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Prescription drug spending in the US exceeded half a trillion dollars in 2020. 1 Spending is driven by high-cost brandname drugs, for which manufacturers freely set prices after approval. 2 Rising brand-name drug prices often translate to payers restricting access, raising premiums, or imposing unaffordable out-of-pocket costs for patients. We evaluated recent trends in prices for newly marketed brand-name drugs.

Background: Among different investigators studying the same exposures and outcomes, there may be a lack of consensus about potential confounders that should be considered as matching, adjustment, or stratification variables in observational studies. Concerns have been raised that confounding factors may affect the results obtained for the alcohol-ischemic heart disease relationship, as well as their consistency and reproducibility across different studies. Therefore, we assessed how confounders are defined, operationalized, and discussed across individual studies evaluating the impact of alcohol on ischemic heart disease risk. Methods: For observational studies included in a recent alcohol-ischemic heart disease meta-analysis, we identified all variables adjusted, matched, or stratified for in the largest reported multivariate model (i.e. potential confounders). We recorded how the variables were measured and grouped them into higher-level confounder domains. Abstracts and Discussion sections were then assessed to determine whether authors considered confounding when interpreting their study findings. Results: 85 of 87 (97.7%) studies reported multivariate analyses for an alcohol-ischemic heart disease relationship. The most common higher-level confounder domains included were smoking (79, 92.9%), age (74, 87.1%), and BMI, height, and/or weight (57, 67.1%). However, no two models adjusted, matched, or stratified for the same higherlevel confounder domains. Most (74/87, 85.1%) articles mentioned or alluded to "confounding" in their Abstract or Discussion sections, but only one stated that their main findings were likely to be affected by residual confounding. There were five (5/87, 5.7%) authors that explicitly asked for caution when interpreting results. Conclusion: There is large variation in the confounders considered across observational studies evaluating the impact of alcohol on ischemic heart disease risk and almost all studies spuriously ignore or eventually dismiss confounding in their conclusions. Given that study results and interpretations may be affected by the mix of potential confounders included within multivariate models, efforts are necessary to standardize approaches for selecting and accounting for confounders in observational studies.

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BackgroundAlthough the peer review process is believed to ensure scientific rigor, enhance research quality, and improve manuscript clarity, many investigators are concerned that the process is too slow, too expensive, too unreliable, and too static. In this feasibility study, we sought to survey corresponding authors of recently published clinical research studies on the speed and efficiency of the publication process.MethodsWeb-based survey of corresponding authors of a 20% random sample of clinical research studies in MEDLINE-indexed journals with Ovid MEDLINE entry dates between December 1 and 15, 2016. Survey addressed perceived manuscript importance before first submission, approximate first submission and final acceptance dates, and total number of journal submissions, external peer reviews, external peer reviewers, and revisions requested, as well as whether authors would have considered publicly sharing their manuscript on an online platform instead of submitting to a peer-reviewed journal.ResultsOf 1780 surveys distributed, 27 corresponding authors opted out or requested that we stop emailing them and 149 emails failed (e.g., emails that bounced n = 64, returned with an away from office message n = 70, or were changed/incorrect n = 15), leaving 1604 respondents, of which 337 completed the survey (21.0%). Respondents and non-respondents were similar with respect to study type and publication journals’ impact factor, although non-respondent authors had more publications (p = 0.03). Among respondents, the median impact factor of the publications’ journal was 2.7 (interquartile range (IQR), 2.0–3.6) and corresponding authors’ median h-index and number of publications was 9 (IQR, 3–20) and 27 (IQR, 10–77), respectively. The median time from first submission to journal acceptance and publication was 5 months (IQR, 3–8) and 7 months (IQR, 5–12), respectively. Most respondents (62.0%, n = 209) rated the importance of their research as a 4 or 5 (5-point scale) prior to submission. Median number of journal submissions was 1 (IQR, 1–2), external peer reviews was 1 (IQR, 1–2), external peer reviewers was 3 (IQR, 2–4), and revisions requested was 1 (IQR, 1–1). Sharing manuscripts to a public online platform, instead of submitting to a peer-reviewed journal, would have been considered by 55.2% (n = 186) of respondents.ConclusionCorresponding authors have high perceptions of their research and reported requiring few manuscript submissions prior to journal acceptance, most commonly by lower impact factor journals.Electronic supplementary materialThe online version of this article (10.1186/s41073-017-0045-8) contains supplementary material, which is available to authorized users.

Key Points Question How often do randomized clinical trials directly compare new single-enantiomer drugs to their existing racemic precursors, and how often are efficacy or safety differences observed? Findings In this systematic review of 15 single-enantiomer racemic drug pairs, 185 direct-comparison randomized clinical trials (median, 2 trials; interquartile range, 1-8 trials) were identified, 124 (67.0%) of which studied 1 drug pair. For 9 single-enantiomer drugs, no randomized clinical trials were identified providing evidence of improved efficacy, based on primary end point results, or safety as compared with their racemic precursors. Meaning Results of this systematic review suggest that most newly marketed single-enantiomer drugs are infrequently directly compared with their existing racemic precursors, and when compared, they are uncommonly found to provide improved efficacy or safety, despite their greater costs.

ImportanceThe Inflation Reduction Act of 2022 gives Medicare the authority to negotiate prices for certain prescription drugs. Which drugs will be selected and how prices will be negotiated remain unclear.ObjectiveTo simulate drug selection and the minimum savings that would have been achieved at statutory ceiling prices if Medicare drug price negotiation had been implemented from 2018 to 2020.Design, Setting, and ParticipantsIn this cross-sectional study, a policy simulation analysis of high-spending prescription drugs in Medicare Part B and Part D that were eligible for negotiation from January 2018 to December 2020 was performed from August 5 to November 20, 2022.ExposuresEligibility criteria for selection and discounts afforded by the statutory ceiling prices for negotiation.Main Outcomes and MeasuresThe main outcomes were characteristics of drugs subject to negotiation and estimated Medicare savings from 2018 to 2020 that would have been achieved through spending at ceiling prices compared with existing net prices accounting for price concessions.ResultsAmong the 40 selected drugs, 35 were primarily reimbursed through Medicare Part D and 5 through Part B and 10 were biologics. The most common therapeutic classes were endocrine (11), neurologic or psychiatric (5), pulmonary (4), rheumatologic or immunologic (4), and cardiovascular (4). Median time from US Food and Drug Administration approval to selection was 12 years (IQR, 10-14 years). Three drugs faced generic competition in the 2 years between selection and price negotiation. For the remaining 37 drugs, estimated net Medicare spending from 2018 to 2020 was $55.3 billion; spending at ceiling prices would have been reduced by an estimated $26.5 billion, which represented 5% of estimated net Medicare drug spending during those 3 years.Conclusions and RelevanceIn this cross-sectional study, simulating the drug price negotiation provisions in the Inflation Reduction Act of 2022 revealed important limitations, including strict selection criteria and the potential for drugs to become ineligible for negotiation during the 2 years between selection and prices taking effect. Despite these limitations, the policy still delivered substantial savings because ceiling prices offered steep discounts, in part, by erasing excess spending from price increases faster than inflation.

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