Professional Education

  • MD, Yale University (2024)
  • BA, Columbia University (2018)

All Publications

  • Medicare Local Coverage Determinations: Evidence Quality Is Stronger For Covered Indications. Health affairs (Project Hope) Moneer, O., Mooghali, M., Moosa, K., Ramachandran, R., Ross, J. S., Dhruva, S. S. 2024; 43 (12): 1712-1718

    Abstract

    Under the 21st Century Cures Act of 2016, a summary of the evidence used to support local coverage determinations, which represent the vast majority of Medicare's coverage decisions for new technologies, must be made publicly accessible. Using reports from the Medicare Coverage Database on local coverage determinations and the medical literature, we examined the availability of these decisions and the quality of evidence cited for therapeutic drugs, biologics, and moderate- or high-risk devices during the period 2015-22 to understand whether evidence strength and generalizability differed for indications with favorable versus unfavorable coverage decisions. Evidence summaries were publicly available for 26 percent of coverage decisions originally effected during 2015-18 and 100 percent during 2019-22. Among the latter, when compared with noncovered indications, indications with favorable coverage decisions cited twice the number of evidence sources (median, four versus two) and more often cited studies with a mean patient age of sixty-five and older (78 percent versus 47 percent). Fewer than one-third of all studies reported race or ethnicity data. There was no significant association between indication coverage and the study design strength of cited clinical studies. Although the 21st Century Cures Act enhanced transparency, clinical evidence that better reflects the Medicare beneficiary population is needed to inform local coverage determinations.

    View details for DOI 10.1377/hlthaff.2024.00182

    View details for PubMedID 39626147

  • Medical Devices Applying for Outpatient Medicare Supplemental Payments. JAMA health forum Moneer, O., Johnston, J. L., Rathi, V. K., Ross, J. S., Dhruva, S. S. 2024; 5 (11): e244016

    Abstract

    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.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.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.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.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.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.

    View details for DOI 10.1001/jamahealthforum.2024.4016

    View details for PubMedID 39546305

    View details for PubMedCentralID PMC11568453

  • Aligning US Agency Policies for Cardiovascular Devices Through the Breakthrough Devices Program. JAMA cardiology Moneer, O., Rathi, V. K., Johnston, J. L., Ross, J. S., Dhruva, S. S. 2023; 8 (12): 1174-1181

    Abstract

    The US Food and Drug Administration (FDA) and Centers for Medicare & Medicaid Services (CMS) have different statutory authorities; FDA evaluates safety and effectiveness for market authorization of medical devices while CMS determines whether coverage is "reasonable and necessary" for its beneficiaries. CMS has recently enacted policies automatically providing supplemental reimbursement for new, costly devices authorized after designation in FDA's Breakthrough Devices Program (BDP) and in June 2023 issued notice for a new Transitional Coverage for Emerging Technologies pathway, accelerating coverage for Breakthrough devices.Aiming to incentivize innovation, FDA awards Breakthrough designations early in device development to expedite market authorization and can accept greater uncertainty in benefit and risk, contingent on postmarket evidence generation. Since 2020, Breakthrough designation has effectively automatically qualified devices to receive supplemental Medicare reimbursement after CMS waived a long-standing requirement that devices demonstrate "substantial clinical improvement" for beneficiaries. Using publicly available information, 3 examples of cardiovascular devices illustrate that the BDP may allow for FDA authorization based on less rigorous evidence, such as single-arm trials focused on surrogate end points with short-term follow-up whose participants are often not representative of Medicare beneficiaries. In 1 case, Breakthrough designation allowed a 30% decrease in enrollment of a trial used to support approval. Initial positive findings for some devices have remained unverified, and in 1 case even partially nullified, by postmarket studies. Manufacturers have also used Breakthrough designations to set the price of devices to facilitate additional pass-through payments, leading to higher short-term and long-term costs to CMS and health care systems.The BDP may qualify new, costly devices for higher and automatic Medicare reimbursement despite evidence not being representative of CMS beneficiaries and persistent uncertainty of benefit and risk. To ensure the best evidence is generated to inform clinical care, FDA could apply more selectivity to BDP eligibility, specify objective criteria for revoking Breakthrough designation when appropriate, and ensure timely postmarket evidence generation, whereas CMS could independently review clinical evidence, advise manufacturers about standards for coverage review, and make supplemental payments and long-term device reimbursement contingent on clinical outcome benefit and postmarket evidence generation.

    View details for DOI 10.1001/jamacardio.2023.3819

    View details for PubMedID 37878306

  • Fulfillment of Postmarket Commitments and Requirements for New Drugs Approved by the FDA, 2013-2016. JAMA internal medicine Brown, B. L., Mitra-Majumdar, M., Darrow, J. J., Moneer, O., Pham, C., Avorn, J., Kesselheim, A. S. 2022; 182 (11): 1223-6

    View details for DOI 10.1001/jamainternmed.2022.4226

    View details for PubMedID 36190713

    View details for PubMedCentralID PMC9531062

  • Generating evidence during a pandemic: what's reliable? BMJ (Clinical research ed.) Wallach, J. D., Moneer, O., Ross, J. S. 2022; 377: o1229

    View details for DOI 10.1136/bmj.o1229

    View details for PubMedID 35577370

  • Agreement of treatment effects from observational studies and randomized controlled trials evaluating hydroxychloroquine, lopinavir-ritonavir, or dexamethasone for covid-19: meta-epidemiological study. BMJ (Clinical research ed.) Moneer, O., Daly, G., Skydel, J. J., Nyhan, K., Lurie, P., Ross, J. S., Wallach, J. D. 2022; 377: e069400

    Abstract

    To systematically identify, match, and compare treatment effects and study demographics from individual or meta-analysed observational studies and randomized controlled trials (RCTs) evaluating the same covid-19 treatments, comparators, and outcomes.Meta-epidemiological study.National Institutes of Health Covid-19 Treatment Guidelines, a living review and network meta-analysis published in The BMJ, a living systematic review with meta-analysis and trial sequential analysis in PLOS Medicine (The LIVING Project), and the Epistemonikos "Living OVerview of Evidence" (L·OVE) evidence database.RCTs in The BMJ's living review that directly compared any of the three most frequently studied therapeutic interventions for covid-19 across all data sources (that is, hydroxychloroquine, lopinavir-ritonavir, or dexamethasone) for any safety and efficacy outcomes. Observational studies that evaluated the same interventions, comparisons, and outcomes that were reported in The BMJ's living review.Safety and efficacy outcomes from observational studies were identified and treatment effects for dichotomous (odds ratios) or continuous (mean differences or ratios of means) outcomes were calculated and, when possible, meta-analyzed to match the treatment effects from individual RCTs or meta-analyses of RCTs reported in The BMJ's living review with the same interventions, comparisons, and outcomes (that is, matched pairs). The analysis compared the distribution of study demographics and the agreement between treatment effects from matched pairs. Matched pairs were in agreement if both observational and RCT treatment effects were significantly increasing or decreasing (P<0.05) or if both treatment effects were not significant (P≥0.05).17 new, independent meta-analyses of observational studies were conducted that compared hydroxychloroquine, lopinavir-ritonavir, or dexamethasone with an active or placebo comparator for any safety or efficacy outcomes in covid-19 treatment. These studies were matched and compared with 17 meta-analyses of RCTs reported in The BMJ's living review. 10 additional matched pairs with only one observational study and/or one RCT were identified. Across all 27 matched pairs, 22 had adequate reporting of demographical and clinical data for all individual studies. All 22 matched pairs had studies with overlapping distributions of sex, age, and disease severity. Overall, 21 (78%) of the 27 matched pairs had treatment effects that were in agreement. Among the 17 matched pairs consisting of meta-analyses of observational studies and meta-analyses of RCTs, 14 (82%) were in agreement; seven (70%) of the 10 matched pairs consisting of at least one observational study or one RCT were in agreement. The 18 matched pairs with treatment effects for dichotomous outcomes had a higher proportion of agreement (n=16, 89%) than did the nine matched pairs with treatment effects for continuous outcomes (n=5, 56%).Meta-analyses of observational studies and RCTs evaluating treatments for covid-19 have summary treatment effects that are generally in agreement. Although our evaluation is limited to three covid-19 treatments, these findings suggest that meta-analyzed evidence from observational studies might complement, but should not replace, evidence collected from RCTs.

    View details for DOI 10.1136/bmj-2021-069400

    View details for PubMedID 35537738

    View details for PubMedCentralID PMC9086409

  • New Drug Postmarketing Requirements and Commitments in the US: A Systematic Review of the Evidence. Drug safety Moneer, O., Brown, B. L., Avorn, J., Darrow, J. J., Mitra-Majumdar, M., Joyce, K. W., Ross, M., Pham, C., Kesselheim, A. S. 2022; 45 (4): 305-318

    Abstract

    After the approval of a new drug, the Food and Drug Administration (FDA) may issue postmarketing requirements (PMRs), studies that the law requires manufacturers to conduct for drugs approved under certain conditions, and postmarketing commitments (PMCs), studies that the FDA and manufacturers agree should be conducted as a condition of approval.With regulators' increasing reliance on gathering important evidence after initial product approval, we sought to assess the track record of PMRs and PMCs by synthesizing information about postmarketing study completion rates, timeliness, study types, and results reporting.A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Studies published in academic journals or government reports that reported original data about the characteristics of PMRs or PMCs were included. Studies of post-approval trial mandates issued by regulators outside the USA were excluded, as were those that addressed post-approval research without mentioning either PMCs or PMRs or a specific approval pathway associated with statutorily required PMRs. Two investigators independently screened and extracted data from studies and reports. Data sources included the Federal Register from 2003 to 2020, FDA backlog reviews from 2008 to 2020, PubMed from January 2006 to April 2021, and the US Government Accountability Office (GAO) database for reports from January 2006 to April 2021. PMR/PMC characteristics (e.g., completion rates, timeliness, results reporting, outcomes) were not meta-analyzed due to the heterogeneity in study designs.Twenty-seven peer-reviewed articles from PubMed, five GAO reports, 17 annual Federal Register notices, and 12 annual backlog reviews were included. Among the 27 studies, 13 reviewed PMRs and PMCs, one reviewed only PMCs, and 13 reviewed only PMRs. A majority of new drugs were approved with at least one PMR or PMC. PMCs were completed at higher rates than PMRs, although delays were common and neither was found to be completed more than two-thirds of the time. Over two-thirds of PMRs and PMCs reported their findings in publications and trial registries. Over half of PMCs and PMRs produced novel information for clinical practice or leading to regulatory action, such as confirmation of benefit or a labeling change.PMRs and PMCs are common for new drugs and can lead to worthwhile outcomes, but are often delayed or incomplete. Greater attention is needed to timely completion, improving transparency of findings, and ensuring that PMRs and PMCs produce optimally useful information for prescribers and patients.

    View details for DOI 10.1007/s40264-022-01152-9

    View details for PubMedID 35182362

    View details for PubMedCentralID 4144867

  • Direct-to-consumer personal genomic tests need better regulation. Nature medicine Moneer, O., Miller, J. E., Shah, N. D., Ross, J. S. 2021; 27 (6): 940-943

    View details for DOI 10.1038/s41591-021-01368-9

    View details for PubMedID 34017136

    View details for PubMedCentralID 6143574

  • Characteristics of Postmarketing Studies for Vaccines Approved by the US Food and Drug Administration, 2006-2020. JAMA network open Moneer, O., Lee, C. C., Avorn, J., Kesselheim, A. S. 2021; 4 (4): e218530

    Abstract

    This cross-sectional study uses data from the US Food and Drug Administration (FDA) to review the postmarketing requirements and commitments attached to new vaccines approved for use in the past 15 years in the United States.

    View details for DOI 10.1001/jamanetworkopen.2021.8530

    View details for PubMedID 33929526

    View details for PubMedCentralID PMC8087952

  • An Overview Of Vaccine Development, Approval, And Regulation, With Implications For COVID-19. Health affairs (Project Hope) Kesselheim, A. S., Darrow, J. J., Kulldorff, M., Brown, B. L., Mitra-Majumdar, M., Lee, C. C., Moneer, O., Avorn, J. 2021; 40 (1): 25-32

    Abstract

    The Food and Drug Administration (FDA) approves vaccines when their benefits outweigh the risks for their intended use. In this article we review the standard FDA approach to vaccine evaluation, which underpins its current approaches to assessment of vaccines to prevent coronavirus disease 2019 (COVID-19). The FDA has established pathways to accelerate vaccine availability before approval, such as Emergency Use Authorization, and to channel resources to high-priority products and allow more flexibility in the evidence required for approval, including accelerated approval based on surrogate markers of effectiveness. Among the thirty-five new vaccines approved in the US from 2006 through October 2020, about two-thirds of their pivotal trials used the surrogate outcome of immune system response, and only one-third evaluated actual disease incidence. Postapproval safety surveillance of new vaccines, and particularly vaccines receiving expedited approval, is crucial. This has generally been accomplished through such mechanisms as the Centers for Disease Control and Prevention (CDC) and FDA Vaccine Adverse Event Reporting System, the CDC Vaccine Safety Datalink, and the CDC Clinical Immunization Safety Assessment Project. Adverse events detected in this way may lead to changes in a vaccine's recommended use or withdrawal from the market. Regulatory oversight of new vaccines must balance speed with rigor to effectively address the pandemic.

    View details for DOI 10.1377/hlthaff.2020.01620

    View details for PubMedID 33211535

  • Covid-19, single-sourced diagnostic tests, and innovation policy JOURNAL OF LAW AND THE BIOSCIENCES Deb, C., Moneer, O., Price, W. 2020; 7 (1): lsaa053

    View details for DOI 10.1093/jlb/lsaa053

    View details for Web of Science ID 000612916400039

    View details for PubMedID 32908672

    View details for PubMedCentralID PMC7454726

  • Electrostatic Screening of Charged Defects in Monolayer MoS<sub>2</sub> JOURNAL OF PHYSICAL CHEMISTRY LETTERS Atallah, T. L., Wang, J., Bosch, M., Seo, D., Burke, R. A., Moneer, O., Zhu, J., Theibault, M., Brus, L. E., Hone, J., Zhu, X. 2017; 8 (10): 2148-2152

    Abstract

    Defects in monolayer transition-metal dichalcogenides (TMDCs) may lead to unintentional doping, charge-carrier trapping, and nonradiative recombination. These effects impair electronic and optoelectronic technologies. Here we show that charged defects in MoS2 monolayers can be effectively screened when they are in contact with an ionic liquid (IL), leading to an increase in photoluminescence (PL) yield by up to two orders of magnitude. The extent of this PL enhancement by the IL correlates with the brightness of each pretreated sample. We propose the existence of two classes of nonradiative recombination centers in monolayer MoS2: (i) charged defects that relate to unintentional doping and may be electrostatically screened by ILs and (ii) neutral defects that remain unaffected by the presence of ILs.

    View details for DOI 10.1021/acs.jpclett.7b00710

    View details for Web of Science ID 000402026500008

    View details for PubMedID 28448150