Virtual versus usual in-office care for multiple sclerosis: The VIRTUAL-MS multi-site randomized clinical trial study protocol.

BACKGROUND: Multiple sclerosis (MS) affects nearly 1 million people and is estimated to cost $85.4 billion in the United States annually. People with MS have significant barriers to receiving care and telemedicine could substantially improve access to specialized, comprehensive care. In cross-sectional analyses, telemedicine has been shown to be feasible, have high patient and clinician satisfaction, reduce patient costs and burden, and enable a reasonable assessment of disability. However, no studies exist evaluating the longitudinal impact of telemedicine care for MS. Here we describe the study protocol for VIRtual versus UsuAL In-office care for Multiple Sclerosis (VIRTUAL-MS). The main objective of the study is to evaluate the impact of telemedicine for MS care on: patient clinical outcomes, economic costs, patient, and clinician experience. METHODS: This two-site randomized clinical trial will enroll 120 adults with a recent diagnosis of MS and randomize 1:1 to receive in-clinic vs. telemedicine care for 24 months. The primary outcome of the study is worsening in any one of the four Multiple Sclerosis Functional Composite 4 (MSFC4) measures at 24 months. Other study outcomes include patient and clinician satisfaction, major healthcare costs, Expanded Disability Status Scale, treatment adherence, and digital outcomes. CONCLUSION: The results of this study will directly address the key gaps in knowledge about longitudinal telemedicine-enabled care in an MS population. It will inform clinical care implementation as well as design of trials in MS and other chronic conditions. TRIAL REGISTRATION: NCT05660187.

Tackling Challenges in Assessing the Economic Value of Tumor-Agnostic Therapies: A Cost-Effectiveness Analysis of Pembrolizumab as a Case Study.

OBJECTIVES: Assessing the value of tumor-agnostic drugs (TAD) is challenging given the potential variability in treatment effects, trials with small sample sizes, different standards of care (SoC), and lack of comparative data from single-arm basket trials. Our study developed and applied novel methods to assess the value of pembrolizumab compared with SoC to inform coverage decisions. METHODS: We developed a partitioned survival model to evaluate the cost-utility of pembrolizumab for previously treated patients with 8 advanced or metastatic microsatellite instability-high or mismatch repair-deficient cancers from a US commercial payer perspective. Efficacy of pembrolizumab was based on data from trials directly or with adjustment using Bayesian hierarchical models. Eight chemotherapy-based external control arms were constructed from the TriNetX electronic health record databases. Tumor-specific health-state utility values were applied. All costs were adjusted to 2022 US dollars. RESULTS: At a lifetime horizon, pembrolizumab was associated with increased effectiveness compared with chemotherapies in colorectal (quality-adjusted life years [QALYs]: +0.64, life years [LYs]: +0.64), endometrial (QALYs: +3.79, LYs: +5.47), and small intestine cancers (QALYs: +1.73, LYs: +2.48), but not for patients with metastatic gastric, cholangiocarcinoma, pancreatic, ovarian, and brain cancers. Incremental cost-effectiveness ratios varied substantially across tumor types. Pembrolizumab was found to be cost-effective in treating colorectal and endometrial cancers (incremental cost-effectiveness ratios: $121 967 and $139 257, respectively), and not cost-effective for other assessed cancers at a $150 000 willingness-to-pay/QALY threshold, compared with SoC chemotherapies. CONCLUSIONS: The cost-effectiveness of TADs can vary by cancers. Using analytic tools such as external controls and Bayesian hierarchical models can tackle several challenges in assessing the value of TADs and uncertainties from basket trials.

Evaluating Policies of Expanding Versus Restricting First-Line Treatment Choices: A Cost-Effectiveness Analysis Framework.

OBJECTIVES: Healthcare payers often implement coverage policies that restrict the utilization of costly new first-line treatments. Cost-effectiveness analysis can be conducted to inform these decisions by comparing the new treatment with an existing one. However, this approach may overlook important factors such as treatment effect heterogeneity and endogenous treatment selection, policy implementation costs, and diverse patient preferences across multiple treatment options. We aimed to develop a cost-effectiveness analysis framework that considers these real-world factors, facilitating the evaluation of alternative policies related to expanding or restricting first-line treatment choices. METHODS: We introduced a metric of incremental cost-effectiveness ratio (ICER) that compares an expanded choice set (CS) including the new first-line treatment with a restricted CS excluding the new treatment. ICER(CS) accounts for treatment selection influenced by heterogeneous treatment effects and policy implementation costs. We examined a basic scenario with 2 standard first-line treatment choices and a more realistic scenario involving diverse preferences toward multiple choices. To illustrate the framework, we conducted a retrospective evaluation of including versus excluding abiraterone acetate plus prednisone (AAP) (androgen deprivation therapy [ADT] + AAP) as a first-line treatment for metastatic hormone-sensitive prostate cancer. RESULTS: The traditional ICERs for ADT + AAP versus ADT alone and ADT+ docetaxel were $104 269 and $206 324/quality-adjusted life-year, respectively. The ICER(CS) for comparing an expanded CS with ADT + AAP with a restricted CS without ADT + AAP was $123 179/quality-adjusted life-year. CONCLUSIONS: The proposed framework provides decision makers with policy-relevant tools, enabling them to assess the cost-effectiveness of alternative policies of expanding versus restricting patients' and physicians' first-line treatment choices.

Real-world treatment patterns and economic burden of post-cataract macular edema.

BACKGROUND: Post-cataract macular edema (PCME) is a condition that can occur in patients following cataract surgery without risk factors and complications. Although 80% of patients experience spontaneous resolution after 3 to 12 months, in persistent cases, it can lead to permanent vision loss if left untreated. There are currently no standardized treatment guidelines for PCME, and there have been limited studies showing the impact of PCME on annual Medicare spending and ophthalmology-related outpatient visits per case compared to those without the complication. This study aims to evaluate real-world treatment patterns and the economic burden of patients with PCME. METHODS: This retrospective claims analysis identified patients from the IBM® MarketScan® Commercial and Medicare Supplemental databases. Patients with (n = 2430) and without (n = 7290) PCME 1 year post cataract surgery were propensity score matched 1:3 based on age, geographic region, diabetes presence, cataract surgery type, and Charlson Comorbidity Index. Treatment pattern analysis for each PCME patient summarized the distribution of medications across lines of therapy. Economic burden analysis compared the mean number and costs of eye-related outpatient visits, optical coherence tomography imaging scans, and ophthalmic medications between the 2 groups using linear regression models. RESULTS: Treatment pattern analysis found 27 different treatment combinations across 6 treatment lines. The most common first-line treatments were topical steroid drops (372 [30%]), topical nonsteroidal anti-inflammatory drug drops (321 [27%]), and intraocular or periocular injectable steroids (189 [15%]). Compared to match controls, PCME patients averaged 6 additional eye-related outpatient office visits (95% CI: 5.7-6.2) resulting in an additional $3,897 (95% CI: $3,475 - $4,319) in total costs. Patients filled 3 more ophthalmology-related outpatient prescription medications (95% CI: 2.8-3.2), adding $371 in total cost (95% CI: $332 - $410). CONCLUSIONS: PCME treatment patterns showed wide clinical variability in treatments and time, specifically regarding injectable treatments and combination therapy. Additionally, significantly higher healthcare resource use and economic burden were found for both patients and payers when comparing PCME patients to non-PMCE controls. These results highlight the need for treatment standardization and demonstrate that interventions targeted at preventing PCME may be valuable.

Health care resource utilization and costs among patients with multiple myeloma with exposure to double-class or triple-class multiple myeloma treatments: A retrospective US claims database analysis.

BACKGROUND: Despite recent advancements in the therapeutic landscape, multiple myeloma (MM) remains incurable. There are multiple treatment options available with a novel mechanism of action, but there is limited evidence describing the economic burden among patients with MM exposed to different drug classes and combinations and across different health care settings. OBJECTIVE: To describe all-cause and MM-related health care resource utilization (HCRU) and costs among patients with MM exposed to different drug classes and combinations (ie, double-class and triple-class-exposed) and characterize the economic burden in different health care settings among these patients with MM. METHODS: We conducted a retrospective cohort study using the IBM MarketScan databases. The study included adult patients (aged ≥18 years) diagnosed with MM between December 1, 2015, and December 31, 2019. The study sample comprised double-class-exposed (DCE) and triple-class-exposed (TCE) cohorts, categorized based on their earliest exposure to different combinations of immunomodulatory drugs, proteasome inhibitors, or targeted monoclonal antibody. Patients with at least 1 subsequent line of therapy following the categorization were included, and the start date of the first subsequent line of therapy was the index date. The primary outcomes were all-cause and MM-related HCRU and costs during the follow-up period. Costs were stratified across 8 care settings defined by place of service. The Kaplan-Meier sample average technique was used to estimate the cumulative mean outcomes, accounting for differential follow-up periods. The outcomes were reported as per patient per month (PPPM). 18 years) diagnosed with MM between December 1, 2015, and December 31, 2019. The study sample comprised double-class-exposed (DCE) and triple-class-exposed (TCE) cohorts, categorized based on their earliest exposure to different combinations of immunomodulatory drugs, proteasome inhibitors, or targeted monoclonal antibody. Patients with at least 1 subsequent line of therapy following the categorization were included, and the start date of the first subsequent line of therapy was the index date. The primary outcomes were all-cause and MM-related HCRU and costs during the follow-up period. Costs were stratified across 8 care settings defined by place of service. The Kaplan-Meier sample average technique was used to estimate the cumulative mean outcomes, accounting for differential follow-up periods. The outcomes were reported as per patient per month (PPPM). RESULTS: The study included 1,521 patients with MM, of whom 1,016 (66.8%) were DCE and 505 (33.2%) were TCE. The mean total all-cause health care costs were $20,338 PPPM, and approximately 85% of the total all-cause costs were MM-related. The mean all-cause and MM-related total costs were driven by overall drug costs primarily attributed to MM treatment and administration costs. The TCE cohort was associated with more HCRU and incurred higher costs than the DCE cohort across all categories. The hospital-based ambulatory setting had the highest all-cause and MM-related costs during the follow-up period: $7,302 (95% CI = $6,801-$7,784) PPPM and $6,695 (95% CI = $6,239-$7,136) PPPM, respectively. CONCLUSIONS: The study findings suggest that the economic burden following exposure to multiple drug classes and combinations is substantial, especially among the TCE cohort and in the ambulatory setting. These findings highlight the need for more effective treatments that can mitigate the economic burden of patients with MM. Future research on the HCRU and costs related to recently approved MM treatments with novel mechanisms is warranted. DISCLOSURES: At the time of this study, Dr Yang was a postdoctoral fellow and the fellowship was supported by GSK. Dr Boytsov is a full-time employee of GSK. Dr Carlson discloses consulting fees from Pfizer, AbbVie, and Genentech. Dr Barthold reports no disclosures.

Quantifying the value of older adult-specific clinical trials: Post-lumpectomy irradiation among older adults with early-stage breast cancer.

INTRODUCTION: Although there is increasing interest in conducting cancer clinical trials in older adults, the benefit of such trials is unclear. We aimed to quantify the real-world clinical and economic effects of two phase 3 trials (CALGB 9343 and PRIME II) which showed that post-lumpectomy radiation therapy (RT) improves loco-regional recurrence but makes no improvement in overall survival among older women with early-stage breast cancer (ESBC). MATERIALS AND METHODS: We developed a health-transition model to quantify the incremental clinical and economic outcomes between scenarios with vs. without older adult-specific trial results from a societal perspective between 2004 and 2018. The transition probabilities in the model were mainly derived from the 10-year results of CALGB 9343. The total number of the affected patient population in the US and the change in the probability of omitting post-lumpectomy RT due to the CALGB 9343 and PRIME II results were derived from a retrospective analysis of the SEER registry data for patients with ESBC. Sensitivity analyses were conducted to calculate the 95% credible interval (CR) of the incremental clinical and economic outcomes between the two scenarios. RESULTS: Between 2004 and 2018, 32,936 (95% CR: 31,512, 34,357) fewer patients received post-lumpectomy RT among those aged 70 years or older diagnosed with ESBC in the US and there was a decrease cost of $419 M USD (95% CR: -$238 M, -$689 M) in scenarios with vs. without older adult-specific trial results. The difference in projected life years (1083 years, 95% CI: -2542, 7985) and QALYs (866 years, 95% CI: -2561, 7780) were not significant. At a willingness-to-pay threshold of $100 k/QALY, the probability of older adult-specific trial results generating a positive net monetary benefit was 98%. DISCUSSION: The CALGB 9343 and PRIME II trial results were associated with a substantial cost-saving in the US society. Our results suggest that older adult-specific clinical trials that demonstrate no survival benefit of an intervention in older adults could be correlated with a significant monetary benefit. Further case studies are needed for different types of older adult-specific trials to understand the value of older adult-specific trials comprehensively.

How does cumulative evidence from older adult-specific trials influence clinical practice? A difference-in-differences analysis in early-stage breast cancer.

BACKGROUND: Despite increasing focus on conducting cancer clinical trials in older adults, it is unclear whether such evidence influences practice patterns. We aimed to estimate the impact of cumulative evidence from older adult-specific trial results from the CALGB 9343 and PRIME II trials that found post-lumpectomy irradiation has little benefit among older adults with early-stage breast cancer (ESBC). METHODS: Patients diagnosed with ESBC between 2000 and 2018 were identified from the SEER registry data. We examined the incremental immediate effect, incremental average yearly effect, and cumulative effect of a series of CALGB 9343 and PRIME II results on the utilization level of post-lumpectomy irradiation. We conducted difference-in-differences analyses, comparing those aged 70 or older vs. <65 years old. RESULTS: The initial 5-year CALGB 9343 results in 2004 led to a significant immediate (-0.038, 95% CI: -0.064, -0.012) and average yearly decrease (-0.008, 95% CI: -0.013, -0.003) in the probability of irradiation use among those aged 70 or older compared to those below 65 years of age. 11-year CALGB 9343 results in 2010 significantly accelerated the average yearly effect by 1.7 percentage points (95% CI: -0.030, -0.004). The other later results did not significantly change the time trend. The cumulative effect of all results between 2004 and 2018 was -26.3 percentage points (95% CI: -0.29, -0.24). CONCLUSION: Cumulative evidence from older adult-specific trials in ESBC led to decreasing use of irradiation over time among elderly patients. The rate of decrease after the initial results was accelerated by long-term follow-up results.

The effectiveness and value of AMX0035 and oral edaravone for amyotrophic lateral sclerosis: A summary from the Institute for Clinical and Economic Review's Midwest Comparative Effectiveness Public Advisory Council.

DISCLOSURES: Funding for this summary was contributed by Blue Cross Blue Shield of MA, California Healthcare Foundation, The Patrick and Catherine Weldon Donaghue Medical Research Foundation, Arnold Ventures, and Kaiser Foundation Health Plan Inc., to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, AbbVie, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy Solutions, Express Scripts, Genentech/ Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health First, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer. Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, Sun Life Financial, uniQure, and United Healthcare. Mr Nikitin, Ms McKenna, Ms Richardson, and Drs Rind and Pearson are employed by ICER. Through their affiliated institutions, Drs Makam, Carlson, and Suh received funding from ICER for the work described in this summary.

Incorporating Dynamic Pricing in Cost-Effectiveness Analysis: Are Known Unknowns Valuable?

BACKGROUND: Current practice in health technology assessment (HTA) of pharmaceuticals conducts cost-effectiveness analyses (CEAs) based on a static price or the estimated price at market launch. Recent publications suggest incorporating dynamic pricing. To test the feasibility and importance of including dynamic pricing, we compared the standard static approach to four dynamic scenarios by replicating US-based HTA evaluations with dynamic pricing inputs. METHODS: The four case examples included omalizumab (Xolair®) for the treatment of allergic asthma, elagolix (Orilissa®) for the treatment of endometriosis, ocrelizumab (Ocrevus®) for the treatment of primary progressive multiple sclerosis (PPMS), and dupilumab (Dupixent®) for the treatment of atopic dermatitis (AD). The primary outcome was the relative percentage change in incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) for two dynamic pricing scenarios versus static pricing. Secondary outcomes included the absolute difference in ICERs versus base-case and an assessment of decision uncertainty. RESULTS: Base-case ICERs were $327,000, $102,000, $700,000, and $102,000 for allergic asthma, endometriosis, PPMS, and AD, respectively. Across scenarios and case examples, the range of ICERs versus base-case varied from decreases of 56% to increases of 232%. The absolute difference in ICERs versus base-case ranged from decreases of $120,000 to increases of $758,000. Conclusions on cost effectiveness were altered in 2/16 scenarios across the four case examples. CONCLUSIONS: Given the decision context that US payers face, with prices varying over time, findings suggest further research to reduce uncertainty around price trajectories, as well as conducting or updating multiple assessments over the lifecycle of pharmaceutical products.

Can we predict trial failure among older adult-specific clinical trials using trial-level factors?

INTRODUCTION: Conducting older adult-specific clinical trials can help overcome the lack of clinical evidence for older adults due to their underrepresentation in clinical trials. Understanding factors contributing to the successful completion of such trials can help trial sponsors and researchers prioritize studies and optimize study design. We aimed to develop a model that predicts trial failure among older adult-specific cancer clinical trials using trial-level factors. MATERIALS AND METHODS: We identified phase 2-4 interventional cancer clinical trials that ended between 2008 and 2019 and had the minimum age limit of 60 years old or older using Aggregate Analysis of ClinicalTrials.gov data. We defined trial failure as closed early for reasons other than interim results or toxicity or completed with a sample of <85% of the targeted size. Candidate trial-level predictors were identified from a literature review. We evaluated eight types of machine learning algorithms to find the best model. Model fitting and testing were performed using 5-fold nested cross-validation. We evaluated the model performance using the area under receiver operating characteristic curve (AUROC). RESULTS: Of 209 older adult-specific clinical trials, 87 were failed trials per the definition of trial failure. The model with the highest AUROC in the validation set was the least absolute shrinkage and selection operator (AUROC in the test set = 0.70; 95% confidence interval [CI]: 0.53, 0.86). Trial-level factors included in the best model were the study sponsor, the number of participating centers, the number of modalities, the level of restriction on performance score, study location, the number of arms, life expectancy restriction, and the number of target size. Among these factors, the number of centers (odds ratio [OR] = 0.83, 95% CI: 0.71, 0.94), study being in non-US only vs. US only (OR = 0.32, 95% CI: 0.12, 0.82), and life expectancy restriction (OR = 2.17, 95% CI: 1.04, 4.73) were significantly associated with the trial failure. DISCUSSION: We identified trial-level factors predictive of trial failure among older adult-specific clinical trials and developed a prediction model that can help estimate the risk of failure before a study is conducted. The study findings could aid in the design and prioritization of future older adult-specific clinical trials.

How Much Does the US Public Value Equity in Health? A Systematic Review.

OBJECTIVES: This systematic review aims to summarize and qualitatively assess published evaluations on the US public's preferences for health equity and their willingness to trade-off efficiency for equity. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension guidelines, we searched MEDLINE and Embase for relevant peer-reviewed publications on this topic before February 2021. We included English-language articles that solicited US preferences regarding efficiency-equity trade-offs and prioritizing healthcare resources based on socioeconomic status, race, disability, or burden of disease. Quantitative and qualitative data captured were decided a priori and iteratively adapted as themes emerged. RESULTS: Fourteen studies were found over a 25-year span. Only 4 focused on resource allocation across social groups. Three distinct notions of fairness were studied: equal distribution of resources, priority to the worse-off, and equal health achieved. We found modest support for equal distribution of resources and willingness to sacrifice efficiency for equity in the United States. Prioritizing the underserved was relatively less studied and received less support and was more preferred when resources were scarce, when allocating resources between social groups, or when participants were informed about the fundamental origins of health inequities. Equal health was the least studied, but received nontrivial support. CONCLUSIONS: The existing literature evaluating the US public's understanding and preferences toward equity was severely limited by the lack of rigorous quantitative studies and heterogeneous attribute selection and fairness definitions. High-quality studies that clearly define fairness, focus on social groups, and apply rigorous methods to quantify equity preferences are needed to integrate the public's value on equity into healthcare decisions.

Does Clinical Evidence of Heterogeneity Impact Treatment Selection? A Case Study of Abiraterone for Metastatic Prostate Cancer.

BACKGROUND: Two pivotal randomized controlled trials (RCTs) demonstrate that abiraterone acetate + prednisone (AAP) combined with androgen deprivation therapy (ADT) significantly extends the survival of men with metastatic hormone-sensitive prostate cancer (mHSPC) compared with ADT alone. Their subgroup analyses indicate that the survival benefit is significant for younger men but not older men. We aimed to assess whether publication of the RCTs was associated with differential real-world AAP utilization by age groups. METHODS: Using TriNetX electronic medical records data collected from 43 healthcare organizations across the United States, we performed a difference-in-differences event study among men with newly diagnosed mHSPC observed from June 2014 to June 2019. Eligible subjects were identified based on a comprehensive published algorithm. We analyzed the change in utilization rate of AAP before versus after publication of the RCTs among men aged <70 years versus ≥70 years, adjusting for demographic factors and clinical conditions. RESULTS: Our study included 6,888 men with newly diagnosed mHSPC with 12,738 observations, of whom 46% were aged <70 years. The prepublication trends of AAP utilization were similar between the age groups, whereas publication of the RCTs was associated with a 3.5% higher adjusted uptake rate of AAP among younger men (95% CI, 1.2%-5.8%) relative to older men. This estimate reflects an uptake rate nearly 3 times higher than would have been expected had younger men followed the same utilization trends as older men. The estimates remained consistent throughout the postpublication period. CONCLUSIONS: Our study suggests that publication of the RCTs was associated with faster uptake of AAP among younger versus older men with newly diagnosed mHSPC, despite the absence of clinical guidance for differential treatment selection. This finding highlights the importance of confirmatory studies among older men, considering the uncertainties of subgroup analyses in RCTs.

Comparative effectiveness of larotrectinib versus entrectinib for the treatment of metastatic NTRK gene fusion cancers.

Aim: To extrapolate clinical trial results to estimate and compare expected progression-free and overall life years (LYs) and quality-adjusted LYs (QALYs) for larotrectinib and entrectinib in patients with colorectal cancer (CRC), soft tissue sarcoma (STS) and brain metastases prior to treatment with larotrectinib or entrectinib. Methods: A naive direct comparison of larotrectinib versus entrectinib was made using partitioned survival modeling methods from clinical trial data. Results: Larotrectinib resulted in an additional 1.58 LYs (1.17 QALYs), 5.81 LYs (2.02 QALYs) and 1.01 LYs in CRC, STS and baseline brain metastases, respectively, compared with entrectinib. Conclusion: Larotrectinib provided life expectancy and QALY gains compared with entrectinib. Additional studies will be beneficial as more patients are treated and survival data develop to better inform comparative effectiveness results.

The potential long-term comparative effectiveness of larotrectinib vs standard of care for treatment of metastatic TRK fusion thyroid cancer, colorectal cancer, and soft tissue sarcoma.

BACKGROUND: Larotrectinib is approved for patients with metastatic TRK fusion cancers, including differentiated thyroid (DTC), colorectal cancer (CRC), and soft tissue sarcoma (STS). Given the basket clinical trial design of larotrectinib, direct comparisons against standard of care in each of the mentioned cancers have not been assessed. Also, owing to the limited duration of follow-up in clinical trials, long-term outcomes for treatments are generally not known or estimated. OBJECTIVE: To compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for patients with metastatic DTC, CRC, and STS who are eligible to receive larotrectinib against patients with unknown NTRK gene fusion status receiving standard-of-care therapy. METHODS: We developed a partitioned survival model to estimate the long-term comparative effectiveness of larotrectinib and standard of care for 3 tumor types. Larotrectinib survival data, assessed by independent review committee, were derived from an updated July 2020 analysis of 19, 8, and 23 adult patients (aged ≥ 18 years) with metastatic TRK fusion DTC, CRC, and STS, respectively. The DTC survival data also included 2 patients aged less than 18 years for a total of 21 patients. Survival estimates for standard of care were derived from published clinical trials. Progressionfree and overall survival for all treatments were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Lognormal) fit to the available data. The final exponential form was selected based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the preprogression and postprogression health states by utility weights derived from publicly available literature. RESULTS: Patients receiving larotrectinib experienced more LYs and QALYs compared with those receiving standard-of-care treatments across all 3 assessed cancer types. In DTC, patients receiving larotrectinib had 7.15-8.26 additional LYs (5.87-6.12 QALYs); in CRC, patients receiving larotrectinib had 1.26-1.27 additional LYs (1.00 QALYs); and in STS, patients receiving larotrectinib had 5.56 additional LYs (1.99 QALYs). CONCLUSIONS: Compared with standard of care in metastatic TRK wild-type cancers, larotrectinib is estimated to result in improved LY and QALY outcomes based on parametric extrapolations of intrial survival data. Because patient-level data were unavailable for adjusted analyses, a cross-trial comparison was performed. Given the limitations of this analytic approach and the small sample size for larotrectinib in trials, future studies should reassess the comparative effectiveness of larotrectinib vs standard of care as treated patients accrue and long-term survival data mature. DISCLOSURES: K. Suh, J. Carlson, and S. Sullivan report consulting fees from Bayer US LLC. F. Xia and T. Williamson are employees of Bayer US LLC. This study was funded by Bayer US LLC. The sponsor had no role in the design of the study and did not have any role in the execution, analyses, interpretation of the data, or decision to submit results.

Assessing Payers' Preferences for Real-World Evidence in the United States: A Discrete Choice Experiment.

OBJECTIVES: To rank the US payers' preferences for attributes of real-world evidence (RWE) studies in the context of chronic disease and to quantify trade-offs among them. METHODS: We conducted a discrete choice experiment in which 180 employees from payer organizations were tasked to choose between 2 RWE studies assuming they were assessing evidence to inform formulary decisions for chronic disease treatment. Each RWE study was characterized by 7 attributes with 3 levels each: very informative, moderately informative, and not measured. We used a D-optimal main-effects design. Survey data were fitted to a conditional logit model to obtain a relative measure of the ranking of importance for each attribute. RESULTS: Clinical outcomes were the most preferred attribute. It was 4.68 times as important as productivity outcomes-the least preferred attribute. It was followed by health-related quality of life (2.78), methodologic rigor (2.09), resource utilization (1.71), and external validity (1.56). CONCLUSIONS: This study provides a quantification of the value payers place on key RWE attributes. Across attributes, payers have higher preferences for clinical and health-related quality of life outcomes than the other attributes. Between attributes' levels, payers prefer high levels of information in clinical outcomes and methodologic rigor but are indifferent in other attributes. Our results bridge the gap between the information that payers seek and the attributes that RWE studies prioritize and effectively guide future research design.

Key learnings from Institute for Clinical and Economic Review's real-world evidence reassessment pilot.

Health technology assessment (HTA) agencies are considering adopting a lifecycle approach to assessments to address uncertainties in the evidence base at launch and to revisit the clinical and economic value of therapies in a dynamic clinical landscape. For reassessments of therapies post launch, HTA agencies are looking to real-world evidence (RWE) to enhance the clinical and economic evidence base, though challenges and concerns in using RWE in decision-making exists. Stakeholders are embarking on demonstration projects to address the challenges and concerns and to further define when and how RWE can be used in HTA decision making. The Institute for Clinical and Economic Review piloted a 24-month observational RWE reassessment. Key learnings from this pilot include identifying the benefits and challenges with using RWE in reassessments and considerations on prioritizing and selecting topics relevant for RWE updates.

Diagnosis and management of TRK fusion cancer.

The tropomyosin receptor kinase (TRK) family of proteins is encoded by neurotrophic tyrosine receptor kinase (NTRK) genes and has a role in the development and normal functioning of the nervous system. NTRK gene fusions have been identified as oncogenic drivers in a wide range of tumors in both adult and pediatric patients. There has recently been a paradigm shift in cancer treatment toward biomarker-based targeted therapies, as an increasing number of actionable targets are being identified across different tumors and/or tumor histologies. These targeted agents offer greater comparative effectiveness and safety vs historical nontargeted standard therapies. The development of drugs that specifically target oncogenic drivers of cancer has led to the emergence of screening technologies to identify the patients most likely to benefit from targeted therapy. This review describes the role of NTRK gene fusions in cancer and outlines the epidemiology of NTRK gene fusions, the therapeutic benefits of targeting TRK fusions with small molecule inhibitors, and recommendations for NTRK gene fusion testing in adult and pediatric patients with cancer, in order to guide treatment decisions.