Health State Utilities for Acute Myeloid Leukaemia: A Time Trade-off Study.

OBJECTIVES: Acute myeloid leukaemia (AML) is an aggressive haematological cancer associated with significant humanistic impact. The current study assessed how the general public in the United Kingdom (UK) values AML health states. METHODS: The composite time trade-off (cTTO) methodology was employed to elicit health state utilities in AML. Pertinent AML literature related to symptom and quality-of-life impact including physical, functional and emotional well-being, as well as the safety profile of AML treatments, were taken into consideration for drafting health state descriptions. Ten health states included in the study were newly diagnosed AML, induction, consolidation, maintenance, long-term follow-up, relapsed/refractory, stem-cell transplant (SCT) procedure, SCT recovery, SCT long-term follow-up with complications and SCT long-term follow-up without complications. The descriptions were validated by haematologists and nurse specialists for clinical accuracy and completeness. A total of 210 individuals from the general UK population participated in the cTTO interviews. Descriptive statistics were computed for health state utility values. RESULTS: The mean age of the participants was 44.0 years (standard deviation [SD] 14.9, range 18-81) and comprised 129 (61.4%) female participants. The utility values ranged from 0.94 (SD 0.13) for SCT long-term follow-up without complications to - 0.21 (SD 0.62) for the SCT procedure. CONCLUSIONS: The study provides health utilities for a range of AML health states, with the SCT procedure health state being valued worse than death. The utilities obtained in this study can be employed as inputs in cost-effectiveness analyses of AML therapies.

Cost-effectiveness analysis for midostaurin versus standard of care in acute myeloid leukemia in the United Kingdom.

AIMS: Midostaurin (MIDO) has been proposed for the treatment of newly-diagnosed adult patients with FMS-like tyrosine kinase 3 mutation-positive (FLT3+) acute myeloid leukemia (AML) in combination with standard chemotherapy. The cost-effectiveness of MIDO and standard of care (SOC) followed by MIDO monotherapy was compared to SOC alone for newly-diagnosed FLT3+ AML in the UK. METHODS: A partitioned survival model was developed from a UK public healthcare system perspective to compare the cost-effectiveness of MIDO plus SOC and SOC over a lifetime horizon. The model included the following health states/partitions: induction, consolidation, monotherapy, complete remission (CR), relapse, stem cell transplantation (SCT), SCT recovery, and post-SCT recovery. Data on CR, overall survival, and adverse events were obtained from a Phase III clinical trial. Overall survival was extrapolated beyond the trial horizon using a 'cure model' approach and data from the Office for National Statistics. Utilities were identified via a systematic review. Routine care utilization was obtained from the National Institute for Health and Care Excellence single technology appraisal for azacitidine in AML (TA399). The costs of drugs and administration, adverse events, hospitalizations, physician visits, and end-of-life care were incorporated. RESULTS: Incremental life years (LYs) and quality-adjusted life years (QALYs) gained by patients on MIDO and SOC versus SOC were 1.67 and 1.47, respectively. At an incremental cost of £54,072 over a lifetime horizon, the ICER was £32,465 per LY and £36,826 per QALY. Sensitivity analyses were generally consistent with the base case findings. CONCLUSIONS: With limited treatments in FLT3+ AML, MIDO represents a clinically significant advance in the management of newly-diagnosed AML. Using a threshold of £50,000 per QALY for end-of-life treatment, MIDO was shown to be a cost-effective option for newly-diagnosed FLT3+ AML.

Systematic review of health state utility values for acute myeloid leukemia.

BACKGROUND: Cost-utility analyses for acute myeloid leukemia (AML) require health state utility values (HSUVs) in order to calculate quality-adjusted life-years (QALYs) for each health state. AIM: This study reviewed AML-related HSUVs that could be used in economic evaluation studies. MATERIALS AND METHODS: EMBASE, MEDLINE, and Cochrane databases were searched from January 2000 to November 2016 for relevant studies that reported quality of life (QoL) and HSUVs in AML. Identified relevant European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 values were mapped to HSUVs. HSUVs for each health state in the AML treatment pathway were then collated. RESULTS: Ten relevant studies were identified. Six were cost-effectiveness analyses utilizing HSUVs for calculation of QALYs, one was an effectiveness analysis (incremental QALY), and two were QoL studies reporting AML-specific utilities. An additional study reported QoL for patients undergoing stem cell transplantation (SCT). Since no study reported HSUVs for relapse, values from a study of secondary AML patients who failed prior treatment for myelodysplastic syndrome were used. Where multiple HSUVs were available, collected values were given priority over assumed values. AML treatment (induction, consolidation, or SCT) was associated with decreased HSUV, while post-treatment complete remission led to increased HSUV. CONCLUSION: There are some methodologically robust HSUVs that can be directly used in economic evaluations for AML. Careful interpretation is advised considering significant differences in methodologies and patient population (inclusion, size). We need to develop HSUVs with larger-sized studies, making greater use of condition-specific data.

Smartphones for Real-time Assessment of Adherence Behavior and Symptom Exacerbation for High-Risk Youth with Asthma: Pilot Study.

BACKGROUND: Youth with asthma who have poor medication adherence, have limited access to care, and are frequently seen in the acute care setting are often termed "high risk." OBJECTIVE: This study aimed to design and test the feasibility of using smartphone technology to assess contextual factors that may impact changes in daily medication adherence and to identify new symptom episodes among high-risk youth with asthma in their home environment. METHODS: Youth aged 8-17 years with high-risk asthma from 2 children's hospitals were eligible for the 2-month study. An app was downloaded on participants' phones at enrollment. Daily text message (short message service) reminders were sent to complete ecological momentary assessment of asthma symptoms and other contextual factors such as emotional state using the app. Bluetooth inhaler devices were used to record timestamps of inhaler use with the ability to review and manually enter data. The acceptability was assessed with surveys, key informant interviews (KII), and frequency of days with asthma data. KII data were used in an iterative design approach to identify challenges, strengths, and suggestions for maximizing use. Generalized linear mixed modeling was used to preliminarily explore contextual factors associated with changes in daily adherence. RESULTS: We enrolled 14 children aged 8-16 years (13/14, 93% were African Americans). Over the 2-month study period, participants reported coughing (42/110, 38%), wheezing (8/111, 7%), chest tightness (9/109, 8%), boredom (57/109, 52%), and 10 new asthma symptom episodes. The controller medication adherence was 30%, which increased significantly on days with asthma symptoms or boredom. Data were received on 89% (606/681) of study days. Surveys and KIIs suggest acceptability among youth and their caregivers. Challenges reported during the study included lost or damaged phones and available memory. CONCLUSIONS: Youth and their caregivers reported the acceptability of using smartphones for real-time asthma monitoring. Overall, the controller medication adherence was low but increased significantly on days with reported asthma symptoms or boredom, suggesting that daily contextual factors may be associated with a change in the adherence behavior.

European Association of Urology Section of Urolithiasis (EULIS) Consensus Statement on Simulation, Training, and Assessment in Urolithiasis.

BACKGROUND: Simulation-based training offers an acceptable adjunct to the traditional mentor-apprentice model in helping trainees to traverse the early stages of the learning curve for ureteroscopy and percutaneous renal surgery. In addition, nontechnical skills are increasingly important in preventing adverse events in the operating room, and simulation-based training can be used for training in such skills. Incorporation of simulation into formalised, standardised, and validated curricula offers an applicable method for training residents. OBJECTIVE: To develop a curriculum for urolithiasis procedures incorporating technical and nontechnical skills training for implementation across Europe. DESIGN, SETTING, AND PARTICIPANTS: An international panel of experts from EULIS, EUREP, ESU and ESUT was consulted in five stages. The study incorporated a mix of qualitative and quantitative data for collection and analysis. Responses were drawn out in (1) an opinion survey and (2) a curriculum development survey, which were discussed in (3) a focus group meeting. Group responses from this meeting were analysed for themes, which were discussed at (4) a focus group meeting, where consensus was reached among the group. Data analysis and integration at this stage were used to draft the curriculum. RESULTS AND LIMITATIONS: All group meetings were transcribed from the focus group discussion. Eight themes were generated, into which all data were categorised. These were: need for a training curriculum; curriculum objectives; curriculum structure; curriculum content; teaching platforms and tools; assessment and certification; validation and implementation; and global integration of the curriculum. A curriculum, including recommended simulators for use, was subsequently proposed. CONCLUSIONS: We propose a comprehensive curriculum for training in urolithiasis. Additional planning is required for full validation and implementation before it can be used to train residents. PATIENT SUMMARY: Stone disease accounts for a major proportion of surgical interventions worldwide. We describe a consensus guideline for effective training of stone surgeons.

Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland.

We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, -£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the probability of capsaicin 8% patch being cost-effective versus pregabalin was 97%. Capsaicin 8% patch is a cost-effective treatment option compared with dose-optimized pregabalin in patients with PNP who have failed one or more previous systemic treatments.