A practical approach for adoption of a hub and spoke model for cell and gene therapies in low- and middle-income countries: framework and case studies.

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.

Supporting Biomarker-Driven Therapies in Oncology: A Genomic Testing Cost Calculator.

BACKGROUND: Adoption of high-throughput, gene panel-based, next-generation sequencing (NGS) into routine cancer care is widely supported, but hampered by concerns about cost. To inform policies regarding genomic testing strategies, we propose a simple metric, cost per correctly identified patient (CCIP), that compares sequential single-gene testing (SGT) vs. multiplex NGS in different tumor types. MATERIALS AND METHODS: A genomic testing cost calculator was developed based on clinically actionable genomic alterations identified in the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets. Using sensitivity/specificity data for SGTs (immunohistochemistry, polymerase chain reaction, and fluorescence in situ hybridization) and NGS and marker prevalence, the number needed to predict metric was monetarized to estimate CCIP. RESULTS: At base case, CCIP was lower with NGS than sequential SGT for advanced/metastatic non-squamous non-small cell lung cancer (NSCLC), breast, colorectal, gastric cancers, and cholangiocarcinoma. CCIP with NGS was also favorable for squamous NSCLC, pancreatic, and hepatic cancers, but with overlapping confidence intervals. CCIP favored SGT for prostate cancer. Alternate scenarios using different price estimates for each test showed similar trends, but with incremental changes in the magnitude of difference between NGS and SGT, depending on price estimates for each test. CONCLUSIONS: The cost to correctly identify clinically actionable genomic alterations was lower for NGS than sequential SGT in most cancer types evaluated. Decreasing price estimates for NGS and the rapid expansion of targeted therapies and accompanying biomarkers are anticipated to further support NGS as a preferred diagnostic standard for precision oncology.

Medicare Drug Price Negotiation in the United States: Implications and Unanswered Questions.

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.

Designing a Value-Based Formulary for a Commercial Health Plan: A Simulated Case Study of Diabetes Medications.

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.

Impact of treatment experience on patient knowledge of colony-stimulating factors among patients receiving cancer chemotherapy: evidence from S1415CD-a large pragmatic trial.

PURPOSE: Primary prophylactic granulocyte colony-stimulating factors (PP-CSFs) are prescribed alongside chemotherapy regimens that carry a significant risk of febrile neutropenia (FN). As part of S1415CD, a prospective, pragmatic trial evaluating the impact of automated orders to improve PP-CSF prescribing, we evaluated patients' baseline knowledge of PP-CSF and whether that knowledge improved following the first cycle of chemotherapy. METHODS: Adult patients with breast, colorectal, or non-small-cell lung cancer initiating chemotherapy were enrolled in S1415CD between January 2016 and April 2020. Eight questions assessing knowledge of CSF indications, risks, benefits, and out-of-pocket costs were included in a baseline survey and in a follow-up survey at the end of the first cycle of chemotherapy. Responses were stratified by the trial arm and whether chemotherapy was low, intermediate, or high FN risk. RESULTS: Of the 3605 eligible patients, 3580 (99.3%) completed the baseline survey, and 3420 (95.5%) completed the follow-up survey. At baseline, 803 (22.4%) patients responded "Don't know" to all 8 questions, and all patients averaged 2.75 correct questions. At follow-up, knowledge increased by 0.34 in the high-FN-risk group (p < 0.001) but declined for the other FN-risk groups. In multivariate analysis, receiving a high-FN-risk regimen and younger age were significantly associated with knowledge improvement. CONCLUSION: Chemotherapy patients had poor knowledge of PP-CSF that improved only modestly among recipients of high-FN-risk chemotherapy. Further efforts to inform patients about the risks, benefits, and costs of PP-CSF may be warranted, particularly for those in whom prophylaxis is indicated. TRIAL REGISTRATION: NCT02728596, April 6, 2016.

Estimating Long-Term Survival Outcomes for Tumor-Agnostic Therapies: Larotrectinib Case Study.

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.

Comparison of Alternative Methods to Assess the Cost-Effectiveness of Tumor-Agnostic Therapies: A Triangulation Approach Using Larotrectinib as a Case Study.

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.

Successes and challenges of implementing a cancer care delivery intervention in community oncology practices: lessons learned from SWOG S1415CD.

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. TRIAL REGISTRATION: NCT02728596 , registered April 5, 2016.

Insulin glargine 300 units/mL for the treatment of individuals with type 2 diabetes in the real world: A review of the DELIVER programme.

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.

Are Drugs Priced in Accordance With Value? A Comparison of Value-Based and Net Prices Using Institute for Clinical and Economic Review Reports.

OBJECTIVES: 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. METHODS: We reviewed ICER final evidence reports from November 2007 to October 2020. List prices were combined with average discounts obtained from SSR Health to estimate net prices. If a drug had been evaluated more than once for the same indication, only the more recent VBP was included. RESULTS: A total of 34 ICER reports provided unique VBPs for 102 drugs. The net price of 81% of drugs exceeded the $100 000 per QALY VBP and 71% exceeded the $150 000 per QALY VBP. The median change in net price needed to reach the $150 000 per QALY VBP was a 36% reduction. The median decrease in net price needed was highest for drugs targeting rare inherited disorders (n = 15; 62%) and lowest for cardiometabolic disorders (n = 6; 162% price increase). The reduction in net prices needed to reach ICER-estimated VBPs was higher for drugs evaluated for the first approved indication, rare diseases, less competitive markets, and if the drug approval occurred before the ICER report became available. CONCLUSION: Net prices are often above VBPs estimated by ICER. Although gaining awareness among decision makers, the long-term impact of ICER evaluations on pricing and access to new drugs continues to evolve.

A pragmatic randomized clinical trial of insulin glargine 300 U/mL vs first-generation basal insulin analogues in insulin-naïve adults with type 2 diabetes: 6-month outcomes of the ACHIEVE Control study.

AIMS: To compare the safety and efficacy of insulin glargine 300 U/mL (Gla-300) versus first-generation standard-of-care basal insulin analogues (SOC-BI; insulin glargine 100 U/mL or insulin detemir) at 6 months. METHODS: In the 12-month, open-label, multicentre, randomized, pragmatic ACHIEVE Control trial, insulin-naïve adults with type 2 diabetes (T2D) and glycated haemoglobin (HbA1c) 64 to 97 mmol/mol (8.0%-11.0%) after ≥1 year of treatment with ≥2 diabetes medications were randomized to Gla-300 or SOC-BI. The composite primary endpoint, evaluated at 6 months, was the proportion of participants achieving individualized HbA1c targets per Healthcare Effectiveness Data and Information Set (HEDIS) criteria without documented symptomatic (blood glucose ≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at any time of the day at 6 months. RESULTS: Of 1651 and 1653 participants randomized to Gla-300 and SOC-BI, respectively, 31.3% and 27.9% achieved the composite primary endpoint at 6 months (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01-1.39; P = 0.03 for superiority); 78.4% and 75.3% had no documented symptomatic or severe hypoglycaemia (OR 1.19, 95% CI 1.01-1.41). Changes from baseline to month 6 in HbA1c, fasting plasma glucose, weight, and BI analogue dose were similar between groups. CONCLUSIONS: Among insulin-naïve adults with poorly controlled T2D, Gla-300 was associated with a statistically significantly higher proportion of participants achieving individualized HEDIS HbA1c targets without documented symptomatic or severe hypoglycaemia (vs SOC-BI) in a real-life population managed in a usual-care setting. The ACHIEVE Control study results add value to treatment decisions and options for patients, healthcare providers, payers and decision makers.

Integrating Formal Technology Assessment into an Integrated Healthcare Delivery System: Smart Innovation.

OBJECTIVES: We designed, developed, and implemented a new hospital-based health technology assessment (HB-HTA) program called Smart Innovation. Smart Innovation is a decision framework that reviews and makes technology adoption decisions. Smart Innovation was meant to replace the fragmented and complex process of procurement and adoption decisions at our institution. Because use of new medical technologies accounts for approximately 50 percent of the growth in healthcare spending, hospitals and integrated delivery systems are working to develop better processes and methods to sharpen their approach to adoption and management of high cost medical innovations. METHODS: The program has streamlined the decision-making process and added a robust evidence review for new medical technologies, aiming to balance efficiency with rigorous evidence standards. To promote system-wide adoption, the program engaged a broad representation of leaders, physicians, and administrators to gain support. RESULTS: To date, Smart Innovation has conducted eleven HB-HTAs and made clinician-led adoption decisions that have resulted in over $5 million dollars in cost avoidance. These are comprised of five laboratory tests, three software-assisted systems, two surgical devices, and one capital purchase. CONCLUSIONS: Smart Innovation has achieved cost savings, avoided uncertain or low-value technologies, and assisted in the implementation of new technologies that have strong evidence. The keys to its success have been the program's collaborative and efficient decision-making systems, partnerships with clinicians, executive support, and proactive role with vendors.

Comparable glycaemic control and hypoglycaemia in adults with type 2 diabetes after initiating insulin glargine 300 units/mL or insulin degludec: The DELIVER Naïve D real-world study.

AIM: To compare glycaemic control, hypoglycaemia and treatment discontinuation of insulin glargine 300 units/mL (Gla-300) and insulin degludec (IDeg) in a real-world study of insulin-naïve adults with type 2 diabetes (T2D). MATERIALS AND METHODS: DELIVER Naive D was a retrospective observational study that used electronic medical record data from the IBM Watson Health Explorys database. Insulin-naïve adults with T2D who started Gla-300 or IDeg between March 2015 and September 2017 were identified. Patients were active in the system for ≥12 months before and ≥6 months after starting Gla-300 or IDeg and had HbA1c measurements during 6-month baseline and 3- to 6-month follow-up. Outcomes were compared among 1:1 propensity score-matched cohorts. RESULTS: In the matched cohorts (n = 638 each), the mean age was 59 years, approximately 53% were male, and mean HbA1c was 9.67% (82 mmol/mol). Mean (SD) HbA1c decreases were comparable in the Gla-300 and IDeg cohorts (-1.67% [2.22] and -1.58% [2.20]; P = 0.51), as were HbA1c target attainment [<7% (53 mmol/mol): 23.8% and 27.4%; P = 0.20; <8% (64 mmol/mol): 55.0% and 57.1%; P = 0.63] and treatment discontinuation (29.2% and 32.6%; P = 0.14). Overall and inpatient/emergency department-associated hypoglycaemia incidences and event rates were similar in both cohorts using fixed 6-month or variable on-treatment follow-up. CONCLUSIONS: Among real-world insulin-naïve adults with T2D, initiation of Gla-300 or IDeg resulted in comparable improvements in glycaemic control and similar rates of hypoglycaemia. These real-world data complement and confirm a randomized trial and other real-world studies.

Analytic Considerations in Applying a General Economic Evaluation Reference Case to Gene Therapy.

The concept of a reference case, first proposed by the US Panel on Cost-Effectiveness in Health and Medicine, has been used to specify the required methodological features of economic evaluations of healthcare interventions. In the case of gene therapy, there is a difference of opinion on whether a specific methodological reference case is required. The aim of this article was to provide a more detailed analysis of the characteristics of gene therapy and the extent to which these characteristics warrant modifications to the methods suggested in general reference cases for economic evaluation. We argue that a completely new reference case is not required, but propose a tailored checklist that can be used by analysts and decision makers to determine which aspects of economic evaluation should be considered further, given the unique nature of gene therapy.

Effective stakeholder engagement: design and implementation of a clinical trial (SWOG S1415CD) to improve cancer care.

BACKGROUND: The Fred Hutchinson Cancer Research Center has engaged an External Stakeholder Advisory Group (ESAG) in the planning and implementation of the TrACER Study (S1415CD), a five-year pragmatic clinical trial assessing the effectiveness of a guideline-based colony stimulating factor standing order intervention. The trial is being conducted by SWOG through the National Cancer Institute Community Oncology Research Program in 45 clinics. The ESAG includes ten patient partners, two payers, two pharmacists, two guideline experts, four providers and one medical ethicist. This manuscript describes the ESAG's role and impact on the trial. METHODS: During early trial development, the research team assembled the ESAG to inform plans for each phase of the trial. ESAG members provide feedback and engage in problem solving to improve trial implementation. Each year, members participate in one in-person meeting, web conferences and targeted email discussion. Additionally, they complete a survey that assesses their satisfaction with communication and collaboration. The research team collected and reviewed stakeholder input from 2014 to 2018 for impact on the trial. RESULTS: The ESAG has informed trial design, implementation and dissemination planning. The group advised the trial's endpoints, regimen list and development of cohort and usual care arms. Based on ESAG input, the research team enhanced patient surveys and added pharmacy-related questions to the component application to assess order entry systems. ESAG patient partners collaborated with the research team to develop a patient brochure and study summary for clinic staff. In addition to identifying recruitment strategies and patient-oriented platforms for publicly sharing results, ESAG members participated as co-authors on this manuscript and a conference poster presentation highlighting stakeholder influence on the trial. The annual satisfaction survey results suggest that ESAG members were satisfied with the methods, frequency and target areas of their engagement in the trial during project years 1-3. CONCLUSIONS: Diverse stakeholder engagement has been essential in optimizing the design, implementation and planned dissemination of the TrACER Study. The lessons described in the manuscript may assist others to effectively partner with stakeholders on clinical research.

Economic Value of Greater Access to Bariatric Procedures for Patients With Severe Obesity and Diabetes.

OBJECTIVE: Designing optimal insurance is important to ensure access to care for individuals that are most likely to benefit. We examined the potential impact of lowering patient cost-sharing for bariatric procedures. METHODS: After defining 10 subgroups by body mass index (BMI) and type 2 diabetes mellitus (T2DM), we analyzed the National Health and Nutrition Examination Survey datasets to estimate the prevalence of each subgroup. The MarketScan claims database provided utilization rates and costs of bariatric procedures. Using an existing cost-effectiveness model, we estimated the economic value of bariatric procedures under various cost-sharing levels (0%-25%) with 2 frameworks: (1) a traditional cost-effectiveness analysis and (2) a new approach that incorporates utilization effects across subgroups. RESULTS: The utilization rate was higher among individuals with T2DM than those without T2DM (90.4 vs. 59.1 cases per 100,000) for bariatric procedures, which were more cost-effective for those with T2DM and a higher BMI. After accounting for utilization effects, the economic value of bariatric surgery was $177 and $63 per individual from a lifetime and a 5-year time horizon, respectively. Under no patient cost-sharing for individuals with BMI≥40 and T2DM, utilization rates were expected to increase by 21 cases per 100,000, resulting in additional $2 realized value per patient and $7.07 million in returns at the US population level. CONCLUSIONS: Cost-sharing is a barrier to uptake of a clinical and cost-effective treatment for severe obesity. Reducing cost-sharing for patients with severe obesity and T2DM could potentially increase the utilization of bariatric procedures and result in greater economic value to payers.

Clinical outcomes in real-world patients with type 2 diabetes switching from first- to second-generation basal insulin analogues: Comparative effectiveness of insulin glargine 300 units/mL and insulin degludec in the DELIVER D+ cohort study.

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.

Price elasticities of pharmaceuticals in a value based-formulary setting.

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.

Returns to scientific publications for pharmaceutical products in the United States.

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.