A Review of Meaningful Change Thresholds for EORTC QLQ-C30 and FACT-G Within Oncology.

OBJECTIVES: This literature review provides an overview of meaningful change thresholds for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and the Functional Assessment of Cancer Therapy - General (FACT-G) used across hematological cancers and solid tumors (melanoma, lung, bladder, and prostate). METHODS: Embase, MEDLINE, and PubMed were searched to identify relevant oncology publications from 2016 to 2021. Label claims from the US Food and Drug Administration and the European Medicines Agency for 7 recently approved drugs (pembrolizumab, atezolizumab, glasdegib, gilteritinib, tisagenlecleucel, axicabtagene ciloleucel, and daratumumab plus hyaluronidase-fihj) were reviewed. RESULTS: Publications providing guidance on meaningful change thresholds for the QLQ-C30 displayed a growing trend away from broad "legacy" thresholds of 10 points for all QLQ-C30 scales), toward deriving "contemporary" thresholds (eg, subscale specific, population specific). Contemporary publications generally provide guidance on selecting thresholds for specific scales that account for improved or worsening thresholds (eg, QLQ-C30 subscales). This trend was not clear for FACT-G, with less new guidance available. Most clinical trials used in regulatory label submissions have used thresholds of 10 points for the QLQ-C30 subscales and 3 to 7 points for the FACT-G total score. Despite the availability of more recent guidelines, contemporary meaningful change thresholds seem slow to emerge in the published literature and regulatory labels. CONCLUSIONS: Trialists should consider using contemporary thresholds, rather than legacy thresholds, for QLQ-C30 endpoints. Thresholds derived for a similar patient-population should be used where available. Further work is required to provide these across a broader range of cancer sites.

Implementing Multilevel Network Meta-Regression for Time-To-Event Outcomes: A Case Study in Relapsed Refractory Multiple Myeloma.

OBJECTIVES: Multilevel network meta-regression (ML-NMR) leverages individual patient data (IPD) and aggregate data from a network of randomized controlled trials (RCTs) to assess the comparative efficacy of multiple treatments, while adjusting for between-study differences. We provide an overview of ML-NMR for time-to-event outcomes and apply it to an illustrative case study, including example R code. METHODS: The case study evaluated the comparative efficacy of idecabtagene vicleucel (ide-cel), selinexor+dexamethasone (Sd), belantamab mafodotin (BM), and conventional care (CC) for patients with triple-class exposed relapsed/refractory multiple myeloma in terms of overall survival. Single-arm clinical trials and real-world data were naively combined to create an aggregate data artificial RCT (aRCT) (MAMMOTH-CC versus DREAMM-2-BM versus STORM-2-Sd) and an IPD aRCT (KarMMa-ide-cel versus KarMMa-RW-CC). With some assumptions, we incorporated continuous covariates with skewed distributions, reported as median and range. The ML-NMR models adjusted for number of prior lines, triple-class refractory status, and age and were compared using the leave-one-out information criterion. We summarized predicted hazard ratios and survival (95% credible intervals) in the IPD aRCT population. RESULTS: The Weibull ML-NMR model had the lowest leave-one-out information criterion. Ide-cel was more efficacious than Sd, BM, and CC in terms of overall survival. Effect modifiers had minimal impact on the model, and only triple-class refractory was a prognostic factor. CONCLUSIONS: We demonstrate an application of ML-NMR for time-to-event outcomes and introduce code that can be used to aid implementation. Given its benefits, we encourage practitioners to utilize ML-NMR when population adjustment is necessary for comparisons of multiple treatments.

Administering selected subscales of patient-reported outcome questionnaires to reduce patient burden and increase relevance: a position statement on a modular approach.

Patient-reported outcome (PRO) questionnaires considered in this paper contain multiple subscales, although not all subscales are equally relevant for administration in all target patient populations. A group of measurement experts, developers, license holders, and other scientific-, regulatory-, payer-, and patient-focused stakeholders participated in a panel to discuss the benefits and challenges of a modular approach, defined here as administering a subset of subscales out of a multi-scaled PRO measure. This paper supports the position that it is acceptable, and sometimes preferable, to take a modular approach when administering PRO questionnaires, provided that certain conditions have been met and a rigorous selection process performed. Based on the experiences and perspectives of all stakeholders, using a modular approach can reduce patient burden and increase the relevancy of the items administered, and thereby improve measurement precision and eliminate wasted data without sacrificing the scientific validity and utility of the instrument. The panelists agreed that implementing a modular approach is not expected to have a meaningful impact on item responses, subscale scores, variability, reliability, validity, and effect size estimates; however, collecting additional evidence for the impact of context may be desirable. It is also important to recognize that adequate rationale and evidence (e.g., of fit-for-purpose status and relevance to patients) and a robust consensus process that includes patient perspectives are required to inform selection of subscales, as in any other measurement circumstance, is expected. We believe that the considerations discussed within (content validity, administration context, and psychometric factors) are relevant across multiple therapeutic areas.

Structured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myeloma.

BACKGROUND: Our aim was to extend traditional parametric models used to extrapolate survival in cost-effectiveness analyses (CEAs) by integrating individual-level patient data (IPD) from a clinical trial with estimates from experts regarding long-term survival. This was illustrated using a case study evaluating survival of patients with triple-class exposed relapsed/refractory multiple myeloma treated with the chimeric antigen receptor (CAR) T cell therapy idecabtagene vicleucel (ide-cel, bb2121) in KarMMa (a phase 2, single-arm trial). METHODS: The distribution of patients expected to be alive at 3, 5, and 10 years given the observed survival from KarMMa (13.3 months of follow-up) was elicited from 6 experts using the SHeffield ELicitation Framework. Quantities of interest were elicited from each expert individually, which informed the consensus elicitation including all experts. Estimates for each time point were assumed to follow a truncated normal distribution. These distributions were incorporated into survival models, which constrained the expected survival based on standard survival distributions informed by IPD from KarMMa. RESULTS: Models for ide-cel that combined KarMMa data with expert opinion were more consistent in terms of survival as well as mean survival at 10 years (survival point estimates under different parametric models were 29-33% at 3 years, 5-17% at 5 years, and 0-6% at 10 years) versus models with KarMMa data alone (11-39% at 3 years, 0-25% at 5 years, and 0-11% at 10 years). CONCLUSION: This case study demonstrates a transparent approach to integrate IPD from trials with expert opinion using traditional parametric distributions to ensure long-term survival extrapolations are clinically plausible.

Health-related quality of life in patients with triple-class exposed relapsed and refractory multiple myeloma treated with idecabtagene vicleucel or standard regimens: patient-reported outcomes from the phase 3, randomised, open-label KarMMa-3 clinical trial.

BACKGROUND: Chimeric antigen receptor T-cell therapy idecabtagene vicleucel (ide-cel) showed significantly improved progression-free survival compared with standard regimens in adults with relapsed and refractory multiple myeloma who had received two to four previous regimens in the ongoing phase 3 KarMMa-3 trial (NCT03651128). This study analysed patient-reported outcomes (PROs), a KarMMa-3 secondary endpoint. METHODS: In the randomised, open-label, phase 3 KarMMa-3 trial, 386 patients in hospitals (≥18 years of age, with measurable disease and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who had received two to four previous regimens-including an immunomodulatory agent, a proteasome inhibitor, and daratumumab-and had documented disease progression after receiving their last dose of the last therapy) were randomly assigned to ide-cel (n=254) or standard regimens (daratumumab, pomalidomide, and dexamethasone; daratumumab, bortezomib, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; carfilzomib and dexamethasone; or elotuzumab, pomalidomide, and dexamethasone; n=132). Patients were expected to complete the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire (QLQ-C30), Multiple Myeloma Module (QLQ-MY20), EQ 5 dimensions (EQ-5D), and EQ-5D visual analogue scale (VAS) at baseline and follow-up timepoints (data cutoff April 18, 2022). PROs included nine prespecified primary domains: EORTC QLQ-C30 GHS-quality of life (QoL), physical functioning, cognitive functioning, fatigue, and pain; QLQ-MY20 disease symptoms and side effects of treatment; and five-level EQ-5D (EQ-5D-5L) index score and EQ-5D visual VAS. Differences in overall least-squares mean changes from baseline to month 20 were analysed using post-hoc constrained longitudinal data analysis. Time to confirmed improvement or deterioration from baseline was analysed using Cox proportional hazard models. FINDINGS: Patients were randomly assigned between May 6, 2019, and April 8, 2022. Overall, the median age was 63 years (IQR 55-68); 151 (39%) patients were female; and 250 (65%) patients were White, 36 (9%) Black or African American, 19 (5%) Hispanic or Latino, 12 (3%) Asian, and seven (2%) of other race. The median follow-up was 18·6 months (IQR 14·0-26·4). PRO compliance was higher than 75% throughout. Overall least-squares mean changes from baseline favoured ide-cel with Hedges' g effect sizes from 0·3 to 0·7 for most domains. Patients in the ide-cel group showed statistically significant and clinically meaningful improvements across the primary PRO domains of interest, with the exception of QLQ-MY20 disease symptoms, side effects of treatment, and EQ-5D-5L index score, which showed improvement across assessment visits but did not exceed the within-group minimally important difference thresholds. The ide-cel group had shorter times to clinically meaningful improvement than the standard regimens group in QLQ-C30 domains except in role functioning, diarrhoea, and financial difficulties; in QLQ-MY20 domains except body image; and in EQ-5D-VAS. INTERPRETATION: Ide-cel offers improved health-related quality of life compared with standard regimens for patients with relapsed and refractory multiple myeloma after previous lines of therapy. The PRO data highlight the extended QoL benefits of a one-time infusion with ide-cel compared with continuous treatment with standard regimens in the treatment of triple-class exposed patients with relapsed and refractory multiple myeloma. FUNDING: 2seventy bio and Celgene, a Bristol Myers Squibb Company.

Cost-effectiveness of idecabtagene vicleucel compared with conventional care in triple-class exposed relapsed/refractory multiple myeloma patients in Canada and France.

BACKGROUND: The chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel) is approved for the treatment of adult patients with relapsed/refractory multiple myeloma (RRMM) who have already received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have progressed on their last therapy. The objective of this study was to assess the cost-effectiveness of ide-cel versus conventional care in Canada and France. METHODS: A partitioned survival model was used to estimate the cost-effectiveness of ide-cel (target dose 450 × 106 CAR T cells) in its approved indication in terms of life-years (LYs), quality-adjusted LYs (QALYs), and costs. Patient-level data from the KarMMa Phase II clinical trial (clinicaltrials.gov NCT03361748) and KarMMa-RW study were used to inform the model; overall and progression-free survival were extrapolated using standard parametric functions after the observed periods. The model adopted Canadian and French societal perspectives over a lifetime horizon. Costs, utilities, discounting (Canada: 1.5%, France: 2.5%), and general population mortality were country-specific. RESULTS: The base case demonstrated that ide-cel was associated with more additional LYs (+2.64 and +2.51) and QALYs (+2.31 and +2.54) than conventional care at incremental costs of CAN$588,490 and €392,251 in Canada and France, respectively. The resulting incremental cost-effectiveness ratio (ICER) for ide-cel was $255,245 per QALY in Canada, and €154,593 per QALY in France. CONCLUSION: Ide-cel was associated with significant survival improvements in terms of both LYs and QALYs in patients with progressive triple-class-exposed RRMM. The ICER for ide-cel was similar to that of other approved and reimbursed RRMM therapies.

Cost-effectiveness of atrial fibrillation screening in Canadian community practice.

Background: Contemporary guidelines recommend opportunistic screening for atrial fibrillation (AF). Objective: The objective of this study was to assess the cost-effectiveness of single time point opportunistic AF screening for patients 65 years and older by using the single-lead electrocardiogram. Methods: An established Markov cohort model was adapted by updating the background mortality estimates, epidemiology, screening efficacy, treatment patterns, resource use, and cost inputs to reflect a Canadian health care setting. Inputs were derived from a contemporary prospective screening study performed in Canadian primary care settings (screening efficacy and epidemiology) and the published literature (unit costs, epidemiology, mortality, utility, and treatment efficacy). The impact of screening and oral anticoagulant treatment on the cost and clinical outcomes was analyzed. A Canadian payer perspective over lifetime was used for analysis, with costs expressed in 2019 Canadian dollars. Results: Among the estimated screening-eligible population of 2,929,301 patients, the screening cohort identified an additional 127,670 AF cases compared with the usual care cohort. The model estimated avoidance of 12,236 strokes and incremental quality-adjusted life-years of 59,577 (0.02 per patient) over lifetime in the screening cohort. Cost savings were substantial because of improved health outcomes, reflecting screening being the dominant strategy (affordable and effective). Model results were robust across sensitivity and scenario analyses. Conclusion: Single time point opportunistic screening of AF using a single-lead electrocardiogram device in Canadian patients 65 years and older without known AF may provide improved health outcomes with cost savings from the perspective of a single payer health care environment.

Real-world treatment patterns and healthcare costs in patients with psoriasis taking systemic oral or biologic therapies.

BACKGROUND: Psoriasis is a chronic, immune-mediated, systemic inflammatory disorder associated with high costs. This study evaluated real-world treatment patterns and associated costs in patients in the United States with psoriasis initiating systemic oral or biologic treatments. METHODS: This retrospective cohort study used IBM® (now Merative™) MarketScan® Commercial and Medicare claims (1 January 2006-31 December 2019) to evaluate patterns of switching, discontinuation, and nonswitching in two cohorts of patients initiating oral or biologic systemic therapy. Total pre-switch and post-switch costs were reported per-patient per-month (PPPM). RESULTS: Each cohort was analyzed (oral, n = 11,993; biologic; n = 9753). Among the oral and biologic cohorts, 32% and 15% discontinued index and any systemic treatment within 1 year of initiation; 40% and 62% remained on index therapy; and 28% and 23% switched treatment, respectively. In the oral and biologic cohorts, total PPPM costs within 1 year of initiation for nonswitchers, patients who discontinued, and patients who switched were $2594, $1402, and $3956, respectively, and $5035, $3112, and $5833, respectively. CONCLUSION: This study identified lower persistence in the oral treatment cohort, higher costs associated with switching, and a need for safe and effective oral treatment options for patients with psoriasis to delay the switch to biologic therapy.

Analysis of patient-reported experiences up to 2 years after receiving idecabtagene vicleucel (ide-cel, bb2121) for relapsed or refractory multiple myeloma: Longitudinal findings from the phase 2 KarMMa trial.

OBJECTIVE: To understand the long-term experience of patients receiving ide-cel chimeric antigen receptor T (CAR T) cell therapy for relapsed or refractory multiple myeloma in the pivotal phase 2 KarMMa trial. METHODS: This qualitative study analyzed semi-structured patient interviews 6-24 months after ide-cel infusion. Thematic analysis with quantitative and longitudinal analyses explored patient perceptions of ide-cel treatment experience, advantages and disadvantages, and long-term health-related quality of life impact. Patient journeys were developed from narrative analysis of perceived treatment benefits with known remission length. RESULTS: Interviews with 45 patients 6-24 months postinfusion were analyzed; all reported ≥ 1 ide-cel treatment advantage, most often related to efficacy (n = 42/45, 93%), few or no side effects (n = 35/45, 78%), and avoidance of other treatments (n = 34/45, 76%). Patients generally reported 6-month improvements in physical health, functioning, emotional well-being, social life, and outlook on the future; these improvements mostly remained "stable" through 18 and 24 months. The most common patient journeys comprised physical, functioning, or emotional benefit with remission < 2 years. CONCLUSIONS: Longitudinal analysis of patient experiences showed sustained benefits and preference for ide-cel up to 24 months after treatment. Trial Registration Number and Date: NCT03361748. December 5, 2017.

Modification of treatment-sequence model with a customizable number of treatments to better reflect contemporary and future clinical practice in moderate to severe psoriasis.

AIMS: Existing treatment-sequence models for psoriasis are limited by lines of treatments included. We sought to more accurately capture the patient experience with an increasing number of treatments while maintaining the complexity and transparency of current models. MATERIALS AND METHODS: We adapted a standard treatment-sequence model for psoriasis with two lines of active treatments followed by best supportive care (BSC). The first line was used to model the targeted treatments for comparison (Biologic A or B). The second line was used potentially to model all treatments (excluding the first-line treatment) before BSC, termed the basket of biologics (BoB). First-line treatment and the BoB were modeled with an induction and maintenance phase. The BoB efficacy was assumed to be the average of all treatments included and the BoB annual discontinuation rate was based on the number of treatments included and their individual annual discontinuation rate. A varying number of treatments in the BoB were tested (1, 5, 10). Model inputs were from published literature. RESULTS: In our example, when the number of treatments in the BoB increased from 1 to 10, the annual discontinuation rate of the BoB dropped from 16.5% to 1.2%. Time on BoB increased from 4.16 to 19.16 years and the time on BSC decreased from 28.28 to 13.29 years. Total costs and quality-adjusted life years increased with an increasing number of treatments in the BoB. LIMITATIONS: The properties of the BoB were simplified in order to maintain the transparency of the model. Results may differ if individual treatments in the BoB are modeled line by line. CONCLUSIONS: Modification with the BoB allows a greater number of treatments within the model, providing a closer reflection of clinical reality, and has implications for evaluation of the long-term cost-effectiveness of psoriasis treatments.

Psoriasis is a chronic skin disease with no cure that causes itchy and painful plaques and scales, most commonly found on the scalp, trunk, elbows, and knees. A variety of treatments are available that can improve the signs and symptoms of psoriasis. Healthcare payers are interested in the costs, benefits, and risks of treatments for all diseases, including those for psoriasis. These payers often use mathematical models to better understand and compare the value of various treatments. With psoriasis, these models usually assume three lines of active therapy and then a final supportive therapy over a patient's lifetime. However, the average number of therapies patients with psoriasis receive is often greater than three, resulting in them spending most of their time on, and switching among, treatments rather than on best supportive care. Therefore, instead of modeling each line of treatment individually, the researchers proposed a modification to the existing model framework, whereby all subsequent treatments are combined into a single basket. This modification allowed for many treatments to be considered over the lifetime of patients with psoriasis and also maintained the model's complexity. The researchers found that as the amount of time on active therapy increased, the amount of time on supportive therapy decreased, treatment costs increased, and patients spent more time with better quality-of-life. The researchers concluded that the proposed model modification more closely resembles clinical practice than the previous model and would be very useful to healthcare payers in better estimating the value of psoriasis treatments.

Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma.

Aim: To compare the efficacy of idecabtagene vicleucel (ide-cel, bb2121) versus conventional care (CC) in triple-class exposed relapsed and refractory multiple myeloma (RRMM) patients. Patients & methods: A matching-adjusted indirect comparison was conducted using individual patient-level data from the pivotal, phase II, single-arm KarMMa trial (NCT03361748) and aggregate-level data from MAMMOTH, the largest independent observational study of CC in heavily pretreated RRMM patients. Results: Ide-cel improved overall response rate (odds ratio: 5.30; 95% CI: 2.96-9.51), progression-free survival (hazard ratio: 0.50; 95% CI: 0.36-0.70) and overall survival (hazard ratio: 0.37; 95% CI: 0.25-0.56) versus CC. Conclusion: These results suggest ide-cel offers improvements in clinical outcomes relative to CC in this heavily pretreated RRMM population.

Cost-consequence of abatacept as first-line therapy in Japanese rheumatoid arthritis patients using IORRA real-world data.

OBJECTIVES: To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database. METHODS: A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score). RESULTS: Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5. CONCLUSIONS: ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers.

Health-related quality of life with idecabtagene vicleucel in relapsed and refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, showed deep, durable responses in patients with triple-class exposed, relapsed and refractory multiple myeloma (RRMM) in the phase 2 KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) trial. We assessed health-related quality of life (HRQoL) among KarMMa patients. The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item multiple myeloma module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (≤72 hours before or same day as lymphodepletion), day of ide-cel treatment, and after ide-cel treatment. Mean changes from baseline that exceeded the predetermined threshold of minimally important difference were deemed clinically meaningful. The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds. Time to stable improvement (≥2 consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method. A total of 126 (98%) of 128 patients treated with ide-cel were included in the HRQoL analysis. Pretreatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population. Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (-8.9) and disease symptoms (-10.2), and by month 2 for fatigue (-7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0). Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment. For triple-class exposed patients with RRMM with a poor prognosis and few treatment options, a single ide-cel infusion provides early, sustained, statistically significant, and clinically meaningful improvements in HRQoL. This study was registered at Clinicaltrials.gov as #NCT03361748.

Patient experience before and after treatment with idecabtagene vicleucel (ide-cel, bb2121): qualitative analysis of patient interviews in the KarMMa trial.

OBJECTIVE: To understand the experience of patients with relapsed and refractory multiple myeloma (RRMM) receiving idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in the pivotal, phase 2 KarMMa trial. METHODS: Optional semi-structured interviews before leukapheresis (pre-treatment) captured expectations and after ide-cel infusion (1, 2, and 3 months post-treatment), assessed treatment experience, ide-cel advantages/disadvantages, and health and well-being. In a mixed-method analysis, treatment experiences were categorized by clinical response status, health and well-being, and self-reported recovery after infusion. RESULTS: Pre-treatment interviews indicated unmet treatment needs. In post-treatment interviews, most patients reported the positives of ide-cel outweighed negatives (69%, n = 27/39). Most common advantages of ide-cel were efficacy (18-64%), favorable side-effect profile (46-68%), and recovery time (13-18%); most common disadvantages were related to side effects (13-20%). When analyzed by clinical response, patients most often had stringent complete or very good partial response and improved health and well-being with mild or severe recovery from the infusion (27/58, 47%). Most patients with minimal clinical response reported mild infusion recovery (5/6, 83%). CONCLUSIONS: Patient interviews before ide-cel treatment showed unmet needs in triple-class exposed RRMM. Post-treatment experiences generally favored ide-cel versus previously received treatments.

Treatment Patterns and Outcomes in Triple-Class Exposed Patients With Relapsed and Refractory Multiple Myeloma: Findings From the Multinational ITEMISE Study.

PURPOSE: Patients with relapsed and refractory multiple myeloma (RRMM) have a poor prognosis and limited treatment options after exposure to an immunomodulatory drug, proteasome inhibitor (PI), and anti-CD38 antibody (triple-class exposure [TCE]). However, current understanding about the management of these patients and associated health care resource use (HCRU) is limited outside the United States. The objective of the International Treatment pattern and resource use Evaluation for Multiple myeloma In a Study of triple-class Exposed patients (ITEMISE) study was to use a physician-developed survey fielded to hematologists across Europe and Canada to assess the treatment, management, HCRU, and end-of-life care for patients with RRMM after TCE. METHODS: The ITEMISE study used a 3-phase Delphi-like approach that consisted of in-depth interviews with 7 hematology experts; the development of a cross-sectional survey fielded to hematologists across Belgium, Canada, France, Germany, Italy, the Netherlands, Spain, Sweden, Switzerland, and the United Kingdom from August to October 2020; and a final workshop of hematology experts to validate the pooled findings. Hematologists were asked to consider the management of patients in the first 3 treatment lines after TCE, including treatment options, treatment duration and outcomes, and frequency of outpatient visits and hospitalizations. FINDINGS: The survey was completed by 202 hematologists (60% from academic hospitals, 38% from other public hospitals, and 2% from private hospitals). Hematologists estimated that 55% of patients would receive active treatment after TCE, the equivalent of fourth-line treatment onward since diagnosis of multiple myeloma. Immunomodulatory drug, anti-CD38 antibody plus immunomodulatory drug, and PI-based regimens (received by 22.5%, 17.8%, and 15.1% of patients, respectively) were reported for first treatment strategy after TCE. Pomalidomide, daratumumab, lenalidomide, bortezomib, and carfilzomib were the most frequently selected antimyeloma agents. Associated outcomes of median overall survival, progression-free survival, and objective response rate for first treatment after TCE were estimated as 12 months, 4 months, and 40%, respectively. HCRU included outpatient visits and unplanned hospitalizations that were commonly reported during treatment after TCE. IMPLICATIONS: Findings indicate an intent to actively treat patients after TCE with a range of combination regimens frequently consisting of immunomodulatory drugs, PIs, and anti-CD38 antibodies, highlighting the lack of standard of care and suggesting a large clinical unmet need. Estimated clinical outcomes are consistent with data from US studies and indicate the poor prognosis for patients after TCE. Substantial HCRU is associated with management of patients after TCE across Europe and Canada, signifying a high patient and societal impact and a need for better treatment options to reduce this burden.

Cost-effectiveness analysis of apixaban versus vitamin K antagonists for antithrombotic therapy in patients with atrial fibrillation after acute coronary syndrome or percutaneous coronary intervention in Spain.

BACKGROUND/OBJECTIVE: AUGUSTUS trial demonstrated that, for patients with atrial fibrillation (AF) having acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), an antithrombotic regimen with apixaban and P2Y12 resulted in less bleeding, fewer hospitalizations, and similar ischemic events than regimens including a vitamin K antagonist (VKA), aspirin, or both. This study objective was to evaluate long-term health and economic outcomes and the cost-effectiveness of apixaban over VKA, as a treatment option for patients with AF having ACS/PCI. METHODS: A lifetime Markov cohort model was developed comparing apixaban versus VKA across multiple treatment strategies (triple [with P2Y12 + aspirin] or dual [with P2Y12] therapy followed by monotherapy [apixaban or VKA]; triple followed by dual and then monotherapy; dual followed by monotherapy). The model adopted the Spanish healthcare perspective, with a 3-month cycle length and costs and health outcomes discounted at 3%. RESULTS: Treatment with apixaban resulted in total cost savings of €883 and higher life years (LYs) and quality-adjusted LYs (QALYs) per patient than VKA (net difference, LYs: 0.13; QALYs: 0.11). Bleeding and ischemic events (per 100 patients) were lower with apixaban than VKA (net difference, -13.9 and -1.8, respectively). Incremental net monetary benefit for apixaban was €3,041, using a willingness-to-pay threshold of €20,000 per QALY. In probabilistic sensitivity analysis, apixaban was dominant in the majority of simulations (92.6%), providing additional QALYs at lower costs than VKA. CONCLUSIONS: Apixaban was a dominant treatment strategy than VKA from both the Spanish payer's and societal perspectives, regardless of treatment strategy considered.

Payer Preferences and Willingness to Pay for Genomic Precision Medicine: A Discrete Choice Experiment.

BACKGROUND: Although precision medicine using genetic information offers significant promise, its uptake and eventual clinical and economic impacts are uncertain. Health care payers will play an important role in evaluating evidence and costs to develop coverage and reimbursement policies. OBJECTIVE: To elicit U.S. health care payer preference for genomic precision medicine to better understand trade-offs among clinical benefits, uncertainty, and cost. METHODS: Using key informant interviewer discussions (N = 6 payers), we identified 6 key attributes of genetic tests important to payers: type of information the test provides (screening vs. treatment prediction), probability that the member has an informative genetic marker, expert agreement on changing medical care based on the marker, quality-of-life gains, life expectancy gains (with statistical uncertainty), and cost to the plan. We designed a stated preference discrete choice experiment using these attributes and administered a web survey to a sample of U.S. health care payers. We used effects coding and analyzed the data using an error component mixed logit modeling approach. RESULTS: The survey response rate was 58% (150 participants completed the survey). Approximately 53% of respondents had previous experience evaluating genetic tests for reimbursement, and 85% had more than 5 years of health care decision-making experience. Payers valued improvements in quality of life the most (marginal willingness to pay [mWTP] of $1,513-$6,076), followed by medical expert agreement on the treatment change (mWTP of $2,881-$3,489). Payers placed a relatively lower value for genetic tests with lower marker probability (mWTP of $2,776 for highest marker probability to $423 for lowest marker probability). Payers mWTP was lowest for resolving uncertainty in quality of life (mWTP of $1,513-$2,031) and life expectancy gains ($536-$1,537). CONCLUSIONS: Payers exhibited a strong preference for genetic tests that improved quality of life, had high expert agreement on changing medical care, and increased life expectancy. These findings suggest that payers will need evidence of clinical utility to support coverage and reimbursement of genomic precision medicine. DISCLOSURES: This study was supported by a grant from the NIH Common Fund and NIA (1U01AG047109-01) via the Personalized Medicine Economics Research (PriMER) project. Unrelated to this study, Veenstra reports consulting fees from Bayer and Halozyme; Basu reports consulting fees from Salutis Consulting; and Reiger reports consulting fees from Roche. Carlson reports grants from Institute for Clinical and Economic Review, during the conduct of this study, and consulting fees from Bayer, Adaptive Biotechnologies, Allergan, Galderma, and Vifor Pharma, unrelated to this study.

Provider preferences for resolving uncertainty and avoiding harms in precision medicine: a discrete choice experiment.

Background: Substantial uncertainty exists about how providers assess the value of genomic testing. Materials & methods: We developed and administered a discrete choice experiment to a national sample of providers. We analyzed responses using an error components mixed logit model. Results: We received responses from 356 providers. The attributes important to providers were patient health and function, life expectancy, cost, expert agreement, and biomarker prevalence. Providers significantly valued reducing uncertainty only when it eliminated the possibility of decreased life expectancy. Providers valued improving certainty about life expectancy gains from 12 ± 18 to 12 ± 6 months at US$400 (US$200-600) versus US$200 (-US$60-500) for 4 ± 4 to 4 ± 2 years. Conclusion: Providers value resolving uncertainty most when it eliminates the possibility of substantial harm.

Intratracheal budesonide-poly(lactide-co-glycolide) microparticles reduce oxidative stress, VEGF expression, and vascular leakage in a benzo(a)pyrene-fed mouse model.

The purpose of this study was to determine whether intratracheally instilled polymeric budesonide microparticles could sustain lung budesonide levels for one week and inhibit early biochemical changes associated with benzo(a)pyrene (B[a]P) feeding in a mouse model for lung tumours. Polymeric microparticles of budesonide-poly (DL-lactide-co-glycolide) (PLGA 50:50) were prepared using a solvent evaporation technique and characterized for their size, morphology, encapsulation efficiency, and in-vitro release. The microparticles were administered intratracheally (i.t.) to B[a]P-fed A/J mice. At the end of one week drug levels in the lung tissue and bronchoalveolar lavage (BAL) were estimated using HPLC and compared with systemic (intramuscular) administration. In addition, in-vivo end points including malondialdehyde (MDA), glutathione (GSH), total protein levels and vascular endothelial growth factor (VEGF) in BAL, and VEGF and c-myc mRNA levels in the lung tissue were assessed at the end of one week following intratracheal administration of budesonide microparticles. Budesonide-PLGA microparticles (1-2 microm), with a budesonide loading efficiency of 69-94%, sustained in-vitro budesonide release for over 21 days. Compared with the intramuscular route, intratracheally administered budesonide-PLGA microparticles resulted in higher budesonide levels in the BAL and lung tissue. In-vivo, B[a]P-feeding increased BAL MDA, lung VEGF mRNA, lung c-myc mRNA, BAL total protein, and BAL VEGF levels by 60, 112, 71, 154, and 78%, respectively, and decreased BAL GSH by 62%. Interestingly, intratracheally administered budesonide-PLGA particles inhibited these biochemical changes. Thus, biodegradable budesonide microparticles sustained budesonide release and reduced MDA accumulation, GSH depletion, vascular leakage, and VEGF and c-myc expression in B[a]P-fed mice, indicating the potential of locally delivered sustained-release particles for inhibiting angiogenic factors in lung cancer.