Ionization Cross Sections of Hydrogen Molecule by Electron and Positron Impact.

We present ionization cross sections of hydrogen molecules by electron and positron impact for impact energies between 20 and 1000 eV. A three-body Classical Trajectory Monte Carlo approximation is applied to mimic the collision system. In this approach, the H2 molecule is modeled by a hydrogen-type atom with one active electron bound to a central core of effective charge with an effective binding energy. Although this model is crude for describing a hydrogen molecule, we found that the total cross sections for positron impact agree reasonably well with the experimental data. For the electron impact, our calculated cross sections are in good agreement with the experimental data in impact energies between 80 eV and 400 eV but are smaller at higher impact energies and larger at lower impact energies. Our calculated cross sections are compared with the scaled cross sections obtained experimentally for an atomic hydrogen target. We also present single differential cross sections as a function of the energy and angle of the ejected electron and scattered projectiles for a 250 eV impact. These are shown to agree well with available data. Impact parameter distributions are also compared for several impact energies.

Health Care Spending Effectiveness: Estimates Suggest That Spending Improved US Health From 1996 To 2016.

Health care spending effectiveness is the ratio of an increase in spending per case of illness or injury to an increase in disability-adjusted life-years (DALYs) averted per case. We report US spending-effectiveness ratios, using comprehensive estimates of health care spending from the Disease Expenditure Project and DALYs from the Global Burden of Disease Study 2017. We decomposed changes over time to estimate spending per case and DALYs averted per case, controlling for changes in population size, age-sex structure, and incidence or prevalence of cases. Across all causes of health care spending and disease burden, median spending was US$114,339 per DALY averted between 1996 and 2016. Twelve of thirty-four causes with the highest spending or highest burden had median spending that was less than $100,000 per DALY averted. Using decomposition results, we calculated an outcome-adjusted health care price index by assigning a dollar value to DALYs averted per case. When we used $100,000 as the dollar value per DALY averted, prices increased by 4 percent more than the broader economy; when we used $150,000 per DALY averted, relative prices fell by 13 percent, meaning that much of the growth in health care spending over time has purchased health improvements.

What might have happened: the impact of interrupting entry of innovative drugs on disease outcomes in the United States.

INTRODUCTION: The study estimated the extent to which drug innovations over the past 30 years may have improved outcomes for six diseases. AREAS COVERED: We analyzed six diseases (ischemic heart disease, lung cancer, breast cancer, human immunodeficiency virus [HIV] infection, type 2 diabetes mellitus, and rheumatoid arthritis [RA]) with significant mortality or morbidity for which there have been major drug innovations over the past 30 years. We used U.S. data from the Global Burden of Disease (GBD) database and a patient registry to perform counterfactual time-series analyses predicting the improved health outcomes that may have been associated with major drug innovations. For 5 conditions using data from the GBD study, years of life lost per individual with the condition could have been higher by 17.1% (breast cancer) to 660.6% (HIV infection) in 2017 had the major drug innovations not been introduced. For RA, using patient registry data, patients' functional status could have been 11.5% worse had biological therapies not been introduced. EXPERT OPINION: Policies targeting drug prices should be broadened to consider the price and value of all health-care services. The societal importance of the pharmaceutical industry's ability to respond rapidly to emerging diseases should be recognized.

Health spending expenditures for commercial plans are predominantly concentrated among a small population of high-intensity consumers across settings of care.

BACKGROUND: Rising health care spending has sparked new efforts to constrain health care expenditures. OBJECTIVE: To explore how health care spending is distributed across consumers and how utilization patterns compare across health care resource expenditures (eg, hospital, outpatient care). METHODS: Using the IQVIA PharMetrics Plus database, we conducted a retrospective claims analysis for the 2018 plan year to examine commercial health care spending and utilization across 5 settings of care: ambulatory services, inpatient services, office visits, pharmacy services, and additional services. RESULTS: Consistent with findings from previous analyses of total health spending, total health care spending for a large commercially insured population was largely concentrated within a small population of high-intensity consumers. These patterns persist when looking at individual segments of spending, including spending on prescription drugs and inpatient and ambulatory services. Inpatient spending was the most concentrated, with 97% of spending occurring within the top tenth percentile of patients. CONCLUSIONS: Our findings suggest that health care spending for commercial plans is predominantly concentrated within a small population of high-intensity consumers across all settings of care. Curbing rising health care spending will require systemwide evaluation of the value of spending within and across settings of care for a subset of high-resource-use patients. This is particularly important for health care settings with the highest concentration of spending, including inpatient care. DISCLOSURES: This study was funded by the National Pharmaceutical Council (NPC). Ciarametaro, Buelt, and Dubois are employed by the NPC. Kleinrock and Campbell are employed by IQVIA, which was contracted by the NPC for data analysis.

The Dollar or Disease Burden: Caps on Healthcare Spending May Save Money, but at What "Cost" to Patients?

OBJECTIVES: Various strategies to address healthcare spending and medical costs continue to be debated and implemented in the United States. To date, these efforts have failed to adequately contain the growth of healthcare cost. An alternative strategy that has elicited rising interest among policymakers is budget caps. As budget caps become more prevalent, it is important to identify which features are needed to ensure success, both in terms of cost reduction and health improvement. METHODS: We explored the impacts of different features of budget caps by comparing hypothetical service level and global budget caps across 3 annual budget cap growth strategies over a 10-year timeframe in 2005-2015 for 8 of the most commonly occurring conditions in the United States. Health was assessed by a measure of disease burden (disability-adjusted life years). RESULTS: The results indicate that budget caps have the potential for creating savings but can also result in patient harm if not designed well. As a result of these findings, 5 principles were developed for designing budget caps and should guide the use of budget caps to address medical spending. CONCLUSIONS: As public discussion grows about the use of budget caps to constrain health spending, it is critical to recognize that the budget cap design and the resulting healthcare provider behavior will determine whether there is potential harm to public health. Budget cap design should consider variability at the condition level, including patient population, improvements in health, treatment costs, and the innovations available, to both create savings and maximize patient health. In assessing the impact of healthcare spending caps on costs and disease burden, we demonstrate that budget cap design determines potential harm to public health.

Stakeholders find that step therapy should be evidence-based, flexible, and transparent: assessing appropriateness using a consensus approach.

BACKGROUND: Step therapy, one approach to utilization management, is used by health plans to ensure safe and clinically appropriate care while managing cost. Several patient and provider groups have each developed principles to guide the appropriate use of step therapy; however, no comprehensive multistakeholder informed set of criteria exist. OBJECTIVE: To assess multistakeholder consensus on criteria for the development and implementation of step therapy for pharmaceutical therapies. Stakeholders were asked to (a) assess the appropriateness of step therapy as a utilization management tool; (b) rate specific criteria across 5 domains (development, implementation, communication, appeals, and evaluation) of step therapy; and (c) categorize these criteria as standards or best practices. METHODS: We conducted a multiphase project culminating in a roundtable of experts representing patient, provider, plan, pharmacy, policy, and ethical perspectives. We first reviewed guiding principles, position statements, and legislative activity to draft criteria regarding step therapy protocol development, implementation, communication, and evaluation. To assess consensus across a convenience sample of experts, we employed an iterative 4-step modified Delphi method. Panelists were asked to (a) rate the overall appropriateness of step therapy, (b) rate the appropriateness of specific criteria, and (c) identify each as a standard or best practice. Appropriateness was rated from 1-9 and categorized in terciles (1-3: not appropriate, 4-6: neither, 7-9: appropriate) to assess quantitative agreement, disagreement, and indeterminate agreement. RESULTS: After the second round of voting, roundtable panelists (n = 16) disagreed on the appropriateness of step therapy for utilization management (50% appropriate, 31.25% neither, and 18.75% inappropriate). Agreement was achieved on 21 criteria across 5 themes (clinical criteria as the foundation for protocol development, implementation of protocols, transparency and communication of processes, navigation of the appeals process, and evaluation of health and administrative impact). Fourteen and seven criteria were categorized as standards and best practices, respectively. CONCLUSIONS: The stakeholders in this panel differed in their assessments of the appropriateness of step therapy but agreed regarding how these protocols should be developed, implemented, communicated, and evaluated. Most criteria were rated as standards that can be used by stakeholders when developing, implementing, and assessing step therapy processes today. DISCLOSURES: This study was funded by the National Pharmaceutical Council. Karmarkar was a fellow at the National Pharmaceutical Council and Duke-Margolis Center for Health Policy at the time this study was conducted. Dubois and Graff are employees of the National Pharmaceutical Council. This work was previously presented as a virtual poster during the AMCP 2020 eLearning Days, April 21-24, 2020.

Are ACOs Ready to be Accountable for Medication Use?

BACKGROUND: Accountable care organizations (ACOs) have the potential to lower costs and improve quality through incentives and coordinated care. However, the design brings with it many new challenges. One such challenge is the optimal use of pharmaceuticals. Most ACOs have not yet focused on this integral facet of care, even though medications are a critical component to achieving the lower costs and improved quality that are anticipated with this new model. OBJECTIVE: To evaluate whether ACOs are prepared to maximize the value of medications for achieving quality benchmarks and cost offsets. METHODS: During the fall of 2012, an electronic readiness self-assessment was developed using a portion of the questions and question methodology from the National Survey of Accountable Care Organizations, along with original questions developed by the authors. The assessment was tested and subsequently revised based on feedback from pilot testing with 5 ACO representatives. The revised assessment was distributed via e-mail to a convenience sample (n=175) of ACO members of the American Medical Group Association, Brookings-Dartmouth ACO Learning Network, and Premier Healthcare Alliance. RESULTS: The self-assessment was completed by 46 ACO representatives (26% response rate). ACOs reported high readiness to manage medications in a few areas, such as transmitting prescriptions electronically (70%), being able to integrate medical and pharmacy data into a single database (54%), and having a formulary in place that encourages generic use when appropriate (50%). However, many areas have substantial room for improvement with few ACOs reporting high readiness. Some notable areas include being able to quantify the cost offsets and hence demonstrate the value of appropriate medication use (7%), notifying a physician when a prescription has been filled (9%), having protocols in place to avoid medication duplication and polypharmacy (17%), and having quality metrics in place for a broad diversity of conditions (22%). CONCLUSIONS: Developing the capabilities to support, monitor, and ensure appropriate medication use will be critical to achieve optimal patient outcomes and ACO success. The ACOs surveyed have embarked upon an important journey towards this goal, but critical gaps remain before they can become fully accountable. While many of these organizations have begun adopting health information technologies that allow them to maximize the value of medications for achieving quality outcomes and cost offsets, a significant lag was identified in their inability to use these technologies to their full capacities. In order to provide further guidance, the authors have begun documenting case studies for public release that would provide ACOs with examples of how certain medication issues have been addressed by ACOs or relevant organizations. The authors hope that these case studies will help ACOs optimize the value of pharmaceuticals and achieve the "triple aim" of improving care, health, and cost. DISCLOSURES: There was no outside funding for this study, and the authors report no conflicts of interest related to the article. Concept and design were primarily from Dubois and Kotzbauer, with help from Feldman, Penso, and Westrich. Data collection was done by Feldman, Penso, Pope, and Westrich, and all authors participated in data interpretation. The manuscript was written primarily by Westrich, with help from all other authors, and revision was done primarily by Lustig and Westrich, with help from all other authors.

Do Patient Preferences Align With Value Frameworks? A Discrete-Choice Experiment of Patients With Breast Cancer.

Purpose. Assess patient preferences for aspects of breast cancer treatments to evaluate and inform the usual assumptions in scoring rubrics for value frameworks. Methods. A discrete-choice experiment (DCE) was designed and implemented to collect quantitative evidence on preferences from 100 adult female patients with a self-reported physician diagnosis of stage 3 or stage 4 breast cancer. Respondents were asked to evaluate some of the treatment aspects currently considered in value frameworks. Respondents' choices were analyzed using logit-based regression models that produced preference weights for each treatment aspect considered. Aggregate- and individual-level preferences were used to assess the relative importance of treatment aspects and their variability across respondents. Results. As expected, better clinical outcomes were associated with higher preference weights. While life extensions with treatment were considered to be most important, respondents assigned great value to out-of-pocket cost of treatment, treatment route of administration, and the availability of reliable tests to help gauge treatment efficacy. Two respondent classes were identified in the sample. Differences in class-specific preferences were primarily associated with route of administration, out-of-pocket treatment cost, and the availability of a test to gauge treatment efficacy. Only patient cancer stage was found to be correlated with class assignment (P = 0.035). Given the distribution of individual-level preference estimates, preference for survival benefits are unlikely to be adequately described with two sets of preference weights. Conclusions. Although value frameworks are an important step in the systematic evaluation of medications in the context of a complex treatment landscape, the frameworks are still largely driven by expert judgment. Our results illustrate issues with this approach as patient preferences can be heterogeneous and different from the scoring weights currently provided by the frameworks.

Are Value-Based Arrangements the Answer We've Been Waiting for?

In response to rising healthcare costs, value-based arrangements (VBAs) have emerged as a mechanism for transforming how we pay for high-cost therapies. As we think about how VBAs fit into the larger effort of the United States healthcare system to transition to value-based payment, it is important to consider the strengths and limitations associated with this model and to set appropriate expectations for what VBAs can realistically achieve. For example, for VBAs to meaningfully affect overall healthcare spending, there needs to be a sufficient number of products that meet the ideal criteria for a value-based contract. These products also need to represent a meaningful share of healthcare spending, and the VBA contracts need to be designed with enough financial risk to actually influence spending. Although there are limited data about the components of current contracts (eg, how much financial risk is involved, product and class specifications), VBAs will likely not be a singular solution for improving healthcare cost containment. Instead, VBAs offer an opportunity for the US healthcare system to achieve higher value for dollars spent when implemented in combination with other value-based payment mechanisms and policies that disincentivize low-value care.

Barriers and Solutions to the Inclusion of Broader Benefits in Biopharmaceutical Value Assessments.

OBJECTIVE: The aim of this was to evaluate how institutional barriers prevent the inclusion of broader individual and societal benefits associated with new health care innovations from being considered when assessing the value of medical treatments and making health care coverage determinations. METHODS: A survey of health insurance providers, pharmacy benefit managers, employee benefit consultancies, and employer group representatives in the United States queried respondents' opinions regarding the feasibility of evaluating indirect treatment benefits in four domains: absenteeism, presenteeism, caregiver burden, and quality of life. RESULTS: Inclusion of indirect benefits (including absenteeism and presenteeism) in the assessment of a treatment's value was of low importance to payers, but higher importance to employer stakeholders. CONCLUSIONS: Therapies that improve physical or mental function accrue benefits both directly and indirectly and can only be adequately assessed if measurement standards for indirect benefits and quantifiable measures are established.

As Value Assessment Frameworks Evolve, Are They Finally Ready for Prime Time?

BACKGROUND: Value assessment frameworks have emerged as tools to assist healthcare decision makers in the United States in assessing the relative value of healthcare services and treatments. As more healthcare decision makers in the United States-including state government agencies, pharmacy benefit managers, employers, and health plans-publicly consider the adoption of value frameworks, it is increasingly important to critically evaluate their ability to accurately measure value and reliably inform decision making. OBJECTIVE: To examine the evolution of the value assessment landscape in the past two years, including new entrants and updated frameworks, and assess if these changes successfully advance the field of value assessment. METHODS: We analyzed the progress of the three currently active value assessment frameworks developed by the Institute for Clinical and Economic Review, the Innovation and Value Initiative, and the National Comprehensive Cancer Network, against six key areas of concern. RESULTS: Value assessment frameworks are moving closer to meeting the challenge of accurately measuring value and reliably informing healthcare decisions. Each of the six concerns has been addressed in some way by at least one framework. CONCLUSIONS: Although value assessments are potential inputs that can be considered for healthcare decision making, none of them should be the sole input for these decisions. Considering the limitations, they should, at most, be only one of many tools in the toolbox.

Reconciling the Seemingly Irreconcilable: How Much Are We Spending on Drugs?

BACKGROUND: Estimates of drug spending are often central to the public policy debate on how to manage healthcare spending in the United States. Nevertheless, common estimates of prescription drug spending vary substantially by source, which can inhibit productive policy dialogue. OBJECTIVES: To review publicly reported estimates of drug spending and uncover the underlying methodological inputs that drive the substantial variation in estimates of prescription drug spending. METHODS: We systematically evaluated 5 estimates of drug spending to identify differences in the underlying methodological inputs and approaches. To uniformly assess and compare estimates, we developed a model to identify the inputs of 3 primary components associated with each estimate: numerator (How is drug cost measured?), denominator (How is healthcare cost measured?), and population (What group of individuals is included in the measurement?). We then applied standardized methodological inputs to each estimate to assess whether variation among estimates could be reconciled. We then conducted a sensitivity analysis to address important limitations. RESULTS: We found that the 18.8 percentage point range in the publicly reported estimates is predominately attributed to methodological differences. Reconciling estimates using a standardized methodological approach reduces this range to 4.0 percentage points. CONCLUSIONS: Because variation in estimates of drug spending is primarily driven by methodological differences, stakeholders should seek to establish a mutually agreed upon methodological approach that is appropriate for the policy question at hand to provide a sound basis for health spending policy discussions.

US care pathways: continued focus on oncology and outstanding challenges.

OBJECTIVES: To update an ongoing assessment of care pathway development, implementation, and evaluation, and to evaluate the emerging relationship between care pathways and other components of value-based care. STUDY DESIGN: Targeted literature review followed by an online survey and in-depth interviews. METHODS: The PubMed/Cochrane databases and gray literature were searched for publications on care pathways (January 1, 2014, to March 3, 2017); a supplemental targeted search was completed in October 2017. Qualitative data were collected via an online survey and semistructured, in-depth interviews with payers, providers, pathway vendors, and opinion leaders. RESULTS: A total of 112 articles or posters were identified in recently published research. The survey and interviews included 32 and 19 respondents, respectively. Care pathways are increasingly driven by providers and provider networks. Overall, we found increased awareness of and adherence to codified best practices or standards, and prioritization of high-quality evidence during development. Research findings suggest stronger links between outcomes-based measures and both physician reimbursement and care pathway evaluation. Integration with other value-based care initiatives, including alternative payment models, is also gradually emerging. CONCLUSIONS: This study identified growing use of high standards of evidence and adoption of other best practices in the development, implementation, and evaluation of care pathways. As the influence of care pathways on patient care continues to expand, additional efforts are needed to increase transparency, disclose conflicts of interest, engage with patients, effectively align care pathways with improvements in patient outcomes, and integrate efficiently with other value-based care initiatives.

Value-based arrangements may be more prevalent than assumed.

OBJECTIVES: To better understand the prevalence of US value-based payment arrangements (VBAs), their characteristics, and the factors that facilitate their success or act as barriers to their implementation. STUDY DESIGN: Surveys were administered to a convenience sample of subject matter experts who were senior representatives from payer organizations and biopharmaceutical manufacturers. These data were supplemented with qualitative interviews in a subsample of survey respondents. METHODS: Descriptive statistics, including percentages for categorical values and mean (SD) and median (interquartile range) for continuous variables, were assessed for quantitative questions. Trained reviewers collated responses to free-text survey questions and the qualitative interviews to identify themes. RESULTS: Of the 25 respondents, 1 manufacturer and 4 payers reported not having explored or negotiated any VBAs. Subsequently, questionnaire results from 11 biopharmaceutical manufacturers and 9 payers who had experience with VBAs were analyzed. More than 70% of VBAs implemented between 2014 and 2017 were not publicly disclosed. Furthermore, although consideration of VBAs as a coverage and payment tool is increasing, VBA implementation is relatively low, with manufacturers and payers reporting that approximately 33% and 60% of early dialogues translate into signed VBA contracts, respectively. Respondents' reasoning for VBA negotiation process breakdowns generally differed by sector and reflected each sector's respective priorities. CONCLUSIONS: This study reveals that the majority of VBAs are not publicly disclosed, which could underestimate their true prevalence and impact. Given the effort required to implement a VBA, future arrangements would likely benefit from a framework or other evaluative tool to help assess VBA pursuit desirability and guide the negotiation and implementation process.

What's Been The Bang For The Buck? Cost-Effectiveness Of Health Care Spending Across Selected Conditions In The US.

The continued rise in health care spending has led to an intense debate among policy makers and other health care stakeholders on how to best manage increasing costs, leading to a focus on cost increases with little consideration of the associated change in outcomes. We identified the extent to which increased medical intervention spending on seven prevalent chronic conditions in the US over a twenty-year period has been a good investment. The results provide disease-level cost-effectiveness ratios for comparing changes in medical care spending to changes in health outcomes for patients diagnosed with one of the conditions. This study has two key findings: First, dollars spent on medical care can be a source of high value creation, and such investment should continue. Second, significant variability in value exists across diseases, which highlights the need for disease-specific spending approaches.

Utilization of High-Cost Interventions for Targeted Clinical Conditions During the Early Stages of ACO Development in a Commercially Insured Population.

This study compared utilization patterns of high-cost services and medications for patients receiving care from Accountable Care Organization (ACO)-participating physicians and those receiving care from non-ACO physicians during the initial phases of ACO development in a commercially insured environment. Patients ≥18 years (≥40 years for chronic obstructive pulmonary disease [COPD]) with prevalent rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 2 diabetes, COPD, or chronic low back pain between January 1, 2012, and August 31, 2014 were identified in the HealthCore Integrated Research DatabaseSM. Patients were assigned to the ACO cohort if their primary treating physician was contracted to the health plan through an ACO agreement. Each clinical condition was stratified for severity of illness. Cohort utilization patterns were compared for the 12-month period following the index encounter. The primary outcome measures show that there was no statistically significant utilization difference between the ACO and non-ACO cohorts for 90% of the 82 comparisons made. It is expected that some measures will achieve significant difference simply because of having this many comparisons, but no clear pattern was identified. This study did not observe statistically significant differences in utilization of high-cost services and medications between ACO and non-ACO cohorts with limited experience in the ACO model. Future analyses with longer study durations, at later stages of ACO development, tracking a more granular level of physician organizational structure, and with designs that integrate clinical and administrative data are essential to better understand the impact of payment innovation strategies using an ACO structure.

The Effect of Medical Technology Innovations on Patient Outcomes, 1990-2015: Results of a Physician Survey.

BACKGROUND: Developments in diagnostics, medical devices, procedures, and prescription drugs have increased life expectancy and quality of life after diagnosis for many diseases. Previous research has shown that, overall, increased investment in medical technology has led to increased health outcomes. In addition, the value of investment in specific innovations, particularly in new pharmaceuticals or biopharmaceuticals, has frequently been shown through an evaluation of the associated health outcomes and costs. Value assessments for all medical technologies and interventions are an important consideration in current debates on access and affordability of health care in the United States. OBJECTIVE: To identify practicing physician impressions of the historical effect of postdiagnosis innovations in medical technology on patient outcomes within the 8 health conditions that have the largest effect on health in the United States. METHODS: National statistics were used to identify the 8 conditions responsible for the most mortality and morbidity within the United States between 1990 and 2014. A physician survey was developed for each major condition to obtain physician opinion on the extent to which pharmaceuticals and biopharmaceuticals, medical devices, diagnostics, and surgical procedures contributed to improvements in postdiagnosis mortality and morbidity outcomes over the evaluated period. Respondents were provided with a fifth category, "cannot allocate," to account for postdiagnosis outcome gains resulting from other factors such as public health interventions. RESULTS: The conditions identified as having the greatest effect on morbidity and mortality since 1990 were breast cancer, ischemic heart disease, human immunodeficiency virus infection, diabetes, unipolar depression, chronic obstructive pulmonary disease, cerebrovascular disease, and lung cancer. After excluding other factors, physicians specializing in these conditions, with a mean of 21.4 years in practice, considered pharmaceuticals and biopharmaceuticals as having the greatest postdiagnosis effect across all 8 conditions, with 56% of outcome gains attributed to this innovation category. Diagnostics was the second biggest contributor at 20%. CONCLUSIONS: Physician perceptions indicated that attention should be paid to value assessments of innovative diagnostics, devices, and surgical procedures, as well as to pharmaceuticals and biopharmaceuticals, before goals for allocating health care expenditures among the different innovations are determined. DISCLOSURES: Funding for this study was provided by the National Pharmaceutical Council, a health policy research group that receives its funding from biopharmaceutical manufacturers. Wamble is employed by RTI Health Solutions, which received funding from the National Pharmaceutical Council to conduct this research. Ciarametaro and Dubois are employed by the National Pharmaceutical Council.

Impact of formulary restrictions on medication intensification in diabetes treatment.

OBJECTIVES: To explore formulary restrictions on noninsulin antihyperglycemic drugs (NIADs) in Medicare Part D plans and to estimate the impact of formulary restrictions on use of NIADs among low-income subsidy (LIS) recipient enrollees with type 2 diabetes (T2D) undergoing treatment intensification. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort of 2919 LIS enrollees with T2D receiving metformin monotherapy during the first quarter of 2012 who intensified treatment later in the year was tracked to assess selection of and days' supply with sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and other NIADs. We tested whether being enrolled in a Part D plan with significant formulary restrictions on sole-source brand name NIADs reduced the likelihood of receiving such agents and, if so, what the impact was on days of therapy with the second agent. A 2-part regression model was estimated with explanatory variables for plan-level restrictions and individual covariates. RESULTS: We found that 63% of study subjects initiated a sulfonylurea, 25% a DPP-4 inhibitor, and 12% another NIAD. Greater restrictions on DPP-4 inhibitors as a class were associated with small reductions in initiation of DPP-4 inhibitors and a concomitant increase in use of sulfonylureas, but neither effect was statistically significant. For individual DPP-4 inhibitors, step therapy requirements on sitagliptin and formulary exclusion of saxagliptin resulted in significant reductions in uptake of the specific drugs but had no significant impact on total days' supply of antihyperglycemic therapy. CONCLUSIONS: Part D formulary restrictions on sole-source brand name NIADs had little impact on patterns of treatment intensification for T2D among LIS recipients enrolled in Medicare Part D plans in 2012.

Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies: systematic review and reanalysis.

OBJECTIVE: Individual patients with the same condition may respond differently to similar treatments. Our aim is to summarise the reporting of person-level heterogeneity of treatment effects (HTE) in multiperson N-of-1 studies and to examine the evidence for person-level HTE through reanalysis. STUDY DESIGN: Systematic review and reanalysis of multiperson N-of-1 studies. DATA SOURCES: Medline, Cochrane Controlled Trials, EMBASE, Web of Science and review of references through August 2017 for N-of-1 studies published in English. STUDY SELECTION: N-of-1 studies of pharmacological interventions with at least two subjects. DATA SYNTHESIS: Citation screening and data extractions were performed in duplicate. We performed statistical reanalysis testing for person-level HTE on all studies presenting person-level data. RESULTS: We identified 62 multiperson N-of-1 studies with at least two subjects. Statistical tests examining HTE were described in only 13 (21%), of which only two (3%) tested person-level HTE. Only 25 studies (40%) provided person-level data sufficient to reanalyse person-level HTE. Reanalysis using a fixed effect linear model identified statistically significant person-level HTE in 8 of the 13 studies (62%) reporting person-level treatment effects and in 8 of the 14 studies (57%) reporting person-level outcomes. CONCLUSIONS: Our analysis suggests that person-level HTE is common and often substantial. Reviewed studies had incomplete information on person-level treatment effects and their variation. Improved assessment and reporting of person-level treatment effects in multiperson N-of-1 studies are needed.