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.

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.

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.

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.

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.

Cost-effectiveness analysis of low-dose direct oral anticoagulant (DOAC) for the prevention of cancer-associated thrombosis in the United States.

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated that low-dose direct oral anticoagulants (DOACs), including rivaroxaban and apixaban, may help reduce the incidence of cancer-associated venous thromboembolism (VTE). METHODS: A cost-utility analysis was performed from the health sector perspective using a Markov state-transition model in patients with cancer who are at intermediate-to-high risk for VTE. Transition probability, relative risk, cost, and utility inputs were obtained from a meta-analysis of the RCTs and relevant epidemiology studies. Differences in cost, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) per patient were calculated over a lifetime horizon. One-way, probabilistic, and scenario sensitivity analyses were conducted. RESULTS: In patients with cancer at intermediate-to-high risk for VTE, treatment with low-dose DOAC thromboprophylaxis for 6 months, compared with placebo, was associated with 32 per 1000 fewer VTE and 11 per 1000 more major bleeding episodes over a lifetime. The incremental cost and QALY increases were $1445 and 0.12, respectively, with an ICER of $11,947 per QALY gained. Key drivers of ICER variations included the relative risks of VTE and bleeding as well as drug cost. This strategy was 94% cost effective at the threshold of $50,000 per QALY. The selection of patients with Khorana scores ≥3 yielded the greatest value, with an ICER of $5794 per QALY gained. CONCLUSIONS: Low-dose DOAC thromboprophylaxis for 6 months appears to be cost-effective in patients with cancer who are at intermediate-to-high risk for VTE. The implementation of this strategy in patients with Khorana scores ≥3 may lead to the highest cost-benefit ratio.

Alternative Approaches to Quality-Adjusted Life-Year Estimation Within Standard Cost-Effectiveness Models: Literature Review, Feasibility Assessment, and Impact Evaluation.

OBJECTIVES: The quality-adjusted life-year (QALY) has been long debated, but alternative estimation approaches have not been comprehensively evaluated. Our objective was to identify alternatives, characterize them by implementation feasibility, and evaluate the impact of implementing feasible options in cost-effectiveness models developed for the Institute for Clinical and Economic Review reports. METHODS: We conducted a literature review combining keywords relating to QALYs, methodology alternatives, and cost-effectiveness in PubMed, EconLit, Web of Science, and MEDLINE. Articles that discussed alternatives to the conventional QALY were included. Alternatives were characterized by type, data availability, calculation burden, and overall implementation feasibility. The subset of feasible alternatives, that is, sufficient data and methodology compatible with incorporation into common modeling approaches, were evaluated according to impact on incremental QALYs, incremental net monetary benefit (iNMB), intervention rankings, and proportion of interventions with a positive iNMB. RESULTS: We identified 28 articles discussing 9 alternatives. Feasible alternatives were using patient preference (PP) data; equity weighting according to baseline utility, fair innings, or proportional QALY shortfall; and the equal value of life-years-gained approach. All alternatives affected the incremental QALY and iNMB outcomes, rankings, and proportion of interventions with a positive iNMB. The PP alternative had the largest and most consistent impact. The PP impact on the proportion of interventions with a positive iNMB, was in the negative direction. CONCLUSIONS: Our work is the first comprehensive evaluation of proposed alternatives to the conventional QALY. We found robust literature but few options that were feasible to be implemented in current healthcare decision-making processes.

Are There Different Evidence Thresholds for Genomic Versus Clinical Precision Medicine? A Value of Information-Based Framework Applied to Antiplatelet Drug Therapy.

BACKGROUND: The threshold of sufficient evidence for adoption of clinically- and genomically-guided precision medicine (PM) has been unclear. OBJECTIVE: To evaluate evidence thresholds for clinically guided PM versus genomically guided PM. METHODS: We develop an "evidence threshold criterion" (ETC), which is the time-weighted difference between expected value of perfect information and incremental net health benefit minus the cost of research, and use it as a measure of evidence threshold that is proportional to the upper bound of disutility to a risk-averse decision maker for adopting a new intervention under decision uncertainty. A larger (more negative) ETC value indicates that only decision makers with low risk aversion would adopt new intervention. We evaluated the ETC plus cost of research (ETCc), assuming the same cost of research for both interventions, over time for a pharmacogenomic (PGx) testing intervention and avoidance of a drug-drug interaction (aDDI) intervention for acute coronary syndrome patients indicated for antiplatelet therapy. We then examined how the ETC may explain incongruous decision making across different national decision-making bodies. RESULTS: The ETCc for PGx increased over time, whereas the ETCc for aDDI decreased to a negative value over time, indicating that decision makers with even low risk aversion will have doubts in adopting PGx, whereas decision makers who are highly risk-averse will continue to have doubts about adopting aDDI. National recommendation bodies appear to be consistent over time within their own decision making, but had different levels of risk aversion. CONCLUSION: The ETC may be a useful metric for assessing policy makers' risk preferences and, in particular, understanding differences in policy recommendations for genomic versus clinical PM.

Defining and Managing High-Priced Cures: Healthcare Payers' Opinions.

OBJECTIVES: Recent regulatory approvals of potentially curative but high-cost treatments have made these therapies a focus of health policy discussions. Cures present new challenges to healthcare payers because they have high upfront costs but have life-long health benefits. The objectives of this study are to understand how healthcare payers define and manage cures. We investigated payers' views on key features of curative treatments and the affordability and value challenges they present. METHODS: We conducted semistructured interviews in 2016 with key informants in US payer organizations. Interviewees were directly involved in coverage determination for highly effective and curative therapies. RESULTS: We contacted 24 individuals and 18 participated. When asked what aspects of cures were important for coverage determination, an equal percentage of respondents (61% each) mentioned clinical and economic factors. In defining a cure, half of respondents included an economic element such as no downstream costs associated with the disease. When asked about challenges, 72% of respondents mentioned uncertainty regarding long-term outcomes and 56% mentioned membership churn and competition. CONCLUSIONS: Payers expressed a novel definition of a cure-which we call a "healthcare cost cure"-that captures both the clinical and economic consequences of treatment. This definition may be more pertinent in fragmentary financing systems that unevenly distribute cure costs and benefits across payers. Overall findings indicate that decision makers desire evidence to ensure that the long-term real-world consequences of covering cures match the expected benefits. Future policies need to balance upfront acquisition costs with downstream financial benefits.

The Cost-Effectiveness of Financial Incentives for Viral Suppression: HPTN 065 Study.

OBJECTIVE: To evaluate the cost-effectiveness of financial incentives for human immunodeficiency virus (HIV) viral suppression compared to standard of care. STUDY DESIGN: Mathematical model of 2-year intervention offering financial incentives ($70 quarterly) for viral suppression (<400 copies/ml3) based on the HPTN 065 clinical trial with HIV patients in the Bronx, NY and Washington, D.C. METHODS: A disease progression model with HIV transmission risk equations was developed following guidelines from the Second Panel on Cost-Effectiveness in Health and Medicine. We used health care sector and societal perspectives, 3% discount rate, and lifetime horizon. Data sources included trial data (baseline N = 16,208 patients), CDC HIV Surveillance data, and published literature. Outcomes were costs (2017 USD), quality-adjusted life years (QALYs), HIV infections prevented, and incremental cost-effectiveness ratio (ICER). RESULTS: Financial incentives for viral suppression were estimated to be cost-saving from a societal perspective and cost-effective ($49,877/QALY) from a health care sector perspective. Compared to the standard of care, financial incentives gain 0.06 QALYs and lower discounted lifetime costs by $4210 per patient. The model estimates that incentivized patients transmit 9% fewer infections than the standard-of-care patients. In the sensitivity analysis, ICER 95% credible intervals ranged from cost-saving to $501,610/QALY with 72% of simulations being cost-effective using a $150,000/QALY threshold. Modeling results are limited by uncertainty in efficacy from the clinical trial. CONCLUSIONS: Financial incentives, as used in HTPN 065, are estimated to improve quality and length of life, reduce HIV transmissions, and save money from a societal perspective. Financial incentives offer a promising option for enhancing the benefits of medication in the United States.

Cost-Effectiveness of a Biopsy-Based 8-Protein Prostate Cancer Prognostic Assay to Optimize Treatment Decision Making in Gleason 3 + 3 and 3 + 4 Early Stage Prostate Cancer.

BACKGROUND: Many patients with Gleason 3 + 3 and 3 + 4 early stage prostate cancer receive invasive treatment but likely derive little or no benefit. A novel 8-protein prognostic assay generates a risk score at time of biopsy that is predictive of prostate cancer aggressiveness and can inform treatment decisions. The objective of this study was to evaluate the cost-effectiveness of using the assay to inform treatment decisions compared with usual care. PATIENTS AND METHODS: We developed a simulation model to estimate quality-adjusted life-year (QALY) and cost outcomes for the 8-protein assay and usual care strategies. Risk classification outcomes, treatment distributions, costs, health state utilities, and mortality rates were derived from the assay's validation study and the peer-reviewed literature. Outcomes included incremental QALYs, costs, and cost-effectiveness ratios. We conducted one-way and probabilistic sensitivity analyses to evaluate the most influential inputs and to explore joint uncertainty in outcomes, respectively. RESULTS: The 8-protein assay strategy resulted in 0.04 more QALY and $700 less in costs compared with usual care (and thus was "dominant"). The cost-effectiveness of the assay strategy was most sensitive to the assay cost, the active surveillance health state utility, and the proportion of low-risk patients receiving active surveillance (vs. treatment) in usual care. In the probabilistic sensitivity analyses, the assay strategy decreased cost and increased QALYs in 86.9% and 58.3% of simulations, respectively. CONCLUSION: Assuming that ongoing prospective studies support the results of retrospective validation studies, the 8-protein prognostic assay strategy for prostate cancer is likely to be a cost-effective alternative to usual guideline-based care in biopsy Gleason 3 + 3 and 3 + 4 early stage prostate cancer.

Economic evaluation of tocilizumab monotherapy compared to adalimumab monotherapy in the treatment of severe active rheumatoid arthritis.

OBJECTIVES: To estimate the cost-effectiveness of tocilizumab (TCZ) monotherapy (Mono) versus adalimumab (ADA) Mono from the US payer perspective in patients with rheumatoid arthritis for whom methotrexate is inappropriate. METHODS: We compared TCZ Mono (8 mg/kg monthly) with ADA Mono (40 mg every other week), using efficacy results from a head-to-head study, ADalimumab ACTemrA (ADACTA). We calculated the incremental cost per responder (achievement of American College of Rheumatology [ACR] 20% improvement criteria, ACR 50% improvement criteria, ACR 70% improvement criteria, or low disease activity score) for TCZ versus ADA at 6 months. A patient-level simulation was used to estimate the lifetime incremental cost per quality-adjusted life-year (QALY) of initiating treatment with TCZ Mono versus ADA Mono. Both drugs are followed by an etanercept-certolizumab-palliative care sequence. Nonresponders discontinue at 6 months; responders experience a constant probability of discontinuation. Discontinuers move to the next treatment. ACR responses produce changes in the Health Assessment Questionnaire (HAQ) score. We mapped the HAQ score to utility to estimate QALYs. Costs include those related to hospitalization and those related to treatment (drug acquisition, administration, and monitoring). Probabilistic and one-way sensitivity analyses were conducted, along with several scenario analyses. RESULTS: Compared with ADA, TCZ was more effective, with an estimated 6-month incremental cost ranging from $6,570 per additional low disease activity score achiever to $14,265 per additional ACR 70% improvement criteria responder. The lifetime incremental cost-effectiveness ratio was $36,944/QALY. CONCLUSIONS: TCZ Mono is projected to be cost-effective compared with ADA Mono in patients with severe rheumatoid arthritis for whom methotrexate is not appropriate, from a US payer perspective.

Cost-effectiveness of a 14-gene risk score assay to target adjuvant chemotherapy in early stage non-squamous non-small cell lung cancer.

Life Technologies has developed a 14-gene molecular assay that provides information about the risk of death in early stage non-squamous non-small cell lung cancer patients after surgery. The assay can be used to identify patients at highest risk of mortality, informing subsequent treatments. The objective of this study was to evaluate the cost-effectiveness of this novel assay. Patients and Methods. We developed a Markov model to estimate life expectancy, quality-adjusted life years (QALYs), and costs for testing versus standard care. Risk-group classification was based on assay-validation studies, and chemotherapy uptake was based on pre- and post-testing recommendations from a study of 58 physicians. We evaluated three chemotherapy-benefit scenarios: moderately predictive (base case), nonpredictive (i.e., the same benefit for each risk group), and strongly predictive. We calculated the incremental cost-effectiveness ratio (ICER) and performed one-way and probabilistic sensitivity analyses. Results. In the base case, testing and standard-care strategies resulted in 6.81 and 6.66 life years, 3.76 and 3.68 QALYs, and $122,400 and $118,800 in costs, respectively. The ICER was $23,200 per QALY (stage I: $29,200 per QALY; stage II: $12,200 per QALY). The ICER ranged from "dominant" to $92,100 per QALY in the strongly predictive and nonpredictive scenarios. The model was most sensitive to the proportion of high-risk patients receiving chemotherapy and the high-risk hazard ratio. The 14-gene risk score assay strategy was cost-effective in 68% of simulations. Conclusion. Our results suggest that the 14-gene risk score assay may be a cost-effective alternative to standard guideline-based adjuvant chemotherapy decision making in early stage non-small cell lung cancer.

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.

The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis.

The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy (ACT) treatment decisions has been evaluated in many previous studies. However, it can be difficult to interpret the collective findings, which were conducted in diverse settings with limited sample sizes. We conducted a systematic review and meta-analysis to synthesize the results and provide insights about ODX utility. Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if patients had ER+, node -, early-stage breast cancer, reported use of ODX to inform actual ACT decisions. Information was summarized and pooled according to: (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients following the treatment suggested by the ODX RS. A total of 23 studies met inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 % intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 % low, 37.4 % intermediate, and 83.4 % high. Low RS patients were significantly more likely to follow the treatment suggested by ODX versus high RS patients RR: 1.07 (1.01­1.14) [corrected].The pooled results are consistent with most individual studies to date. The increased proportion of intermediate scores relative to original estimates may have implications for the clinical utility and cost impacts of testing. In addition, low versus high RS patients were significantly more likely to follow the ODX results, suggesting a tendency toward less aggressive treatment, despite a high ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use versus standard approaches, suggesting that additional studies are warranted.

Getting our priorities straight: a novel framework for stakeholder-informed prioritization of cancer genomics research.

PURPOSE: Prioritization of translational research on genomic tests is critically important given the rapid pace of innovation in genomics. The goal of this study was to evaluate a stakeholder-informed priority-setting framework in cancer genomics. METHODS: An external stakeholder advisory group including patients/consumers, payers, clinicians, and test developers used a modified Delphi approach to prioritize six candidate cancer genomic technologies during a 1-day meeting. Nine qualitative priority-setting criteria were considered. We used a directed, qualitative content-analysis approach to investigate the themes of the meeting discussion. RESULTS: Stakeholders primarily discussed six of the original nine criteria: clinical benefits, population health impacts, economic impacts, analytical and clinical validity, clinical trial implementation and feasibility, and market factors. Several new priority-setting criteria were identified from the workshop transcript, including "patient-reported outcomes," "clinical trial ethics," and "trial recruitment." The new criteria were incorporated with prespecified criteria to develop a novel priority-setting framework. CONCLUSION: This study highlights key criteria that stakeholders can consider when prioritizing comparative effectiveness research for cancer genomic applications. Applying an explicit priority-setting framework to inform investment in comparative effectiveness research can help to ensure that critical factors are weighed when deciding between many potential research questions and trial designs.

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.