Joseph S Ross’s research while affiliated with University of New Haven and other places

Although medical devices are widely used in clinical practice, clinicians and the public have limited access to information on how devices are tested, regulated, and used, posing challenges to patient safety. This article uses Cook Medical's Celect inferior vena cava (IVC) filter, a medical device used for prevention of pulmonary embolism, as a case study of the transparency gap in medical device regulation. Recently unsealed court documents from litigation related to Celect reveal that the device's clinical study protocol did not follow U.S. Food and Drug Administration (FDA) guidance for IVC filter testing and that study outcome definitions for IVC perforation had lower sensitivity for detecting adverse events than those recommended by professional societies. Furthermore, a comparison of court documents and the public record indicates that adverse events and patient deaths were misreported to FDA reviewers and were inaccurately reported in the published literature and on the device label, providing patients and clinicians with inaccurate information about the device's safety. The Celect IVC filter case demonstrates the need for regulatory reforms to ensure that critical safety data are accessible to the FDA, clinicians, and patients to inform decision making.

Importance Medicare transitional pass-through payments (TPTPs) provide supplemental reimbursement that is intended to facilitate adoption of new devices in the outpatient setting. The US Centers for Medicare & Medicaid Services (CMS) have historically evaluated manufacturer applications for TPTPs based on newness, cost, and evidence of substantial clinical improvement, ie, the traditional pathway. In 2020, CMS introduced an alternative pathway to allow US Food and Drug Administration (FDA)-designated breakthrough devices to qualify for supplemental reimbursement without demonstrating substantial clinical improvement. Objective To characterize CMS TPTP approval rates and the premarket evidence used by FDA to support authorization of new outpatient medical devices considered for CMS TPTP. Design and Setting This was a cross-sectional study of TPTP applications for new outpatient medical devices from 2017 to 2023. Using the Federal Register, CMS Outpatient Prospective Payment System final rules for fiscal years 2017 through 2023 were obtained, from which all manufacturer applications for TPTPs were identified. For each application, the CMS TPTP review pathway (traditional/alternative), CMS final decision (award/deny), and FDA authorization pathway were assessed. Main Outcomes and Measures Characteristics of devices considered for CMS TPTPs and design, effectiveness end points, and patient demographic characteristics of premarket clinical studies used to support FDA authorization. Results CMS approved 17 of 43 (40%) applications for TPTPs, including all 8 (100%) alternative pathway applications for breakthrough devices and 9 of 35 applications (26%) using the traditional pathway. Devices approved for TPTPs were more likely to have been assessed in premarket clinical studies than devices denied TPTPs (12/17 [71%] vs 2/26 [8%]). Among the 14 premarket studies of TPTP-approved devices, 8 (57%) used surrogate markers as primary effectiveness end points and 5 (42%) did not meet all primary end points. The median (IQR) percentage of female, Black, and Hispanic patients among the trials that reported demographic data was 26% (17%-36%), 6% (2%-17%), and 4% (3%-5%), respectively. Conclusions and Relevance The findings of this cross-sectional analysis indicated that CMS more commonly awarded supplemental outpatient payment through TPTPs for devices assessed in premarket clinical studies to support FDA authorization. However, these studies often lacked generalizability to Medicare beneficiaries, used surrogate markers of effectiveness, or did not meet all primary end points. As more breakthrough devices receive FDA authorization and effectively qualify for automatic supplemental payments, strengthening premarket clinical evidence requirements for CMS TPTP approvals would provide better information to guide clinical decision-making and ensure that supplemental reimbursement enhances care for Medicare beneficiaries.

This study evaluates representation of older adults, women, and people of Black race and Hispanic ethnicity in Centers for Medicare & Medicaid Services national coverage determination (NCD) and coverage with evidence development (CED)–approved studies.

This study analyzes the extent and persistence of payments to physicians from competing manufacturers after receipt of payment from manufacturers of first-in-class products entering 6 novel therapeutic classes.

This cross-sectional study analyzes data from the National Health Interview Survey to examine the prevalence of cost-related prescription drug rationing by adults with obesity.

In 2017, the National Library of Medicine (NLM) added a voluntary field for conflict of interest (COI) statements (“posted COI”) on the abstract page of PubMed, but the extent to which it is used is unknown. This repeated cross-sectional study examined journals and articles indexed on PubMed from 2016 through 2021. We described the proportion of all journals with at least one article that included a posted COI and the percentage of all articles that included a posted COI over time. We also examined 100 randomly selected articles published between June 2021 and May 2022 from each of the 40 highest impact journals. For these, we established whether the articles had published COIs, and, of these, the proportion that included a posted COI. Among approximately 7,000 journals publishing articles each year, the proportion of journals with at least one article with a posted COI statement increased from 25.9% in 2016 to 33.2% in 2021. Among nearly 400,000 articles published each year, the proportion of articles that included a posted COI also increased from 9.0% in 2016 to 43.0% in 2021. Among 3,888 articles published in the 40 highest impact journals in 2021–2022, 30.2% (95% CI: 28.7%-31.6%) had published COIs; of these, 63.3% (95% CI: 60.4%-66.0%) included a posted COI. Use of the PubMed COI statement has increased since it became available in 2017, but adoption is still limited, even among high impact journals. NLM should carry out additional outreach to journals that are not using the statement to promote greater transparency of COIs.

Objectives To compare the premarket and postmarket evidence of safety and efficacy of direct oral anticoagulants approved for stroke prevention in atrial fibrillation patients across four major regulatory agencies. Design Cross-sectional. Setting European Medicines Association (EMA), US Food and Drug Administration (FDA), Health Canada and Australian Therapeutic Goods Administration (TGA). Participants Apixaban, dabigatran, edoxaban and rivaroxaban marketing authorisations. Outcome measures Concordance among regulatory agencies with respect to (1) premarket evidence used to establish efficacy and safety and (2) postmarket safety boxed warnings and postmarketing study requirements. Results Apixaban, dabigatran and rivaroxaban were approved by each of the four regulatory agencies; edoxaban was only not approved by TGA. For premarket efficacy evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for three (75%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for four (100%) drugs and number of phase 2 trials for three (75%) drugs. For the premarket safety evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for two (50%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for three (75%) drugs and number of phase 2 trials for zero (0%) drugs. For postmarket safety information, FDA was the only agency that issued boxed warnings (for three (75%) drugs). Additionally, EMA and TGA required postmarketing studies (for four (100%) and two (50%) drugs, respectively), while FDA and Health Canada did not have any postmarketing requirements. Conclusions There was a high degree of concordance in the phase 3 trial premarket evidence used to establish efficacy and safety of direct oral anticoagulant approvals across four major regulatory agencies, but discordance in the phase 2 trial premarket evidence used, as well as in postmarket safety boxed warnings and postmarketing study requirements. These discrepancies highlight opportunities for further harmonisation in the evaluation and regulation of medical products globally.