Publications

No abstract available

Background: The overall burden of bronchiectasis on patients and healthcare systems has not been comprehensively described. Here, we present the findings of a systematic literature review that assessed the clinical and socioeconomic burden of bronchiectasis with subanalyses by aetiology (PROSPERO registration: CRD42023404162).

Methods: Embase, MEDLINE and the Cochrane Library were searched for publications relating to bronchiectasis disease burden (December 2017-December 2022). Journal articles and congress abstracts reporting on observational studies, randomised controlled trials and registry studies were included. Editorials, narrative reviews and systematic literature reviews were included to identify primary studies. PRISMA guidelines were followed.

Results: 1585 unique publications were identified, of which 587 full texts were screened and 149 were included. A further 189 citations were included from reference lists of editorials and reviews, resulting in 338 total publications. Commonly reported symptoms and complications included dyspnoea, cough, wheezing, sputum production, haemoptysis and exacerbations. Disease severity across several indices and increased mortality compared with the general population was reported. Bronchiectasis impacted quality of life across several patient-reported outcomes, with patients experiencing fatigue, anxiety and depression. Healthcare resource utilisation was considerable and substantial medical costs related to hospitalisations, treatments and emergency department and outpatient visits were accrued. Indirect costs included sick pay and lost income.

Conclusions: Bronchiectasis causes significant clinical and socioeconomic burden. Disease-modifying therapies that reduce symptoms, improve quality of life and reduce both healthcare resource utilisation and overall costs are needed. Further systematic analyses of specific aetiologies and paediatric disease may provide more insight into unmet therapeutic needs.

Background: The Centers for Medicare and Medicaid Services (CMS) recently announced the Maximum Fair Price for the first 10 Medicare Part D drugs selected for price negotiation. By February 2025, CMS should announce the list of Part D drugs to be negotiated with implementation of the negotiated prices in 2027.

Objective: To identify up to 15 Medicare Part D single-source drugs anticipated to be selected by CMS for price negotiation in 2025.

Methods: We followed selection criteria identified in the Inflation Reduction Act and CMS guidance to identify drugs. We projected 2023 Part D gross spending using 2020-2022 data reported by CMS and linear prediction models. We ranked products according to the projected spending figure and identified those not eligible for selection because of (1) number of years since approval, (2) availability of a biosimilar or generic version, (3) approval for a single orphan indication, (4) whole human blood or plasma-derived, or (5) eligibility for the small biotech exception.

Results: We identified 13 products likely subject to Medicare drug price negotiation, including 4 anticancer therapies, 3 noninsulin antidiabetic products, 2 inhalers, 1 antifibrotic therapy, 1 gastrointestinal agent, 1 enzyme replacement therapy, and 1 product indicated for dyskinesia. These 13 products each had projected annual gross Part D spending more than $1 billion. We identified 7 additional products with uncertainty to complete the list of 15, including an insulin, an antiviral, an antibiotic, an immunologic agent, an antidiabetic, and 2 cancer drugs. These products had projected gross Part D spending between $877 million and $1.399 billion. Twenty-two products with comparable levels of spending were deemed ineligible for selection because of availability of a generic or biosimilar version (10 products), insufficient years since approval (8 products), eligibility for the small biotech exception (3 products), and expected market discontinuation (1 product).

Conclusions: Our identification of products anticipated to be selected for negotiation in 2025 (with implementation of negotiated prices in 2027) will help inform manufacturers, payers, patients, and policymakers of the products that will likely see a decrease in Medicare drug prices as result of negotiation. We identified 22 products with levels of spending that are comparable with those anticipated to be selected for negotiation but are not eligible, primarily because of generic or biosimilar availability or insufficient time on market.

Background: The impacts of disease and treatment on a patient’s family members and informal caregivers are known as “family spillover effects.” Although many formal value frameworks call for the consideration of these effects, they are often not included in health technology assessments (HTAs) and cost-effectiveness analyses (CEAs). A formal evaluation of stakeholder perspectives may help address the disconnect for inclusion of family spillover effects observed in practice.

Objective: To develop stakeholder-driven recommendations for the measurement and use of family spillover effects in the United States and to identify research opportunities.

Methods: We first conducted a targeted literature review of US-based CEAs and HTA reports from the past 10 years to assess the current use of family spillover effects. We then used a purposeful sampling technique to conduct 25 qualitative interviews with outcomes researchers, patient advocates, health economists, and health policy and payer experts to gather perspectives on when and how family spillover effects should be considered in HTA processes. We conducted a thematic analysis of the interview transcripts to identify key themes and develop preliminary recommendations. Finally, we conducted an online workshop with 8 stakeholders to discuss, rate, and refine preliminary recommendations to develop final recommendations.

Results: A key theme identified in the stakeholder interviews was the role that data availability, analyst preferences, and prior precedence play in limiting the inclusion of spillover effects in HTAs. Additional themes included support for the inclusion of both qualitative and quantitative spillover effects and the need to capture broad and diverse impacts across populations. We developed 15 recommendations from the consensus building workshop addressing measurement, CEA modeling, and HTA processes. Key recommendations included (1) a transparent process for deciding when family spillover effects should be included, (2) measurement of direct and indirect costs with priority based on the magnitude of impact, (3) the use of validated measures, (4) the use of proxy information and expert elicitation when quality data are unavailable, and (5) the use of a modified impact inventory table for transparency of included effects. Research opportunities included patient involvement in family spillover effect research and HTAs, mapping algorithms and non-preference-based caregiver measures to generate utilities, and consensus best practices for modeling.

Conclusions: The inconsistent inclusion of family spillover effects in HTAs and CEAs remains a persistent challenge. The stakeholder-driven recommendations and research opportunities identified in this study may help improve the transparency, measurement, and use of family spillover effects in assessing the clinical and economic value of novel medical technologies.

To estimate the future annual prevalence of patients with peripheral T-cell lymphoma in the United States (US) and to predict the impact of frontline treatment on progression-free survival and overall survival in the year 2026 with and without the availability of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP), based on the ECHELON-2, 5-year follow-up results.

The Inflation Reduction Act allows Medicare to negotiate prices on a limited set of drugs that are not necessarily the highest priced or lowest value. Across payers, interest in lowering drug spending remains high. he National Academy of Medicine recommends basing drug prices on value, tying prices to the magnitude of benefit to preserve incentives for innovation.2 One way to do this is to set prices to achieve a certain cost-effectiveness threshold. Value-based prices (VBPs) are estimated by the Institute for Clinical and Economic Review (ICER), an independent nonprofit that reviews all available evidence of a drug’s clinical effectiveness vs its economic cost to estimate its value. Reports of ICER reviews are increasingly used by US payers in drug price negotiations. The objective of this study was to estimate how annual US drug spending would change if prices for drugs were set to the ICER-reported VBP.

Objectives: Value-based insurance design has been suggested as an effective approach to ensure access to highvalue medications in health insurance markets. Premera Blue Cross, a large regional health plan, implemented a value-based formulary (VBF) for pharmaceuticals in 2010 that explicitly used cost-effectiveness analysis to inform medication co-payments. This study assesses the impact of a VBF on adherence and patient and health plan expenditures on 3 chronic disease states: diabetes, hypertension, and hyperlipidemia. Study design: Interrupted time series design of employer-sponsored plans from 2006 to 2013. Beneficiaries exposed to the VBF formed the intervention group, and beneficiaries in similar plans without any changes in pharmacy benefits formed the control group. Methods: We measured medication expenditures from member, health plan, and member-plus-health plan (overall) perspectives and medication adherence as proportion of days covered. We conducted an exploratory analysis of medication utilization classifying medications according to whether co-payments moved up or down in the year following VBF implementation. Results: For the diabetes cohort, there was a statistically significant reduction in member and overall expenditures of $5 per member per month (PMPM) and $9 PMPM, respectively. For the hypertension cohort, there was a statistically significant reduction in member expenditures of $4 PMPM and an increase in health plan expenditures of $3 PMPM. There were no statistically significant effects on hyperlipidemia cohort expenditures or on medication adherence in any of the 3 disease cohorts. Exploratory analyses suggest that patients in the diabetes and hyperlipidemia cohorts were switching to higher-value medications.

Empirical estimates of price elasticities of demand (PED) for pharmaceuticals suggest that they are relatively price inelastic. However, in many settings, a medication and its substitutes and complements face simultaneous differential changes in prices that affect the observed “composite” PED. We exploit an implementation of a value-based formulary (VBF) that utilized drug-specific incremental cost-effectiveness ratios (ICERs) to inform drug copayments, resulting in increases in copayments for some medications and decreases in copayments for others. We first show theoretically that by changing the price of a medication and its substitute in opposite directions, VBF designs can leverage cross-price effects to increase the range of composite PEDs. We then empirically estimate PED and welfare effects using a consumer surplus approach. Overall PED was -0.16, similar to the RAND Health Insurance Experiment estimate. However, there was substantial dispersion of PED across the VBF copayment tiers ranging from -0.09 to -0.87 with a statistically significant trend aligned with the levels of value as reflected by the ICER estimates (p < 0.001). The net welfare increase was $147,000 for the cohort or $28 per member over the postpolicy year. Further experimentations of VBF designs with alternative cost-effectiveness thresholds, copayment levels and value definitions could be quite promising for improving welfare.

BACKGROUND: The National Academy of Medicine has called for value-based drug formularies to address health plan prescription drug spending while maintaining access to high-value medicines. Thirty employer-sponsored plans implemented a “Value-Based Formulary-essentials” (VBF-e) program that uses cost-effectiveness evidence to inform cost-sharing and coverage exclusion. OBJECTIVE: To evaluate if the VBF-e was associated with changes in medication use and patient out-of-pocket spending and health plan spending on prescription drugs and other health care. METHODS: This was a cohort study using a difference-in-differences design from 2015 through 2019 with 1 year of follow-up after VBF-e implementation at Premera Blue Cross, the largest nonprofit health plan in the Pacific Northwest. The VBF-e exposure group was composed of all individuals aged younger than 65 years and enrolled at least 12 months prior to their employer group’s VBF-e implementation date. The contemporaneous control group was composed of propensity score-matched individuals with the same inclusion criteria but their employer group that did not implement VBF-e. We prespecified the following outcomes: days of medication on hand overall and by VBF-e tier (high-value generic, brand, and specialty drugs were in tiers 1 to 3, respectively, and low-value drugs were in tier 4 or excluded from coverage); prescription drug spending; and other health care use (emergency department visits, hospital days, and outpatient visits). RESULTS: Comparing 12,111 exposed (mean age = 36.0; 49.8% female sex) participants with 24,222 control participants (mean age = 34.7; 49.6% female sex), VBF-e reduced use of low-value drugs by 0.3 days per member per month (PMPM) (95% CI = -0.5 to -0.1; 17% decrease) for tier 4 drugs and 0.4 days PMPM (95% CI = -0.5 to -0.4; 83% decrease) for excluded drugs. High-value specialty drug use increased by 0.1 days PMPM (95% CI = 0.0-0.1; 123% increase). Health plan spending decreased by $14 PMPM (95% CI = -26 to -4) and member out-of-pocket spending increased by $1 PMPM (95% CI = 1-2). Other health care use did not change significantly. CONCLUSIONS: An exclusion formulary informed by cost-effectiveness evidence reduced low-value drug use, increased high-value specialty drug use, reduced health plan spending, and increased member out-of-pocket spending without increasing acute care use. DISCLOSURES: This research was supported by a grant from the Patrick and Catherine Weldon Donaghue Medical Research Foundation’s Greater Value Portfolio Program. Study Registration Number: NCT04904055.

Objectives: By September 2024, the Centers for Medicare and Medicaid Services (CMS) will publicly report the negotiated prices (Maximum Fair Prices) for the first 10 drugs selected for price negotiation. We estimate initial price offers based on net prices, statutorily defined ceilings, and comparative effectiveness data for the 10 drugs and their therapeutic alternatives.

Methods: We utilized net prices and other price benchmarks for the 10 drugs and their therapeutic alternatives. We searched for data on comparative clinical effectiveness for the primary indications. We outlined a range of plausible initial price offers based on CMS guidance and our interpretation of regulatory intent.

Results: For ibrutinib and ustekinumab, statutorily defined ceiling prices will likely determine the initial price offers. The integration of net pricing and clinical evidence from comparator branded products will inform the initial price offers for apixaban, empagliflozin, etanercept, and insulin aspart. Rivaroxaban and sacubitril/valsartan have therapeutic alternatives that are generics; therefore, CMS may apply a discount to current net prices. To achieve savings in the negotiation of dapagliflozin and sitagliptin, CMS will have to leverage additional negotiation factors because statutory defined ceilings and net prices of therapeutic alternatives are similar or higher.

Conclusions: This analysis sheds light on important price benchmarks and clinical evidence factors for the determination of the initial price offers. Although we were not able to simulate the offer and counter-offer process, our findings provide a transparent and systematic way to produce initial offers that are consistent with CMS guidance.

Aim: We investigated the effect of shortening time between innovations with the accelerated approval (AA) pathway on patient outcomes for three solid tumors. Methods: This real-world analysis evaluated patients receiving sequential AA pathway-approved innovations after initial treatment with existing therapies in three solid tumor case studies. Outcomes attributable to AA were estimated and assumed approval occurred at the time of conversion to approval and extrapolated to the US population.

The prevalence of locally advanced/metastatic urothelial carcinoma (la/mUC) is not well characterized in Canada. This knowledge gap contributes to uncertainty of the population-level burden of disease associated with la/mUC, which has important implications for decision-makers and providers seeking to assess the opportunity of newly approved and emerging therapies reshaping the bladder cancer treatment landscape. We develop a simulation model to estimate contemporary, population-level burden of disease for la/mUC in Canada.

Intensified therapies convey a survival advantage over androgen deprivation therapy (ADT) alone in metastatic hormone sensitive prostate cancer (mHSPC) (Feyerabend 2018, Smith 2022). Real-world evidence has found intensified therapies are largely underutilized (Heath 2022). We sought to identify area- and patient-level factors associated with intensification of therapy among mHSPC patients treated in US health systems.

Objective: To quantify the annual budget impact if all US commercially insured type 1 diabetes mellitus patients on basal-bolus therapy (T1DMBBT), type 2 diabetes mellitus patients on basal-oral therapy (T2DMBOT), and type 2 diabetes mellitus patients on basal-bolus therapy (T2DMBBT) switched from insulin glargine (IGlar) to insulin degludec (IDeg).

Background: Cancer Care Delivery (CCD) research studies often require practice-level interventions that pose challenges in the clinical trial setting. The SWOG Cancer Research Network (SWOG) conducted S1415CD, one of the first pragmatic cluster-randomized CCD trials to be implemented through the National Cancer Institute (NCI) Community Oncology Program (NCORP), to compare outcomes of primary prophylactic colony stimulating factor (PP-CSF) use for an intervention of automated PP-CSF standing orders to usual care. The introduction of new methods for study implementation created challenges and opportunities for learning that can inform the design and approach of future CCD interventions. Methods: The order entry system intervention was administered at the site level; sites were affiliated NCORP practices that shared the same chemotherapy order system. 32 sites without existing guideline-based PP-CSF standing orders were randomized to the intervention (n = 24) or to usual care (n = 8). Sites assigned to the intervention participated in tailored training, phone calls and onboarding activities administered by research team staff and were provided with additional funding and external IT support to help them make protocol required changes to their order entry systems. Results: The average length of time for intervention sites to complete reconfiguration of their order sets following randomization was 7.2 months. 14 of 24 of intervention sites met their individual patient recruitment target of 99 patients enrolled per site. Conclusions: In this paper we share seven recommendations based on lessons learned from implementation of the S1415CD intervention at NCORP community oncology practices representing diverse geographies and patient populations across the U. S. It is our hope these recommendations can be used to guide future implementation of CCD interventions in both research and community settings.

Objectives Neratinib is an efficacious HER2-targeted agent for HER2+ ESBC, although its potential clinical benefits among the incident U.S. HR+ HER2+ high-risk ESBC patient population following use of T-DM1 or pertuzumab have not been quantified. Our objective was to estimate the long-term potential treatment benefits of neratinib in this target population.
Methods We developed a Markov model to quantify the prevention of local/regional and distant recurrences and deaths with the addition of neratinib (compared to no neratinib). We estimated population size from published sources, including population-based SEER and National Cancer Database electronic registries and clinical trials. High-risk was defined as HR+ patients who did not achieve a pathologic complete response (no pCR) with neoadjuvant therapy or were upstaged to stage IIB/III or higher following surgery for those only treated adjuvantly. Survival probabilities were extrapolated to a 10-year time horizon using parametric survival models derived from the ExteNET neratinib trial and clinical trials of T-DM1 (KATHERINE) and pertuzumab (APHINITY). The primary outcomes were recurrences (local/regional and distant) and breast cancer deaths prevented following neratinib treatment. Results We calculated 10,654 (no pCR: 9,845; upstaged adjuvant: 809) incident high-risk patients who would potentially have neratinib treatment in the U.S. in 2022. Initial model results estimated neratinib use could potentially prevent 872 (829; 43, respectively) recurrences, including 784 (749; 35, respectively) distant recurrences and 632 (604; 28, respectively) breast cancer deaths over a 10-year period. Probabilistic sensitivity analyses indicated a range of 547 to 872 distant recurrences and 511 to 656 breast cancer deaths prevented. Conclusions Our model results suggest that among patients with high-risk HR+ HER2+ ESBC treated with extended adjuvant neratinib post-T-DM1 or -pertuzumab, a substantial number of recurrences and deaths might be prevented.

Transformative cell and gene therapies have now launched worldwide, and many potentially curative cell and gene therapies are in development, offering the prospect of significant health gains for patients. Access to these therapies depend on decisions made by health technology assessment (HTA) and payer organizations. We sought to describe the emerging cell and gene therapies market access landscape by analyzing 17 US commercial payer medical policies, and HTA reports from five European countries and Canada. We found that some US health plans applied coverage restrictions more often than others (four plans applied restrictions in all decisions, while four plans applied restrictions in <30% of decisions). The European and Canadian HTA bodies recommend access to fewer therapies than US health plans, reflecting a more stringent approach in the context of limited evidence and high scientific uncertainty that is commonly associated with these treatments. Our findings suggest that patient access to approved cell and gene therapies is restricted in all regions studied, though the nature of these restrictions differs between US health plans and the European/Canada HTA recommendations. Payers, HTA groups, pharmaceutical companies, and other stakeholders should collaborate to more clearly define the "uncertainties" and develop market access policies that balance benefits of early access with ongoing data collection to close evidence gaps over time.

BACKGROUND: Nonadherence and nonpersistence to antidepressants in major depressive disorder (MDD) are common and associated with poor clinical and functional outcomes and increased health care resource utilization (HCRU) and costs. However, contemporary real-world evidence on the economic effect of antidepressant nonadherence and nonpersistence is limited. OBJECTIVE: To assess the effect of nonadherence and nonpersistence to antidepressants on HCRU and costs in adult patients with MDD enrolled in U.S. commercial and Medicare supplemental insurance plans. METHODS: This was a retrospective new-user cohort study using administrative claims data from the IBM MarketScan Commercial and Medicare Supplemental databases from January 1, 2010, to December 31, 2018. We identified adult patients with MDD aged ≥ 18 years who initiated antidepressant therapy for a new MDD episode between January 1, 2011, and December 31, 2017. Twelve-month total all-cause HCRU and costs (2019 U.S. dollars) were characterized for patients who were adherent/nonadherent and persistent/nonpersistent to antidepressants at 6 months. Adherence was defined as having proportion of days covered (PDC) ≥ 80%, and persistence was defined as having continuous antidepressant therapy without a ≥ 30-day gap. Multivariable negative binomial regression and 2-part models adjusted for baseline characteristics were used to estimate incidence rate ratios (IRRs) for HCRU and incremental costs of nonadherence and nonpersistence, respectively. RESULTS: A total of 224,645 patients with MDD (commercial: n = 209,422; Medicare supplemental: n = 15,223) met all study inclusion criteria. Approximately half of patients were nonadherent (commercial: 48%; Medicare supplemental: 50%) or nonpersistent (commercial: 49%; Medicare supplemental: 52%) to antidepressants at 6 months. After controlling for baseline characteristics, nonadherent patients experienced significantly more inpatient hospitalizations (commercial, adjusted IRR [95% CI]: 1.34 [1.29 to 1.39]; Medicare supplemental: 1.19 [1.12 to 1.28]) and emergency room (ER) visits (commercial, adjusted IRR [95% CI]: 1.43 [1.40 to 1.45]; Medicare supplemental: 1.28 [1.21 to 1.36]) compared with adherent patients. Similar results were observed in nonpersistent patients. Adjusted mean differences revealed that nonadherent and nonpersistent patients accumulated significantly higher medical costs (commercial: $568 [95% CI: $354 to $764] and $491 [$284 to $703]; Medicare supplemental: $1,621 [$314 to $2,774] and $1,764 [$451 to $2,925]), inpatient costs (commercial: $650 [$490 to $801] and $564 [$417 to $716]; Medicare supplemental: $1,546 [$705 to $2,308] and $1,567 [$778 to $2,331]), and ER costs (commercial: $130 [$115 to $143] and $129 [$115 to $142]; Medicare supplemental: $82 [$23 to $150] and $80 [$18 to $150]), and incurred significantly lower pharmacy costs (commercial: -$561 [-$601 to -$521] and -$576 [-$616 to -$540]; Medicare supplemental: -$510 [-$747 to -$227] and -$596 [-$830 to -$325]) compared with adherent and persistent patients, respectively. CONCLUSIONS: This study found more hospitalizations and ER use and higher total medical costs among patients who were nonadherent and nonpersistent to antidepressants at 6 months. Strategies that promote better adherence and persistence may lower HCRU and medical costs in patients with MDD. DISCLOSURES: This study was sponsored by Allergan, which was involved in the study design; data collection, analysis, and interpretation of data; and decision to present these results. Ta was supported by a training grant provided to the University of Washington by Allergan at the time this study was conducted. Tung and Gillard are employees of Allergan. Oliveri is an employee of Genesis Research. Sullivan and Devine have no financial disclosures. This study was presented as a poster at AMCP 2020 (Virtual Meeting), April 21-24, 2020.

Background: Approximately one-half of all heart failure (HF) consists of heart failure with preserved ejection fraction (HFpEF) or heart failure with mid-range ejection fraction (HFmrEF). Although several recent trials have investigated treatments for HFpEF/HFmrEF, there is limited insight on the long-term clinical trajectory of this population. Objectives: The purpose of this study was to model clinical outcomes in patients with symptomatic (NYHA functional class II-IV) HFpEF/HFmrEF over 10 years. Methods: We developed a Markov model with stable HF, HF hospitalization, and death states to follow a cohort of patients with HFpEF/HFmrEF treated with standard of care (SoC) recommended by the American Heart Association/American College of Cardiology/Heart Failure Society of America. Population characteristics and clinical event probabilities were derived from recent phase 3 HFpEF/HFmrEF trials. We used weighted averages for control and sodium-glucose cotransporter-2 inhibitor outcomes. SoC was informed by baseline treatments reported in clinical trials. Results: In a cohort of U.S. patients with HFpEF/HFmrEF treated with SoC, our model estimated 0.53 cumulative HF hospitalizations per patient over 10 years. Overall, 37% had at least 1 HF hospitalization, and 26% experienced cardiovascular death. The model estimated 6.1 years of life expectancy from age 72 and total cost of care over this time of $123,900. Conclusions: HFpEF/HFmrEF is associated with high rates of HF hospitalization and cardiovascular mortality based on contemporary clinical trials in this population. Furthermore, clinical trial results are likely to be more optimistic than real-world outcomes. Continuing to optimize care and treatment may reduce clinical burden and improve population health.
Keywords: HFmrEF; HFpEF; costs; heart failure; hospitalizations; mortality.

We sought to model the clinical outcomes in a cohort of patients with symptomatic (New York Heart Association [NYHA] class II-IV) HFpEF/HFmrEF treated with SoC over a lifetime horizon.

Recent federal drug price control proposals have included mechanisms to benchmark US prices to international prices. These international price referencing (IRP) proposals recommend that the US government develop an index based on prices paid by a group of higher-income countries and restrict US prices to a narrow range of the index. IRP is a policy tool used across the globe to control drug costs, particularly in markets in which health care resources are limited. If IRP is implemented in the United States, where the drug industry derives roughly 50% of global pharmaceutical sales, what impact might it have on innovation and access? In this brief commentary, we explore this question in the context of cell and gene therapies (CGTs) (evolving therapeutics that have high clinical potential as well as uncertainty and risk). Many CGTs are in development, and the world faces a challenge in providing access. Pressure to provide access to patients who would benefit may create greater global concerns about health equity and access. We conclude that an IRP policy in the United States might exacerbate access problems to promising CGTs and impact innovation and population health. Disclosures: Funding for this project was provided by Novartis Gene Therapies, Inc. Sean D Sullivan has received research support from and served as a consultant to Novartis Gene Therapies, Inc. Omar Dabbous is an employee of Novartis Gene Therapies, Inc., and owns stock and other equities. Louis P Garrison has received consulting fees from BioMarin, Inc., and Novartis Gene Therapies, Inc. Kiera D Sullivan has no conflicts to report. The opinions expressed in this commentary are solely those of the authors and not necessarily their institutions.

Background: To perform a systematic review/meta-analysis evaluating the efficacy and safety of anti-arrhythmic drugs (AADs) in the treatment of atrial fibrillation (AF). Methods: Database searches (accessed April 2009) were conducted to identify randomised controlled trials (RCTs). Comparators of interest included all AADs, rate/rhythm strategies or catheter ablation in comparison with AADs. Primary AADs of interest were restricted to Class IC (flecainide and propafenone) and Class III (amiodarone, dofetilide, dronedarone and sotalol). Data were analysed on an intention-to-treat basis and meta-analysis performed using the Peto odds ratio (OR)/fixed-effect model. Results: 113 publications met inclusion criteria. Of these, 74 publications considered an AAD of primary interest. The odds of AF recurrence were generally significantly lower with all active treatments versus non-active control. Dronedarone was the only AAD to show a (non-significant) trend towards reducing the odds of mortality with a narrow CI (OR 0.85 [0.66, 1.09]). Withdrawals due to adverse events (AEs), incidence of serious adverse events (SAEs) and treatment discontinuation were increased following active treatment compared with control, with few significant differences reported between active treatments. Data for other morbidity outcomes such as cardiovascular mortality, hospitalizations or persistence/compliance and health-related quality of life (HRQoL) were limited and meta-analyses were not possible for these outcomes. Conclusion: The current meta-analysis confirms the efficacy of AADs in preventing AF recurrence, although their use is associated with a greater incidence of AEs and treatment discontinuation. Further RCTs are required to establish the benefit of AADs in the management of both morbidity outcomes and HRQoL.

Biologic therapies play a critical role in modern medical practice but also present challenges for payers, patients, and other stakeholders because of their high cost. Biosimilars can mitigate the cost pressures of reference biologic therapy because they are typically priced at least 25% lower, providing a means to administer cutting-edge biologic therapy while also managing cost of care. In fact, the US health care system has saved an estimated $23.6 billion from use of biosimilars. However, the market is still in a nascent phase of development, and early cost-saving successes are not guaranteed to persist unless sustainable market conditions are established. To better understand the perspectives of stakeholders about opportunities and threats to the sustainability of the US biosimilar market, a multistakeholder roundtable discussion was convened in December of 2023 and included health care payers, providers, self-insured employers, a manufacturer, and a biosimilar research and advocacy organization. The objective of this commentary, authored by the roundtable participants, is to posit specific opportunities and threats that stakeholders should consider to better facilitate sustainable biosimilar market conditions in the United States. We highlight key points, including (1) biosimilar price volatility with large quarter-on-quarter declines for most products; (2) perverse economic incentives that encourage providers to use more expensive reference products because reimbursement dynamics make them more profitable; (3) complex rebate structures that create barriers to biosimilar access; and (4) ongoing changes to the legal and regulatory environment, including evidence requirements to gain “interchangeable” status. We conclude with an overview of potential policy solutions to address the sustainability opportunities and threats. The authors welcome the opportunity to advance this dialogue toward action and encourage additional stakeholders to join the effort. We are optimistic that, through informed decision-making and compromise, we can collectively achieve a robust and sustainable US biosimilars market that appropriately benefits all stakeholders.

No abstract available

Aims: To compare 12-month clinical effectiveness of insulin glargine 300 units/mL (Gla-300) versus first-generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla-100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla-300 or Gla-100/IDet) in a real-world setting. Methods: DELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla-300 (Gla-300 switchers) and were propensity score-matched (1:1) to patients who switched to Gla-100 or IDet (Gla-100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (<7% and <8%), and incidence and event rates of hypoglycaemia (all-hypoglycaemia and hypoglycaemia associated with an inpatient/emergency department [ED] contact). Results: HbA1c reductions were similar following switching to Gla-300 or Gla-100/IDet (-0.51% vs. -0.53%; p = .67), and patients showed similar attainment of HbA1c goals. Patients in both cohorts had comparable all-hypoglycaemia incidence and event rates. However, the Gla-300 switcher cohort had a significantly lower risk of inpatient/ED-associated hypoglycaemia (adjusted odds ratio: 0.73, 95% confidence interval: 0.60-0.89; p = .002) and experienced significantly fewer inpatient/ED-associated hypoglycaemic events (0.21 vs. 0.33 events per patient per year; p < .001). Conclusion: In patients with T2D at high risk of hypoglycaemia, switching to Gla-300 or Gla-100/IDet achieved similar HbA1c reductions and glycaemic goal attainment, but Gla-300 switchers had a significantly lower risk of hypoglycaemia associated with an inpatient/ED contact during 12 months after switching.

Aims: To compare clinical outcomes in patients with type 2 diabetes (T2D) switching from insulin glargine 100 units/mL (Gla-100) or insulin detemir (IDet) to insulin glargine 300 units/mL (Gla-300) or insulin degludec (IDeg). Materials and methods: We conducted a retrospective, observational study of electronic medical records for Gla-300/IDeg adult switchers (March 1, 2015 to January 31, 2017) with active records for 12-month baseline (glycated haemoglobin [HbA1c] used a 6-month baseline period) and 6-month follow-up periods. Gla-300 and IDeg switchers were propensity score-matched using baseline demographic and clinical characteristics. Outcomes were HbA1c change and goal attainment (among patients with HbA1c captured at follow-up), and hypoglycaemia with fixed follow-up (intention-to-treat [ITT]; 6 months) and variable follow-up (on-treatment [OT]; to discontinuation or 6 months). Results: Each matched cohort comprised 1592 patients. The mean decrease in HbA1c and HbA1c goal (<7.0% [53 mmol/mol] and <8.0% [64 mmol/mol]) attainment rates were similar for Gla-300 (n = 742) and IDeg (n = 727) switchers. Using fixed follow-up (ITT method), hypoglycaemia incidence decreased significantly from baseline with Gla-300 (all hypoglycaemia: 15.6% to 12.7%; P = .006; hypoglycaemia associated with inpatient/emergency department [ED] encounter: 5.3% to 3.5%; P = .007), but not with IDeg. After adjusting for baseline hypoglycaemia, no significant differences in hypoglycaemia incidence and event rate were found at follow-up (ITT) for Gla-300 vs IDeg. Using variable follow-up (OT), hypoglycaemia incidence was similar in both groups, but Gla-300 switchers had a lower inpatient/ED hypoglycaemia event rate at follow-up (adjusted rate ratio 0.56; P = .016). Conclusions: In a real-world setting, switching from Gla-100 or IDet to Gla-300 or IDeg was associated with similar improvements in glycaemic control and hypoglycaemia in adult patients with T2D.

The United States is a relatively free-pricing market for pharmaceutical manufacturers to set list prices at the product launch. Few drug price controls exist, and federal price negotiation as a policy has historically been politically untenable. After decades of debate on whether the federal government, specifically the Medicare program, should more actively manage drug prices, the US Congress passed legislation authorizing Medicare to directly negotiate prices with manufacturers. The purpose of this article is to describe elements and implementation of the price negotiation provisions and then comment on the potential impacts on payers, innovations, and the pharmaceutical industry. While impacting only a few drugs each year in the beginning, price negotiation in the Medicare program will have secondary and long-term effects in the US market and beyond. It is clear that in the United States, the Medicare market for drugs will no longer be a free-pricing environment in the industry.

This study aimed to estimate and compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for pediatric and young adult patients with primary CNS solid tumors or infantile fibrosarcoma eligible to receive larotrectinib (primary CNS / infantile fibrosarcoma) or entrectinib (primary CNS / extracranial solidtumors)

Background: Larotrectinib is approved for patients with advanced NTRK gene fusion-positive solid tumors. Prior studies demonstrated promising results with larotrectinib compared with other systemic therapy. However, comparisons to checkpoint inhibitors, such as nivolumab or pembrolizumab, have not been done.

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.

Identification and workup of pulmonary nodules (PNs) can be essential to early diagnosis and management of non-small cell lung cancer (NSCLC). Clinical management of PNs is often guided by physician judgement or a quantitative risk model coupled with threshold-based decision making. Most often the patient’s nodule risk category is low to moderate where further evaluation is required, and guidelines are unclear, leading to unnecessary invasive interventions. A blood-based integrated classifier (IC) rule-out test, Nodify XL2®, may be utilized to help reclassify PNs into a lower risk category and avoid unnecessary invasive interventions. This economic analysis aimed to estimate the budget impact of a blood-based IC test from a US Medicare payer perspective.

Identification and workup of pulmonary nodules (PNs) can be essential to early diagnosis and management of non-small cell lung cancer (NSCLC). Clinical management of PNs is often guided by physician judgement or a quantitative risk model coupled with threshold-based decision making. Most often the patient’s nodule risk category is low to moderate where further evaluation is required, and guidelines are unclear, leading to unnecessary invasive interventions. A blood-based integrated classifier (IC) rule-out test, Nodify XL2®, may be utilized to help reclassify PNs into a lower risk category and avoid unnecessary invasive interventions. This economic analysis aimed to estimate the budget impact of a blood-based IC test from a US commercial payer perspective.

An estimated 80% of pulmonary nodules (PNs) fall in a “low to moderate risk” category1 of lung cancer in which appropriateness of invasive procedure intervention is unclear. These PNs are frequently sent for invasive interventions only to be identified as benign. A blood-based integrated classifier (IC) can be utilized for PNs to reclassify nodules that are “likely benign” and avoid unnecessary interventions and complications. This study aimed to estimate the economic impact of a blood-based IC for PN risk assessment from a US Medicare payer perspective. Methods A budget impact model was developed to evaluate use of a blood-based IC test within a hypothetical 1 million-member US Medicare health plan over a 2-year time horizon. Blood-based IC test use within a Medicare payer system was compared to standard of care without the test. Model inputs included stage shifts in non-small cell lung cancer (NSCLC), procedures costs, and downstream costs. Results In a hypothetical Medicare health plan of 1 million members without the blood-based auto-antibody test, an estimated 1,701 patients would undergo invasive procedure to characterize their PN with approximately 1,102 identified as benign. An estimated $188,335,223 would be spent on nodule workup, invasive procedures, and cancer treatments. In the scenario with the blood-based IC test, it is estimated that there would be a 35.2% reduction in invasive procedures and an estimated savings of $3,506,824 over 2 years. The incremental cost per-member per-month (PMPM) is -$0.292. Conclusions The model results indicate that the use of a blood-based IC test for patients with pulmonary nodules would likely result in a minimal budget impact, or true cost savings, from a US Medicare health plan perspective. References: 1. Tanner NT, et al. Chest. 2015; 148(6): 1405 – 1414.

Identification and workup of pulmonary nodules (PNs) can be essential to early diagnosis and management of non-small cell lung cancer (NSCLC). Clinical management of PNs is often guided by physician judgement or a quantitative risk model coupled with threshold-based decision making. Most often the patient’s nodule risk category is low tomoderate where further evaluation is required, and guidelines are unclear. In these scenarios, a blood-based auto-antibody (AAb), test, Nodify CDT®, may be utilized to help up-classify the risk of malignancy to better inform management and treatment decisions. This economic analysis aimed to estimate the budget impact of a blood-based AAb test from a US Medicare payer perspective.

Identification and workup of pulmonary nodules (PNs) can be essential to early diagnosis and management of non-small cell lung cancer (NSCLC). Clinical management of PNs is often guided by physician judgement or a quantitative risk model coupled with threshold-based decision making. Most often the patient’s nodule risk category is low tomoderate where further evaluation is required, and guidelines are unclear. In these scenarios, a blood-based auto-antibody (AAb), test, Nodify CDT®, may be utilized to help up-classify the risk of malignancy to better inform management and treatment decisions. This economic analysis aimed to estimate the budget impact of a blood-based AAb test from a US commercial payer perspective.

Drug-specific clinical and health economic and outcomes research (HEOR) publications have amassed, but their effect on drug sales is largely unknown. We estimated the impact of publications on pharmaceutical sales in 3 markets (statins, rheumatoid arthritis, and asthma drugs) with varying generic competition. An event-study approach with fixed effects and difference-in-fixed-effects modeling was used to estimate the causal effects of drug-specific publications on subsequent quarter’s drug-specific sales and volume. High-impact clinical and HEOR publications have significant positive effects on sales (mediated through price) and volume in the statin market (high generic competition). High-impact clinical publications have a significant positive effect on sales (mediated through volume) in low-generic competition market (asthma). The effects of publications in the rheumatoid arthritis market (no generic competition) on sales were null. Manufacturers’ investment in clinical and HEOR publications needs to be strategic and should be anticipated and complemented by public investments in such studies.

Background: Colorectal cancer (CRC) is the second most common cause of cancer death globally. Recent clinical trials suggest an emerging role for HER2 as a potential clinically relevant biomarker in CRC. Testing for HER2 in CRC is not standard practice; consequently, the prevalence of HER2 positivity (HER2+) in patients with CRC remains uncertain.

Human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is a biologically aggressive form of breast cancer (BC) associated with substantial disease burden and poor survival, although the prognosis for patients has improved significantly since the introduction of HER2-directed therapies. Nationally representative cancer registries in the United States (US) currently do not capture disease recurrence, so the prevalence of HER2+ MBC is unknown. We develop a model to estimate current prevalence of HER2+ MBC in the US and predict future prevalence by incorporating the potential impact of emerging therapies.

Background: Urothelial carcinoma (UC) is a common malignancy with significant associated mortality. Recent clinical trials suggest an emerging role for HER2-targeted therapy. Testing for HER2 expression in UC is not part of current routine clinical practice. In consequence, the prevalence of HER2 expression in UC is not well defined.

Background: Nirmatrelvir/ritonavir (NMV/r) is indicated for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19. NMV/r has also been authorized for emergency use by the US Food and Drug Administration for the treatment of mild-to-moderate COVID-19 in pediatric patients (aged 226512 years and weighing at least 40 kg) who are at high risk for progression to severe COVID-19. Understanding the budget impact of introducing NMV/r for the treatment of adults with COVID-19 is of key interest to US payers.

Objective: To estimate the annual budget impact of introducing NMV/r in a US commercial health plan setting in the current Omicron COVID-19 era.

Methods: A budget impact model was developed to assess the impact of NMV/r on health care costs in a hypothetical 1-million-member commercial health insurance plan over a 1-year period in the US population; clinical and cost inputs were derived from published literature with a focus on studies in the recent COVID-19 era that included vaccinated population and predominance of the Omicron variant. In the base-case analysis, it was assumed the only effect of NMV/r was a reduction in incidence (not severity) of hospitalization or death; its potential effect on post-COVID conditions was assessed in a scenario analysis. Outcomes included the number of hospitalizations, total cost, per patient per year (PPPY) costs, and per member per month (PMPM) costs. Sensitivity and scenario analyses were conducted to assess uncertainty around key model inputs.

Results: An estimated 29,999 adults were eligible and sought treatment with oral antiviral for COVID-19 over 1 year. The availability of NMV/r was estimated to reduce the number of hospitalizations by 647 with a total budget impact of $2,733,745, $91 PPPY, and $0.23 PMPM. NMV/r was cost saving when including post-COVID conditions with a -$1,510,780 total budget impact, a PPPY cost of -$50, and a PMPM cost of -$0.13. Sensitivity analyses indicated results were most sensitive to the risk of hospitalization under supportive care, risk of hospitalization with NMV/r treatment and cost of NMV/r.

Conclusions: Treatment with NMV/r in the current COVID-19 era is estimated to result in substantial cost offsets because of reductions in hospitalization and modest budget impact to potential overall cost savings.

Objective: To describe headache-related health resource usage in chronic and episodic migraine across six countries.

In the rapidly evolving landscape of biotechnologies, cell and gene therapies are being developed and adopted at an unprecedented pace. However, their access and adoption remain limited, particularly in low- and middle-income countries (LMICs). This study aims to address this critical gap by exploring the potential of applying a hub and spoke model for cell and gene therapy delivery in LMICs. We establish the identity and roles of relevant stakeholders, propose a hub and spoke model for cell and gene therapy delivery, and simulate its application in Brazil and the Middle East and North Africa. The development and simulation of this model were informed by a comprehensive review of academic articles, grey literature, relevant websites, and publicly available data sets. The proposed hub and spoke model is expected to expand availability of and access to cell and gene therapy in LMICs and presents a comprehensive framework for the roles of core stakeholders, laying the groundwork for more equitable access to these lifesaving therapies. More research is needed to explore the practical adoption and implications of this model.

Background: During the COVID-19 pandemic, Test-Trace-Isolate (TTI) programs have been recommended as a risk mitigation strategy. However, many governments have hesitated to implement them due to their costs. This study aims to estimate the cost-effectiveness of implementing a national TTI program to reduce the number of severe and fatal cases of COVID-19 in Colombia. Methods: We developed a Markov simulation model of COVID-19 infection combined with a Susceptible-Infected-Recovered structure. We estimated the incremental cost-effectiveness of a comprehensive TTI strategy compared to no intervention over a one-year horizon, from both the health system and the societal perspective. Hospitalization and mortality rates were retrieved from Colombian surveillance data. We included program costs of TTI intervention, health services utilization, PCR diagnosis test, productivity loss, and government social program costs. We used the number of deaths and quality-adjusted life years (QALYs) as health outcomes. Sensitivity analyses were performed. Findings: Compared with no intervention, the TTI strategy reduces COVID-19 mortality by 67%. In addition, the program saves an average of $1,045 and $850 per case when observed from the social and the health system perspective, respectively. These savings are equivalent to two times the current health expenditures in Colombia per year. Interpretation: The TTI program is a highly cost-effective public health intervention to reduce the burden of COVID-19 in Colombia. TTI programs depend on their successful and speedy implementation. Funding: This study was supported by the Colombian Ministry of Health through award number PUJ-04519-20 received by EPQ AVO and SDS declined to receive any funding support for this study. The contents are the responsibility of all the individual authors.

Background: Multiple myeloma is a progressive cancer for which there is no cure. Despite treatment, almost all patients eventually experience periods of disease relapse and remission. With the increasing use of novel therapies, including bortezomib, lenalidomide, carfilzomib, pomalidomide, and panobinostat, benchmarks for assessing the value of these therapies in treating patients with relapsed or refractory multiple myeloma (RRMM) are needed for physicians and payers alike.

Objectives: To develop a model framework and to calculate an annual estimate of the total costs per patient for the treatment of patients with RRMM using 7 common treatment regimens, including bortezomib plus dexamethasone; panobinostat, bortezomib, and dexamethasone; lenalidomide plus dexamethasone; lenalidomide, bortezomib, and dexamethasone; carfilzomib; carfilzomib, lenalidomide, and dexamethasone; and pomalidomide plus dexamethasone. Methods: The expenditures for drugs and their administration, for prophylaxis and adverse event monitoring, and for the treatment of grade 3 or 4 adverse events were included in the calculations of the total pharmacy and medical costs. The drug costs were based on published pricing and labeled dosing schedules; the adverse event prophylaxis and monitoring costs were obtained from peer-reviewed publications; and the adverse event incidence rates were obtained from each regimen’s prescribing information and from clinical trials. All the costs were summed over the duration of therapy for which the drugs were administered and were calculated separately for commercial and Medicare plans. The duration of therapy for each regimen was the time for which a patient had to be receiving the regimen to obtain 12 months of progression-free survival based on the duration-of-therapy to progression-free survival ratio observed from published clinical trials and/or the drug’s labeling. Results: The pharmacy costs were highest for pomalidomide plus dexamethasone, whereas the medical costs were highest for the combination of carfilzomib, lenalidomide, and dexamethasone. The total cost associated with available treatments for RRMM was highest for regimens that included lenalidomide (approximate range, $126,000-$256,000). Only bortezomib plus dexamethasone and the combination of panobinostat, bortezomib, and dexamethasone had total costs that were lower than $125,000 per patient. Conclusion: This study represents the first model developed to comprehensively estimate the costs of managing RRMM with all currently approved and guideline-recommended regimens in the United States. As such, it provides the framework and basis for further budget impact analyses and for cost-effectiveness comparisons with these regimens.

OnabotulinumtoxinA is indicated for headache prophylaxis in patients with chronic migraine, but its effect on healthcare resource use is unknown. We analyzed data from an open-label study of 230 chronic migraine patients refractory to ≥2 oral prophylactics who presented to a headache specialty clinic and who were treated with two cycles of onabotulinumtoxinA. Frequency and cost of migraine-related healthcare resource use, including visits to emergency departments, urgent care, or hospitalization, were compared for the 6 months before and after initial treatment. Costs were based on publicly available sources.

Background: Larotrectinib and entrectinib are FDA-approved therapies for patients with non-small cell lung cancer (NSCLC) with neurotrophic receptor tyrosine kinase gene fusion (TRK fusion-positive) whose cancer has metastasized and progressed. Early evidence indicates that these targeted therapies may offer dramatic survival benefits versus traditional cytotoxic regimens, but it remains uncertain how larotrectinib and entrectinib compare with each other.

Objective: To simulate and compare expected life-years and quality-adjusted life-years (QALYs) for both TRK inhibitors.

Methods: We developed a partitioned survival model to project the long-term comparative effectiveness of larotrectinib versus entrectinib in second-line treatment of metastatic NSCLC. Larotrectinib survival data were derived from a 13-month follow-up of 12 patients with TRK fusion-positive NSCLC in the NCT02122913 (phase 1) and NCT02576431 (NAVIGATE) trials. Entrectinib survival data were derived from a 13-month follow-up of 10 patients with TRK fusion-positive NSCLC in the ALKA-372-001, STARTRK-1, and STARTRK-2 trials. For larotrectinib and entrectinib progression-free survival and overall survival (OS), in-trial survival was extrapolated using parametric curve fits. Exponential fits were selected for all survival models based on minimal Bayesian information criteria and clinical plausibility. Lifetime survival curves were used to estimate expected mean/median survival. QALYs were estimated by applying preprogression and postprogression health state utilities derived from the literature.

Results: In the base case, treatment with larotrectinib and entrectinib resulted in 5.4 and 1.2 median preprogression life-years and 7.0 and 1.8 median total life-years, respectively. Mean preprogression life-years (QALYs) were 7.5 (5.0) and 1.9 (1.2), and mean total life-years (QALYs) were 9.2 (5.8) and 4.4 (2.4), respectively.

Conclusions: Among TRK inhibitors for metastatic NSCLC, larotrectinib is estimated to provide improved life-year and QALY outcomes versus entrectinib based on parametric extrapolations of in-trial survival data. Our analysis is limited by lack of NSCLC-specific data on entrectinib OS, the small samples of patients with NSCLC in the trials, and a cross-trial comparison. Future studies should re-evaluate the comparative effectiveness of larotrectinib versus entrectinib as more patients are treated and as long-term survival data mature. Disclosures: Funding for this study was contributed by Bayer Healthcare, which reviewed the manuscript drafts, and employees contributed to the manuscript as coauthors. Xia and Williamson are employees of Bayer Healthcare. Roth, Carlson, and Sullivan are consultants to Bayer Healthcare and retain rights to all final revisions to the manuscript. Carlson also reports fees from Adaptive Biotechnologies, unrelated to this work. Roth reports consulting fees from BMS, unrelated to this work. PubMed Disclaimer Conflict of interest statement Funding for this study was contributed by Bayer Healthcare, which reviewed the manuscript drafts, and employees contributed to the manuscript as coauthors. Xia and Williamson are employees of Bayer Healthcare. Roth, Carlson, and Sullivan are consultants to Bayer Healthcare and retain rights to all final revisions to the manuscript. Carlson also reports fees from Adaptive Biotechnologies, unrelated to this work. Roth reports consulting fees from BMS, unrelated to this work.

Purpose: Axicabtagene ciloleucel (axi-cel) was recently approved for treatment of relapsed or refractory (R/R) large B-cell lymphoma (LBCL) following two or more prior therapies. As the first CAR T-cell therapy available for adults in the US, there are important questions about clinical and economic value. The objective of this study was to assess the cost-effectiveness of axi-cel compared to salvage chemotherapy using a decision model and a US payer perspective. Materials and methods: A decision model was developed to estimate life years (LYs), quality-adjusted life years (QALYs), and lifetime cost for adult patients with R/R LBCL treated with axi-cel vs salvage chemotherapy (R-DHAP). Patient-level analyses of the ZUMA-1 and SCHOLAR-1 studies were used to inform the model and to estimate the proportion achieving long-term survival. Drug and procedure costs were derived from US average sales prices and Medicare reimbursement schedules. Future healthcare costs in long-term remission was derived from per capita Medicare spending. Utility values were derived from patient-level data from ZUMA-1 and external literature. One-way and probabilistic sensitivity analyses evaluated uncertainty. Outcomes were calculated over a lifetime horizon and were discounted at 3% per year. Results: In the base case, LYs, QALYs, and lifetime costs were 9.5, 7.7, and $552,921 for axi-cel vs 2.6, 1.1, and $172,737 for salvage chemotherapy, respectively. The axi-cel cost per QALY gained was $58,146. Cost-effectiveness was most sensitive to the fraction achieving long-term remission, discount rate, and axi-cel price. The likelihood that axi-cel is cost-effective was 95% at a willingness to pay of $100,000 per QALY. Conclusion: Axi-cel is a potentially cost-effective alternative to salvage chemotherapy for adults with R/R LBCL. Long-term follow-up is necessary to reduce uncertainties about health outcomes.

The Headache Impact Test (HIT)-6 was developed and has been validated in patients with various types of headache. The objective of this study was to report the psychometric properties of the HIT-6 among patients with chronic migraine.

Objective: The Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) has been shown to have good psychometric performance in measuring headache impact in migraine patients, but its properties specifically in chronic migraine (CM) patients are unknown. The objective of this study was to evaluate the psychometric properties of the MSQ in a group of CM patients undergoing prophylactic treatment.

Importance: Colony-stimulating factors are prescribed to patients undergoing chemotherapy to reduce the risk of febrile neutropenia. Research suggests that 55% to 95% of colony-stimulating factor prescribing is inconsistent with national guidelines.

Objective: To examine whether a guideline-based standing order for primary prophylactic colony-stimulating factors improves use and reduces the incidence of febrile neutropenia.

Design, setting, and participants: This cluster randomized clinical trial, the Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER), involved 32 community oncology clinics in the US. Participants were adult patients with breast, colorectal, or non-small cell lung cancer initiating cancer therapy and enrolled between January 2016 and April 2020. Data analysis was performed from July to October 2021.

Interventions: Sites were randomized 3:1 to implementation of a guideline-based primary prophylactic colony-stimulating factor standing order system or usual care. Automated orders were added for high-risk regimens, and an alert not to prescribe was included for low-risk regimens. Risk was based on National Comprehensive Cancer Network guidelines.
Main outcomes and measures: The primary outcome was to find an increase in colony-stimulating factor use among high-risk patients from 40% to 75%, a reduction in use among low-risk patients from 17% to 7%, and a 50% reduction in febrile neutropenia rates in the intervention group. Mixed model logistic regression adjusted for correlation of outcomes within a clinic.
Results: A total of 2946 patients (median [IQR] age, 59.0 [50.0-67.0] years; 2233 women [77.0%]; 2292 White [79.1%]) were enrolled; 2287 were randomized to the intervention, and 659 were randomized to usual care. Colony-stimulating factor use for patients receiving high-risk regimens was high and not significantly different between groups (847 of 950 patients [89.2%] in the intervention group vs 296 of 309 patients [95.8%] in the usual care group). Among high-risk patients, febrile neutropenia rates for the intervention (58 of 947 patients [6.1%]) and usual care (13 of 308 patients [4.2%]) groups were not significantly different. The febrile neutropenia rate for patients receiving high-risk regimens not receiving colony-stimulating factors was 14.9% (17 of 114 patients). Among the 585 patients receiving low-risk regimens, colony-stimulating factor use was low and did not differ between groups (29 of 457 patients [6.3%] in the intervention group vs 7 of 128 patients [5.5%] in the usual care group). Febrile neutropenia rates did not differ between usual care (1 of 127 patients [0.8%]) and the intervention (7 of 452 patients [1.5%]) groups. Conclusions and relevance: In this cluster randomized clinical trial, implementation of a guideline-informed standing order did not affect colony-stimulating factor use or febrile neutropenia rates in high-risk and low-risk patients. Overall, use was generally appropriate for the level of risk. Standing order interventions do not appear to be necessary or effective in the setting of prophylactic colony-stimulating factor prescribing.

Background: Indacaterol 27.5 µg/glycopyrrolate 15.6 µg (IND/GLY 27.5/15.6 µg) inhalation powder, a twice-daily, fixed-dose combination of a long-acting beta2-agonist (LABA) and a long-acting antimuscarinic antagonist (LAMA), is indicated in the US for long-term maintenance treatment of airflow obstruction in patients with COPD. The safety and efficacy of IND/GLY 27.5/15.6 µg have been established, but cost-effectiveness is not yet known. This study compared the cost-effectiveness of IND/GLY 27.5/15.6 µg with other long-acting COPD maintenance therapies.

Background: Chronic kidney disease (CKD) is a progressive and irreversible disease often associated with type 2 diabetes (T2D). CKD is associated with an elevated risk of cardiovascular (CV) evnts, increased mortality, and diminished quality of life. Finerenone is a new treatment for patients with CKD and T2D that delays CKD progression and reduces CV complications.
Objective: To describe the approach and structure of a costeffectiveness model for finerenone for patients with CKD and T2D and compare it with existing economic models in CKD. Methods: A de novo cost-effectiveness model (FINE-CKD model), reflective of FIDELIO-DKD results, was developed for finerenone. The FINE-CKD model was designed and implemented in accordance with published guidance on modeling and was developed with input from economic and clinical experts. The final model approach was evaluated against existing modeling structures in CKD identified through a systematic literature review. Results and conclusions: The FINE-CKD model structure follows recommended modeling guidelines and has been designed in accordance with the best practices of modeling in CKD, while also incorporating important features of the FIDELIO-DKD design and results. The approach is consistent with the published literature, ensuring transparency and minimizing uncertainty that can arise from unnecessary complexity. The FINE-CKD model allows for reliable assessment of benefits and costs related to the use of finerenone in patients with CKD and T2D, and it is a reliable assessment of cost-effectiveness.

Background: The FINE-CKD model was developed to estimate the cost-effectiveness of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Objective: To perform internal and external validation by comparing the model estimates with trial results and outcomes from other models. Methods: Incidence rates from trials were compared with the model predictions. Statistical tests were then performed to assess whether modeled event rates aligned with trial observations. A cross-validation was also performed using the online version of the SHARP CKD-Cardiovascular Disease (SHARP CKD-CVD) model, with population characteristics from the finerenone trials analyzed. Where no finerenone data were available, the default SHARP CKD-CVD values were used. Comparison of the results considered the ranges from both models. Results: The outcomes of the FINE-CKD model reflect the event rates observed in the trials. Based on the results of the statistical tests, the hypothesis of no difference between observed and modeled events cannot be rejected for any of the outcomes. The results of the FINE-CKD model are within the ranges from the SHARP CKD-CVD model. Disease progressions align across the models; however, incident kidney failure events in the SHARP CKD-CVD model were higher. This can be explained by simulation of more severely affected patients in the SHARP CKD-CVD model. Conclusions: This study demonstrates that the FINE-CKD model adequately reflects the clinical data and provides reliable extrapolation relative to the existing predictive tools while also being conservative in its approach.

To estimate the future annual prevalence of patients with stage III/IV classic Hodgkin lymphoma in the United States (US) and to predict the impact of frontline treatment on progression-free survival (PFS) and stem-cell transplantation (SCT) use in the year 2026 in settings with and without brentuximab, vedotin, doxorubicin, vinbalstine, and dacarbazine (A+AVD), based on the 5-year update of the ECHELON-1 trial results.

The six-year ECHELON-1 update showed a survival advantage for frontline (1 L) A + AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) vs ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stage III/IV classic Hodgkin lymphoma (cHL). As clinical trials have limited ability to track patients for extended periods, we developed an oncology simulation model using ECHELON-1 data to estimate population-based cHL outcomes in the US over 10 years (through 2031).

Background: A 2010 study on the impact of cancer mortality on productivity costs found Hodgkin lymphoma to have the second largest productivity cost lost per death in the United States. The ECHELON-1 trial demonstrated that frontline brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) improves overall survival (OS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in stage III/IV classical Hodgkin lymphoma (cHL), reducing the risk of death to 41% (hazard ratio = 0.59; 95% CI = 0.40-0.88; P = 0.009). Objectives: To assess the estimated impact of frontline treatment choice on mortality and productivity using an oncology simulation model informed by ECHELON-1 data.

Background: Economic evaluations often measure an intervention effect with mean overall survival (OS). Emerging types of cancer treatments offer the possibility of being “cured” in that patients can become long-term survivors whose risk of death is the same as that of a disease-free person. Describing cured and noncured patients with one shared mean value may provide a biased assessment of a therapy with a cured proportion. Objective: The purpose of this article is to explain how to incorporate the heterogeneity from cured patients into health economic evaluation. Methods: We analyzed clinical trial data from patients with advanced melanoma treated with ipilimumab (Ipi; n = 137) versus glycoprotein 100 (gp100; n = 136) with statistical methodology for mixture cure models. Both cured and noncured patients were subject to background mortality not related to cancer. Results: When ignoring cured proportions, we found that patients treated with Ipi had an estimated mean OS that was 8 months longer than that of patients treated with gp100. Cure model analysis showed that the cured proportion drove this difference, with 21% cured on Ipi versus 6% cured on gp100. The mean OS among the noncured cohort patients was 10 and 9 months with Ipi and gp100, respectively. The mean OS among cured patients was 26 years on both arms. When ignoring cured proportions, we found that the incremental cost-effectiveness ratio (ICER) when comparing Ipi with gp100 was $324,000/quality-adjusted life-year (QALY) (95% confidence interval $254,000-$600,000). With a mixture cure model, the ICER when comparing Ipi with gp100 was $113,000/QALY (95% confidence interval $101,000-$154,000). Conclusions: This analysis supports using cure modeling in health economic evaluation in advanced melanoma. When a proportion of patients may be long-term survivors, using cure models may reduce bias in OS estimates and provide more accurate estimates of health economic measures, including QALYs and ICERs.

Respiratory syncytial virus (RSV) infection is the most common cause of lower respiratory tract infection and the leading cause of hospitalization among young children, incurring high annual costs among US children under the age of 5 years. Palivizumab has been found to be effective in reducing hospitalization and preventing serious lower respiratory tract infections in high-risk infants. This paper presents a systematic review of the cost-effectiveness studies of palivizumab and describes the main highlights of a round table discussion with clinical, payer, economic, research method, and other experts. The objectives of the discussion were to (1) review the current state of clinical, epidemiology, and economic data related to severe RSV disease; (2) review new cost-effectiveness estimates of RSV immunoprophylaxis in US preterm infants, including a review of the field’s areas of agreement and disagreement; and (3) identify needs for further research.

Background: Current treatments for recurrent or metastatic cervical cancer (r/mCC) do not offer satisfactory clinical benefits, with most patients progressing beyond first-line (1L) treatment. With new treatments under investigation, understanding current treatment patterns, the impact of newly approved therapies, and total costs of care for r/mCC are important.

Methods: A retrospective analysis of a US commercial insurance claims database to identify adult patients with r/mCC between 2015 and Q1-2020; defining 1L treatment as the first administration of systemic treatment without concomitant chemoradiation or surgery. Patient characteristics, treatment regimens, duration of therapy, and total costs of care were evaluated for each line of therapy.

Aim: The cost-effectiveness of treatment options (anticholinergics, β3-adrenoceptor agonists, onabotulinumtoxinA, sacral nerve stimulation and percutaneous tibial stimulation [the latter two including new rechargeable neurostimulators]) for the management of overactive bladder (OAB) were compared with best supportive care (BSC) using a previously published Markov model.

Background and aims: Guidelines recommend that high-risk patients with atherosclerotic cardiovascular disease (ASCVD) be treated with maximally tolerated statins to lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major adverse cardiovascular events. In patients whose LDL-C remains elevated, non-statin adjunct therapies, including ezetimibe (EZE), bempedoic acid (BA), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are recommended.

Methods: The impact of BA and EZE in a fixed-dose combination (FDC) on LDL-C goal attainment was evaluated using a simulation model developed for a United States cohort of high-risk adults with ASCVD. Treatment was simulated for 73,056 patients not at goal (LDL-C >70 mg/dL), comparing BA + EZE (FDC), EZE only, and no oral adjunct therapy (NOAT). The addition of PCSK9 inibitors was assumed after 1 year in patients not at LDL-C goal. Treatment efficacy was estimated from clinical trials. Patient-level outcomes were predicted over a 10-year horizon accounting for treatment discontinuation and general mortality.

Results: Baseline mean age of the cohort was 67 years, most were White (79%) and male (56%). A majority had established coronary artery disease (75%), 48% had diabetes, and mean LDL-C was 103.0 mg/dL. After 1 year, 79% of patients achieved LDL-C goal (mean, 61.1 mg/dL) with BA + EZE (FDC) compared to 58% and 42% with EZE (71.7 mg/dL) and NOAT (78.4 mg/dL), respectively.

Conclusions: This simulation shows that adding BA + EZE (FDC) to maximally tolerated statins would result in more patients achieving LDL-C goal than adding EZE alone or NOAT.

To assess the feasibility of developing a comprehensive, disease-based model of chronic schizophrenia from the perspectives of multiple stakeholders in the United States.

To conduct a systematic review to evaluate persistence to and switching of triptan therapy for the acute treatment of migraine.

Background: 23 million Americans suffer from migraine headaches, incurring more than $1 billion in direct medical costs each year (with another $13 billion in indirect productivity losses). Triptans are the most common treatment of choice for these patients; however, adherence and persistence to triptans are poor. Partly due to poor adherence to therapy, the ability of triptans to reduce the utilization of other medical services and prescription drugs remains unclear. OBJECTIVES: To (a) assess changes in the utilization of medical services and relevant prescription drugs after patients suffering from episodic migraines begin triptan therapy and (b) further investigate the relationship between concomitant opioid use among triptan-treated migraine patients and further utilization of medical services and prescription drugs.

Misdiagnosis of bipolar I disorder (BP-I) as major depressive disorder (MDD) leads to increased healthcare resource utilization and costs. Routine screening is a judicious strategy to help identify BP-I in patients with depressive symptoms or in those who may have been misdiagnosed with MDD. The Rapid Mood Screener (RMS) is a 6-item self-administered screening tool that was developed to differentiate BP-I from MDD in patients with depressive symptoms3; it can be easily administered in under 2 minutes in a routine care setting. n Excel-based decision-tree model was developed to estimate the number of correct diagnoses and overall total direct healthcare costs over a 3-year time frame for a hypothetical cohort of 1000 RMS-screened versus unscreened patients in a US health plan.

Introduction: Misdiagnosis of bipolar I disorder (BP-I) as major depressive disorder (MDD) leads to increased healthcare resource utilization and costs. The cost-effectiveness of the Rapid Mood Screener (RMS), a tool to identify BP-I in patients with depressive symptoms, was assessed in patients diagnosed with MDD presenting with depressive episodes.

Context: Limited data exist regarding how depression diagnosed at different times relative to a cancer diagnosis may affect healthcare utilization at end of life (EOL).
Objectives: To assess the relationship between depression and health care utilization at EOL among older adults (ages >=67) diagnosed with advanced non-small cell lung cancer (NSCLC) from 2009 to 2011. Methods: Using the SEER-Medicare database, we fit multivariable logistic regression models to explore the association of depression with duration of hospice stay plus high-intensity care, for example inpatient admissions, in-hospital death, emergency department visits, and chemotherapy at EOL. We used a regression model to evaluate hospice enrollment, accounting for the competing risk of death. Results: Among 13,827 subjects, pre-cancer depression was associated with hospice enrollment (sub-hazard ratio 1.19, 95% confidence interval [CI] 1.11-1.28), 90 + hospice days (adjusted odds ratio [aOR] 1.29, 95% CI 1.06-1.58), and lower odds of most utilization; we found no association with EOL chemotherapy. Diagnosis-time depression was associated with hospice enrollment (SHR 1.16, 95% CI 1.05-1.29) but not high-intensity utilization. Post-diagnosis depression was associated with lower hospice enrollment (SHR 0.80, 95% CI 0.74-0.85) and higher odds of ICU admission (aOR 1.18, 95% CI 1.01-1.37). Conclusion: EOL healthcare utilization varied by timing of depression diagnosis. Those with pre-cancer depression had lower odds of high-intensity healthcare, were more likely to utilize hospice, and have longer hospice stays. Regular depression screening and treatment may help patients optimize decision-making for EOL care. Additionally, hospice providers may need additional resources to attend to mental health needs in this population.

To systematically identify all published literature on the adverse health outcomes, cardiovascular (CV) risk factors or events, and patient and physician perspectives regarding risk associated with attenuated androgens in hereditary angioedema.

In clinical trials of treatments for pulmonary arterial hypertension (PAH), objective measures, such as 6-min walk distance (6MWD) are limited in their ability to characterize the impact of PAH therapy from a patient’s perspective. Few clinical studies have evaluated the primary effects of pharmacologic treatment on patient-reported outcomes, such as symptoms, health-related quality of life (HRQoL), and productivity. MOTION (NCT02191137) is a prospective, multicenter, single-arm, open-label, phase 4 trial designed to assess whether riociguat monotherapy will improve patient-reported outcomes in patients with PAH in the United States who are not currently on treatment. Following a screening period of up to 14 days, eligible subjects will receive riociguat (0.5-2.5 mg TID) during a 10-week titration phase and a 14-week maintenance phase. The primary endpoint is change from baseline in the Living with Pulmonary Hypertension (LPH) questionnaire, a disease-specific HRQoL measure, after 24 weeks of riociguat treatment. The Short Form-12 Health Survey (SF-12) and the Work Limitations Questionnaire 8 (WLQ-8) will also be utilized to assess patient-reported outcomes. Other variables include change from baseline in World Health Organization functional class, 6MWD, and modified Borg Dyspnea Index. In addition, accelerator band activity will be validated against the 6MWD test. Safety will also be assessed. The MOTION trial will provide information on the effect of riociguat on patient-reported outcomes in PAH patients in the United States who are not currently on active treatment through the use of disease-specific and generic HRQoL measures (LPH and SF-12) and a measure of worker productivity (WLQ-8).

Momelotinib is a newly approved Janus kinase inhibitor (JAKi) that can provide substantial spleen, symptom, and anemia benefits for patients with myelofibrosis, but the value associated with its use vs other treatment options is unclear. We developed a cost-effectiveness model to estimate total costs and quality-adjusted life-years (QALYs) of momelotinib vs pacritinib or vs best available therapy (BAT; as observed in the phase 3 SIMPLIFY-2 trial), current standard-of-care treatment options in JAKi-experienced patients.

Waldenström’s macroglobulinemia (WM) is a rare B-cell malignancy of which Bruton’s tyrosine kinase (BTK) plays a critical role in B-cell receptor signaling. Zanubrutinib, a highly selective, next-generation BTK inhibitor, was approved for the treatment of adult patients with WM in the (US) on August 31, 2021, expanding treatment options for patients with WM. To estimate the budget impact of providing access to zanubrutinib for the treatment of adult patients with WM from the US healthcare payer perspective.

This study aimed to estimate the cost per responder (CPR) for zanubrutinib versus ibrutinib in relapsed or refractory chronic lymphocytic leukemia / small lymphocytic leukemia from a payer perspective in the United States (US).

Constipation-predominant irritable bowel syndrome (IBS-C) is associated with chronic bowel and abdominal symptoms. The burden and impact of these symptoms in healthcare resource utilization is unknown. To describe abdominal symptom burden in patients with IBS-C and the influence of abdominal symptoms on care-seeking behavior, healthcare resource use, and treatment satisfaction.

Introduction: Dupilumab significantly improves signs and symptoms of atopic dermatitis (AD), including pruritus, symptoms of anxiety and depression, and health-related quality of life versus placebo in adults with moderate-to-severe AD. Since the cost-effectiveness of dupilumab has not been evaluated, the objective of this analysis was to estimate a value-based price range in which dupilumab would be considered cost-effective compared with supportive care (SC) for treatment of moderate-to-severe AD in an adult population. Methods: A health economic model was developed to evaluate from the US payer perspective the long-term costs and benefits of dupilumab treatment administered every other week (q2w). Dupilumab q2w was compared with SC; robustness of assumptions and results were tested using sensitivity and scenario analyses. Clinical data were derived from the dupilumab LIBERTY AD SOLO trials; healthcare use and cost data were from health insurance claims histories of adult patients with AD. The annual price of maintenance therapy with dupilumab to be considered cost-effective was estimated for decision thresholds of US$100,000 and $150,000 per quality-adjusted life-year (QALY) gained. Results: In the base case, the annual maintenance price for dupilumab therapy to be considered cost-effective would be $28,770 at a $100,000 per QALY gained threshold, and $39,940 at a $150,000 threshold. Results were generally robust to parameter variations in one-way and probabilistic sensitivity analyses. Conclusion: Dupilumab q2w compared with SC is cost-effective for the treatment of moderate-to-severe AD in US adults at an annual price of maintenance therapy in the range of $29,000-$40,000 at the $100,000-$150,000 per QALY thresholds.

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.

Adherence and persistence rates differ among oral anticoagulants (OACs) in atrial fibrillation (AF) patients, and suboptimal adherence is associated with poor clinical outcomes. This study aimed to evaluate variations in adherence and persistence to OACs among AF patients across stroke risk (CHA2DS2-VASc) and bleeding risk (HAS-BLED2) strata.

BACKGROUND: The rising prevalence and associated public health burden of obesity has led to advancements in pharmaceuticals for weight management. Semaglutide 2.4 mg, an anti-obesity medication (AOM) recently approved by the US Food and Drug Administration, has demonstrated clinically relevant weight loss in its phase 3 clinical trials. Economic evaluation comparing semaglutide 2.4 mg with other available weight management therapies is essential to inform payers for decision-making. OBJECTIVES: To assess the cost-effectiveness of semaglutide 2.4 mg in the treatment of adult patients with obesity (ie, body mass index [BMI] ≥ 30) and adult patients who are overweight (ie, BMI 27-29.9) with 1 or more weight-related comorbidities from a US third-party payer perspective. METHODS: A cohort Markov model was constructed to compare semaglutide 2.4 mg with the following comparators: no treatment, diet and exercise (D&E), and 3 branded AOMs (liraglutide 3 mg, phentermine-topiramate, and naltrexone-bupropion). All AOMs, including semaglutide 2.4 mg, were assumed to be taken in conjunction with D&E. Changes in BMI, blood pressure, cholesterol level, experience of acute and chronic obesity-related complications, costs, and quality-adjusted life years (QALYs) were simulated over 30 years based on pivotal trials of the AOMs and other relevant literature. Drug and health care prices reflect 2021 standardized values. Cost-effectiveness was examined with a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Sensitivity analyses were conducted to test the robustness of the cost-effectiveness results to plausible variation in model inputs. RESULTS: In the base-case analysis, treatment with semaglutide 2.4 mg was estimated to improve QALYs by 0.138 to 0.925 and incur higher costs by $3,254 to $25,086 over the 30-year time horizon vs comparators. Semaglutide 2.4 mg is cost-effective against all comparators at the prespecified WTP threshold, with the incremental cost per QALY gained ranging from $23,556 to $144,296 per QALY gained. In the sensitivity analysis, extended maximum treatment duration, types of subsequent treatment following therapy discontinuation, and weight-rebound rates were identified as key drivers for model results. The estimated probability of semaglutide 2.4 mg being cost-effective compared with comparators ranged from 67% to 100% when varying model parameters and assumptions. CONCLUSIONS: As a long-term weight management therapy, semaglutide 2.4 mg was estimated to be cost-effective compared with no treatment, D&E alone, and all other branded AOM comparators under a WTP threshold of $150,000 per QALY gained over a 30-year time horizon. DISCLOSURES: Financial support for this research was provided by Novo Nordisk Inc. The study sponsor was involved in several aspects of the research, including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. Dr Kim and Ms Ramasamy are employees of Novo Nordisk Inc. Ms Kumar and Dr Burudpakdee were employees of Novo Nordisk Inc at the time this study was conducted. Dr Sullivan received research support from Novo Nordisk Inc for this study. Drs Wang, Song, Wu, Ms Xie, and Ms Sun are employees of Analysis Group, Inc, who received consultancy fees from Novo Nordisk Inc in connection with this study.

BACKGROUND: Caring for children with hemophilia A (HA) impacts many aspects of parents’ lives. How this translates to caregivers’ utilization of health services is unknown, and its elicitation can inform future evaluations of interventions that address caregiver burden for HA. OBJECTIVE: To understand the impact of caring for children with HA on parents’ utilization of nonmental and mental health services by comparing 1-year costs and number of claims with parents of children without HA. METHODS: Retrospective matched cohort study using MarketScan commercial medical and pharmacy claims from 2011 to 2019. Children with HA were male sex, aged younger than 18 years, dependent policyholders, and had at least 1 HA-related medical claim from 2011 to 2018 and either an HA-related procedure or drug claim. Parents of children with HA (PCH) were primary or secondary policyholders, shared the same family ID as children with HA, and were continuously enrolled for 1-year post-index. PCH were matched (1:2) with parents of children without HA on age, sex, beneficiary type, child’s age, number of children, index month and year, health plan type, employment status, and region. Primary outcomes were nonmental and mental health care costs (2020 US dollars). Secondary outcomes were number of nonmental health outpatient claims and utilization of mental health outpatient or drug claim. Subgroup analyses excluding parents with HA were also conducted. Productivity loss was also explored. Outcomes were compared using 2-sided, paired t-tests, and McNemar test. RESULTS: 1,068 PCH met inclusion criteria and were matched to 2,122 control parents. Mean 1-year cost for PCH was higher for nonmental health (mean difference $1,826 [95% CI = -1,000 to 4,652; P = 0.20]) and similar for mental health services (mean difference $14 [95% CI = -77 to 105; P = 0.76]). When parents with HA were excluded in the subgroup analyses, mental health cost was significantly higher for PCH (mean difference $676 [95% CI = 399 to 953; P < 0.001]). PCH had more nonmental health outpatient claims compared with parents of children without HA (mean difference 1.9 [95% CI = -1.1 to 4.9; P = 0.21]) and were 1.2 times (95% CI = 0.99 to 1.45; P = 0.07) more likely to have a mental health outpatient or drug claim. CONCLUSIONS: PCH had moderately higher health care costs and utilization compared with parents of children without HA; however, these results were not statistically significant. Future studies to better characterize HA disease severity and assess its impact on caregiver burden or to expand caregivers to spouses of adult patients with HA may be warranted. Limitations include inability to ascertain severity of HA in children and the use of claims data to capture complex effects on health care utilization. DISCLOSURES: Dr. Kim's postdoctoral fellowship is supported by Genentech, Inc. Dr. Raimundo is an employee of Genentech, Inc.

Human epidermal growth factor receptor 2 (HER2) amplification or overexpression is estimated to occur rarely (~3–5%) in colorectal cancer (CRC). In patients with CRC, HER2 is an emerging biomarker for targeted therapy and may be predictive of potential resistance to epidermal growth factor receptor-targeted therapy. National Comprehensive Cancer Network treatment guidelines recommend HER2 directed therapies as systemic therapy options for patients with metastatic CRC (mCRC) who have tumors that are RAS/BRAF wild-type and have HER2 amplification or overexpression (HER2-positive [HER2+]). A current and comprehensive understanding of the epidemiology of HER2 in CRC in the United States (US) and globally is needed. We estimate the prevalence of patients with CRC in the US and globally who are HER2+ (overexpression or amplification) overall, and by primary tumor location and by RAS status (eg, RAS wild-type) in the published literature.

Purpose: Primary prophylactic colony-stimulating factors (PP-CSFs) are prescribed to reduce febrile neutropenia (FN) but their benefit for intermediate FN risk regimens is uncertain. Within a pragmatic, randomized trial of a standing order entry (SOE) PP-CSF intervention, we conducted a substudy to evaluate the effectiveness of SOE for patients receiving intermediate-risk regimens. Methods: TrACER was a cluster randomized trial where practices were randomized to usual care or a guideline-based SOE intervention. In the primary study, sites were randomized 3:1 to SOE of automated PP-CSF orders for high FN risk regimens and alerts against PP-CSF use for low-risk regimens versus usual care. A secondary 1:1 randomization assigned 24 intervention sites to either SOE to prescribe or an alert to not prescribe PP-CSF for intermediate-risk regimens. Clinicians were allowed to over-ride the SOE. Patients with breast, colorectal, or non-small-cell lung cancer were enrolled. Mixed-effect logistic regression models were used to test differences between randomized sites. Results: Between January 2016 and April 2020, 846 eligible patients receiving intermediate-risk regimens were registered to either SOE to prescribe (12 sites: n = 542) or an alert to not prescribe PP-CSF (12 sites: n = 304). Rates of PP-CSF use were higher among sites randomized to SOE (37.1% v 9.9%, odds ratio, 5.91; 95% CI, 1.77 to 19.70; P = .0038). Rates of FN were low and identical between arms (3.7% v 3.7%).
Conclusion: Although implementation of a SOE intervention for PP-CSF significantly increased PP-CSF use among patients receiving first-line intermediate-risk regimens, FN rates were low and did not differ between arms. Although this guideline-informed SOE influenced prescribing, the results suggest that neither SOE nor PP-CSF provides sufficient benefit to justify their use for all patients receiving

No abstract available

Objective: Glucagon-like peptide-1 receptor agonists (GLP1s) are effective antiobesity drugs and the subject of intense debate around insurance coverage due to the large prevalence of obesity and overweight. The estimation of the budget impact associated with GLP1 insurance coverage requires estimates of GLP1 prices that account for manufacturer discounts. The authors applied a peer-reviewed method to estimate the net prices of GLP1s after manufacturer discounts. Methods: The authors estimated manufacturer discounts for each product as the difference between the gross sales estimated at list price and manufacturer-reported revenue. From this difference, the authors subtracted discounts to government programs, including 340B, Medicaid, and the Medicare Part D coverage gap, and attributed the remaining amount to manufacturer discounts provided in the commercial market. Results: Manufacturer discounts for GLP1s approved for obesity were estimated at 41%, which translated into net prices of $717 to $761 per month of supply. Manufacturer discounts for GLP1s approved for type 2 diabetes ranged from 54% to 59%, which translated into net prices of $312 to $469 per month of supply. Conclusions: The magnitude of manufacturer discounts underscores the need to consider net price information in studies that inform private and public payers’ decision-making around coverage of GLP1s for obesity.

Background: The Centers for Medicare and Medicaid Services (CMS) are currently negotiating prices with pharmaceutical manufacturers for the first 10 Part D drugs selected for Medicare drug price negotiation. Non-publicly available data, including the net prices of selected drugs and their therapeutic alternatives, will play a central role in the determination of the maximum fair prices (MFPs). Objective: To estimate price benchmarks involved in the derivation of the starting point of the CMS initial price offer for the 10 drugs selected for Medicare price negotiation. Methods: For the 10 drugs selected for negotiation, we reported (1) the list price, (2) the net price after manufacturer discounts, (3) the maximum negotiated price based on the minimum statutory discount, and (4) the ceiling of the MFP, estimated as the lowest of the latter 2. We also estimated net prices for therapeutic alternatives to the selected drugs. Net prices were estimated using peer-reviewed methodology that isolates commercial discounts negotiated between payers and manufacturers from mandatory discounts under government programs. All price benchmarks were estimated at the product level, for 30-day equivalent dosing, using 2021 data. Results: 6 products (apixaban, rivaroxaban, empagliflozin, sacubitril/valsartan, etanercept, and insulin aspart) had therapeutic alternatives with lower net prices, which will be integrated with clinical benefit data in the derivation of initial price offers. The other 4 products (ustekinumab, ibrutinib, sitagliptin, and dapagliflozin) had therapeutic alternatives with higher net prices than the drugs selected for negotiation. For ibrutinib and ustekinumab, prices based on the minimum discounts were considerably lower than the estimated net prices and will likely set the starting point of the initial price offer. For dapagliflozin and sitagliptin, the starting point of the initial price offer will likely resemble their existing net prices. Conclusions: Our analyses identify different negotiation scenarios for the first 10 drugs selected for Medicare price negotiation, based on key elements involved in the derivation of the initial price offer. Our analyses can help improve transparency in the negotiation process, because the CMS is not required to reveal the information used in the derivation of price offers.

Under the 2022 Inflation Reduction Act, the Centers for Medicare and Medicaid Services (CMS) are able to negotiate prices for topselling drugs in the Medicare Part B and D programs. In determining initial price offers, CMS will compare the prices and clinical benefits of the drugs subject to negotiation to the prices and clinical benefits of therapeutic alternatives. Despite the central role that the selection of therapeutic alternatives will play in the price negotiations, the available guidance published by CMS provides few details about how the organization will undertake this process, which will be particularly complex for drugs approved for more than one indication. To better inform the selection process, we identified all US Food and Drug Administration-approved indications for the first 10 drugs subject to negotiation. Using 2020-2021 Medicare claims data, we identified Medicare Part D beneficiaries using each of the 10 drugs. We extracted medical claims with diagnosis codes for each of the approved indications to report the relative treated prevalence of use by indication for each drug. We reviewed published clinical guidelines to identify relevant therapeutic alternatives for each of the indications. We integrated the evidence on the relative treated prevalence of indications and clinical guidelines to propose therapeutic alternatives for each of the 10 drugs. We describe challenges that CMS may face in selecting therapeutic alternatives.

Background: Migraine is a common neurological disease affecting 12% of Americans and millions worldwide. Medication adherence has been studied extensively in many chronic conditions, with poor adherence adversely affecting treatment outcomes. However, little is known about adherence to oral prophylaxis for migraine. Objective: To examine the literature on assessing oral prophylaxis medication adherence and persistence among migraine patients.

Background: Approximately half of patients with high-risk HER2-positive early-stage breast cancer (ESBC) do not have pathologic complete response (pCR) after neoadjuvant therapy. The residual burden of disease among this population has not been previously quantified. Materials and methods: We used decision-modeling techniques to simulate recurrence, progression from locoregional to distant cancer, breast cancer-related mortality, and mortality from other causes over a 10-year period in a hypothetical cohort. We derived progression probabilities primarily from the KATHERINE trial of T-DM1 (ado-trastuzumab emtansine) and mortality outcomes from the published literature. Modeled outcomes included recurrences, breast cancer deaths, deaths from other causes, direct medical costs, and costs due to lost productivity. To estimate the residual disease burden, we compared outcomes from a cohort of patients treated with T-DM1 versus a hypothetical cohort with no disease recurrence. Results: We estimated that 9,300 people would experience incident high-risk HER2-positive ESBC in the United States in 2021 based on cancer surveillance databases, clinical trial data, and expert opinion. We estimated that, in this group, 2,118 would experience disease recurrence, including 1,576 distant recurrences, and 1,358 would experience breast cancer deaths. This residual disease burden resulted in 6,435 life-years lost versus the recurrence-free cohort, and healthcare-related costs totaling $644 million, primarily associated with treating distant cancers. Conclusion: Patients with HER2-positive ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of neoadjuvant treatment. There is substantial clinical and economic value in further reducing the residual disease burden in this population.

Hyperhidrosis (HH) is a condition characterized by excessive sweat production beyond what is physiologically required to maintain normal thermal homeostasis. Studies have indicated that HH has a negative impact on health-related quality of life (HRQOL) through increased risk of comorbid conditions such as depression and anxiety and impairments to social life, including social embarrassment, intimacy interference, impairments in daily living activities and employment. There are few FDA-approved treatments for PAHH, and off-label treatments and surgical procedures are limited by tolerability and adverse events. Glycopyrronium tosylate (GT) is a topical anticholinergic recently approved by the US Food and Drug Administration for the treatment of PAHH in patients ≥9 years of age (glycopyrronium cloth, 2.4%, for topical use). No treatment guidelines currently exist for PAHH; however, a treatment algorithm by the International Hyperhidrosis Society (IHHS) recommends initiating treatment with a glycopyrronium cloth which contains GT or topical antiperspirants containing aluminum or zirconium salts as first-line therapy. We compare the cost-effectiveness of first-line topical therapy options, GT vs. topical aluminum chloride, for the treatment of PAHH from the US commercial payer perspective.

Objectives: Risk-sharing agreements (RSAs) between drug manufacturers and payers link coverage and reimbursement to real-world performance or utilization of medical products. These arrangements have garnered considerable attention in recent years. However, greater use outside the United States raises questions as to why their use has been limited in the US private sector, and whether their use might increase in the evolving US healthcare system. Study design: To understand current trends, success factors, and challenges in the use of RSAs, we conducted a review of RSAs, interviews, and a survey to understand key stakeholders’ experiences and expectations for RSAs in the US private sector.Methods: Trends in the numbers of RSAs were assessed using a database of RSAs. We also conducted in-depth interviews with stakeholders from pharmaceutical companies, payer organizations, and industry experts in the United States and European Union. In addition, we administered an online survey with a broader audience to identify perceptions of the future of RSAs in the United States.Results: Most manufacturers and payers expressed interest in RSAs and see potential value in their use. Due to numerous barriers associated with outcomes-based agreements, stakeholders were more optimistic about financial-based RSAs. In the US private sector, however, there remains considerable interest–improved data systems and shifting incentives (via health reform and accountable care organizations) may generate more action.Conclusions: In the US commercial payer markets, there is continued interest among some manufacturers and payers in outcomes-based RSAs. Despite continued discussion and activity, the number of new agreements is still small.

Maintenance avelumab (maintA) following first-line (1L) therapy in patients with advanced urothelial carcinoma (aUC) prolonged overall survival (OS) in the JAVELIN Bladder 100 trial. MaintA is the new standard of care for patients with aUC who have no evidence of disease progression following 1L platinum-based therapy (PBT) in the NCCN2 and ESMO treatment guidelines with level 1 evidence. JAVELIN measured OS from initiation of maintA among a subgroup of the overall aUC 1L-treated population with receipt of maintA based on a conditional eligibility. Patients who progressed on or immediately following PBT were not included in JAVELIN; as a result, the OS of the maintA-ineligible subgroup and of the overall population of patients treated with 1L PBT with the intention to receive maintA (1L PBT maintA-intended) is unknown. To address this, we used disease modeling to estimate the OS of patients with aUC who received 1L treatment, including both maintA-eligible and -ineligible patients, measured from initiation of 1L PBTto align OS in patients receiving maintA with the common initiation point, so as to benchmark with other 1L clinical trials.

Objective: First-line (1L) maintenance avelumab prolonged overall survival (OS) in patients with advanced urothelial carcinoma (aUC) in JAVELIN Bladder 100. OS was measured from maintenance initiation in patients with disease control following 1L platinum-based therapy (PBT). The OS impact of maintenance for the 1L PBT-treated population is unknown since it was not measured from 1L initiation, nor can it be benchmarked with other 1L therapies. To characterize the OS impact of maintenance avelumab, we used an oncology simulation model to estimate the OS of maintenance-eligible and -ineligible patients with aUC from 1L PBT initiation.

As differences in trial design prevent indirect comparisons between JAVELIN Bladder 100, a maintenance study, and other studies of 1L therapies by traditional methods such as network meta-analysis, we used simulation modeling to estimate the impact of maintenance avelumab from the initiation of 1L therapy in cis-ineligible patients with la/mUC to contextualize outcomes with EV + pembrolizumab.

This study aimed to estimate the budget impact of access to zanubrutinib + obinutuzumab for thetreatment of relapsed/refractory follicular lymphoma in the third line or later setting in adult patients from a US healthcare payer perspective.

This ISPOR Good Practices report provides a framework for assessing the suitability of electronic health records data for use in health technology assessments (HTAs). Although electronic health record (EHR) data can fill evidence gaps and improve decisions, several important limitations can affect its validity and relevance. The ISPOR framework includes 2 components: data delineation and data fitness for purpose. Data delineation provides a complete understanding of the data and an assessment of its trustworthiness by describing (1) data characteristics; (2) data provenance; and (3) data governance. Fitness for purpose comprises (1) data reliability items, ie, how accurate and complete the estimates are for answering the question at hand and (2) data relevance items, which assess how well the data are suited to answer the particular question from a decision-making perspective. The report includes a checklist specific to EHR data reporting: the ISPOR SUITABILITY Checklist. It also provides recommendations for HTA agencies and policy makers to improve the use of EHR-derived data over time. The report concludes with a discussion of limitations and future directions in the field, including the potential impact from the substantial and rapid advances in the diffusion and capabilities of large language models and generative artificial intelligence. The report’s immediate audiences are HTA evidence developers and users. We anticipate that it will also be useful to other stakeholders, particularly regulators and manufacturers, in the future.

Background: Real-world data regarding the impact of onabotulinumtoxinA on healthcare resource utilization and costs for post-stroke spasticity are scarce. Objective: To compare differences in 12-month healthcare resource utilization and costs before and after post-stroke spasticity management including onabotulinumtoxinA.

Brentuximab vedotin versus physician’s choice of methotrexate (MTX) or bexarotene (BEX) significantly improved progression-free survival (PFS) (median PFS, 16.7 vs. 3.5 months) and delayed time to subsequent treatment (8.4 vs. 3.7 months), with similar overall survival in patients with CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL), two types of cutaneous T-cell lymphomas. We assessed the cost-effectiveness of brentuximab vedotin versus MTX or BEX from a Canadian healthcare payer perspective in the indicated population.

In patients with established atherosclerotic cardiovascular disease (ASCVD), guidelines recommend adding a non-statin therapy to statin therapy if low-density lipoprotein cholesterol (LDL-C) remains ≥ 70 mg/dL in moderate-, high-, or very high–risk patients. Bempedoic acid (BA), an adenosine triphosphate citrate lyase inhibitor, was approved in February 2020 for the treatment of adults with established ASCVD or heterozygous familial hypercholesterolemia who require additional LDL-C lowering on maximally tolerated statin therapy. A recent simulation of German patients with ASCVD5 evaluated the impact of adjunct BA on LDL-C goal achievement in patients not at goal after statin and EZE therapy (< 55 mg/dL and reduction ≥ 50% based on European Society of Cardiology/European Atherosclerosis Society guidelines). Differences between the German and US patient populations, LDL-C goals, and treatment practices limit the generalizability of these results for a US population. To explore the impact of adjunct BA + EZE (FDC) on LDL-C goal attainment in a real-world US cohort of patients with ASCVD on statin therapy who are not at goal.

Use an analytical model to determine the impact of adherence on the effectiveness of MCED screening programs, using lung and pancreatic cancer to illustrate our findings.

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.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

Biosimilars are biologic medications that are highly similar to, and have no clinically meaningful differences from, existing approved biologics known as “reference products”. Typically, biosimilars are priced below their reference products, creating an economic incentive for use to reduce expenses. However, a variety of challenges to biosimilar uptake have arisen across global markets,threaten market sustainability, and may create disincentives to pursue development of additional biosimilars in the future. We conduct a targeted literature review(TLR) of the biosimilars literature to identify key sustainability dimensions of this market to inform future research, stakeholder interactions, and policy initiatives aimed at ensuring the long-term viability of global biosimilars markets.

This review sought to characterize the inclusion of family and informal caregiver spillover effects in value assessments conducted by ICER.

Objectives: The healthcare expenditure for managing diabetes with glucose-lowering medications has been substantial in the United States. We simulated a novel, value-based formulary (VBF) design for a commercial health plan and modeled possible changes in spending and utilization of antidiabetic agents. Methods: We designed a 4-tier VBF with exclusions in consultation with health plan stakeholders. The formulary information included covered drugs, tiers, thresholds, and cost sharing amounts. The value of 22 diabetes mellitus drugs was determined primarily in terms of incremental cost-effectiveness ratios. Using pharmacy claims database (2019-2020), we identified 40 150 beneficiaries who were on the included diabetes mellitus medicines. We simulated future health plan spending and out-of-pocket costs with 3 VBF designs, using published own price elasticity estimates. Results: The average age of the cohort is 55 years (51% female). Compared with the current formulary, the proposed VBF design with exclusions is estimated to reduce total annual health plan spending by 33.2% (current: $33 956 211; VBF: $22 682 576), saving $281 in annual spending per member (current: $846; VBF: $565) and $100 in annual out-of-pocket spending per member (current: $119; VBF: $19). Implementing the full VBF with new cost shares, along with exclusions, has the potential to achieve the greatest savings, compared with the 2 intermediate VBF designs (ie, VBF with prior cost sharing and VBF without exclusions). Sensitivity analyses using various price elasticity values showed declines in all spending outcomes. Conclusion: Designing a VBF with exclusions in a US employer-based health plan has the potential to reduce health plan and patient spending.

BACKGROUND: Hemophilia A (HA) is a rare, inherited, serious bleeding disorder characterized by a deficiency of blood clotting factor VIII (FVIII). HA is associated with considerable economic burden. OBJECTIVE: To identify, review, and summarize published studies on the health care resource use and costs of managing HA in the United States using a targeted literature review.

BACKGROUND: Performance-based risksharing arrangements (PBRSAs) have continued to emerge and evolve over the last 2 decades. To date, most of the attention and available literature have focused on pharmaceuticals. OBJECTIVE: To assess the current status and trends regarding the use of PBRSAs for diagnostics and devices in the United States. METHODS: We reviewed publicly available PBRSAs for diagnostics and devices using the University of Washington Performance Based Risk Sharing Database. We augmented the review using PubMed, Google, and payer and industry websites. Key words and phrases such as outcomes-based, value-based, coverage with evidence development, performance-based, and risk-sharing were used in combination with device or diagnostic. To characterize arrangements in terms of product and market attributes, we extracted data for each product, including arrangement descriptions, arrangement type, year, therapeutic area, product manufacturer, payer, and product type. Arrangements were analyzed using descriptive statistics. RESULTS: Fifty-two arrangements were identified between the years 2001 and 2019, with 30 (57.7%) for devices and 22 (42.3%) for diagnostic tests. Among these, 23 (44.2%) were coverage with evidence development (CED), only in research; 17 (32.7%) were performance-linked reimbursement (PLR); and 12 (23.1%) were CED, only with research. The majority of arrangements for devices were developed in cardiology (12, 40%), endocrinology (4, 13.3%), and radiology (3, 10%). Most of arrangements for identified diagnostic tests were in oncology (17, 77.3%). Over time, there has been a trend towards increasing adoption of PLR and CED, only with research, especially since 2014. CONCLUSIONS: This is the first study to comprehensively review PBRSA arrangements for diagnostics and devices in the United States. Our findings demonstrated that there is substantial PBRSA activity for devices and diagnostics, and the pace of PBRSA adoption appears to be increasing in terms of frequency and variety. These arrangements have implications for managed care into the future as the health care system shifts towards value-based care and value-based pricing to contain cost for payers and ensure value in the patient populations. DISCLOSURES: No funding supported this study. The authors have nothing to disclose.

Larotrectinib and entrectinib are tumor-agnostic tropomyosin receptor kinase (TRK) inhibitors that are indicated for the treatment of advanced or metastatic solid tumor cancers with neurotrophic tyrosine receptor kinase (NTRK) gene fusions. Regulatory approval of both agents was based on data from single-arm phase 1/2 studies, including tumor-agnostic basket trials. In the absence of randomized controlled trials, there remains a paucity of data to demonstrate the comparative effectiveness of larotrectinib and entrectinib vs established standard-of-care treatments in cancers with NTRK gene fusions. Furthermore, no studies have directly compared the 2 agents. This article reviews what is known about the comparative effectiveness of larotrectinib and entrectinib vs standard therapies in TRK fusion cancer and examines the comparative effectiveness of the 2 TRK inhibitors. Historical and intrapatient comparisons suggest that TRK inhibitors improve disease response compared with preexisting treatments across most tumor histologies; indirect and limited comparisons of phase 1/2 data and preliminary simulation modeling suggest a potential advantage for larotrectinib over entrectinib in terms of clinical response and survival. Although limited, these data provide some insight into the position of these treatments in established treatment paradigms for TRK fusion cancer, a setting where real-world evidence will be slow to accrue due to the rare nature of these tumors but may be the only way in the future to answer the outstanding questions regarding these 2 agents. Meanwhile, we need to try to obtain the maximum benefit that can be achieved for our patients using the currently available knowledge.

Our objective was to identify and characterize publicly available cases and related trends for performance-based risk-sharing arrangements (PBRSAs). We performed a review of PBRSAs over the past 20 years (1993-2013) using available databases and reports from colleagues and healthcare experts. These were categorized according to a previously published taxonomy of scheme types and assessed in terms of the underlying product and market attributes for each scheme. Macro-level trends were identified related to the timing of scheme adoption, countries involved, types of arrangements, and product and market factors. Our search yielded 148 arrangements. From this set, 65 arrangements included a coverage with an evidence development component, 20 included a conditional treatment continuation component, 54 included a performance-linked reimbursement component, and 42 included a financial utilization component. Each type of scheme addresses fundamental uncertainties that exist when products enter the market. The pace of adoption appears to be slowing, but new countries continue to implement PBRSAs. Over this 20-year period, there has been a consistent movement toward arrangements that minimize administrative burden. In conclusion, the pace of PBRSA adoption appears to be slowing but still has traction in many health systems. These remain a viable coverage and reimbursement mechanism for a wide range of medical products. The long-term viability and growth of these arrangements will rest in the ability of the parties to develop mutually beneficial arrangements that entail minimal administrative burden in their development and implementation.

Objectives: Nirmatrelvir/ritonavir (NMV/r) is an orally administered antiviral indicated for the outpatient treatment of patients with mild-to-moderate COVID-19 at high risk for disease progression to severe illness. We estimated the cost-effectiveness of NMV/r versus best supportive care for patients with mild-to-moderate COVID-19 at high risk for progression to severe illness from a US health sector perspective.

Objectives: The aim of this study was to identify and quantify the characteristics of studies associated with the likelihood of publication. Study design and setting: We searched for manuscripts that tracked cohorts of clinical studies (“cohorts”) that from launch to publication. We explored the association of study characteristics with the probability of publication via traditional meta-analyses and meta-regression using random effects models. Results: The literature review identified 85 cohorts of studies that met our inclusion criteria. The probability of publication was significantly higher for studies whose characteristics were favorable (odds ratio [OR] = 2.04; 95% confidence interval [CI]: 1.62, 2.57) or statistically significant (OR = 2.07; 95% CI: 1.52, 2.81), had a multicenter design (OR = 1.32; 95% CI: 1.16, 1.45), and were of later regulatory phase (3/4 vs. 1/2, OR = 1.34; 95% CI: 1.14, 1.49). Industry funding was modestly associated with lower (OR = 0.81; 95% CI: 0.67, 0.99) probability of publication. An exploratory analysis of effect modification revealed that the effect of the study characteristic “favorable results” on likelihood for publication was stronger for industry-funded studies. Conclusion: The study characteristics of favorable and significant results were associated with greater probability of publication.

To estimate the annual budget impact of introducing NMV/r in a U.S. commercial health plan setting in the current Omicron variant COVID-19 era.

Background: Imatinib, a first-generation tyrosine kinase inhibitor (TKI), and the newer second-generation TKIs have dramatically improved outcomes for patients with chronic myelogenous leukemia (CML). A previous model estimated the potential cost-savings over the next 2 years after the loss of patent exclusivity for imatinib in the United States in 2016 and its availability in a generic form. Payers have indeed realized meaningful savings, but it took 2 years for the prices of generic imatinib to decline substantially. Objective: To quantify the cost-savings for a US health plan from the passive substitution of generic imatinib and the impact of step-edit therapy with the use of generic imatinib before coverage of a second-generation TKI. Methods: We updated the previously published model utilizing hypothetical 1-million-member commercial and Medicare plans to include current TKI use and pricing combined with recent epidemiologic data.

BACKGROUND: The ECHELON-2 5-year update showed continued clinically meaningful improvements in progression-free survival (PFS) and overall survival with frontline (1L) A+CHP (brentuximab vedotin in combination with cyclophosphamide, doxorubicin, prednisone) vs CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in CD30-expressing peripheral T-cell lymphomas (PTCLs). OBJECTIVE: To estimate PTCL annual prevalence in the United States in 2031 without and with A+CHP using data from the ECHELON-2 5-year update.

Objectives: The study objective was to investigate the economic value of tumor-agnostic therapies when only single-arm effectiveness data are available at launch by applying multiple methodologies to establish comparative effectiveness. Methods: In the absence of direct comparative data, 3 methods were used to estimate the counterfactual: (1) a historical control based on a systematic literature review for each tumor site from the larotrectinib trials, (2) an intracohort comparison using the previous line of therapy time to progression from larotrectinib trials, and (3) a nonresponder control that applied outcomes for larotrectinib nonresponders. Cost-effectiveness was modeled using the partitioned survival approach. Stochastic parameter uncertainty was assessed in a probabilistic sensitivity analysis (PSA). A triangulated estimate of the mean cost-effectiveness result was generated combining all 3 counterfactual estimates. Results: Incremental cost-effectiveness ratios were similar across the 3 methodologies in the deterministic analysis ranging from £83 868 (95% uncertainty interval [UI] £65 698-£107 668) to £104 922 per quality-adjusted life-year (95% UI £80 132-£139 658). PSA results for each method substantially overlapped when plotted on the cost-effectiveness plane. Weighting PSA results for each method equally in the triangulation method produced an incremental cost-effectiveness ratios of £95 587 per quality-adjusted life-year gained (95% UI £70 449-£137 431).
Conclusions: In the absence of direct comparative data, different methods of estimating a counterfactual are possible, each with strengths and limitations. Triangulating results across the methods provides a composite view of the total uncertainty and a more consistent estimation of the cost-effectiveness of the tumor-agnostic intervention compared with choosing a single method.

Background: Larotrectinib is a precision oncology treatment for solid tumors with neurotrophic tyrosine receptor kinase (NTRK) gene fusions. Larotrectinib efficacy has been evaluated in single-arm basket trials with limited follow-up and sample sizes at the initial regulatory approval due to the rarity of solid tumors with NTRK gene fusion. Objectives: We aim to demonstrate that trends in progression-free survival (PFS) and overall survival (OS) in survival data with longer follow-up may be predicted from long-term survival estimates from survival data with shorter follow-up, including predictions for median survival when it is not observed in the trial. Methods: Patient-level data were pooled from 3 clinical trials (NCT02122913, NCT02576431, and NCT02637687) using the 2018 and 2020 data cuts for the same subset of pediatric and adult patients. The Weibull distribution was selected for survival models. Survival predictions using 2018 data were compared to 2020 Kaplan-Meier (KM) curves. Results: A total of 102 patients representing 15 tumor types were included in the analysis, with a mean age of 37 years. When comparing PFS from the 2018 survival prediction to observed 2020 KM data, the 12-month PFS rate was identical (66.6%). The 36-month PFS rate was lower for the 2018 prediction (35.3%) compared to 2020 KM data (44.4%). The median OS had not yet been reached in either data cut but was predicted to be 90 months using the 2018 data. When comparing OS from the 2018 survival prediction to the observed 2020 KM data, the 12-month OS rate was 89.0% and 86.6% and the 48-month OS rate was 67.2% and 63.0%, respectively. Conclusion: Long-term PFS predictions deviated from observed PFS rates due to response differences across tumor types and heavy censoring towards the end of the survival curve. However, for OS, the 48-month survival prediction was consistent with the observed 2020 KM estimate.

Purpose: Larotrectinib, a highly specific tropomyosin receptor kinase (TRK) inhibitor, previously demonstrated high response rates in single-arm trials of patients with TRK fusion-positive cancer, but there are limited data on comparative effectiveness against standard-of-care (SoC) regimens used in routine health care practice, before widespread adoption of TRK inhibitors as SoC for TRK fusion-positive cancers. Matching-adjusted indirect comparison, a validated methodology that balances population characteristics to facilitate cross-trial comparisons, was used to compare the overall survival (OS) of larotrectinib versus non-TRK-inhibitor SoC. Materials and methods: Individual patient data from three larotrectinib trials (ClinicalTrials.gov identifiers: NCT02122913, NCT02637687, and NCT02576431) were compared with published aggregate real-world data from patients with locally advanced/metastatic TRK fusion-positive cancer identified in the Flatiron Health/Foundation Medicine database. OS was defined as the time from advanced/metastatic disease diagnosis to death. After matching population characteristics, the analyses included (1) a log-rank test of equality to test whether the two groups were similar before larotrectinib initiation; and (2) estimation of treatment effect of larotrectinib versus non-TRK-inhibitor SoC. These analyses are limited to prognostic variables available in real-world data. Results: Eighty-five larotrectinib patients and 28 non-TRK-inhibitor SoC patients were included in the analyses. After matching, log-rank testing showed no difference in baseline characteristics between the two groups (P = .31). After matching, larotrectinib was associated with a 78% lower risk of death, compared with non-TRK-inhibitor SoC (adjusted hazard ratio, 0.22 [95% CI, 0.09 to 0.52]; P = .001); median OS was 39.7 months (95% CI: 16.4, NE [not estimable]) for larotrectinib and 10.2 months (95% CI: 7.2, 14.1) for SoC. Conclusion: Matching-adjusted indirect comparison analyses suggest longer OS with larotrectinib, compared with non-TRK-inhibitor SoC, in adult patients with TRK fusion-positive cancer.

Our objective was to characterize patterns of preventive medication use in persons with episodic migraine (EM) and chronic migraine (CM).

Dry eye disease (DED) is a common ophthalmic disorder, with a prevalence of ranging from 5-33% globally and a substantial economic burden. Cyclosporine ophthalmic solution 0.09% (CEQUA) is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients with dry eye. It is a novel nanomicellar formulation of cyclosporine, which encapsulates cyclosporine for improved bioavailability and easier pre-corneal tear-film penetration after topical ocular administration. A budget impact model was developed to estimate the impact of introducing cyclosporine ophthalmic solution 0.09% for the treatment of DED from the perspective of a US health plan.

Locally advanced or metastatic urothelial carcinoma (la/mUC) is an incurable disease with poor long-term survival. The National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guideline recommendation for first-line (1L) treatment of la/mUC is gemcitabine + cisplatin (GC) or gemcitabine + carboplatin (GCa). For patients whose disease has not progressed following a platinum-based therapy, avelumab maintenance therapy is recommended. However, 1L treatment of Ia/mUC is an area of ongoing innovation and evaluation of novel treatment regimens with new clinical trials completed in recent years aiming to improve on standard of care (SOC). The objective of this study was to compare outcomes of all approved and investigational 1L regimens with SOC in the context of recently published data on newer treatment regimens by updating and expanding a previously reported systematic literature review (SLR) and network meta-analysis (NMA) of phase 2/3 randomized control trials (RCTs).

The primary treatment goal for Alzheimer’s disease (AD) is to slow or stop disease progression. This study estimated the value, from various perspectives, of slowed disease progression (SDP) compared with natural history (NH) in early AD.

Migraine is a disabling neurological disease that affects 14.7 % of Europeans. Studies evaluating the economic impact of migraine are complex to conduct adequately and with time become outdated as healthcare systems evolve. This study sought to quantify and compare direct medical costs of chronic migraine (CM) and episodic migraine (EM) in five European countries.

Cholinesterase inhibitors and memantine are medications used in the treatment of Alzheimer’s disease (AD). These agents have been shown to reduce the rate of AD progression in randomized trials. The objective of this study is to evaluate the association between treatment with cholinesterase inhibitors or memantine and the probability of transitioning to a more severe Clinical Dementia Rating (CDR) state.

Mild Alzheimer’s disease (AD) is often difficult to differentiate from mild cognitive impairment (MCI) or non-AD dementias. A multitude of diagnostic biomarkers and advanced imaging strategies have been developed to aid in the diagnosis and management of AD. We sought to review and analyze the published evidence on key test characteristics of major diagnostic strategies to formulate best estimates of sensitivity (SN) and specificity (SP).

Background: Multiple myeloma is an incurable B-cell malignancy with a natural history that involves alternating periods of remission and subsequent relapse. For relapsed and/or refractory multiple myeloma (RRMM), the typical patient currently receives more lines of therapy than has been feasible in the past, translating into longer progression-free survival (PFS). Consequently, cost issues have become more prominent because patients may be offered newer and more expensive therapies during a more prolonged overall treatment course. Objective: To estimate the economic impact of adding panobinostat to a U.S. health plan formulary as a treatment option with bortezomib and dexamethasone for patients with RRMM previously treated with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), using a budget impact and cost-benefit model. Methods: Total costs of commonly used salvage therapy regimens were combined with market share data and population prevalence estimates of RRMM to yield the total cost of treatment, from the perspective of a U.S. third-party payer (commercial or Medicare) with a time horizon of 1 year. Comparator treatment regimens included bortezomib-dexamethasone, lenalidomide-dexamethasone, lenalidomide-bortezomib-dexamethasone, carfilzomib monotherapy, carfilzomib-lenalidomide-dexamethasone, and pomalidomide-dexamethasone. Costs (2015 U.S. dollars) included drug costs for oral oncology agents, medical and administration costs for injectable oncology agents, costs of adverse event (AE) prophylaxis and monitoring, and costs of grade 3/4 AEs. Results: In a hypothetical health plan with 1 million members, the annual number of RRMM patients with previous PI and IMiD treatments was estimated at 16 and 118 for a commercial and Medicare plan, respectively. Introduction of panobinostat as part of the panobinostat-bortezomib-dexamethasone regimen was not expected to result in a substantial budget impact to either commercial or Medicare plans, with an incremental cost < $0.01 per member per month. Panobinostat-bortezomib-dexamethasone had a low cost per treated patient per month without progression, owing to the minimal increase in expenditure over existing bortezomib-based regimens and long median PFS, compared with median duration of treatment.Conclusions: Adding panobinostat to a plan formulary as a treatment option is expected to be cost neutral (and potentially cost saving in the context of new and more expensive treatment regimens). With a low cost per month without progression, panobinostat-bortezomib-dexamethasone represents good value for the money. Disclosures: Funding for this study was sponsored by Novartis, East Hanover, New Jersey. Bloudek and Kish are employees of Xcenda, a consulting company contracted by Novartis to conduct this analysis. Roy, Globe, and Kuriakose are employees of Novartis. Siegel is on the advisory boards and speaker's bureau of Celgene, Onyx/Amgen, Millennium/Takeda, and Novartis and is on the advisory boards of Merck. Jagannath is a consultant to Sanofi, Bristol-Meyers Squibb, and Celgene. Orloski is a contractor to Xcenda and provided medical writing support, which was funded by Novartis. Study design and concept were contributed by Bloudek, Roy, and Kish, assisted by Globe. Bloukek took the lead in data collection, along with Kish, and data interpretation was performed by Siegal, Jagannath, Globe, and Kuriakose. The manuscript was written primarily by Orloski, along with Roy and Kish, and revised by Roy, along with Siegal, Jagannath, Globe, Orloski, and Kuriakose.

In recent years, switch maintenance therapy (SMT) has become SoC in several cancer types; however, emerging new treatments evaluated using traditional randomized controlled trials (RCTs) offer potential survival gains. SMT patient populations and trial design have fundamental differences from traditional RCTs preventing direct comparison. We sought to identify HTA evaluations conducted across cancer types that compared SMTs with traditional RCTs to suggest possible approaches to overcome challenges in conducting indirect treatment comparisons.

BACKGROUND: Ulcerative colitis is a chronic immune-mediated inflammatory condition of the large intestine and rectum. Several targeted immune modulators (TIMs) have demonstrated effectiveness for the treatment of moderate to severe ulcerative colitis and are approved by the FDA. Patients may try multiple TIMs, and currently there are no biomarkers or prognostic factors to guide choice of treatment sequence. In 2020, the Institute for Clinical and Economic Review (ICER) conducted a review of TIMs for the treatment of ulcerative colitis as individual agents relative to conventional treatment but did not address the relative ranking of various treatment sequences to each other. OBJECTIVE: To extend the ICER framework to identify the optimal treatment sequence as informed by metrics such as maximizing incremental net health benefit (NHB), minimizing incremental total cost, or maximizing incremental quality-adjusted life-years (QALYs).

The Institute for Clinical and Economic Review (ICER) is an independent organization that reviews drugs and devices with a focus on emerging agents. As part of their evaluation, ICER estimates value-based prices (VBP) at $50 000 to $150 000 per quality-adjusted life-year (QALY) gained thresholds. We compared actual estimated net prices to ICER-estimated VBPs.

Stroke is the most common cause of upper and lower limb spasticity. Management of spasticity is associated with a substantial socioeconomic burden, with healthcare costs estimated to be 4 times higher for stroke survivors with spasticity compared with stroke survivors without spasticity. OnabotulinumtoxinA was approved by the US Food and Drug Administration (FDA) in 2010 for the treatment of upper limb spasticity in adults and in 2016 for the treatment of lower limb spasticity in adults. To date, no studies have investigated the impact of onabotulinumtoxinA treatment on healthcare resource utilization (HRU) and costs in the real world among patients with stroke-related spasticity. We assess the impact of onabotulinumtoxinA on HRU and costs among patients with stroke-related spasticity by comparing differences in 12-month HRU and costs before versus after initiation of onabotulinumtoxinA treatment in the United States.

Background: Imatinib was the first BCR-ABL tyrosine kinase inhibitor (TKI) approved in the United States for the treatment of patients with chronic myelogenous leukemia and is currently the most prescribed TKI. The impending loss of patent exclusivity for imatinib has the potential to reduce costs for payers. Objective: The primary objectives of this study were to estimate the economic impact of the loss of patent exclusivity for branded imatinib and to calculate the relative impact of requiring prior authorization (PA) for the use of generic imatinib before a branded TKI. The secondary objective was to evaluate the potential relative cost impact of using a preferred branded TKI in addition to the PA requirement for generic imatinib before a branded TKI.

The objectives of this systematic literature review (SLR) were to identify published cost-effectiveness models of treatments for chronic rhinosinusitis with nasal polyps to understand methodologies used in the models, including model structure and data source/input.

Acute urticaria is treated across various emergency departments (ED). As of October 2019, an intravenous (IV) formulation of the second-generation H1-antihistamine, cetirizine, has been FDA approved for the treatment of acute urticaria. Prior to the approval of IV cetirizine, the only IV H 1-antihistamine treatment available was first-generation diphenhydramine, which can cause sedation and anticholinergic effects. In a phase 3 clinical trial, IV cetirizine demonstrated efficacy in treating acute urticaria based on reduction in 2-hour patient-reported pruritus scores, with a shorter duration of ED visits compared to IV diphenhydramine and fewer return visits. We compare ED budget impact between IV diphenhydramine vs IV cetirizine as treatment options for acute urticaria by modeling clinical, facility and cost parameters for hospital formulary considerations.

Locally advanced or metastatic urothelial carcinoma (la/mUC) is an incurable disease with poor long-term survival. Systematic literature reviews (SLRs) and network meta-analyses (NMAs) have been performed in 1L la/mUC 4-11 ; however, since 2018 only one SLR/NMA has included contemporary data for PD-1/L1 inhibitors and other therapies in the 1L setting, but it is now outdated and lacks stratification by cisplatin eligibility. This SLR and NMA of randomised controlled trials (RCTs) compared outcomes of alternative 1L regimens for la/mUC with standard of care (SOC), stratified according to cisplatin eligibility, to better understand unmet needs in this setting.

To estimate the budget impact of adding bempedoic acid as a treatmentoption for major adverse cardiovascular event (MACE) prevention inpatients with high cardiovascular risk from a US payer perspective.

Background: Atopic dermatitis is a chronic inflammatory skin disease that can negatively impact work productivity and daily activities. Ruxolitinib cream, a Janus kinase inhibitor, demonstrated efficacy and safety in patients with atopic dermatitis in two phase III studies (TRuE-AD1 and TRuE-AD2). Objective: This post hoc analysis sought to describe the effects of ruxolitinib cream on work productivity and activity impairment from pooled data from the phase III studies, to estimate indirect costs due to atopic dermatitis, and to estimate the incremental cost savings with ruxolitinib cream versus vehicle cream.

To estimate the overall indirect costs due to workplace impairment associated with atopic dermatitis, based on data from phase 3 studies, in patients who applied ruxolitinib cream vs vehicle.

The advent of imatinib, the first-generation tyrosine kinase inhibitor (TKI), dramatically changed the treatment landscape and significantly improved survival outcomes of patients with chronic myelogenous leukemia (CML). Since loss of exclusivity (LOE) and the entry of a generic imatinib in the United States (US) in February 2016, US payers have started realizing savings. However, generic prices have taken 2 years to decline substantially.Here, we evaluate the impact of generic imatinib and the impact of formulary management on actual prices and savings over a 5-year period from LOE.

Objective: We demonstrate a new model framework as an innovative approach to more accurately estimate and project prevalence and survival outcomes in oncology.

Estimates of disease prevalence are crucial for health services planning and resource allocation. With respect to cancer, incidence and mortality can often be calculated directly from data collected by cancer registries and national health statistics. In contrast, cancer prevalence can only be derived from survival and mortality data over a long follow-up period. Therefore, economic and epidemiologic models in oncology often use indirect approaches to calculate disease prevalence using median overall survival (OS). In this study, we propose an alternative approach that provides more accurate estimates of prevalence.

Evidence from randomized controlled trials (RCTs) has shown that second-generation basal insulin (BI) analogues, insulin glargine 300 U/mL (Gla-300) and insulin degludec (IDeg), provide similar glycaemic control, with a lower risk of hypoglycaemia compared with the first-generation BI analogue insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes (T2D). However, the highly selected participants and frequent follow-up of RCTs may not be truly representative of real-life clinical practice. It is important to assess the safety and effectiveness of these second-generation BI analogues in real-life clinical practice settings. The DELIVER programme utilized electronic healthcare records from the United States to compare clinical outcomes in people with T2D who received either Gla-300 or other BI analogues in real-world clinical practice. This review provides a concise overview of the results of the DELIVER studies. Overall, Gla-300 provided similar antihyperglycaemic effectiveness and a lower risk of hypoglycaemia versus the first-generation BI analogues Gla-100 and insulin detemir in people with T2D who had switched BIs. In those who were insulin-naïve, initiation with Gla-300 versus Gla-100 was associated with significantly better antihyperglycaemic effectiveness and similar or lower hypoglycaemic risk. Both glycaemic control and hypoglycaemia risk were also shown to be similar with Gla-300 and IDeg, in people who had switched BIs and in those who were insulin-naïve. In addition, the DELIVER 2 study reported that people with T2D who switched to Gla-300 had reduced healthcare resource utilization, with an overall saving of US$1439 per person per year compared with those who switched to another BI analogue. Overall, the real-world DELIVER programme showed that the glycaemic control with a low risk of hypoglycaemia observed with Gla-300 in RCTs was also seen in standard clinical practice.

Objective: To characterize adherence with antidepressants, antiepileptic drugs, and beta blockers as prophylaxis against migraine in typical clinical practice.

Aim: Stakeholder engagement is central to comparative effectiveness research yet there are gaps in definitions of success. We used a framework developed by Lavallee et al. defining effective engagement criteria to evaluate stakeholder engagement during a pragmatic cluster-randomized trial. Methods: Semi-structured interviews were developed from the framework and completed to learn about members’ experiences. Interviews were analyzed in a deductive approach for themes related to the effective engagement criteria. Results: Thirteen members participated and described: respect for ideas, time to achieve consensus, access to information and continuous feedback as areas of effective engagement. The primary criticism was lack of diversity. Discussion: Feedback was positive, particularly among themes of respect, trust and competence, and led to development of a list of best practices for engagement. The framework was successful for evaluating engagement. Conclusion: Standardized frameworks allow studies to formally evaluate their stakeholder engagement approach and develop best practices for future research.

Background: Although chronic migraine is associated with substantial disability and costs, few treatments have been shown to be effective. OnabotulinumtoxinA (Botox, Allergan Inc., Irvine, CA) is the first treatment to be licensed in the UK for the prophylaxis of headaches in adults with chronic migraine. This study aims to evaluate the cost-effectiveness of onabotulinumtoxinA in this indication in the UK.

In well-functioning markets, a hedonic pricing scheme can reflect the marginal valuation of various attributes of a differentiated product at market equilibrium. It serves as an important tool to inform pricing of a new product with a specific combination of attributes. Because health cannot be bought and sold in a market setting, and health care markets are distorted by insurance or government subsidies, direct valuation of a health intervention as a differentiated good through observed market prices is difficult. In this article, we discuss the rationale of using stated preference methods for developing a hedonic value framework for health insurance products to inform the decision on whether a product should be covered or subsidized by insurance, given its price. This value index will not reflect marginal value at market equilibrium, as in a hedonic pricing scheme, but would capture the distribution of marginal value in the population. We discuss how affordability concerns can be integrated into the development of a hedonic valuation model. We compare this framework with traditional cost-effectiveness analysis and also the existing value frameworks put forth by various organizations. The framework can be adopted to inform other decisions such as pricing. We argue that developing such a comprehensive and decision-theoretic value framework is feasible and, if successful, can serve to inform health care resource allocation in this country for decades to come in a systematic manner.

Patients treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have shown either sustained remission or rapid progression. Traditional survival modeling may underestimate outcomes in these situations, by assuming the same mortality rate for all patients. To illustrate this issue, we compare standard parametric models to mixture cure models for estimating long-term overall survival in patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel). Compared to standard models without cure proportions, mixture cure models have similar fit, but substantially different extrapolated survival. Standard models (Weibull and generalized gamma) estimate mean survival of 2.0 years (95% CI (1.5, 3.0)) and 3.0 years (95% CI (1.7, 5.6)), respectively, compared to 15.7 years (95% CI (9.3, 21.1)) and 17.5 yrs (12.0, 22.8) from mixture cure models (using Weibull and generalized gamme distributions). For cancer therapies where substantial fractions achieve long term remission, our results suggest that assumptions of the modeling approach should be considered. Given sufficient follow-up, mixture cure models may provide a more accurate estimate of long-term overall survival compared with standard models.

Colony stimulating factors (CSF) are widely prescribed to avoid febrile neutropenia (FN) among cancer patients receiving chemotherapy, but studies show their use is often not consistent with practice guidelines. In addition, there is limited high quality evidence assessing benefits and harms of primary prophylactic-CSF (PP-CSF) in the setting of chemotherapy that poses an intermediate risk of FN. To address these issues, with funding from the Patient Centered Outcomes Research Institute (PCORI) and the National Cancer Institute’s Community Oncology Research Program, SWOG is sponsoring a prospective, cluster randomized controlled pragmatic trial of an automated order entry protocol for PP-CSF among patients with breast, lung and colorectal cancer receiving myelosuppressive chemotherapy, with a nested randomized controlled trial of PP-CSF for patients receiving intermediate risk chemotherapy. Primary outcomes include adherence to practice guidelines, overall rates of FN and rates of FN among persons receiving intermediate risk chemotherapy. The study, the first pragmatic trial in the National Cancer Institute’s cancer cooperative clinical trials network, will provide critical evidence to inform physician and patient decision-making around PP-CSF use and practice policies regarding automated orders in cancer components.

No abstract available

The objective of this literature review was to evaluate the costs associated with the use of long-acting insulin analogues (LAIAs) compared with non-LAIA agents, including human insulin, oral antidiabetic drugs, and other injectable therapies, in the treatment of patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).