The estimated annual financial impact of gene therapy in the United States.

Gene therapy is a new class of medical treatment that alters part of a patient's genome through the replacement, deletion, or insertion of genetic material. While still in its infancy, gene therapy has demonstrated immense potential to treat and even cure previously intractable diseases. Nevertheless, existing gene therapy prices are high, raising concerns about its affordability for U.S. payers and its availability to patients. We assess the potential financial impact of novel gene therapies by developing and implementing an original simulation model which entails the following steps: identifying the 109 late-stage gene therapy clinical trials underway before January 2020, estimating the prevalence and incidence of their corresponding diseases, applying a model of the increase in quality-adjusted life years for each therapy, and simulating the launch prices and expected spending of all available gene therapies annually. The results of our simulation suggest that annual spending on gene therapies will be approximately $20.4 billion, under conservative assumptions. We decompose the estimated spending by treated age group as a proxy for insurance type, finding that approximately one-half of annual spending will on the use of gene therapies to treat non-Medicare-insured adults and children. We conduct multiple sensitivity analyses regarding our assumptions and model parameters. We conclude by considering the tradeoffs of different payment methods and policies that intend to ensure patient access to the expected benefits of gene therapy.

International Reference Pricing in the Context of US Drug Policy.

International reference prices (IRP), also called external reference prices, are widely used across developed nations. IRP uses the prices paid in other countries to either inform negotiations with the pharmaceutical industry or as a cap on market prices. The authors review the application of IRP to cap the prices of negotiated outcomes in the context of US proposals for changing the way prescription drug prices are established for the Medicare program. They examine the economic, political, and administrative issues associated with the use of IRP, and they summarize the evidence on the impacts of IRP.

Selection on noise constrains variation in a eukaryotic promoter.

Genetic variation segregating within a species reflects the combined activities of mutation, selection, and genetic drift. In the absence of selection, polymorphisms are expected to be a random subset of new mutations; thus, comparing the effects of polymorphisms and new mutations provides a test for selection. When evidence of selection exists, such comparisons can identify properties of mutations that are most likely to persist in natural populations. Here we investigate how mutation and selection have shaped variation in a cis-regulatory sequence controlling gene expression by empirically determining the effects of polymorphisms segregating in the TDH3 promoter among 85 strains of Saccharomyces cerevisiae and comparing their effects to a distribution of mutational effects defined by 236 point mutations in the same promoter. Surprisingly, we find that selection on expression noise (that is, variability in expression among genetically identical cells) appears to have had a greater impact on sequence variation in the TDH3 promoter than selection on mean expression level. This is not necessarily because variation in expression noise impacts fitness more than variation in mean expression level, but rather because of differences in the distributions of mutational effects for these two phenotypes. This study shows how systematically examining the effects of new mutations can enrich our understanding of evolutionary mechanisms. It also provides rare empirical evidence of selection acting on expression noise.

The effect of increased cost-sharing on low-value service use.

We examine the effect of a value-based insurance design (VBID) program implemented at a large public employer in the state of Oregon. The program substantially increased cost-sharing for several healthcare services likely to be of low value for most patients: diagnostic services (e.g., imaging services) and surgeries (e.g., spinal surgeries for pain). Using a difference-in-differences design coupled with granular, administrative health insurance claims data over the period 2008-2012, we estimate the change in low-value service use among beneficiaries before and after program implementation relative to a comparison group not exposed to the VBID. Our findings suggest that the VBID significantly reduced the use of targeted services, with an implied elasticity of demand of -0.22. We find no evidence that the VBID led to substitution to non-targeted services or increased overall healthcare costs. However, we also observe no evidence that the program led to cost-savings.

Prescription Drug Use under Medicare Part D: A Linear Model of Nonlinear Budget Sets.

Medicare Part D enrollees face a complicated decision: they dynamically choose prescription drug consumption in each period given difficult-to-find prices and a non-linear budget set. We use Part D claims data to estimate a flexible model of consumption that accounts for non-linear prices, dynamic responses, and salience. We use reduced form price responses from a linear regression of consumption on coverage range prices to compare performance under several models of behavior. We find small price elasticities, substantial myopia, and that salient characteristics impact consumption beyond their effect on prices. A hyperbolic discounting model with salience fits the data best.

Choice Inconsistencies among the Elderly: Evidence from Plan Choice in the Medicare Part D Program: Reply.

We explore the in- and out- of sample robustness of tests for choice inconsistencies based on parameter restrictions in parametric models, focusing on tests proposed by Ketcham, Kuminoff and Powers (KKP). We argue that their non-parametric alternatives are inherently conservative with respect to detecting mistakes. We then show that our parametric model is robust to KKP's suggested specification checks, and that comprehensive goodness of fit measures perform better with our model than the expected utility model. Finally, we explore the robustness of our 2011 results to alternative normative assumptions highlighting the role of brand fixed effects and unobservable characteristics.

The Oregon experiment--effects of Medicaid on clinical outcomes.

BACKGROUND: Despite the imminent expansion of Medicaid coverage for low-income adults, the effects of expanding coverage are unclear. The 2008 Medicaid expansion in Oregon based on lottery drawings from a waiting list provided an opportunity to evaluate these effects. METHODS: Approximately 2 years after the lottery, we obtained data from 6387 adults who were randomly selected to be able to apply for Medicaid coverage and 5842 adults who were not selected. Measures included blood-pressure, cholesterol, and glycated hemoglobin levels; screening for depression; medication inventories; and self-reported diagnoses, health status, health care utilization, and out-of-pocket spending for such services. We used the random assignment in the lottery to calculate the effect of Medicaid coverage. RESULTS: We found no significant effect of Medicaid coverage on the prevalence or diagnosis of hypertension or high cholesterol levels or on the use of medication for these conditions. Medicaid coverage significantly increased the probability of a diagnosis of diabetes and the use of diabetes medication, but we observed no significant effect on average glycated hemoglobin levels or on the percentage of participants with levels of 6.5% or higher. Medicaid coverage decreased the probability of a positive screening for depression (-9.15 percentage points; 95% confidence interval, -16.70 to -1.60; P=0.02), increased the use of many preventive services, and nearly eliminated catastrophic out-of-pocket medical expenditures. CONCLUSIONS: This randomized, controlled study showed that Medicaid coverage generated no significant improvements in measured physical health outcomes in the first 2 years, but it did increase use of health care services, raise rates of diabetes detection and management, lower rates of depression, and reduce financial strain.

Evolving Choice Inconsistencies in Choice of Prescription Drug Insurance.

We study choice over prescription insurance plans by the elderly using government administrative data to evaluate how these choices evolve over time. We find large "foregone savings" from not choosing the lowest cost plan that has grown over time. We develop a structural framework to decompose the changes in "foregone welfare" from inconsistent choices into choice set changes and choice function changes from a fixed choice set. We find that foregone welfare increases over time due primarily to changes in plan characteristics such as premiums and out-of-pocket costs; we estimate little learning at either the individual or cohort level.

Choice Inconsistencies among the Elderly: Evidence from Plan Choice in the Medicare Part D Program: Reply.

We explore the in- and out-of-sample robustness of tests for choice inconsistencies based on parameter restrictions in parametric models, focusing on tests proposed by Ketcham, Kuminoff, and Powers (2016). We argue that their nonparametric alternatives are inherently conservative with respect to detecting mistakes. We then show that our parametric model is robust to KKP's suggested specification checks, and that comprehensive goodness of fit measures perform better with our model than the expected utility model.Finally, we explore the robustness of our 2011 results to alternative normative assumptions highlighting the role of brand fixed effects and unobservable characteristics.

An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation.

The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA's authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules.

Contrasting properties of gene-specific regulatory, coding, and copy number mutations in Saccharomyces cerevisiae: frequency, effects, and dominance.

Genetic variation within and between species can be shaped by population-level processes and mutation; however, the relative impact of "survival of the fittest" and "arrival of the fittest" on phenotypic evolution remains unclear. Assessing the influence of mutation on evolution requires understanding the relative rates of different types of mutations and their genetic properties, yet little is known about the functional consequences of new mutations. Here, we examine the spectrum of mutations affecting a focal gene in Saccharomyces cerevisiae by characterizing 231 novel haploid genotypes with altered activity of a fluorescent reporter gene. 7% of these genotypes had a nonsynonymous mutation in the coding sequence for the fluorescent protein and were classified as "coding" mutants; 2% had a change in the S. cerevisiae TDH3 promoter sequence controlling expression of the fluorescent protein and were classified as "cis-regulatory" mutants; 10% contained two copies of the reporter gene and were classified as "copy number" mutants; and the remaining 81% showed altered fluorescence without a change in the reporter gene itself and were classified as "trans-acting" mutants. As a group, coding mutants had the strongest effect on reporter gene activity and always decreased it. By contrast, 50%-95% of the mutants in each of the other three classes increased gene activity, with mutants affecting copy number and cis-regulatory sequences having larger median effects on gene activity than trans-acting mutants. When made heterozygous in diploid cells, coding, cis-regulatory, and copy number mutant genotypes all had significant effects on gene activity, whereas 88% of the trans-acting mutants appeared to be recessive. These differences in the frequency, effects, and dominance among functional classes of mutations might help explain why some types of mutations are found to be segregating within or fixed between species more often than others.

Growth and variability in health plan premiums in the individual insurance market before the Affordable Care Act.

Before we can evaluate the impact of the Affordable Care Act on health insurance premiums in the individual market, it is critical to understand the pricing trends of these premiums before the implementation of the law. Using rates of increase in the individual insurance market collected from state regulators, this issue brief documents trends in premium growth in the pre-ACA period. From 2008 to 2010, premiums grew by 10 percent or more per year. This growth was also highly variable across states, and even more variable across insurance plans within states. The study suggests that evaluating trends in premiums requires looking across a broad array of states and plans, and that policymakers must examine how present and future changes in premium rates compare with the more than 10 percent per year premium increases in the years preceding health reform.

COVID-19 Vaccines: Moderna And Pfizer-BioNTech Use Varied By Urban, Rural Counties.

We investigated county-level variation in mRNA COVID-19 vaccine use among Medicare beneficiaries throughout the United States. There was greater use of Pfizer-BioNTech vaccines than Moderna vaccines in urban areas for first and booster doses.

Public and Private Options in Practice: The Military Health System.

Recent debates over health care reform, including in the context of the Military Health System (MHS) and Veterans Administration, highlight the dispute between public and private provision of health care services. Using novel data on childbirth claims from the MHS and drawing on the combination of plausibly exogenous patient moves and heterogeneity across bases in the availability of base hospitals, we identify the impact of receiving obstetrical care on versus off military bases. We find evidence that off-base care is associated with slightly greater resource intensity, but also notably better outcomes, suggesting marginal efficiency gains from care privatization.