- Email: [email protected]
Health State Utilities Associated with Treatment Options for Acute Myeloid Leukemia (AML)
A448
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
generally inadequate and required further clarification by the NCPE in almost every case.The utility values implemented in the HTAs differed greatly between submissions, and sensitivity analyses showed significant impact on model outcomes in some cases. Conclusions: Submissions did not address all of the requirements for health outcome data specified in the NCPE submission template. Greater adherence to the NCPE submission template could reduce requests for clarification by the NCPE and reduce delays in the review process. PCN198 Minimal Impact on Patients’ Health Utilities Associated with Adverse Events in Metastatic Merkel Cell Carcinoma Patients on Treatment with Avelumab Kaufman H1, Hunger M2, Hennessy M3, Schlichting M4, Bharmal M4 1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA, 2Mapi Group, Munich, Germany, 3EMD Serono, Billerica, MA, USA, 4Merck KGaA, Darmstadt, Germany
Objectives: The anti-PD-L1 avelumab is the first FDA-approved treatment for metastatic Merkel cell carcinoma (mMCC), a rare, aggressive skin cancer. Avelumab has a safety profile that includes infusion reactions and a low incidence of immunerelated adverse events (AEs). This research aims to explore the association between different types of AEs and EQ-5D utility in avelumab-treated patients. Methods: EQ-5D data from a phase 2 single-arm trial (NCT02155647) of 88 patients with mMCC after failing first-line chemotherapy were analyzed. Date of data cutoff was 12 months after enrolment of the last subject. EQ-5D was assessed at baseline, week 7, every 6 weeks thereafter, and at the end-of-treatment visit. For each assessment, presence of ongoing AEs was based on start and end dates of all AEs reported in the trial. Linear mixed models were fitted to estimate reductions in utility for various AE types, adjusted for disease progression (using RECIST 1.1; determined by an IERC). Results: Among 70 evaluable patients, 322 observations were analyzed. Mean utility at baseline was 0.799 (SD: 0.155) for the US, and 0.823 (SD: 0.196) for the UK tariff, respectively. In 37 of 322 observations, patients completed the EQ-5D while experiencing a treatment-emergent grade 3/4 AE. Mean reduction in utility for treatment-emergent grade 3/4 AEs was -0.024 (95% CI: -0.066; 0.018) and -0.017 (95% CI: -0.065; 0.031) based on US and UK value sets, respectively. These utility reductions and those for treatment-related or treatment-emergent AEs of any grade, and immune-related AEs, were not clinically relevant based on published estimates of minimally important differences (US, 0.06; UK, 0.07-0.09). Only serious AEs (13 observations) were associated with clinically meaningful reduction in utility (-0.061 for US; -0.098 for UK). Conclusions: The impact on health utility from patients’ perspective during avelumab treatment was minimal for all AEs evaluated and marginal for serious AEs. PCN199 Estimating Utilities / Disutilities for High Risk Metastatic HormoneSensitive Prostate Cancer (MHSPC) and Treatment-Related Adverse Events Hall F1, de Freitas HM2, Kerr C1, Ito T1, Nafees B3, Lloyd AJ4, Penton J1, Hadi M2, Pham T5 1Janssen-Cilag, UK, High Wycombe, UK, 2Mapi Group, London, UK, 3Nafees Consulting, London, UK, 4Acaster Lloyd Consulting Limited, London, UK, 5Mapi Group, Boston, MD, USA
Objectives: Patients with metastatic hormone-sensitive prostate cancer (mHSPC) have widespread disease and are responsive to hormone therapy. Patients classified as ‘high-risk’ have more aggressive disease (at least two of the following: Gleason score ≥ 8; ≥ 3 bone lesions; visceral metastasis). Symptoms of mHSPC and treatment burden can substantially impact patients’ health-related quality of life (HRQL), however, health utility data in this setting are scarce. This study aimed to capture UK societal utility values for high-risk mHSPC and burdensome treatment-related adverse events (AEs). Methods: Literature review and interviews with mHSPC patients (n= 4) and oncology specialists (n= 5) informed AE selection and healthstate wording. Three base-states described a high-risk mHSPC patient: receiving androgen deprivation therapy (ADT) [BS1]; receiving docetaxel+ADT [BS2]; completed docetaxel treatment, still receiving ADT [BS3]. Descriptions of six severe AEs were combined with BS2. Health-states were validated with additional oncology specialists (n= 6) and piloted with UK participants (cognitive debrief). A UK general public sample (n= 200) valued health states using visual analogue scale (VAS) rating and Time Trade-Off (TTO) interview methods. Disutility of AEs on BS2 were calculated using Generalised Estimating Equation (GEE) model to account for correlating data. Results: Mean TTO values for BS1-3 were 0.71 (SD= 0.26), 0.63 (SD= 0.29) and 0.68 (SD= 0.26) and for BS2+AEs were 0.58 (fluid retention), 0.58 (alopecia), 0.54 (fatigue), 0.48 (reduced immunity), 0.41 (nausea+vomiting), and 0.40 (diarrhoea). Subtraction of means showed BS2+diarrhoea (-0.23) had largest decline in mean utility. GEE model found significant disutility for all AEs, with BS2+nausea+vomiting having the largest impact (GEE model coefficient -0.21; CI: -0.24, -0.16). Conclusions: In this study, utility values across mHSPC health-states showed a clinically plausible trend and significant impact of AEs, underlining the importance of accounting for impaired HRQL when assessing treatments for mHSPC. Disutility weights associated with severe AEs quantify their HRQL impact for use within economic modelling. PCN200 Health State Utilities Associated with Treatment Options for Acute Myeloid Leukemia (AML) Matza LS1, Deger K1, Howell T1, Hillgruber NK2, Yeager AM3, Hogge D4, Fisher V5, Louie AC5, Chung KC6 1Evidera, Bethesda, MD, USA, 2Moffitt Cancer Center, Tampa, FL, USA, 3University of Arizona Cancer Center, Tucson, AZ, USA, 4Gordon and Leslie Diamond Health Care Centre, Vancouver, BC, Canada, 5Jazz Pharmaceuticals, Inc, Palo Alto, CA, USA, 6Jazz Pharmaceuticals, Palo Alto, CA, USA
Objectives: AML treatment typically involves initial remission induction therapy (usually chemotherapy with cytarabine plus an anthracycline, such as daunorubicin [e.g., 7+3 regimen]) followed by post-induction consolidation therapy (additional chemotherapy and/or blood/marrow transplant [BMT]). CPX-351 is a novel dual-drug
liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic drug ratio. Compared with 7+3, CPX-351 improves overall survival in older adults with untreated high-risk or secondary AML and differs in its mode of administration. The purpose of this study was to estimate health state utilities associated with AML treatment strategies. Methods: In time trade-off interviews with a 1-year time horizon, participants from the UK general population (London, Edinburgh) valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML in temporary remission. The decrease in utility when adding these treatment regimens represents the disutility of each type of induction/consolidation. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: 200 participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. The addition of any chemotherapy to one year of temporary remission significantly decreased utility (P < 0.0001). Induction had a mean disutility of –0.11 with CPX-351 and –0.15 with 7+3. Mean disutility for consolidation ranged from –0.03 with outpatient CPX-351 to –0.11 with inpatient 5+2. Utilities were also assessed for other AML treatments (e.g., BMT, low-intensity regimens). Conclusions: Induction and consolidation chemotherapy were consistently associated with decreases in health state utility values, but consistently less disutility was seen with CPX-351 versus 7+3 across treatment phases. These utilities may be useful in cost-utility models comparing the value of AML treatments. PCN201 No EQ-5D? Analysis of Alternative Utility Value Sources Used in Nice Appraisals for Oncology Indications Beale RC1, Wickstead RM1, Chen G2, Walker E1, Griffiths M1 Medical Consulting Ltd, London, UK, 2Costello Medical Consulting Ltd, Cambridge, UK
1Costello
Objectives: The National Institute for Health and Care Excellence (NICE) reference case states that utility values should be based on health-related quality of life (HRQoL) measures reported directly by patients and valued with public preferences, preferably using the EuroQoL-5 dimensions questionnaire (EQ-5D). We investigated the health state utility values (HSUVs) used in oncology appraisals submitted to NICE, the extent to which EQ-5D data were available, and views of the NICE Committees on alternative approaches of sourcing HSUVs. Methods: NICE oncology appraisals published between January 2015 and April 2017 were reviewed; details of the drug, indication, source of base case HSUVs, Evidence Review Group (ERG) and Committee comments on the HSUVs, and final recommendation were extracted. Multiple technology appraisals, Cancer Drugs Fund reappraisals, or appraisals not using a typical 3- or 4-health state oncology health economic model were excluded. Results: Of the 30 appraisals reviewed, 17/30 (57%) used EQ-5D data from the intervention’s pivotal trial to inform at least one HSUV; 5/30 (17%) mapped HRQoL data from the intervention’s pivotal trial to EQ-5D, 5/30 (17%) used EQ-5D data from an alternative source (e.g. a comparator clinical trial), and 3/30 (10%) did not use EQ-5D data to inform any HSUVs. Mapping to EQ-5D was generally wellreceived by the Committee; validated mapping algorithms from large datasets were preferred. Alternative sources of HSUVs were also accepted if HSUVs were derived from an appropriate patient population and used in previous NICE appraisals; failure to convert US-valued EQ-5D data to the UK and double-counting of adverse event disutility were strongly criticised. Conclusions: The majority of oncology appraisals had EQ-5D data collected from the intervention’s pivotal trial. Whilst HSUV sources deviating from the NICE reference case attracted criticism from the ERG, there are measures manufacturers may take to mitigate such feedback, and Committees appear willing to accept alternative HSUV sources. PCN202 Factors Contributing to the Ceiling Effect Among Patients with Prostate Cancer who Were Judged to Have “Full-Health” by EQ-5D-5L Murasawa H1, Matsuoka Y2, Tanaka N3, Takeda Y1, Uchikawa S1, Noto S4, Shimozuma K1 University, Kusatsu, Japan, 2Kagawa University, Kagawa, Japan, 3Nara Medical University, Kashihara, Japan, 4Niigata University of Health and Welfare, Niigata, Japan
1Ritsumeikan
Objectives: The first Japanese guidelines for the economic evaluation of drugs and medical devices were officially approved in 2016. These guidelines recommend using utility values, especially those evaluated with EuroQol Five-Dimensional Questionnaire (EQ-5D). Recently, a Japanese version of the EQ-5D five level (5L) value set was developed. However, the ceiling effect that can be judged as full health (utility value = 1) was not fully improved comparing to the previous 3L version. We aimed to identify the factors that contributed to the ceiling effect among patients with prostate cancer by using EQ-5D-5L. Methods: A cross-sectional study utilized self-administered EQ-5D-5L as the generic health-related QOL and the Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) as the disease-specific instrument. Two hundred Japanese patients with prostate cancer in two hospitals were recruited (100 patients in each). Utility values were calculated, and the correlation of values between EQ-5D-5L and FACT-P was checked using least-square method. The physicians in charge reported the patient characteristics. Step-wise selection and logistic regression analysis were used to identify demographic and medical factors associated with subjective judgment of full health. Results: Selfadministered questionnaires and medical characteristics were obtained from 161 patients. The EQ-5D-5L utility value was positively correlated with FACT-P score (r= 0.57, p< 0.001). The EQ-5D-5L utility values (standard deviation) for localized, advanced, and castration-resistant prostate cancer (CRPC) were 0.86 (0.16), 0.87 (0.14) and 0.80 (0.18), respectively. Of the patients, 47.8% were judged to be at full health by EQ-5D-5L, although only one patient showed the maximum FACT-P score. Regression analysis suggested that full health was affected by age (β = -0.10, p< 0.001) and months since the last treatment (β = 0.01, p= 0.004). Conclusions: The age of patients and months since the last treatment significantly contributed to the ceiling effect of EQ-5D-5L utility values. We obtained the utility values of localized, advanced, and CRPC.
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
generally inadequate and required further clarification by the NCPE in almost every case.The utility values implemented in the HTAs differed greatly between submissions, and sensitivity analyses showed significant impact on model outcomes in some cases. Conclusions: Submissions did not address all of the requirements for health outcome data specified in the NCPE submission template. Greater adherence to the NCPE submission template could reduce requests for clarification by the NCPE and reduce delays in the review process. PCN198 Minimal Impact on Patients’ Health Utilities Associated with Adverse Events in Metastatic Merkel Cell Carcinoma Patients on Treatment with Avelumab Kaufman H1, Hunger M2, Hennessy M3, Schlichting M4, Bharmal M4 1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA, 2Mapi Group, Munich, Germany, 3EMD Serono, Billerica, MA, USA, 4Merck KGaA, Darmstadt, Germany
Objectives: The anti-PD-L1 avelumab is the first FDA-approved treatment for metastatic Merkel cell carcinoma (mMCC), a rare, aggressive skin cancer. Avelumab has a safety profile that includes infusion reactions and a low incidence of immunerelated adverse events (AEs). This research aims to explore the association between different types of AEs and EQ-5D utility in avelumab-treated patients. Methods: EQ-5D data from a phase 2 single-arm trial (NCT02155647) of 88 patients with mMCC after failing first-line chemotherapy were analyzed. Date of data cutoff was 12 months after enrolment of the last subject. EQ-5D was assessed at baseline, week 7, every 6 weeks thereafter, and at the end-of-treatment visit. For each assessment, presence of ongoing AEs was based on start and end dates of all AEs reported in the trial. Linear mixed models were fitted to estimate reductions in utility for various AE types, adjusted for disease progression (using RECIST 1.1; determined by an IERC). Results: Among 70 evaluable patients, 322 observations were analyzed. Mean utility at baseline was 0.799 (SD: 0.155) for the US, and 0.823 (SD: 0.196) for the UK tariff, respectively. In 37 of 322 observations, patients completed the EQ-5D while experiencing a treatment-emergent grade 3/4 AE. Mean reduction in utility for treatment-emergent grade 3/4 AEs was -0.024 (95% CI: -0.066; 0.018) and -0.017 (95% CI: -0.065; 0.031) based on US and UK value sets, respectively. These utility reductions and those for treatment-related or treatment-emergent AEs of any grade, and immune-related AEs, were not clinically relevant based on published estimates of minimally important differences (US, 0.06; UK, 0.07-0.09). Only serious AEs (13 observations) were associated with clinically meaningful reduction in utility (-0.061 for US; -0.098 for UK). Conclusions: The impact on health utility from patients’ perspective during avelumab treatment was minimal for all AEs evaluated and marginal for serious AEs. PCN199 Estimating Utilities / Disutilities for High Risk Metastatic HormoneSensitive Prostate Cancer (MHSPC) and Treatment-Related Adverse Events Hall F1, de Freitas HM2, Kerr C1, Ito T1, Nafees B3, Lloyd AJ4, Penton J1, Hadi M2, Pham T5 1Janssen-Cilag, UK, High Wycombe, UK, 2Mapi Group, London, UK, 3Nafees Consulting, London, UK, 4Acaster Lloyd Consulting Limited, London, UK, 5Mapi Group, Boston, MD, USA
Objectives: Patients with metastatic hormone-sensitive prostate cancer (mHSPC) have widespread disease and are responsive to hormone therapy. Patients classified as ‘high-risk’ have more aggressive disease (at least two of the following: Gleason score ≥ 8; ≥ 3 bone lesions; visceral metastasis). Symptoms of mHSPC and treatment burden can substantially impact patients’ health-related quality of life (HRQL), however, health utility data in this setting are scarce. This study aimed to capture UK societal utility values for high-risk mHSPC and burdensome treatment-related adverse events (AEs). Methods: Literature review and interviews with mHSPC patients (n= 4) and oncology specialists (n= 5) informed AE selection and healthstate wording. Three base-states described a high-risk mHSPC patient: receiving androgen deprivation therapy (ADT) [BS1]; receiving docetaxel+ADT [BS2]; completed docetaxel treatment, still receiving ADT [BS3]. Descriptions of six severe AEs were combined with BS2. Health-states were validated with additional oncology specialists (n= 6) and piloted with UK participants (cognitive debrief). A UK general public sample (n= 200) valued health states using visual analogue scale (VAS) rating and Time Trade-Off (TTO) interview methods. Disutility of AEs on BS2 were calculated using Generalised Estimating Equation (GEE) model to account for correlating data. Results: Mean TTO values for BS1-3 were 0.71 (SD= 0.26), 0.63 (SD= 0.29) and 0.68 (SD= 0.26) and for BS2+AEs were 0.58 (fluid retention), 0.58 (alopecia), 0.54 (fatigue), 0.48 (reduced immunity), 0.41 (nausea+vomiting), and 0.40 (diarrhoea). Subtraction of means showed BS2+diarrhoea (-0.23) had largest decline in mean utility. GEE model found significant disutility for all AEs, with BS2+nausea+vomiting having the largest impact (GEE model coefficient -0.21; CI: -0.24, -0.16). Conclusions: In this study, utility values across mHSPC health-states showed a clinically plausible trend and significant impact of AEs, underlining the importance of accounting for impaired HRQL when assessing treatments for mHSPC. Disutility weights associated with severe AEs quantify their HRQL impact for use within economic modelling. PCN200 Health State Utilities Associated with Treatment Options for Acute Myeloid Leukemia (AML) Matza LS1, Deger K1, Howell T1, Hillgruber NK2, Yeager AM3, Hogge D4, Fisher V5, Louie AC5, Chung KC6 1Evidera, Bethesda, MD, USA, 2Moffitt Cancer Center, Tampa, FL, USA, 3University of Arizona Cancer Center, Tucson, AZ, USA, 4Gordon and Leslie Diamond Health Care Centre, Vancouver, BC, Canada, 5Jazz Pharmaceuticals, Inc, Palo Alto, CA, USA, 6Jazz Pharmaceuticals, Palo Alto, CA, USA
Objectives: AML treatment typically involves initial remission induction therapy (usually chemotherapy with cytarabine plus an anthracycline, such as daunorubicin [e.g., 7+3 regimen]) followed by post-induction consolidation therapy (additional chemotherapy and/or blood/marrow transplant [BMT]). CPX-351 is a novel dual-drug
liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic drug ratio. Compared with 7+3, CPX-351 improves overall survival in older adults with untreated high-risk or secondary AML and differs in its mode of administration. The purpose of this study was to estimate health state utilities associated with AML treatment strategies. Methods: In time trade-off interviews with a 1-year time horizon, participants from the UK general population (London, Edinburgh) valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML in temporary remission. The decrease in utility when adding these treatment regimens represents the disutility of each type of induction/consolidation. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: 200 participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. The addition of any chemotherapy to one year of temporary remission significantly decreased utility (P < 0.0001). Induction had a mean disutility of –0.11 with CPX-351 and –0.15 with 7+3. Mean disutility for consolidation ranged from –0.03 with outpatient CPX-351 to –0.11 with inpatient 5+2. Utilities were also assessed for other AML treatments (e.g., BMT, low-intensity regimens). Conclusions: Induction and consolidation chemotherapy were consistently associated with decreases in health state utility values, but consistently less disutility was seen with CPX-351 versus 7+3 across treatment phases. These utilities may be useful in cost-utility models comparing the value of AML treatments. PCN201 No EQ-5D? Analysis of Alternative Utility Value Sources Used in Nice Appraisals for Oncology Indications Beale RC1, Wickstead RM1, Chen G2, Walker E1, Griffiths M1 Medical Consulting Ltd, London, UK, 2Costello Medical Consulting Ltd, Cambridge, UK
1Costello
Objectives: The National Institute for Health and Care Excellence (NICE) reference case states that utility values should be based on health-related quality of life (HRQoL) measures reported directly by patients and valued with public preferences, preferably using the EuroQoL-5 dimensions questionnaire (EQ-5D). We investigated the health state utility values (HSUVs) used in oncology appraisals submitted to NICE, the extent to which EQ-5D data were available, and views of the NICE Committees on alternative approaches of sourcing HSUVs. Methods: NICE oncology appraisals published between January 2015 and April 2017 were reviewed; details of the drug, indication, source of base case HSUVs, Evidence Review Group (ERG) and Committee comments on the HSUVs, and final recommendation were extracted. Multiple technology appraisals, Cancer Drugs Fund reappraisals, or appraisals not using a typical 3- or 4-health state oncology health economic model were excluded. Results: Of the 30 appraisals reviewed, 17/30 (57%) used EQ-5D data from the intervention’s pivotal trial to inform at least one HSUV; 5/30 (17%) mapped HRQoL data from the intervention’s pivotal trial to EQ-5D, 5/30 (17%) used EQ-5D data from an alternative source (e.g. a comparator clinical trial), and 3/30 (10%) did not use EQ-5D data to inform any HSUVs. Mapping to EQ-5D was generally wellreceived by the Committee; validated mapping algorithms from large datasets were preferred. Alternative sources of HSUVs were also accepted if HSUVs were derived from an appropriate patient population and used in previous NICE appraisals; failure to convert US-valued EQ-5D data to the UK and double-counting of adverse event disutility were strongly criticised. Conclusions: The majority of oncology appraisals had EQ-5D data collected from the intervention’s pivotal trial. Whilst HSUV sources deviating from the NICE reference case attracted criticism from the ERG, there are measures manufacturers may take to mitigate such feedback, and Committees appear willing to accept alternative HSUV sources. PCN202 Factors Contributing to the Ceiling Effect Among Patients with Prostate Cancer who Were Judged to Have “Full-Health” by EQ-5D-5L Murasawa H1, Matsuoka Y2, Tanaka N3, Takeda Y1, Uchikawa S1, Noto S4, Shimozuma K1 University, Kusatsu, Japan, 2Kagawa University, Kagawa, Japan, 3Nara Medical University, Kashihara, Japan, 4Niigata University of Health and Welfare, Niigata, Japan
1Ritsumeikan
Objectives: The first Japanese guidelines for the economic evaluation of drugs and medical devices were officially approved in 2016. These guidelines recommend using utility values, especially those evaluated with EuroQol Five-Dimensional Questionnaire (EQ-5D). Recently, a Japanese version of the EQ-5D five level (5L) value set was developed. However, the ceiling effect that can be judged as full health (utility value = 1) was not fully improved comparing to the previous 3L version. We aimed to identify the factors that contributed to the ceiling effect among patients with prostate cancer by using EQ-5D-5L. Methods: A cross-sectional study utilized self-administered EQ-5D-5L as the generic health-related QOL and the Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) as the disease-specific instrument. Two hundred Japanese patients with prostate cancer in two hospitals were recruited (100 patients in each). Utility values were calculated, and the correlation of values between EQ-5D-5L and FACT-P was checked using least-square method. The physicians in charge reported the patient characteristics. Step-wise selection and logistic regression analysis were used to identify demographic and medical factors associated with subjective judgment of full health. Results: Selfadministered questionnaires and medical characteristics were obtained from 161 patients. The EQ-5D-5L utility value was positively correlated with FACT-P score (r= 0.57, p< 0.001). The EQ-5D-5L utility values (standard deviation) for localized, advanced, and castration-resistant prostate cancer (CRPC) were 0.86 (0.16), 0.87 (0.14) and 0.80 (0.18), respectively. Of the patients, 47.8% were judged to be at full health by EQ-5D-5L, although only one patient showed the maximum FACT-P score. Regression analysis suggested that full health was affected by age (β = -0.10, p< 0.001) and months since the last treatment (β = 0.01, p= 0.004). Conclusions: The age of patients and months since the last treatment significantly contributed to the ceiling effect of EQ-5D-5L utility values. We obtained the utility values of localized, advanced, and CRPC.