £28,006 per QALY gained (incremental costs, £1,935; incremental QALYs, 0.07), and the ICER was £17,437 per LYG gained (incremental LYs, 0.11). The ICUR for FFX compared with GEM was £33,020 per QALY gained (incremental costs, £8,130; incremental QALYs, 0.247), and the ICER was £22,291 per LYG gained (incremental LYs, 0.365). Conclusions: The availability of less costly and more effective options such as FFX and CAP+GEM, make NABP+GEM, OX+GEM, and CIS+GEM less preferred regimens in the management of MPC in the UK.
EE2 Is it Really Cost-Effective to Risk-Assess all Hospitalized Patients for Pressure Ulcers Every Nursing-Shift? Padula WV1, Onyekwere U1, Makic MB2, Wald HL2, Epstein Z3, Meltzer DO4 Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2University of Colorado, Aurora, CO, USA, 3Pomona College, Claremont, CA, USA, 4University of Chicago, Chicago, IL, USA
1Johns
Objectives: Hospital-acquired pressure ulcers are localized skin injuries that cause significant morbidity and mortality, and are costly to treat. Following the International Guidelines for pressure ulcer prevention reduce rates over standard care, but require risk-assessment among all patients each nursing-shift using the Braden Scale. The relative value of only continually risk-assessing at-risk patients – about 7% of hospitalizations – is uncertain. Our objective was to analyze the cost-effectiveness of nursing resources to risk-assess all patients or select riskgroups identified by machine learning compared to standard care. Methods: We obtained patient-level data on 43,787 encounters from a university hospital EHR between 2011-2014, including daily Braden scores. Longitudinal arrays of adult inpatients with ≥ 10 Braden scores were classified into 5 risk-groups: very high-risk [6-9]; high-risk [10-11]; moderate-risk [12-14]; at-risk [15-18]; lowrisk [19-23]. We constructed a 10-state Markov model using supervised machine learning to calculate age-adjusted transition probabilities between risk-groups, pressure ulcer states and discharge states. Costs (2015 $US) and lifetime qualityadjusted life years (QALYs) related to pressure ulcer outcomes were added to the Markov model to compare the cost-utility of standard care, continual risk-assessment in all risk-groups or only follow-up risk-assessment in higher risk-groups. Probabilistic sensitivity analysis (PSA) tested model uncertainty at $100,000/QALY willingness-to-pay from the U.S. societal perspective. Results: Risk-assessing all patients every nursing-shift was cost-effective ($5,193, 15.43 QALYs) compared to standard care ($5,139, 14.00 QALYs) at an increment cost-effectiveness ratio of $37/ QALY. Follow-up risk-assessment only among patients with Braden scores < 19 dominated standard care ($1,745, 14.03 QALYs) in 50.89% of PSA simulations with small QALY gains. Follow-up among patients with lower Braden scores decreased costs at fewer QALYs. Conclusions: Our analysis using real-world data maintains that follow-up risk-assessment among all patients cost-effectively prevents pressure ulcers. Hospitals should encourage nurses’ adherence to International Guidelines on risk-assessment to prevent patient harm.
EE3 The Cost-Effectiveness of Bariatric Surgery in Germany, France, Italy and the United Kingdom Belarbi S1, Kusel J2, Thomas MG2 SAS, Issy-Les-Moulineaux, France, 2Costello Medical Consulting Ltd, Cambridge, UK
1Ethicon
Objectives: Obesity is a growing epidemic in Europe. The objective was to investigate the cost-effectiveness of bariatric surgery for obesity across four European countries. Methods: A Markov model was developed to compare the long-term (20 year) outcomes and costs for patients who receive bariatric surgery (gastric bypass, sleeve gastrectomy, adjustable gastric banding, duodenal switch) to those who receive diet and exercise programmes. The model was adapted for the German, French, Italian and UK healthcare systems. Body mass index (BMI) change, type II diabetes mellitus (T2DM), stroke, myocardial infarction, cancer, knee pain and sleep apnoea were included; inputs for these were taken from recent network metaanalyses. Utilities and costs were sourced from the literature and the healthcare system tariffs. The populations considered were patients with BMI≥ 40 or BMI≥ 35 with obesity-related comorbidities, and the subpopulation of T2DM patients. Results: Compared to those receiving conventional care, patients undergoing bariatric surgery were found to live longer and have fewer cases of stroke, myocardial infarction, cancer, knee pain and sleep apnoea. Bariatric surgery was associated with an incremental cost-effectiveness ratio (ICER) of € 125, € 88 and £859 per qualityadjusted life year (QALY) gained versus conventional care for France, Italy and the UK, respectively. Bariatric surgery dominated conventional care in Germany, with cost savings per patient of € 429 and QALY gains of 2.6. Bariatric surgery was associated with an ICER of less than € 10,000/QALY in 100% of probabilistic simulations, for all countries. Differences between countries were driven by differences in the cost of surgery and treatment of comorbidities. Results were similar in the T2DM population. Conclusions: Bariatric surgery is predicted to improve patient outcomes and be highly cost-effective compared to diet and exercise programmes in all four European countries investigated. Further updates to the model are planned. EE4 Cost Effectiveness of Nivolumab Monotherapy for the Treatment of Advanced Melanoma Patients in the United Kingdom Meng Y1, Hertel N2, Ellis J2, Johnson H3, Philips Z1, Roskell N1, Lee D1 Health Solutions, Sheffield, UK, 2Bristol-Myers Squibb Pharmaceuticals, Uxbridge, UK, 3Helen Johnson Consulting Ltd, Welwyn Garden City, UK
1BresMed
Objectives: Nivolumab was the first programmed death receptor 1 (PD1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients. We evaluated the cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Methods: A Markov state-transition model was developed in Excel®to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and ipilimumab, dabrafenib and vemurafenib for BRAF mutation-positive patients. Covariate-adjusted parametric curves for time-to-progression, pre-progression survival and post-progression survival were fitted based on patient-level data from two trials, including long-term ipilimumab survival data, and were used to populate the progression-free, progressed and death state for nivolumab, ipilimumab and dacarbazine. Indirect treatment comparisons between nivolumab, ipilimumab and dacarbazine were informed by these covariateadjusted parametric curves, allowing differences in patient characteristics to be accounted for. Due to the lack of patient-level data, Kaplan–Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib. Patient utilities and resource use data were based on trial data or sourced from the literature. Patients are assumed to receive nivolumab until there is no further clinical benefit, assumed to be the first of progressive disease by RECIST, unacceptable toxicity or two years of treatment. Results: Based on the nivolumab list price and assumed discounted comparator prices, nivolumab is the most cost-effective treatment option in both BRAF mutation-negative and mutation-positive patients, with incremental cost-effectiveness ratios of £24,483 and £17,362 per quality-adjusted life year, respectively. The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves. Conclusions: The analyses show that nivolumab is a cost-effective treatment for advanced melanoma patients in England and received a positive recommendation by NICE.
BREAKOUTS – SESSION VII
DATABASE USE IN OUTCOMES RESEARCH STUDIES DB1 Mortality Excess Due To Clostridium Difficile Infection - A National Database Analysis Bouee S1, Levy Bachelot L2, Ravonimbola H2, Longepierre L1, Godard C2, Gourmelen J3, Barbut F4 1CEMKA, Bourg La Reine, France, 2MSD France, Courbevoie, France, 3UMS 011 - Inserm - UVSQ, Villejuif, France, 4Laboratory for Clostridium Difficile, Paris, France
Objectives: Several researches have led to contradictory results on the question whether there was an excess mortality rate in CDI patients. The objective of this study was to estimate the increase of mortality attributable to Clostridium difficile infection (CDI). Methods: A French cohort of patients with a first episode of ICD hospitalized between 2007 and 2014 was extracted from a 1% representative sample of subjects covered by the general health insurance (EGB database, ≈600,000 patients). The one year incidence of deaths was estimated and compared to a control group with no CDI (2 controls per case) matched on a propensity score (PS). PS was calculated with the variables: age, gender, Charlson index, duration of stay, year of