About

Thomas R. Fleming is an Emeritus faculty member at the University of Washington, associated with the Department of Biostatistics. His contact information includes an email address (tfleming@uw.edu) and a phone number (+1 206 543-1044). He is connected to the University of Washington in Seattle, WA, and is involved in the academic community through his affiliation with the Department of Biostatistics. No additional biographical details, research focus, or key contributions are provided on the page.

Research topics

• Intensive care medicine
• Medicine
• Immunology
• Internal medicine
• Pathology
• Virology

Selected publications

• The federated trials approach; an opportunity for global collaboration in health emergencies

  EClinicalMedicine · 2026-02-25 · 1 citations

  articleOpen access

  The gold standard for providing confirmatory evidence to regulatory agencies is a single sponsor conducting a randomised, controlled clinical trial (RCT). But emerging situations like the mpox outbreak can complicate launching large, single, global trials that meet the needs of multiple stakeholders, including multinational funders and regulators. Drawing on lessons from the mpox outbreak, we propose an alternative approach: the federated trial design. This approach ensures that individual trials launch quickly and that a rigorous, prespecified, conjoined analysis using combined data supports joint regulatory decisions. Early engagement with regulatory agencies is crucial to arranging such a conjoined analysis. Federating trials can support regulatory decision-making when they include a prespecified conjoined analysis that is sufficiently rigorous. Essential steps include harmonising individual trial protocols, aligning data standards, and arranging for a single Data Monitoring Committee to review a combined, multi-trial analysis. The classical single-trial approach remains the gold standard, but investigators should consider federated trials in emergencies that complicate conducting single trials. In such crises, investigators need to explain clearly why standalone evidence from participating RCTs is not obtainable. The federated trials design cannot replace the classical design, but can provide timely, robust evidence in crises such as public health emergencies.

  PublisherDOI

• Reflections on FDA Draft Guidance on Bayesian Methods in Trials—Protecting Scientific Integrity and Evidentiary Standards

  JAMA · 2026-03-23 · 1 citations

  article

  This Perspective discusses the use of bayesian methods in clinical trials and the importance of having US Food and Drug Administration (FDA) guidance that provides substantive insights about the methods’ proper role.

  PublisherDOI

• Salvaging information from paused or stopped clinical studies

  Clinical Trials · 2025-07-12 · 1 citations

  letterOpen access
  PublisherDOI

• Reliably Assessing Duration of Protection for Coronavirus Disease 2019 Vaccines

  UNC Libraries · 2025-05-10

  articleOpen access

  Decision making about vaccination and boosting schedules for coronavirus disease 2019 (COVID-19) hinges on reliable methods for evaluating the longevity of vaccine protection. We show that modeling of protection as a piecewise linear function of time since vaccination for the log hazard ratio of the vaccine effect provides more reliable estimates of vaccine effectiveness at the end of an observation period and also detects plateaus in protective effectiveness more reliably than the standard method of estimating a constant vaccine effect over each time period. This approach will be useful for analyzing data pertaining to COVID-19 vaccines and other vaccines for which rapid and reliable understanding of vaccine effectiveness over time is desired.

  PublisherDOI

• Rejoinder to Commentaries on the “Monitoring OS in Pivotal Trials in Indolent Cancers” Article

  Statistics in Biopharmaceutical Research · 2025-04-03

  article1st authorCorresponding
  PublisherDOI

• A Perspective on the Appropriate Implementation of ICH E9(R1) Addendum Strategies for Handling Intercurrent Events

  Statistics in Medicine · 2025-05-01 · 7 citations

  articleOpen access1st authorCorresponding

  In randomized clinical trials, stopping study medication, use of rescue treatment, and other intercurrent events can complicate interpretation of results. The ICH E9(R1) Addendum on estimands stimulated important cross-disciplinary discussions on trial objectives. Unfortunately, with influence of the Addendum, many trials have proposed analyzing primary endpoints using "while on treatment", "hypothetical", or "principal stratum" strategies that handle intercurrent events in ways that use post-randomization outcomes to exclude information from randomized participants and don't preserve integrity of randomization, or that don't reliably capture the intervention's meaningful net effects. These approaches have inherent limitations in ability to draw scientifically rigorous inference on clinically relevant causal effects important for decisions about adopting interventions. We describe advantages of trials with standard-of-care control arms targeting estimands using "treatment policy" approaches for intercurrent events, while potentially incorporating other meaningful intercurrent events, such as death, into the primary endpoint applying a composite strategy. Well-designed and -conducted trials targeting such estimands achieve scientifically rigorous causal inference through analyzes that protect the integrity of randomization. Such estimands also provide meaningful information relevant to real-world settings because they (1) are unconditional in nature i.e., they don't condition on post-treatment circumstances that might not be many participants' experiences; and (2) properly evaluate the experimental intervention within a regimen that includes possible ancillary care that would be clinically appropriate in real-world settings. We hope to add clarity about appropriate strategies for intercurrent events and how to improve design, conduct, and analysis of clinical trials to address questions of greatest clinical importance reliably.

  PublisherOA PDFDOI

• The Effectiveness of NP001 on Long Term Survival of Patients with Amyotrophic Lateral Sclerosis: The IKARIA Study

  SSRN Electronic Journal · 2024-01-01 · 4 citations

  preprintOpen access
  PublisherDOI

• Methods for the estimation of direct and indirect vaccination effects by combining data from individual‐ and cluster‐randomized trials

  Statistics in Medicine · 2024-02-13 · 3 citations

  articleOpen access

  Both individually and cluster randomized study designs have been used for vaccine trials to assess the effects of vaccine on reducing the risk of disease or infection. The choice between individually and cluster randomized designs is often driven by the target estimand of interest (eg, direct versus total), statistical power, and, importantly, logistic feasibility. To combat emerging infectious disease threats, especially when the number of events from one single trial may not be adequate to obtain vaccine effect estimates with a desired level of precision, it may be necessary to combine information across multiple trials. In this article, we propose a model formulation to estimate the direct, indirect, total, and overall vaccine effects combining data from trials with two types of study designs: individual-randomization and cluster-randomization, based on a Cox proportional hazards model, where the hazard of infection depends on both vaccine status of the individual as well as the vaccine status of the other individuals in the same cluster. We illustrate the use of the proposed model and assess the potential efficiency gain from combining data from multiple trials, compared to using data from each individual trial alone, through two simulation studies, one of which is designed based on a cholera vaccine trial previously carried out in Matlab, Bangladesh.

  PublisherOA PDFDOI

• VV116 or Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19

  UNC Libraries · 2024-08-31 · 1 citations

  articleOpen accessSenior author

  To the Editor: Cao and colleagues (Feb. 2 issue)1 report that the oral antiviral agent VV116 was noninferior to nirmatrelvir–ritonavir in alleviating Covid-19–related symptoms.

  PublisherDOI

• Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on ‘Feels, Functions, Survives’. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency

  American Journal of Respiratory and Critical Care Medicine · 2024-01-04 · 73 citations

  articleOpen access

  Abstract Background Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA’s ‘feels, functions, survives’ criteria. Results Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include ‘feels, functions, survives’ measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences—namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients’ quality of life and survival.

  PublisherOA PDFDOI

Recent grants

• Statistical Issues in AIDS Research

  NIH · $10.1M · 1989–2029

• Statistical Issues in AIDS Research

  NIH · $7.4M · 1989–2019

• NIH Grant T32AI007450

  NIH · $1.9M · 2013

• NIH Grant U01AI046702

  NIH · $49.5M · 2008

• NIH Grant U01AI068617

  NIH · $28.8M · 2013

Frequent coauthors

• Martina Deseyve

  116 shared

• Laura Guay

  Milken Institute

  114 shared

• J. Brooks Jackson

  University of Iowa

  114 shared

• Lynne Mofenson

  Elizabeth Glaser Pediatric AIDS Foundation

  111 shared

• Francis Mmiro

  MUJHU Research Collaboration

  111 shared

• Philippa Musoke

  MUJHU Research Collaboration

  110 shared

• Susan H. Eshleman

  Johns Hopkins University

  109 shared

• Mark Mirochnick

  Boston University

  109 shared

Education

• PhD, Statistics

  University of Maryland, College Park

  1976