- Email: [email protected]
Utility Meta-Regression; Frequentist Vs Bayesian Approaches in Multiple Myeloma
A450
VA L U E I N H E A LT H 2 0 ( 2 0 1 7 ) A 3 9 9 – A 8 1 1
patients were 78.522±0.742, and those of metastatic breast cancer patients were 71.472±1.464 (p< 0.0001). The corresponding correlations between utilities and VAS scores in primary breast cancer patients were 0.25, whereas those for metastatic breast cancer patients were 0.50. Conclusions: We identified that both health state values and the VAS scores of metastatic breast cancer patients were lower than those of primary breast cancer patients. However, the correlation of utilities and the VAS scores of metastatic breast cancer patients was higher than that of primary breast cancer patients. PCN209 A Quality-Adjusted Time without Symptoms of Disease And Toxicity (Q-TWIST) Analysis Comparing Nivolumab and Therapy Of Investigator’s Choice (IC) in Patients with Recurrent or Metastatic (R/M) Platinum-Refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN) (Checkmate 141) Simpson S1, Cocks K1, Contente M2, DeRosa M3, Taylor F3, Shaw JW4 1Adelphi Mill, Bollington, Cheshire, UK, 2Bristol-Myers Squibb Pharmaceuticals Ltd, Uxbridge, Middlesex, UK, 3Adelphi Values, Boston, MA, USA, 4Bristol-Myers Squibb, Lawrenceville, NJ, USA
Objectives: Nivolumab provided survival, health-related quality-of-life, and healthcare resource utilization benefits versus single-agent therapy of IC (methotrexate, docetaxel, or cetuximab) in patients with platinum-refractory R/M SCCHN in CheckMate 141 (NCT02105636). Here we compared between-treatment differences in overall benefit using a Q-TWiST analysis. Methods: Overall survival was partitioned into 3 health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST), and relapse (REL). TOX was defined as time spent with all-cause grade 3–4 adverse events after randomization, prior to disease progression. TWiST was defined as the time not in TOX or REL. REL was defined as the time between progression and death. Mean duration of each state was calculated for each treatment group using Kaplan-Meier analysis. Utility values from the 3-level EQ-5D (EQ-5D-3L) questionnaire collected in the trial were used to calculate Q-TWiST as the utility-weighted sum of the mean health state durations. Bootstrapping (500 samples) was used to estimate time in each health state and to compare estimates between treatment groups. A threshold analysis was conducted across ranges of TOX and REL values from 0 to 1 to illustrate the full range of possible results. Results: A total of 361 patients (nivolumab, n= 240; IC, n= 121) were included in the analysis. Median duration of follow-up for survivors was 15.7 months. The between-group difference in Q-TWiST score was 1.23 months (95% CI: 1.18, 1.28) favoring nivolumab, P< 0.0001. The nivolumab group experienced a significantly longer mean time in TWiST (3.82 vs 2.78 months) and in REL (4.02 vs 3.30 months) compared with the IC group (P< 0.0001). Mean time in TOX was shorter for nivolumab versus IC (0.30 vs 0.37 months; P< 0.0001). Conclusions: In this analysis, quality-adjusted survival was significantly improved with nivolumab compared with IC in patients with R/M SCCHN. Results appeared to be related to a between-group difference in mean overall survival. PCN210 Utility Meta-Regression; Frequentist Vs Bayesian Approaches in Multiple Myeloma Hatswell AJ1, Burns D1, Baio G2, Wadelin F3 Health Solutions, Sheffield, UK, 2University College London, London, UK, 3Nottingham University Hospital, Nottingham, UK
1BresMed
Objectives: Utility values are used in health technology assessment to measure the health-related quality of life impacts of new products, typically taken from a single source. In contrast, meta-analysis synthesizing all available information is a requirement for clinical data. Consequently, utility values currently used to inform health technology assessments lack consistency by ignoring data from the other sources. This analysis presents a standard frequentist meta-regression and a novel and Bayesian approach to the synthesis of utility values. Methods: A literature review for all published utility data in multiple myeloma was conducted, in conjunction with analysis of patient registries across all stages of disease (2,445 patients, over 9,000 completed EQ-5D questionnaires), and of a clinical trial including 669 patients. This information was then synthesized using two distinct approaches – frequentist meta-regression and Bayesian statistical modelling. These approaches were compared in terms of the results produced, internal validity, and efficiency of estimation. Results: The systematic review identified 13 papers giving 27 utility values across multiple lines of treatment including some values not linked to a specific disease stage. Analysis of the two datasets produced 9 further values. Both frequentist and Bayesian meta-regression produced similar overall results; low utility on diagnosis (0.53), increasing to approximately 0.65 on first treatment then decreasing with each subsequent treatment class to approximately 0.50 after four classes of treatment. In all analyses, strong evidence was found to suggest an association between stem cell transplant and an increase of 0.06 in patient utility. Conclusions: Both Bayesian and frequentist approaches produced internally consistent utility estimates across the treatment pathway. However, the Bayesian approach more accurately represents the uncertainty in the clinical data, and allows non stage specific utilities to be used as prior beliefs. This exemplifies how Bayesian analyses can be performed using a simple and flexible framework. PCN211 Health Related Quality of Life in Cancer Immunotherapy: Previously Treated, Locally Advanced or Metastatic Non-SmallCell Lung Cancer Purchase J1, Paracha N2, Abdulla A2 1Roche Products Ltd, Welwyn Garden City, UK, 2F. Hoffman-La Roche, Basel, Switzerland
Objectives: To assess the different methodologies utilised to present Health Related Quality of Life (HRQoL) of patients with metastatic cancer, and to compare the impact of such methodologies for an immunotherapy in the treatment of
second line non-small-cell lung cancer (NSCLC). Methods: The 10 most recent published technology appraisals in oncology were taken from the National Institute of Health and Care Excellence (NICE) website, and reviewed to determine the approach taken to elicit and present HRQoL data. From this, 4 methodologies were tested on atezolizumab, an anti-programmed death-ligand 1 (PD-L1) antibody for the treatment of NSCLC after prior chemotherapy using data collected from the OAK trial: PFS/PD, time-to-death, on treatment/off treatment, and a combination of on treatment/off treatment and time-to-death. Results: The 10 published NICE technology appraisals spanned a multitude of different indications in oncology, including lung cancer, breast cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, multiple myeloma and chronic lymphocytic leukaemia. Several appraisals utilised a traditional Progression-Free Survival (PFS)/Stable Disease and Progressed Disease (PD) approach to implement health state utility values (HSUV’s). However, others incorporated a time-to-death, “time lived with disease”, or an on treatment/off treatment approach. The different methodologies generated different cumulative quality of life gain for atezolizumab versus docetaxel, up to a difference of 0.04 QALYs, or 2 weeks of perfect health: a significant period of time for a patient with a median overall survival of 13.8 months. Conclusions: The methodologies used to determine total quality of life gain in the appraisal of treatments can impact outcomes considerably. Therefore it’s important to ensure methodologies are clinically accepted, validated, and representative of the disease area and treatment under consideration. PCN212 Qualitative Exploration of the Real-World Experiences of Men Receiving or Refusing Chemotherapy (Docetaxel) for the Treatment of Metastatic Hormone-Sensitive Prostate Cancer (MHSPC) Ito T1, Grant L2, Mills A3, Heselwood A3, Gater A2 1Janssen-Cilag, UK, High Wycombe, UK, 2Adelphi Values Ltd, Bollington, Cheshire, UK, 3Adelphi Research UK, Bollington, UK
Objectives: Evidence from recent studies highlighted that administration of docetaxel plus androgen deprivation therapy in men with metastatic hormone sensitive prostate cancer (mHSPC) can prolong survival. As docetaxel is a cytotoxic therapy, however, there is a need to understand the experiences of men with mHSPC receiving docetaxel, and those of their carers, in a real-world setting. Methods: Semistructured qualitative interviews were conducted with men with mHSPC (n= 26) and carers (n= 14) to elicit in-depth data concerning their experiences of docetaxel. Men were also asked to record their experiences in a diary for 7 days. Interviews were also conducted with men who refused treatment with docetaxel (n= 5). Participants were recruited from five European countries (France, Germany, UK, Italy and Spain) and all interviews were conducted in the local language by trained qualitative interviewers. Data was analysed using thematic analysis. Results: At the outset of therapy, men reported a willingness to take docetaxel to prolong their life, despite being fearful of the potential side effects and impacts on their daily lives. Those refusing to take docetaxel cited concerns regarding side effects and negative experiences of other men, as reasons for their decision. The majority of men experienced benefits associated with docetaxel, evident by reduced prostate-specific antigen levels. However, a wide range of side effects and impacts on daily life were reported, such as nausea, diarrhoea, fatigue and others. Variations in individual experiences and their ability to tolerate side effects were evident. Carers were also negatively impacted by docetaxel treatment, despite their efforts to stay positive and support the patients. Conclusions: Men with mHSPC and their carers were largely satisfied with the perceived efficacy of docetaxel but reported concerns regarding side effects and associated impacts. Informed by this study, the experiences of men with mHSPC receiving docetaxel are currently being explored in a larger quantitative study. PCN213 Preferences for Survival in Non-Small Cell Lung Cancer: Swinging for Home Runs or Base Hits? Hauber AB1, Penrod JR2, Gebben D1, Musallam L2 1RTI Health Solutions, Research Triangle Park, NC, USA, 2Bristol-Myers Squibb, Princeton, NJ, USA
Objectives: Studies of outcome preferences in oncology have presented the value that patients and physicians place on improvements in mean or median progression-free or overall survival. Furthermore, a recent study showed that patients with metastatic melanoma or breast cancer prefer treatments with greater potential for long-term survival, even when expected survival is no different, a phenomenon termed the “value of hope.” Our objective was to evaluate oncologist and patient preferences for advanced non-small cell lung cancer (NSCLC) treatments, defined by mean expected overall survival (ES), best-case survival (BCS), worst-case survival (WCS), and treatment toxicities. Methods: A discrete-choice experiment (DCE) was administered online to oncologists and patients with NSCLC. Each treatment profile in the DCE was defined by different levels of ES, BCS, and WCS, along with fatigue, nausea, and risk of febrile neutropenia. BCS and WCS were defined as the expected survival for the top and bottom 15% of patients, respectively. In separate surveys, physicians and patients chose among pairs of profiles representing possible second-line treatments for advanced NSCLC. Data were examined using random parameters logit analysis. Results: A total of 102 physicians completed the survey. The preference weight for each 1-month improvement in BCS was positive, independent of the effect of all other attributes. The preference weight for ES was also positive and statistically significant, but the preference weight for WCS was not statistically significant. Severe nausea and severe fatigue were statistically significantly (negatively) more important to treatment choice than mild-to-moderate nausea or fatigue, respectively. A 10% risk of febrile neutropenia was statistically significantly preferred to a 40% risk. The patient data collection is ongoing. Conclusions: ES, BCS, and toxicities impacted physicians’ choice of advanced NSCLC treatments. Strong preference for longer BCS, holding ES, WCS, and toxicities constant, confirms that the “value of hope” matters to oncologists in the advanced NSCLC setting.
VA L U E I N H E A LT H 2 0 ( 2 0 1 7 ) A 3 9 9 – A 8 1 1
patients were 78.522±0.742, and those of metastatic breast cancer patients were 71.472±1.464 (p< 0.0001). The corresponding correlations between utilities and VAS scores in primary breast cancer patients were 0.25, whereas those for metastatic breast cancer patients were 0.50. Conclusions: We identified that both health state values and the VAS scores of metastatic breast cancer patients were lower than those of primary breast cancer patients. However, the correlation of utilities and the VAS scores of metastatic breast cancer patients was higher than that of primary breast cancer patients. PCN209 A Quality-Adjusted Time without Symptoms of Disease And Toxicity (Q-TWIST) Analysis Comparing Nivolumab and Therapy Of Investigator’s Choice (IC) in Patients with Recurrent or Metastatic (R/M) Platinum-Refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN) (Checkmate 141) Simpson S1, Cocks K1, Contente M2, DeRosa M3, Taylor F3, Shaw JW4 1Adelphi Mill, Bollington, Cheshire, UK, 2Bristol-Myers Squibb Pharmaceuticals Ltd, Uxbridge, Middlesex, UK, 3Adelphi Values, Boston, MA, USA, 4Bristol-Myers Squibb, Lawrenceville, NJ, USA
Objectives: Nivolumab provided survival, health-related quality-of-life, and healthcare resource utilization benefits versus single-agent therapy of IC (methotrexate, docetaxel, or cetuximab) in patients with platinum-refractory R/M SCCHN in CheckMate 141 (NCT02105636). Here we compared between-treatment differences in overall benefit using a Q-TWiST analysis. Methods: Overall survival was partitioned into 3 health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST), and relapse (REL). TOX was defined as time spent with all-cause grade 3–4 adverse events after randomization, prior to disease progression. TWiST was defined as the time not in TOX or REL. REL was defined as the time between progression and death. Mean duration of each state was calculated for each treatment group using Kaplan-Meier analysis. Utility values from the 3-level EQ-5D (EQ-5D-3L) questionnaire collected in the trial were used to calculate Q-TWiST as the utility-weighted sum of the mean health state durations. Bootstrapping (500 samples) was used to estimate time in each health state and to compare estimates between treatment groups. A threshold analysis was conducted across ranges of TOX and REL values from 0 to 1 to illustrate the full range of possible results. Results: A total of 361 patients (nivolumab, n= 240; IC, n= 121) were included in the analysis. Median duration of follow-up for survivors was 15.7 months. The between-group difference in Q-TWiST score was 1.23 months (95% CI: 1.18, 1.28) favoring nivolumab, P< 0.0001. The nivolumab group experienced a significantly longer mean time in TWiST (3.82 vs 2.78 months) and in REL (4.02 vs 3.30 months) compared with the IC group (P< 0.0001). Mean time in TOX was shorter for nivolumab versus IC (0.30 vs 0.37 months; P< 0.0001). Conclusions: In this analysis, quality-adjusted survival was significantly improved with nivolumab compared with IC in patients with R/M SCCHN. Results appeared to be related to a between-group difference in mean overall survival. PCN210 Utility Meta-Regression; Frequentist Vs Bayesian Approaches in Multiple Myeloma Hatswell AJ1, Burns D1, Baio G2, Wadelin F3 Health Solutions, Sheffield, UK, 2University College London, London, UK, 3Nottingham University Hospital, Nottingham, UK
1BresMed
Objectives: Utility values are used in health technology assessment to measure the health-related quality of life impacts of new products, typically taken from a single source. In contrast, meta-analysis synthesizing all available information is a requirement for clinical data. Consequently, utility values currently used to inform health technology assessments lack consistency by ignoring data from the other sources. This analysis presents a standard frequentist meta-regression and a novel and Bayesian approach to the synthesis of utility values. Methods: A literature review for all published utility data in multiple myeloma was conducted, in conjunction with analysis of patient registries across all stages of disease (2,445 patients, over 9,000 completed EQ-5D questionnaires), and of a clinical trial including 669 patients. This information was then synthesized using two distinct approaches – frequentist meta-regression and Bayesian statistical modelling. These approaches were compared in terms of the results produced, internal validity, and efficiency of estimation. Results: The systematic review identified 13 papers giving 27 utility values across multiple lines of treatment including some values not linked to a specific disease stage. Analysis of the two datasets produced 9 further values. Both frequentist and Bayesian meta-regression produced similar overall results; low utility on diagnosis (0.53), increasing to approximately 0.65 on first treatment then decreasing with each subsequent treatment class to approximately 0.50 after four classes of treatment. In all analyses, strong evidence was found to suggest an association between stem cell transplant and an increase of 0.06 in patient utility. Conclusions: Both Bayesian and frequentist approaches produced internally consistent utility estimates across the treatment pathway. However, the Bayesian approach more accurately represents the uncertainty in the clinical data, and allows non stage specific utilities to be used as prior beliefs. This exemplifies how Bayesian analyses can be performed using a simple and flexible framework. PCN211 Health Related Quality of Life in Cancer Immunotherapy: Previously Treated, Locally Advanced or Metastatic Non-SmallCell Lung Cancer Purchase J1, Paracha N2, Abdulla A2 1Roche Products Ltd, Welwyn Garden City, UK, 2F. Hoffman-La Roche, Basel, Switzerland
Objectives: To assess the different methodologies utilised to present Health Related Quality of Life (HRQoL) of patients with metastatic cancer, and to compare the impact of such methodologies for an immunotherapy in the treatment of
second line non-small-cell lung cancer (NSCLC). Methods: The 10 most recent published technology appraisals in oncology were taken from the National Institute of Health and Care Excellence (NICE) website, and reviewed to determine the approach taken to elicit and present HRQoL data. From this, 4 methodologies were tested on atezolizumab, an anti-programmed death-ligand 1 (PD-L1) antibody for the treatment of NSCLC after prior chemotherapy using data collected from the OAK trial: PFS/PD, time-to-death, on treatment/off treatment, and a combination of on treatment/off treatment and time-to-death. Results: The 10 published NICE technology appraisals spanned a multitude of different indications in oncology, including lung cancer, breast cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, multiple myeloma and chronic lymphocytic leukaemia. Several appraisals utilised a traditional Progression-Free Survival (PFS)/Stable Disease and Progressed Disease (PD) approach to implement health state utility values (HSUV’s). However, others incorporated a time-to-death, “time lived with disease”, or an on treatment/off treatment approach. The different methodologies generated different cumulative quality of life gain for atezolizumab versus docetaxel, up to a difference of 0.04 QALYs, or 2 weeks of perfect health: a significant period of time for a patient with a median overall survival of 13.8 months. Conclusions: The methodologies used to determine total quality of life gain in the appraisal of treatments can impact outcomes considerably. Therefore it’s important to ensure methodologies are clinically accepted, validated, and representative of the disease area and treatment under consideration. PCN212 Qualitative Exploration of the Real-World Experiences of Men Receiving or Refusing Chemotherapy (Docetaxel) for the Treatment of Metastatic Hormone-Sensitive Prostate Cancer (MHSPC) Ito T1, Grant L2, Mills A3, Heselwood A3, Gater A2 1Janssen-Cilag, UK, High Wycombe, UK, 2Adelphi Values Ltd, Bollington, Cheshire, UK, 3Adelphi Research UK, Bollington, UK
Objectives: Evidence from recent studies highlighted that administration of docetaxel plus androgen deprivation therapy in men with metastatic hormone sensitive prostate cancer (mHSPC) can prolong survival. As docetaxel is a cytotoxic therapy, however, there is a need to understand the experiences of men with mHSPC receiving docetaxel, and those of their carers, in a real-world setting. Methods: Semistructured qualitative interviews were conducted with men with mHSPC (n= 26) and carers (n= 14) to elicit in-depth data concerning their experiences of docetaxel. Men were also asked to record their experiences in a diary for 7 days. Interviews were also conducted with men who refused treatment with docetaxel (n= 5). Participants were recruited from five European countries (France, Germany, UK, Italy and Spain) and all interviews were conducted in the local language by trained qualitative interviewers. Data was analysed using thematic analysis. Results: At the outset of therapy, men reported a willingness to take docetaxel to prolong their life, despite being fearful of the potential side effects and impacts on their daily lives. Those refusing to take docetaxel cited concerns regarding side effects and negative experiences of other men, as reasons for their decision. The majority of men experienced benefits associated with docetaxel, evident by reduced prostate-specific antigen levels. However, a wide range of side effects and impacts on daily life were reported, such as nausea, diarrhoea, fatigue and others. Variations in individual experiences and their ability to tolerate side effects were evident. Carers were also negatively impacted by docetaxel treatment, despite their efforts to stay positive and support the patients. Conclusions: Men with mHSPC and their carers were largely satisfied with the perceived efficacy of docetaxel but reported concerns regarding side effects and associated impacts. Informed by this study, the experiences of men with mHSPC receiving docetaxel are currently being explored in a larger quantitative study. PCN213 Preferences for Survival in Non-Small Cell Lung Cancer: Swinging for Home Runs or Base Hits? Hauber AB1, Penrod JR2, Gebben D1, Musallam L2 1RTI Health Solutions, Research Triangle Park, NC, USA, 2Bristol-Myers Squibb, Princeton, NJ, USA
Objectives: Studies of outcome preferences in oncology have presented the value that patients and physicians place on improvements in mean or median progression-free or overall survival. Furthermore, a recent study showed that patients with metastatic melanoma or breast cancer prefer treatments with greater potential for long-term survival, even when expected survival is no different, a phenomenon termed the “value of hope.” Our objective was to evaluate oncologist and patient preferences for advanced non-small cell lung cancer (NSCLC) treatments, defined by mean expected overall survival (ES), best-case survival (BCS), worst-case survival (WCS), and treatment toxicities. Methods: A discrete-choice experiment (DCE) was administered online to oncologists and patients with NSCLC. Each treatment profile in the DCE was defined by different levels of ES, BCS, and WCS, along with fatigue, nausea, and risk of febrile neutropenia. BCS and WCS were defined as the expected survival for the top and bottom 15% of patients, respectively. In separate surveys, physicians and patients chose among pairs of profiles representing possible second-line treatments for advanced NSCLC. Data were examined using random parameters logit analysis. Results: A total of 102 physicians completed the survey. The preference weight for each 1-month improvement in BCS was positive, independent of the effect of all other attributes. The preference weight for ES was also positive and statistically significant, but the preference weight for WCS was not statistically significant. Severe nausea and severe fatigue were statistically significantly (negatively) more important to treatment choice than mild-to-moderate nausea or fatigue, respectively. A 10% risk of febrile neutropenia was statistically significantly preferred to a 40% risk. The patient data collection is ongoing. Conclusions: ES, BCS, and toxicities impacted physicians’ choice of advanced NSCLC treatments. Strong preference for longer BCS, holding ES, WCS, and toxicities constant, confirms that the “value of hope” matters to oncologists in the advanced NSCLC setting.