• A Cornucopia of Maximum Likelihood Algorithms

    Item Type Journal Article
    Author Kenneth Lange
    Author Xun-Jian Li
    Author Hua Zhou
    Date 2025-08-04
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://www.tandfonline.com/doi/full/10.1080/00031305.2025.2526535
    Accessed 8/10/2025, 4:22:59 PM
    Pages 1-11
    Publication The American Statistician
    DOI 10.1080/00031305.2025.2526535
    Journal Abbr The American Statistician
    ISSN 0003-1305, 1537-2731
    Date Added 8/10/2025, 4:22:59 PM
    Modified 8/10/2025, 4:23:46 PM

    Tags:

    • mle
    • computing
    • maximum-likelihood-estimation
    • optimization
  • A double-blind randomised placebo-controlled trial of percutaneous coronary intervention for the relief of stable angina without antianginal medications: design and rationale of the ORBITA-2 trial

    Item Type Journal Article
    Author Alexandra Nowbar Nowbar
    Author Christopher Rajkumar
    Author Michael Foley
    Author Fiyyaz Ahmed-Jushuf
    Author James Howard Howard
    Author Henry Seligman
    Author Ricardo Petraco
    Author Sayan Sen
    Author Sukhjinder Nijjer Nijjer
    Author Matthew Shun-Shin Shun-Shin
    Author Thomas Keeble Keeble
    Author Afzal Sohaib
    Author David Collier
    Author Patrick McVeigh
    Author Frank Harrell Harrell
    Author Darrel Francis Francis
    Author Rasha Al-Lamee Al-Lamee
    Date 04/2022
    Short Title A double-blind randomised placebo-controlled trial of percutaneous coronary intervention for the relief of stable angina without antianginal medications
    Library Catalog DOI.org (Crossref)
    URL https://eurointervention.pcronline.com/doi/10.4244/EIJ-D-21-00649
    Accessed 12/28/2025, 10:04:33 AM
    Volume 17
    Pages 1490-1497
    Publication EuroIntervention
    DOI 10.4244/EIJ-D-21-00649
    Issue 18
    ISSN 1774-024X
    Date Added 12/28/2025, 10:04:33 AM
    Modified 12/28/2025, 10:04:33 AM
  • A double-blind, randomised, placebo-controlled trial of the coronary sinus Reducer in refractory angina: design and rationale of the ORBITA-COSMIC trial

    Item Type Journal Article
    Author Michael J. Foley
    Author Christopher A. Rajkumar
    Author Fiyyaz Ahmed-Jushuf
    Author Florentina Simader
    Author Rachel H. Pathimagaraj
    Author Sukhjinder Nijjer
    Author Sayan Sen
    Author Ricardo Petraco
    Author Gerald Clesham
    Author Thomas Johnson
    Author Frank E. Harrell Jr
    Author Peter Kellman
    Author Darrel Francis
    Author Matthew Shun-Shin
    Author James Howard
    Author Graham D. Cole
    Author Rasha Al-Lamee
    Date 02/2024
    Short Title A double-blind, randomised, placebo-controlled trial of the coronary sinus Reducer in refractory angina
    Library Catalog DOI.org (Crossref)
    URL https://eurointervention.pcronline.com/doi/10.4244/EIJ-D-23-00567
    Accessed 12/28/2025, 10:15:21 AM
    Volume 20
    Pages e216-e223
    Publication EuroIntervention
    DOI 10.4244/EIJ-D-23-00567
    Issue 3
    ISSN 1969-6213
    Date Added 12/28/2025, 10:15:21 AM
    Modified 12/28/2025, 10:15:21 AM
  • A Predictive Model for Amblyopia Risk Factor Diagnosis after Photoscreening

    Item Type Journal Article
    Author Dakota Vaughan
    Author Frank E. Harrell
    Author Sean P. Donahue
    Date 09/2022
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0161642022003311
    Accessed 12/28/2025, 10:08:37 AM
    Volume 129
    Pages 1065-1067
    Publication Ophthalmology
    DOI 10.1016/j.ophtha.2022.04.026
    Issue 9
    Journal Abbr Ophthalmology
    ISSN 01616420
    Date Added 12/28/2025, 10:08:37 AM
    Modified 12/28/2025, 10:08:37 AM
  • Assessment of Awake Prone Positioning in Hospitalized Adults With COVID-19: A Nonrandomized Controlled Trial

    Item Type Journal Article
    Author Edward Tang Qian
    Author Cheryl L. Gatto
    Author Olga Amusina
    Author Mary Lynn Dear
    Author William Hiser
    Author Reagan Buie
    Author Sunil Kripalani
    Author Frank E. Harrell
    Author Robert E. Freundlich
    Author Yue Gao
    Author Wu Gong
    Author Cassandra Hennessy
    Author Jillann Grooms
    Author Megan Mattingly
    Author Shashi K. Bellam
    Author Jessica Burke
    Author Arwa Zakaria
    Author Eduard E. Vasilevskis
    Author Frederic T. Billings
    Author Jill M. Pulley
    Author Gordon R. Bernard
    Author Christopher J. Lindsell
    Author Todd W. Rice
    Author Vanderbilt Learning Healthcare System Platform Investigators
    Author Robert Dittus
    Author Shon Dwyer
    Author Paul Harris
    Author Tina Hartert
    Author Jim Hayman
    Author Catherine Ivory
    Author Kevin Johnson
    Author Ruth Kleinpell
    Author Lee Ann Liska
    Author Patrick Luther
    Author Jay Morrison
    Author Thomas Nantais
    Author Mariann Piano
    Author Kris Rhem
    Author Russell Rothman
    Author Matt Semler
    Author Robin Steaban
    Author Philip Walker
    Author Consuelo Wilkins
    Author Adam Wright
    Author Autumn Zuckerman
    Date 2022-06-01
    Language en
    Short Title Assessment of Awake Prone Positioning in Hospitalized Adults With COVID-19
    Library Catalog DOI.org (Crossref)
    URL https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2791385
    Accessed 12/28/2025, 10:06:25 AM
    Volume 182
    Pages 612
    Publication JAMA Internal Medicine
    DOI 10.1001/jamainternmed.2022.1070
    Issue 6
    Journal Abbr JAMA Intern Med
    ISSN 2168-6106
    Date Added 12/28/2025, 10:06:25 AM
    Modified 12/28/2025, 10:06:25 AM
  • Association of step counts over time with the risk of chronic disease in the All of Us Research Program

    Item Type Journal Article
    Author Hiral Master
    Author Jeffrey Annis
    Author Shi Huang
    Author Joshua A. Beckman
    Author Francis Ratsimbazafy
    Author Kayla Marginean
    Author Robert Carroll
    Author Karthik Natarajan
    Author Frank E. Harrell
    Author Dan M. Roden
    Author Paul Harris
    Author Evan L. Brittain
    Abstract Abstract The association between physical activity and human disease has not been examined using commercial devices linked to electronic health records. Using the electronic health records data from the All of Us Research Program, we show that step count volumes as captured by participants’ own Fitbit devices were associated with risk of chronic disease across the entire human phenome. Of the 6,042 participants included in the study, 73% were female, 84% were white and 71% had a college degree, and participants had a median age of 56.7 (interquartile range 41.5–67.6) years and body mass index of 28.1 (24.3–32.9) kg m –2 . Participants walked a median of 7,731.3 (5,866.8–9,826.8) steps per day over the median activity monitoring period of 4.0 (2.2–5.6) years with a total of 5.9 million person-days of monitoring. The relationship between steps per day and incident disease was inverse and linear for obesity ( n  = 368), sleep apnea ( n  = 348), gastroesophageal reflux disease ( n  = 432) and major depressive disorder ( n  = 467), with values above 8,200 daily steps associated with protection from incident disease. The relationships with incident diabetes ( n  = 156) and hypertension ( n  = 482) were nonlinear with no further risk reduction above 8,000–9,000 steps. Although validation in a more diverse sample is needed, these findings provide a real-world evidence-base for clinical guidance regarding activity levels that are necessary to reduce disease risk.
    Date 11/2022
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://www.nature.com/articles/s41591-022-02012-w
    Accessed 12/28/2025, 10:09:21 AM
    Volume 28
    Pages 2301-2308
    Publication Nature Medicine
    DOI 10.1038/s41591-022-02012-w
    Issue 11
    Journal Abbr Nat Med
    ISSN 1078-8956, 1546-170X
    Date Added 12/28/2025, 10:09:21 AM
    Modified 12/28/2025, 10:09:21 AM
  • Bayesian Analytical Methods in Cardiovascular Clinical Trials: Why, When, and How

    Item Type Journal Article
    Author Samuel Heuts
    Author Michal J. Kawczynski
    Author Ahmed Sayed
    Author Sarah M. Urbut
    Author Arthur M. Albuquerque
    Author John M. Mandrola
    Author Sanjay Kaul
    Author Frank E. Harrell
    Author Andrea Gabrio
    Author James M. Brophy
    Date 01/2025
    Language en
    Short Title Bayesian Analytical Methods in Cardiovascular Clinical Trials
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0828282X24011309
    Accessed 12/28/2025, 10:28:51 AM
    Volume 41
    Pages 30-44
    Publication Canadian Journal of Cardiology
    DOI 10.1016/j.cjca.2024.11.002
    Issue 1
    Journal Abbr Canadian Journal of Cardiology
    ISSN 0828282X
    Date Added 12/28/2025, 10:28:51 AM
    Modified 12/28/2025, 10:30:13 AM

    Tags:

    • rct
    • teaching-mds
    • bayes
    • basic
  • Bayesian Expectile Joint Model With Varying Coefficient for Longitudinal and Semi‐Competing Risks Data

    Item Type Journal Article
    Author Feng Gu
    Author Jiaqing Chen
    Author Jinjing Wang
    Author Yibo Long
    Author Xiaofan Wang
    Author Yangxin Huang
    Abstract ABSTRACT In the realm of clinical medical research, semi‐competing risks data are usually observed in practice, yet there are few studies on the joint models of longitudinal and semi‐competing risks data. In this paper, a joint model for longitudinal and semi‐competing risks data is proposed. Based on the expectile regression, a linear mixed‐effects longitudinal sub‐model is formulated, and a Cox proportional hazards survival sub‐model is considered under the framework of semi‐competing risks. The two sub‐models are linked by a shared longitudinal trajectory function. To accommodate the time‐varying relationship between the longitudinal response variable and covariates, as well as to introduce flexibility to the structural linkage between longitudinal and survival processes, we incorporate the time‐varying coefficients into the joint model in the form of nonparametric functions. The simultaneous Bayesian inference method is utilized to estimate the model parameters, which not only overcomes the convergence problem, but also improves the accuracy of the parameter estimation while effectively reducing the computational burden. The simulation studies are conducted to assess the performance of the proposed joint model and methodology. Finally, we analyze a dataset from the Multicenter AIDS Cohort Study to illustrate the real application of the proposed model and method. In both simulation studies and empirical analyses, joint modeling methods demonstrate performance that meets expected effects.
    Date 08/2025
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://onlinelibrary.wiley.com/doi/10.1002/sim.70219
    Accessed 8/10/2025, 4:35:09 PM
    Volume 44
    Pages e70219
    Publication Statistics in Medicine
    DOI 10.1002/sim.70219
    Issue 18-19
    Journal Abbr Statistics in Medicine
    ISSN 0277-6715, 1097-0258
    Date Added 8/10/2025, 4:35:09 PM
    Modified 8/10/2025, 4:36:21 PM

    Tags:

    • rct
    • multiple-endpoints
    • competing-risk
    • bayes
    • cox-model
    • shared-parameter
    • expectile
  • Bayesian statistics for clinical research

    Item Type Journal Article
    Author Ewan C Goligher
    Author Anna Heath
    Author Michael O Harhay
    Date 09/2024
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0140673624012959
    Accessed 1/28/2026, 2:49:13 PM
    Volume 404
    Pages 1067-1076
    Publication The Lancet
    DOI 10.1016/S0140-6736(24)01295-9
    Issue 10457
    Journal Abbr The Lancet
    ISSN 01406736
    Date Added 1/28/2026, 2:49:13 PM
    Modified 1/28/2026, 2:49:42 PM

    Tags:

    • basic
    • bayes
    • teaching-mds
  • Combining Missing Data Imputation and Internal Validation in Clinical Risk Prediction Models

    Item Type Journal Article
    Author Junhui Mi
    Author Rahul D. Tendulkar
    Author Sarah M. C. Sittenfeld
    Author Sujata Patil
    Author Emily C. Zabor
    Abstract ABSTRACT Methods to handle missing data have been extensively explored in the context of estimation and descriptive studies, with multiple imputation being the most widely used method in clinical research. However, in the context of clinical risk prediction models, where the goal is often to achieve high prediction accuracy and to make predictions for future patients, there are different considerations regarding the handling of missing covariate data. As a result, deterministic imputation is better suited to the setting of clinical risk prediction models, since the outcome is not included in the imputation model and the imputation method can be easily applied to future patients. In this paper, we provide a tutorial demonstrating how to conduct bootstrapping followed by deterministic imputation of missing covariate data to construct and internally validate the performance of a clinical risk prediction model in the presence of missing data. Simulation study results are provided to help guide when imputation may be appropriate in real‐world applications.
    Date 08/2025
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://onlinelibrary.wiley.com/doi/10.1002/sim.70203
    Accessed 8/10/2025, 4:31:30 PM
    Volume 44
    Pages e70203
    Publication Statistics in Medicine
    DOI 10.1002/sim.70203
    Issue 18-19
    Journal Abbr Statistics in Medicine
    ISSN 0277-6715, 1097-0258
    Date Added 8/10/2025, 4:31:30 PM
    Modified 8/10/2025, 4:32:40 PM

    Tags:

    • bootstrap
    • validation
    • multiple-imputation
    • missing
  • Combining multiple imputation with internal model validation in clinical prediction modeling: a systematic methodological review

    Item Type Journal Article
    Author Sinclair Awounvo
    Author Meinhard Kieser
    Author Manuel Feißt
    Date 8/2025
    Language en
    Short Title Combining multiple imputation with internal model validation in clinical prediction modeling
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0895435625002495
    Accessed 8/10/2025, 4:51:27 PM
    Pages 111916
    Publication Journal of Clinical Epidemiology
    DOI 10.1016/j.jclinepi.2025.111916
    Journal Abbr Journal of Clinical Epidemiology
    ISSN 08954356
    Date Added 8/10/2025, 4:51:27 PM
    Modified 8/10/2025, 4:52:00 PM

    Tags:

    • validation
    • multiple-imputation
    • review
    • missing
  • Commentary on van Lancker et al

    Item Type Journal Article
    Author Frank E Harrell
    Date 08/2024
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://journals.sagepub.com/doi/10.1177/17407745241251609
    Accessed 12/28/2025, 10:23:09 AM
    Volume 21
    Pages 412-414
    Publication Clinical Trials
    DOI 10.1177/17407745241251609
    Issue 4
    Journal Abbr Clinical Trials
    ISSN 1740-7745, 1740-7753
    Date Added 12/28/2025, 10:23:09 AM
    Modified 12/28/2025, 10:23:09 AM
  • Comparison Is Not a Zero-Sum Game: Exploring Advanced Measures of Healthcare Ethics Consultation

    Item Type Journal Article
    Author Kelly W. Harris
    Author Thomas V. Cunningham
    Author D. Micah Hester
    Author Kelly Armstrong
    Author Ahra Kim
    Author Frank E. Harrell
    Author Joseph B. Fanning
    Date 2021-04-03
    Language en
    Short Title Comparison Is Not a Zero-Sum Game
    Library Catalog DOI.org (Crossref)
    URL https://www.tandfonline.com/doi/full/10.1080/23294515.2020.1844820
    Accessed 12/28/2025, 9:57:59 AM
    Volume 12
    Pages 123-136
    Publication AJOB Empirical Bioethics
    DOI 10.1080/23294515.2020.1844820
    Issue 2
    Journal Abbr AJOB Empirical Bioethics
    ISSN 2329-4515, 2329-4523
    Date Added 12/28/2025, 9:57:59 AM
    Modified 12/28/2025, 9:57:59 AM
  • Complementary strengths of the Neyman-Rubin and graphical causal frameworks

    Item Type Preprint
    Author Tetiana Gorbach
    Author Xavier de Luna
    Author Juha Karvanen
    Author Ingeborg Waernbaum
    Abstract This article contributes to the discussion on the relationship between the Neyman-Rubin and the graphical frameworks for causal inference. We present specific examples of data-generating mechanisms - such as those involving undirected or deterministic relationships and cycles - where analyses using a directed acyclic graph are challenging, but where the tools from the Neyman-Rubin causal framework are readily applicable. We also provide examples of data-generating mechanisms with M-bias, trapdoor variables, and complex front-door structures, where the application of the Neyman-Rubin approach is complicated, but the graphical approach is directly usable. The examples offer insights into commonly used causal inference frameworks and aim to improve comprehension of the languages for causal reasoning among a broad audience.
    Date 2025
    Library Catalog DOI.org (Datacite)
    URL https://arxiv.org/abs/2512.09130
    Accessed 12/11/2025, 8:27:21 AM
    Rights Creative Commons Attribution 4.0 International
    Extra Version Number: 1
    DOI 10.48550/ARXIV.2512.09130
    Repository arXiv
    Date Added 12/11/2025, 8:27:21 AM
    Modified 12/11/2025, 8:28:25 AM

    Tags:

    • causal
    • Neyman-Pearson

    Notes:

    • <h2>Other</h2> Under consideration at The American Statistician; not yet accepted

  • Covariate Adjustment in Cardiovascular Randomized Controlled Trials

    Item Type Journal Article
    Author Leah Pirondini
    Author John Gregson
    Author Ruth Owen
    Author Tim Collier
    Author Stuart Pocock
    Date 05/2022
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S2213177922001743
    Accessed 1/3/2026, 8:47:52 AM
    Volume 10
    Pages 297-305
    Publication JACC: Heart Failure
    DOI 10.1016/j.jchf.2022.02.007
    Issue 5
    Journal Abbr JACC: Heart Failure
    ISSN 22131779
    Date Added 1/3/2026, 8:47:52 AM
    Modified 1/3/2026, 8:48:24 AM

    Tags:

    • rct
    • teaching-mds
    • covariate-adjustment
    • ancova
  • Daily angina documentation versus subsequent recall: development of a symptom smartphone app

    Item Type Journal Article
    Author Alexandra N Nowbar
    Author James P Howard
    Author Matthew J Shun-Shin
    Author Christopher Rajkumar
    Author Michael Foley
    Author Arunima Basu
    Author Akshit Goel
    Author Sapna Patel
    Author Ahmer Adnan
    Author Catherine J Beattie
    Author Thomas R Keeble
    Author Afzal Sohaib
    Author David Collier
    Author Patrick McVeigh
    Author Frank E Harrell
    Author Darrel P Francis
    Author Rasha K Al-Lamee
    Abstract Abstract Aims The traditional approach to documenting angina outcomes in clinical trials is to ask the patient to recall their symptoms at the end of a month. With the ubiquitous availability of smartphones and tablets, daily contemporaneous documentation might be possible. Methods and results The ORBITA-2 symptom smartphone app was developed with a user-centred iterative design and testing cycle involving a focus group of previous ORBITA participants. The feasibility and acceptability were assessed in an internal pilot of participants in the ongoing ORBITA-2 trial. Seven days of app entries by ORBITA-2 participants were compared with subsequent participant recall at the end of the 7-day period. The design focus group tested a prototype app. They reported that the final version captured their symptoms and was easy to use. In the completion assessment group, 141 of 142 (99%) completed the app in full and 47 of 141 (33%) without reminders. In the recall assessment group, 29 of 29 (100%) participants said they could recall the previous day’s symptoms, and 82% of them recalled correctly. For 2 days previously, 88% said they could recall and of those, 87% recalled correctly. The proportion saying they could recall their symptoms fell progressively thereafter: 89, 67, 61, 50%, and at 7 days, 55% (P &lt; 0.001 for trend). The proportion of recalling correctly also fell progressively to 55% at 7 days (P = 0.04 for trend). Conclusion Episode counts of angina are difficult to recall after a few days. For trials such as ORBITA-2 focusing on angina, daily symptom collection via a smartphone app will increase the validity of the results.
    Date 2022-07-06
    Language en
    Short Title Daily angina documentation versus subsequent recall
    Library Catalog DOI.org (Crossref)
    URL https://academic.oup.com/ehjdh/article/3/2/276/6566267
    Accessed 12/28/2025, 10:06:56 AM
    Rights https://creativecommons.org/licenses/by-nc/4.0/
    Volume 3
    Pages 276-283
    Publication European Heart Journal - Digital Health
    DOI 10.1093/ehjdh/ztac015
    Issue 2
    ISSN 2634-3916
    Date Added 12/28/2025, 10:06:56 AM
    Modified 12/28/2025, 10:06:56 AM
  • Dealing with continuous variables and modelling non-linear associations in healthcare data: practical guide

    Item Type Journal Article
    Author Pedro Lopez-Ayala
    Author Richard D Riley
    Author Gary S Collins
    Author Tobias Zimmermann
    Date 2025-07-16
    Language en
    Short Title Dealing with continuous variables and modelling non-linear associations in healthcare data
    Library Catalog Crossref
    URL https://www.bmj.com/lookup/doi/10.1136/bmj-2024-082440
    Accessed 7/16/2025, 1:29:28 PM
    Rights http://www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy
    Extra Publisher: BMJ
    Volume 390
    Pages e082440
    Publication BMJ
    DOI 10.1136/bmj-2024-082440
    ISSN 1756-1833
    Date Added 7/16/2025, 1:29:28 PM
    Modified 7/16/2025, 1:30:25 PM

    Tags:

    • teaching-mds
    • regression
    • categorization-of-continuous-variables
    • categorization
    • spline
    • fractional-polynomial
  • Developing clinical prediction models: a step-by-step guide

    Item Type Journal Article
    Author Orestis Efthimiou
    Author Michael Seo
    Author Konstantina Chalkou
    Author Thomas Debray
    Author Matthias Egger
    Author Georgia Salanti
    Date 2024-09-03
    Language en
    Short Title Developing clinical prediction models
    Library Catalog DOI.org (Crossref)
    URL https://www.bmj.com/lookup/doi/10.1136/bmj-2023-078276
    Accessed 7/29/2025, 5:12:14 PM
    Pages e078276
    Publication BMJ
    DOI 10.1136/bmj-2023-078276
    Journal Abbr BMJ
    ISSN 1756-1833
    Date Added 7/29/2025, 5:12:14 PM
    Modified 7/29/2025, 5:13:27 PM

    Tags:

    • teaching-mds
    • variable-selection
    • bootstrap
    • validation
    • design
    • strategy
    • rms
  • Development and Validation of a Model to Predict Neonatal Abstinence Syndrome

    Item Type Journal Article
    Author Stephen W. Patrick
    Author James C. Slaughter
    Author Frank E. Harrell
    Author Peter R. Martin
    Author Katherine Hartmann
    Author Judith Dudley
    Author Shannon Stratton
    Author William O. Cooper
    Date 02/2021
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S002234762031297X
    Accessed 12/28/2025, 9:51:10 AM
    Volume 229
    Pages 154-160.e6
    Publication The Journal of Pediatrics
    DOI 10.1016/j.jpeds.2020.10.030
    Journal Abbr The Journal of Pediatrics
    ISSN 00223476
    Date Added 12/28/2025, 9:51:10 AM
    Modified 12/28/2025, 9:51:10 AM
  • Development and Validation of a Model to Predict Postdischarge Opioid Use After Cesarean Birth

    Item Type Journal Article
    Author Sarah S. Osmundson
    Author Alese Halvorson
    Author Kristin N. Graves
    Author Clara Wang
    Author Stephen Bruehl
    Author Carlos G. Grijalva
    Author Dan France
    Author Katherine Hartmann
    Author Shilpa Mokshagundam
    Author Frank E. Harrell
    Abstract OBJECTIVE: To develop and validate a prediction model for postdischarge opioid use in patients undergoing cesarean birth. METHODS: We conducted a prospective cohort study of patients undergoing cesarean birth. Patients were enrolled postoperatively, and they completed pain and opioid use questionnaires 14 days after cesarean birth. Clinical data were abstracted from the electronic health record (EHR). Participants were prescribed 30 tablets of hydrocodone 5 mg–acetaminophen 325 mg at discharge and were queried about postdischarge opioid use. The primary outcome was total morphine milligram equivalents used. We constructed three proportional odds predictive models of postdischarge opioid use: a full model with 34 predictors available before hospital discharge, an EHR model that excluded questionnaire data, and a reduced model. The reduced model used forward selection to sequentially add predictors until 90% of the full model performance was achieved. Predictors were ranked a priori based on data from the literature and prior research. Predictive accuracy was estimated using discrimination (concordance index). RESULTS: Between 2019 and 2020, 459 participants were enrolled and 279 filled the standardized study prescription. Of the 398 with outcome measurements, participants used a median of eight tablets (interquartile range 1–18 tablets) after discharge, 23.5% used no opioids, and 23.0% used all opioids. Each of the models demonstrated high accuracy predicting postdischarge opioid use (concordance index range 0.74–0.76 for all models). We selected the reduced model as our final model given its similar model performance with the fewest number of predictors, all obtained from the EHR (inpatient opioid use, tobacco use, and depression or anxiety). CONCLUSION: A model with three predictors readily found in the EHR—inpatient opioid use, tobacco use, and depression or anxiety—accurately estimated postdischarge opioid use. This represents an opportunity for individualizing opioid prescriptions after cesarean birth.
    Date 05/2022
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://journals.lww.com/10.1097/AOG.0000000000004759
    Accessed 12/28/2025, 10:05:02 AM
    Volume 139
    Pages 888-897
    Publication Obstetrics & Gynecology
    DOI 10.1097/AOG.0000000000004759
    Issue 5
    ISSN 0029-7844
    Date Added 12/28/2025, 10:05:02 AM
    Modified 12/28/2025, 10:05:02 AM
  • Development and Validation of Cervical Prediction Models for Patient-Reported Outcomes at 1 Year After Cervical Spine Surgery for Radiculopathy and Myelopathy

    Item Type Journal Article
    Author Kristin R. Archer
    Author Mohamad Bydon
    Author Inamullah Khan
    Author Hui Nian
    Author Jacquelyn S. Pennings
    Author Frank E. Harrell
    Author Ahilan Sivaganesan
    Author Silky Chotai
    Author Matthew J. McGirt
    Author Kevin T. Foley
    Author Steven D. Glassman
    Author Praveen V. Mummaneni
    Author Erica F. Bisson
    Author John J. Knightly
    Author Christopher I. Shaffrey
    Author Anthony L. Asher
    Author Clinton J. Devin
    Abstract Study Design. Retrospective analysis of prospectively collected registry data. Objective. To develop and validate prediction models for 12-month patient-reported outcomes of disability, pain, and myelopathy in patients undergoing elective cervical spine surgery. Summary of Background Data. Predictive models have the potential to be utilized preoperatively to set expectations, adjust modifiable characteristics, and provide a patient-centered model of care. Methods. This study was conducted using data from the cervical module of the Quality Outcomes Database. The outcomes of interest were disability (Neck Disability Index:), pain (Numeric Rating Scale), and modified Japanese Orthopaedic Association score for myelopathy. Multivariable proportional odds ordinal regression models were developed for patients with cervical radiculopathy and myelopathy. Patient demographic, clinical, and surgical covariates as well as baseline patient-reported outcomes scores were included in all models. The models were internally validated using bootstrap resampling to estimate the likely performance on a new sample of patients. Results. Four thousand nine hundred eighty-eight patients underwent surgery for radiculopathy and 2641 patients for myelopathy. The most important predictor of poor postoperative outcomes at 12-months was the baseline Neck Disability Index score for patients with radiculopathy and modified Japanese Orthopaedic Association score for patients with myelopathy. In addition, symptom duration, workers’ compensation, age, employment, and ambulatory and smoking status had a statistically significant impact on all outcomes ( P  < 0.001). Clinical and surgical variables contributed very little to predictive models, with posterior approach being associated with higher odds of having worse 12-month outcome scores in both the radiculopathy and myelopathy cohorts ( P  < 0.001). The full models overall discriminative performance ranged from 0.654 to 0.725. Conclusions. These predictive models provide individualized risk-adjusted estimates of 12-month disability, pain, and myelopathy outcomes for patients undergoing spine surgery for degenerative cervical disease. Predictive models have the potential to be used as a shared decision-making tool for evidence-based preoperative counselling. Level of Evidence: 2.
    Date 2020-11-15
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://journals.lww.com/10.1097/BRS.0000000000003610
    Accessed 12/28/2025, 9:48:51 AM
    Volume 45
    Pages 1541-1552
    Publication Spine
    DOI 10.1097/BRS.0000000000003610
    Issue 22
    ISSN 0362-2436, 1528-1159
    Date Added 12/28/2025, 9:48:51 AM
    Modified 12/28/2025, 9:48:51 AM
  • Did Finerenone Improve Health Status in the FINEARTS Trial?

    Item Type Journal Article
    Author Javed Butler
    Author Muhammad Shariq Usman
    Author Frank E. Harrell
    Author Milton Packer
    Date 01/2025
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0735109724106055
    Accessed 12/28/2025, 10:40:53 AM
    Volume 85
    Pages 190-195
    Publication Journal of the American College of Cardiology
    DOI 10.1016/j.jacc.2024.12.005
    Issue 2
    Journal Abbr Journal of the American College of Cardiology
    ISSN 07351097
    Date Added 12/28/2025, 10:40:53 AM
    Modified 12/28/2025, 10:40:53 AM
  • EEG-based model and antidepressant response

    Item Type Journal Article
    Author Gustav Nilsonne
    Author Frank E. Harrell
    Date 01/2021
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://www.nature.com/articles/s41587-020-00768-5
    Accessed 12/28/2025, 9:50:28 AM
    Volume 39
    Pages 27-27
    Publication Nature Biotechnology
    DOI 10.1038/s41587-020-00768-5
    Issue 1
    Journal Abbr Nat Biotechnol
    ISSN 1087-0156, 1546-1696
    Date Added 12/28/2025, 9:50:28 AM
    Modified 12/28/2025, 9:50:28 AM
  • Effect of a pragmatic home-based mobile health exercise intervention after transcatheter aortic valve replacement: a randomized pilot trial

    Item Type Journal Article
    Author Brian R Lindman
    Author Linda D Gillam
    Author Megan Coylewright
    Author Frederick G P Welt
    Author Sammy Elmariah
    Author Stephanie A Smith
    Author David A McKeel
    Author Natalie Jackson
    Author Kush Mukerjee
    Author Harrison Cloud
    Author Narden Hanna
    Author Jenelle Purpura
    Author Hannah Ellis
    Author Vong Martinez
    Author Alexandra M Selberg
    Author Shi Huang
    Author Frank E Harrell
    Abstract Abstract Aims Impaired physical function is common in patients undergoing transcatheter aortic valve replacement (TAVR) and associated with worse outcomes. Participation in centre-based cardiac rehabilitation (CR) after cardiovascular procedures is sub-optimal. We aimed to test a home-based mobile health exercise intervention as an alternative or complementary approach. Methods and results At five centres, after a run-in period, eligible individuals treated with TAVR were randomized 1:1 at their 1-month post-TAVR visit to an intervention group [activity monitor (AM) with personalized daily step goal and resistance exercises] or a control group for 6 weeks. Among 50 participants, average age was 76 years, 34% were female, average STS score was 2.9 ± 1.8, and 40% had Short Physical Performance Battery (SPPB) ≤9. Daily compliance with wearing the AM and performing exercises averaged 85–90%. In the intention to treat population, there was no evidence that the intervention improved the co-primary endpoints: daily steps +769 (95% CI −244 to +1783); SPPB +0.68 (−0.27 to 1.53); and Kansas City Cardiomyopathy Questionnaire −1.7 (−9.1 to 7.1). The intervention did improve secondary physical activity parameters, including moderate-to-intense daily active minutes (P &lt; 0.05). In a pre-specified analysis including participants who did not participate in CR (n = 30), the intervention improved several measures of physical activity: +1730 (100–3360) daily steps; +66 (28–105) daily active minutes; +53 (27–80) moderate-to-intense active minutes; and −157 (−265 to −50) sedentary minutes. Conclusion  Among selected participants treated with TAVR, this study did not provide evidence that a pragmatic home-based mobile health exercise intervention improved daily steps, physical performance or QoL for the overall cohort. However, the intervention did improve several measures of daily activity, particularly among individuals not participating in CR. Trial registry Clinicaltrials.gov NCT03270124.
    Date 2021-05-04
    Language en
    Short Title Effect of a pragmatic home-based mobile health exercise intervention after transcatheter aortic valve replacement
    Library Catalog DOI.org (Crossref)
    URL https://academic.oup.com/ehjdh/article/2/1/90/6128571
    Accessed 12/28/2025, 9:55:21 AM
    Rights http://creativecommons.org/licenses/by-nc/4.0/
    Volume 2
    Pages 90-103
    Publication European Heart Journal - Digital Health
    DOI 10.1093/ehjdh/ztab007
    Issue 1
    ISSN 2634-3916
    Date Added 12/28/2025, 9:55:21 AM
    Modified 12/28/2025, 9:55:47 AM

    Tags:

    • collaboration
  • Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial

    Item Type Journal Article
    Author Wesley H. Self
    Author Matthew W. Semler
    Author Lindsay M. Leither
    Author Jonathan D. Casey
    Author Derek C. Angus
    Author Roy G. Brower
    Author Steven Y. Chang
    Author Sean P. Collins
    Author John C. Eppensteiner
    Author Michael R. Filbin
    Author D. Clark Files
    Author Kevin W. Gibbs
    Author Adit A. Ginde
    Author Michelle N. Gong
    Author Frank E. Harrell
    Author Douglas L. Hayden
    Author Catherine L. Hough
    Author Nicholas J. Johnson
    Author Akram Khan
    Author Christopher J. Lindsell
    Author Michael A. Matthay
    Author Marc Moss
    Author Pauline K. Park
    Author Todd W. Rice
    Author Bryce R. H. Robinson
    Author David A. Schoenfeld
    Author Nathan I. Shapiro
    Author Jay S. Steingrub
    Author Christine A. Ulysse
    Author Alexandra Weissman
    Author Donald M. Yealy
    Author B. Taylor Thompson
    Author Samuel M. Brown
    Author National Heart, Lung, and Blood Institute PETAL Clinical Trials Network
    Date 2020-12-01
    Language en
    Short Title Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19
    Library Catalog DOI.org (Crossref)
    URL https://jamanetwork.com/journals/jama/fullarticle/2772922
    Accessed 12/28/2025, 9:49:35 AM
    Volume 324
    Pages 2165
    Publication JAMA
    DOI 10.1001/jama.2020.22240
    Issue 21
    Journal Abbr JAMA
    ISSN 0098-7484
    Date Added 12/28/2025, 9:49:35 AM
    Modified 12/28/2025, 9:49:35 AM
  • Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure

    Item Type Journal Article
    Author Zachary L. Cox
    Author Sean P. Collins
    Author Gabriel A. Hernandez
    Author A. Thomas McRae
    Author Beth T. Davidson
    Author Kirkwood Adams
    Author Mark Aaron
    Author Luke Cunningham
    Author Cathy A. Jenkins
    Author Christopher J. Lindsell
    Author Frank E. Harrell
    Author Christina Kampe
    Author Karen F. Miller
    Author William B. Stubblefield
    Author JoAnn Lindenfeld
    Date 04/2024
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0735109724003760
    Accessed 12/28/2025, 9:40:29 AM
    Volume 83
    Pages 1295-1306
    Publication Journal of the American College of Cardiology
    DOI 10.1016/j.jacc.2024.02.009
    Issue 14
    Journal Abbr Journal of the American College of Cardiology
    ISSN 07351097
    Date Added 12/28/2025, 9:40:29 AM
    Modified 12/28/2025, 9:40:29 AM
  • Empirical analyses and simulations showed that different machine and statistical learning methods had differing performance for predicting blood pressure

    Item Type Journal Article
    Author Peter C. Austin
    Author Frank E. Harrell
    Author Douglas S. Lee
    Author Ewout W. Steyerberg
    Abstract Abstract Machine learning is increasingly being used to predict clinical outcomes. Most comparisons of different methods have been based on empirical analyses in specific datasets. We used Monte Carlo simulations to determine when machine learning methods perform better than statistical learning methods in a specific setting. We evaluated six learning methods: stochastic gradient boosting machines using trees as the base learners, random forests, artificial neural networks, the lasso, ridge regression, and linear regression estimated using ordinary least squares (OLS). Our simulations were informed by empirical analyses in patients with acute myocardial infarction (AMI) and congestive heart failure (CHF) and used six data-generating processes, each based on one of the six learning methods, to simulate continuous outcomes in the derivation and validation samples. The outcome was systolic blood pressure at hospital discharge, a continuous outcome. We applied the six learning methods in each of the simulated derivation samples and evaluated performance in the simulated validation samples. The primary observation was that neural networks tended to result in estimates with worse predictive accuracy than the other five methods in both disease samples and across all six data-generating processes. Boosted trees and OLS regression tended to perform well across a range of scenarios.
    Date 2022-06-03
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://www.nature.com/articles/s41598-022-13015-5
    Accessed 12/28/2025, 10:07:38 AM
    Volume 12
    Pages 9312
    Publication Scientific Reports
    DOI 10.1038/s41598-022-13015-5
    Issue 1
    Journal Abbr Sci Rep
    ISSN 2045-2322
    Date Added 12/28/2025, 10:07:38 AM
    Modified 12/28/2025, 10:07:38 AM
  • Evaluating Medical Therapy for Calcific Aortic Stenosis

    Item Type Journal Article
    Author Brian R. Lindman
    Author Devraj Sukul
    Author Marc R. Dweck
    Author Mahesh V. Madhavan
    Author Benoit J. Arsenault
    Author Megan Coylewright
    Author W. David Merryman
    Author David E. Newby
    Author John Lewis
    Author Frank E. Harrell
    Author Michael J. Mack
    Author Martin B. Leon
    Author Catherine M. Otto
    Author Philippe Pibarot
    Date 12/2021
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0735109721077445
    Accessed 12/28/2025, 10:00:13 AM
    Volume 78
    Pages 2354-2376
    Publication Journal of the American College of Cardiology
    DOI 10.1016/j.jacc.2021.09.1367
    Issue 23
    Journal Abbr Journal of the American College of Cardiology
    ISSN 07351097
    Date Added 12/28/2025, 10:00:13 AM
    Modified 12/28/2025, 10:00:13 AM
  • Evolution and optimization of clinical trial endpoints and design in pulmonary arterial hypertension

    Item Type Journal Article
    Author Marco Caccamo
    Author Frank E. Harrell
    Author Anna R. Hemnes
    Abstract Abstract Selection of endpoints for clinical trials in pulmonary arterial hypertension (PAH) is challenging because of the small numbers of patients and the changing expectations of patients, clinicians, and regulators in this evolving therapy area. The most commonly used primary endpoint in PAH trials has been 6‐min walk distance (6MWD), leading to the approval of several targeted therapies. However, single surrogate endpoints such as 6MWD or hemodynamic parameters may not correlate with clinical outcomes. Composite endpoints of clinical worsening have been developed to reflect patients' overall condition more accurately, although there is no standard definition of worsening. Recently there has been a shift to composite endpoints assessing clinical improvement, and risk scores developed from registry data are increasingly being used. Biomarkers are another area of interest, although brain natriuretic peptide and its N ‐terminal prohormone are the only markers used for risk assessment or as endpoints in PAH. A range of other genetic, metabolic, and immunologic markers is currently under investigation, along with conventional and novel imaging modalities. Patient‐reported outcomes are an increasingly important part of evaluating new therapies, and several PAH‐specific tools are now available. In the future, alternative statistical techniques and trial designs, such as patient enrichment strategies, will play a role in evaluating PAH‐targeted therapies. In addition, modern sequencing techniques, imaging analyses, and high‐dimensional statistical modeling/machine learning may reveal novel markers that can play a role in the diagnosis and monitoring of PAH.
    Date 07/2023
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://onlinelibrary.wiley.com/doi/10.1002/pul2.12271
    Accessed 12/28/2025, 10:12:00 AM
    Volume 13
    Pages e12271
    Publication Pulmonary Circulation
    DOI 10.1002/pul2.12271
    Issue 3
    Journal Abbr Pulm. circ.
    ISSN 2045-8940, 2045-8940
    Date Added 12/28/2025, 10:12:00 AM
    Modified 12/28/2025, 10:12:00 AM
  • Explainable AI in healthcare: to explain, to predict, or to describe?

    Item Type Journal Article
    Author Alex Carriero
    Author Anne De Hond
    Author Bram Cappers
    Author Fernando Paulovich
    Author Sanne Abeln
    Author Karel Gm Moons
    Author Maarten Van Smeden
    Date 2025-12-05
    Language en
    Short Title Explainable AI in healthcare
    Library Catalog DOI.org (Crossref)
    URL https://diagnprognres.biomedcentral.com/articles/10.1186/s41512-025-00213-8
    Accessed 12/5/2025, 7:59:48 AM
    Volume 9
    Pages 29
    Publication Diagnostic and Prognostic Research
    DOI 10.1186/s41512-025-00213-8
    Issue 1
    Journal Abbr Diagn Progn Res
    ISSN 2397-7523
    Date Added 12/5/2025, 7:59:48 AM
    Modified 12/5/2025, 8:00:45 AM

    Tags:

    • causal-inference
    • variable-importance
    • causal
    • explainable-ai

    Notes:

    • Figure 1 is a nice summary of colliders, confounders, etc.

  • Exploration of an alternative to body mass index to characterize the relationship between height and weight for prediction of metabolic phenotypes and cardiovascular outcomes

    Item Type Journal Article
    Author Megan M. Shuey
    Author Shi Huang
    Author Rebecca T. Levinson
    Author Eric Farber‐Eger
    Author Katherine N. Cahill
    Author Joshua A. Beckman
    Author John R. Koethe
    Author Heidi J. Silver
    Author Kevin D. Niswender
    Author Nancy J. Cox
    Author Frank E. Harrell
    Author Quinn S. Wells
    Abstract Abstract Objective Body mass index (BMI) is the most commonly used predictor of weight‐related comorbidities and outcomes. However, the presumed relationship between height and weight intrinsic to BMI may introduce bias with respect to prediction of clinical outcomes. A series of analyses comparing the performance of models representing weight and height as separate interacting variables to models using BMI were performed using Vanderbilt University Medical Center's deidentified electronic health records and landmark methodology. Methods Use of BMI or height‐weight interaction in prediction models for established weight‐related cardiometabolic traits and metabolic syndrome was evaluated. Specifically, prediction models for hypertension, diabetes mellitus, low high‐density lipoprotein, and elevated triglycerides, atrial fibrillation, coronary artery disease, heart failure, and peripheral artery disease were developed. Model performance was evaluated using likelihood ratio, R 2 , and Somers' Dxy rank correlation. Differences in model predictions were visualized using heat maps. Results Compared to BMI, the maximally flexible height‐weight interaction model demonstrated improved prediction, higher likelihood ratio, R 2 , and Somers' Dxy rank correlation, for event‐free probability for all outcomes. The degree of improvement to the prediction model differed based on the outcome and across the height and weight range. Conclusions Because alternative measures of body composition such as waist‐to‐hip ratio are not routinely collected in the clinic clinical risk models quantifying risk based on height and weight measurements alone are essential to improve practice. Compared to BMI, modeling height and weight as independent, interacting variables results in less bias and improved predictive accuracy for all tested traits. Considering an individual's height and weight opposed to BMI is a better method for quantifying individual disease risk.
    Date 02/2022
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://onlinelibrary.wiley.com/doi/10.1002/osp4.543
    Accessed 12/28/2025, 10:01:37 AM
    Volume 8
    Pages 124-130
    Publication Obesity Science & Practice
    DOI 10.1002/osp4.543
    Issue 1
    Journal Abbr Obesity Science & Practice
    ISSN 2055-2238, 2055-2238
    Date Added 12/28/2025, 10:01:37 AM
    Modified 12/28/2025, 10:02:26 AM

    Tags:

    • collaboration
    • cv
    • bmi
  • Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Coronary Artery Disease

    Item Type Journal Article
    Author Michael J. Foley
    Author Christopher A. Rajkumar
    Author Fiyyaz Ahmed-Jushuf
    Author Florentina Simader
    Author Shayna Chotai
    Author Henry Seligman
    Author Krzysztof Macierzanka
    Author John R. Davies
    Author Thomas R. Keeble
    Author Peter O’Kane
    Author Peter Haworth
    Author Helen Routledge
    Author Tushar Kotecha
    Author Gerald Clesham
    Author Rupert Williams
    Author Jehangir Din
    Author Sukhjinder S. Nijjer
    Author Nick Curzen
    Author Manas Sinha
    Author Ricardo Petraco
    Author James Spratt
    Author Sayan Sen
    Author Graham D. Cole
    Author Frank E. Harrell
    Author James P. Howard
    Author Darrel P. Francis
    Author Matthew J. Shun-Shin
    Author Rasha Al-Lamee
    Author Christopher Rajkumar
    Author Michael Foley
    Author Fiyyaz Ahmed-Jushuf
    Author Florentina Simader
    Author Sashiananthan Ganesananthan
    Author Danqi Wang
    Author Muhammad Mohsin
    Author Rachel Pathimagaraj
    Author Brian Wang
    Author Krzysztof Macierzanka
    Author Ricardo Petraco
    Author Ramzi Khamis
    Author Graham Cole
    Author James Howard
    Author Jamil Mayet
    Author Darrel Francis
    Author Matthew Shun-Shin
    Author Rasha Al-Lamee
    Author Arif Kokhar
    Author Aisha Gohar
    Author Ioannis Lampadakis
    Author Henry Seligman
    Author Sukhjinder Njjer
    Author Sayan Sen
    Author Punit Ramrakha
    Author Raffi Kaprielian
    Author Iqbal Malik
    Author Masood Khan
    Author Amarjit Sethi
    Author Rodney Foale
    Author Thomas Keeble
    Author Kare Tang
    Author John Davies
    Author Reto Gamma
    Author Gerald Clesham
    Author Jason Dungu
    Author Alamgir Kabir
    Author Shah Mohd Nazri
    Author Peter O’Kane
    Author Jonathan Hinton
    Author Jehangir Din
    Author Alexandra Nowbar
    Author Tushar Kotecha
    Author Peter Haworth
    Author James Spratt
    Author Rupert Williams
    Author Claudia Cosgrove
    Author Pitt Lim
    Author Helen Routledge
    Author Lal Mughal
    Author Jasper Trevelyan
    Author Manas Sinha
    Author Nick Curzen
    Author James Wilkinson
    Author Rohit Sirohi
    Author Alison Calver
    Author John Rawlins
    Author Richard Jabbour
    Author Neil Ruparelia
    Author Joban Sehmi
    Author Tim Kinnaird
    Author Fairoz Abdul
    Author Vasileios Panoulas
    Author Afzal Sohaib
    Author David Collier
    Author Frank E. Harrell
    Abstract BACKGROUND: ORBITA-2 (the Placebo-Controlled Trial of Percutaneous Coronary Intervention for the Relief of Stable Angina) provided evidence for the role of percutaneous coronary intervention (PCI) for angina relief in stable coronary artery disease. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are often used to guide PCI; however, their ability to predict placebo-controlled angina improvement is unknown. METHODS: Participants with angina, ischemia, and stable coronary artery disease were enrolled, and anti-anginal medications were stopped. Participants reported angina episodes daily for 2 weeks using the ORBITA smartphone symptom application (ORBITA-app). At the research angiogram, FFR and iFR were measured. After sedation and auditory isolation, participants were randomized to PCI or placebo before entering a 12-week blinded follow-up phase with daily angina reporting. The ability of FFR and iFR, analyzed as continuous variables, to predict the placebo-controlled effect of PCI was tested using Bayesian proportional odds modeling. RESULTS: Invasive physiology data were available for 279 patients (140 PCI and 139 placebo). The median (interquartile range) age was 65 years (59.0–70.5), and 223 (79.9%) were male. Median FFR was 0.60 (0.46–0.73), and median iFR was 0.76 (0.50–0.86). The lower the FFR or iFR, the greater the placebo-controlled improvement with PCI across all end points. There was strong evidence that a patient with an FFR at the lower quartile would have a greater placebo-controlled improvement in angina symptom score with PCI than a patient at the upper quartile (FFR, 0.46 versus 0.73: odds ratio, 2.01; 95% credible interval, 1.79–2.26; probability of interaction, >99.9%). Similarly, there was strong evidence that a patient with an iFR at the lower quartile would have greater placebo-controlled improvement in angina symptom score with PCI than a patient with an iFR at the upper quartile (iFR, 0.50 versus 0.86: odds ratio, 2.13; 95% credible interval, 1.87–2.45; probability of interaction, >99.9%). The relationship between benefit and physiology was seen in both Rose angina and Rose nonangina. CONCLUSIONS: Physiological stenosis severity, as measured by FFR and iFR, predicts placebo-controlled angina relief from PCI. Invasive coronary physiology can be used to target PCI to those patients who are most likely to experience benefit. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03742050.
    Date 2025-01-21
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.072281
    Accessed 12/28/2025, 10:30:42 AM
    Volume 151
    Pages 202-214
    Publication Circulation
    DOI 10.1161/CIRCULATIONAHA.124.072281
    Issue 3
    Journal Abbr Circulation
    ISSN 0009-7322, 1524-4539
    Date Added 12/28/2025, 10:30:42 AM
    Modified 12/28/2025, 10:30:42 AM
  • Guideline-Directed Medical Therapy and Outcomes in the ISCHEMIA Trial

    Item Type Journal Article
    Author David J. Maron
    Author Jonathan D. Newman
    Author Rebecca Anthopolos
    Author Ying Lu
    Author Susanna Stevens
    Author William E. Boden
    Author Kreton Mavromatis
    Author Jason Linefsky
    Author Rajesh G. Nair
    Author Olga Bockeria
    Author Gilbert Gosselin
    Author Gian P. Perna
    Author Elena Demchenko
    Author David Foo
    Author Michael D. Shapiro
    Author Mary Ann Champagne
    Author Christie Ballantyne
    Author Peter McCullough
    Author Jose Luis Lopez-Sendon
    Author Frank Rockhold
    Author Frank Harrell
    Author Yves Rosenberg
    Author Gregg W. Stone
    Author Sripal Bangalore
    Author Harmony R. Reynolds
    Author John A. Spertus
    Author Judith S. Hochman
    Date 04/2025
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0735109725003213
    Accessed 12/28/2025, 10:44:24 AM
    Volume 85
    Pages 1317-1331
    Publication Journal of the American College of Cardiology
    DOI 10.1016/j.jacc.2025.01.028
    Issue 12
    Journal Abbr Journal of the American College of Cardiology
    ISSN 07351097
    Date Added 12/28/2025, 10:44:24 AM
    Modified 12/28/2025, 10:44:24 AM
  • Impact of Insurance Status and Region on Angiotensin Receptor–Neprilysin Inhibitor Prescription During Heart Failure Hospitalizations

    Item Type Journal Article
    Author Giovanni Davogustto
    Author Quinn S. Wells
    Author Frank E. Harrell
    Author Stephen J. Greene
    Author Dan M. Roden
    Author Lynne W. Stevenson
    Date 05/2024
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S2213177924001616
    Accessed 12/28/2025, 10:17:42 AM
    Volume 12
    Pages 864-875
    Publication JACC: Heart Failure
    DOI 10.1016/j.jchf.2024.02.003
    Issue 5
    Journal Abbr JACC: Heart Failure
    ISSN 22131779
    Date Added 12/28/2025, 10:17:42 AM
    Modified 12/28/2025, 10:17:42 AM
  • Impact of metabolic and weight components on incident asthma using a real-world cohort

    Item Type Journal Article
    Author Melissa H. Bloodworth
    Author Patrick J. Staso
    Author Shi Huang
    Author Eric Farber-Eger
    Author Kevin D. Niswender
    Author Frank E. Harrell
    Author Quinn S. Wells
    Author Leonard B. Bacharier
    Author Megan M. Shuey
    Author Katherine N. Cahill
    Date 12/2024
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S1081120624015096
    Accessed 12/28/2025, 10:26:16 AM
    Volume 133
    Pages 660-666.e5
    Publication Annals of Allergy, Asthma & Immunology
    DOI 10.1016/j.anai.2024.09.005
    Issue 6
    Journal Abbr Annals of Allergy, Asthma & Immunology
    ISSN 10811206
    Date Added 12/28/2025, 10:26:16 AM
    Modified 12/28/2025, 10:26:16 AM
  • Impact of the COVID-19 Pandemic on Medical Grand Rounds Attendance: Comparison of In-Person and Remote Conferences

    Item Type Journal Article
    Author Ken Monahan
    Author Edward Gould
    Author Todd Rice
    Author Patty Wright
    Author Eduard Vasilevskis
    Author Frank Harrell
    Author Monique Drago
    Author Sarah Mitchell
    Abstract Background Many academic medical centers transitioned from in-person to remote conferences due to the COVID-19 pandemic, but the impact on faculty attendance is unknown. Objective This study aims to evaluate changes in attendance at medical grand rounds (MGR) following the transition from an in-person to remote format and as a function of the COVID-19 census at Vanderbilt Medical Center. Methods We obtained the faculty attendee characteristics from Department of Medicine records. Attendance was recorded using a SMS text message–based system. The daily COVID-19 census was recorded independently by hospital administration. The main attendance metric was the proportion of eligible faculty that attended each MGR. Comparisons were made for the entire cohort and for individual faculty. Results The observation period was from March 2019 to June 2021 and included 101 MGR conferences with more than 600 eligible faculty. Overall attendance was unchanged during the in-person and remote formats (12,536/25,808, 48.6% vs 16,727/32,680, 51.2%; P=.44) and did not change significantly during a surge in the COVID-19 census. Individual faculty members attendance rates varied widely. Absolute differences between formats were less than –20% or greater than 20% for one-third (160/476, 33.6%) of faculty. Pulmonary or critical care faculty attendance increased during the remote format compared to in person (1450/2616, 55.4% vs 1004/2045, 49.1%; P<.001). A cloud-based digital archive of MGR lectures was accessed by <1% of faculty per conference. Conclusions Overall faculty attendance at MGR did not change following the transition to a remote format, regardless of the COVID-19 census, but individual attendance habits fluctuated in a bidirectional manner. Incentivizing the use of a digital archive may represent an opportunity to increase faculty consumption of MGR.
    Date 2024-1-3
    Language en
    Short Title Impact of the COVID-19 Pandemic on Medical Grand Rounds Attendance
    Library Catalog DOI.org (Crossref)
    URL https://mededu.jmir.org/2024/1/e43705
    Accessed 12/28/2025, 10:13:48 AM
    Volume 10
    Pages e43705
    Publication JMIR Medical Education
    DOI 10.2196/43705
    Journal Abbr JMIR Med Educ
    ISSN 2369-3762
    Date Added 12/28/2025, 10:13:48 AM
    Modified 12/28/2025, 10:13:48 AM
  • Impact of Tissue Expander Surface Texture on Two-Stage Breast Reconstruction Outcomes: A Combined Analysis

    Item Type Journal Article
    Author Benjamin C. Park
    Author Alexandra L. Alving-Trinh
    Author Heather L. Prigmore
    Author Frank E. Harrell
    Author Karim Sarhane
    Author Jeremy T. Joseph
    Author Harrison Thomas
    Author Alexander L. Lupi
    Author Galen Perdikis
    Author Kent K. Higdon
    Abstract Background: With ongoing investigations of the impact of device texturing on breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), studies have begun comparing complication profiles of tissue expanders. However, there is a paucity of timing and severity data of complications. The aim of this study was to provide a comparative survival analysis of postoperative complications between smooth (STEs) and textured tissue expanders (TTEs) in breast reconstruction. Methods: A single-institution experience with tissue expander breast reconstruction was reviewed for complications up to 1 year after second-stage reconstruction from 2014 to 2020. Demographics, comorbidities, operation-related variables, and complications were evaluated. Kaplan-Meier curves, Cox proportional hazard models, and a consensus-based ordinal logistic regression model were used to compare complication profiles. Results: Of 919 total patients, 600 (65.3%) received TTEs and 319 (34.7%) received STEs. There was increased risk of infection ( P < 0.0001), seroma ( P = 0.046), expander malposition ( P < 0.0001), and wound dehiscence ( P = 0.019) in STEs compared with TTEs. However, there was also a decreased risk of capsular contracture ( P = 0.005) in STEs compared with TTEs. Failure of breast reconstruction ( P < 0.001) and wound dehiscence ( P = 0.018) occurred significantly earlier in STEs compared with TTEs. Predictors for significantly higher severity complications included the following: smooth tissue expander use ( P = 0.007), shorter time to complication ( P < 0.0001), higher body mass index ( P = 0.005), smoking history ( P = 0.025), and nipple-sparing mastectomy ( P = 0.012). Conclusions: Differences in the timing and severity of complications contribute to the safety profiles of tissue expanders. STEs are associated with increased odds of higher severity and earlier complications. Therefore, tissue expander selection may depend on underlying risk factors and severity predictors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
    Date 06/2024
    Language en
    Short Title Impact of Tissue Expander Surface Texture on Two-Stage Breast Reconstruction Outcomes
    Library Catalog DOI.org (Crossref)
    URL https://journals.lww.com/10.1097/PRS.0000000000010763
    Accessed 12/28/2025, 10:18:24 AM
    Volume 153
    Pages 1053e-1062e
    Publication Plastic & Reconstructive Surgery
    DOI 10.1097/PRS.0000000000010763
    Issue 6
    ISSN 0032-1052
    Date Added 12/28/2025, 10:18:24 AM
    Modified 12/28/2025, 10:18:24 AM
  • Ischemia on Dobutamine Stress Echocardiography Predicts Efficacy of PCI

    Item Type Journal Article
    Author Fiyyaz Ahmed-Jushuf
    Author Michael J. Foley
    Author Christopher A. Rajkumar
    Author Shayna Chotai
    Author Florentina A. Simader
    Author Danqi Wang
    Author Krzysztof Macierzanka
    Author Joban Sehmi
    Author Gajen Kanaganayagam
    Author Guy Lloyd
    Author Niall Keenan
    Author Nina Bual
    Author John R. Davies
    Author Thomas R. Keeble
    Author Peter D. O’Kane
    Author Peter Haworth
    Author Helen Routledge
    Author Tushar Kotecha
    Author Rupert Williams
    Author Jehangir Din
    Author Sukhjinder S. Nijjer
    Author Nick Curzen
    Author Manas Sinha
    Author Neil Ruparelia
    Author Reto Gamma
    Author James C. Spratt
    Author Graham D. Cole
    Author Frank E. Harrell
    Author James P. Howard
    Author Darrel P. Francis
    Author Matthew J. Shun-Shin
    Author Rasha K. Al-Lamee
    Author Christopher Rajkumar
    Author Michael Foley
    Author Fiyyaz Ahmed-Jushuf
    Author Florentina Simader
    Author Sashiananthan Ganesananthan
    Author Danqi Wang
    Author Muhammad Mohsin
    Author Rachel Pathimagaraj
    Author Brian Wang
    Author Krzysztof Macierzanka
    Author Ricardo Petraco
    Author Ramzi Khamis
    Author Graham Cole
    Author James Howard
    Author Jamil Mayet
    Author Darrel Francis
    Author Matthew Shun-Shin
    Author Rasha Al-Lamee
    Author Arif Kokhar
    Author Aisha Gohar
    Author Ioannis Lampadakis
    Author Henry Seligman
    Author Sukhjinder Njjer
    Author Sayan Sen
    Author Punit Ramrakha
    Author Raffi Kaprielian
    Author Iqbal Malik
    Author Masood Khan
    Author Amarjit Sethi
    Author Rodney Foale
    Author Thomas Keeble
    Author Kare Tang
    Author John Davies
    Author Reto Gamma
    Author Gerald Clesham
    Author Jason Dungu
    Author Alamgir Kabir
    Author Shah Mohd Nazri
    Author Peter O’Kane
    Author Jonathan Hinton
    Author Jehangir Din
    Author Alexandra Nowbar
    Author Tushar Kotecha
    Author Peter Haworth
    Author James Spratt
    Author Rupert Williams
    Author Claudia Cosgrove
    Author Pitt Lim
    Author Helen Routledge
    Author Lal Mughal
    Author Jasper Trevelyan
    Author Manas Sinha
    Author Nick Curzen
    Author James Wilkinson
    Author Rohit Sirohi
    Author Alison Calver
    Author John Rawlins
    Author Richard Jabbour
    Author Neil Ruparelia
    Author Joban Sehmi
    Author Tim Kinnaird
    Author Fairoz Abdul
    Author Vasileios Panoulas
    Author Afzal Sohaib
    Author David Collier
    Author Frank E. Harrell
    Date 05/2025
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0735109725053008
    Accessed 12/28/2025, 10:45:01 AM
    Volume 85
    Pages 1740-1753
    Publication Journal of the American College of Cardiology
    DOI 10.1016/j.jacc.2025.02.034
    Issue 18
    Journal Abbr Journal of the American College of Cardiology
    ISSN 07351097
    Date Added 12/28/2025, 10:45:01 AM
    Modified 12/28/2025, 10:45:01 AM
  • LASSO-Based Survival Prediction Modeling with Multiply Imputed Data: A Case Study in Tuberculosis Mortality Prediction

    Item Type Journal Article
    Author Md. Belal Hossain
    Author Mohsen Sadatsafavi
    Author James C. Johnston
    Author Hubert Wong
    Author Victoria J. Cook
    Author Mohammad Ehsanul Karim
    Date 2025-08-04
    Language en
    Short Title LASSO-Based Survival Prediction Modeling with Multiply Imputed Data
    Library Catalog DOI.org (Crossref)
    URL https://www.tandfonline.com/doi/full/10.1080/00031305.2025.2526545
    Accessed 8/10/2025, 4:29:44 PM
    Pages 1-12
    Publication The American Statistician
    DOI 10.1080/00031305.2025.2526545
    Journal Abbr The American Statistician
    ISSN 0003-1305, 1537-2731
    Date Added 8/10/2025, 4:29:44 PM
    Modified 8/10/2025, 4:30:16 PM

    Tags:

    • cox-model
    • multiple-imputation
    • lasso
    • missing
    • stacking
  • Learning From What We Do, and Doing What We Learn: A Learning Health Care System in Action

    Item Type Journal Article
    Author Christopher J. Lindsell
    Author Cheryl L. Gatto
    Author Mary Lynn Dear
    Author Reagan Buie
    Author Todd W. Rice
    Author Jill M. Pulley
    Author Tina V. Hartert
    Author Sunil Kripalani
    Author Frank E. Harrell
    Author Daniel W. Byrne
    Author Mitchell C. Edgeworth
    Author Robin Steaban
    Author Robert S. Dittus
    Author Gordon R. Bernard
    Abstract Different models of learning health systems are emerging. At Vanderbilt University Medical Center, the Learning Health Care System (LHS) Platform was established with the goal of creating generalizable knowledge. This differentiates the LHS Platform from other efforts that have adopted a quality improvement paradigm. By supporting pragmatic trials at the intersection of research, operations, and clinical care, the LHS Platform was designed to yield evidence for advancing content and processes of care through carefully designed, rigorous study. The LHS Platform provides the necessary infrastructure and governance to leverage translational, transdisciplinary team science to inform clinical and operational decision making across the health system. The process transforms a clinical or operational question into a research question amenable to a pragmatic trial. Scientific, technical, procedural, and human infrastructure is maintained for the design and execution of individual LHS projects. This includes experienced pragmatic trialists, project management, data science inclusive of biostatistics and clinical informatics, and regulatory support. Careful attention is paid to stakeholder engagement, including health care providers and the community. Capturing lessons from each new study, the LHS Platform continues to mature with plans to integrate implementation science and to complement clinical and process outcomes with cost and value considerations. The Vanderbilt University Medical Center LHS Platform is now a pillar of the health care system and leads the evolving culture of learning from what we do and doing what we learn.
    Date 09/2021
    Language en
    Short Title Learning From What We Do, and Doing What We Learn
    Library Catalog DOI.org (Crossref)
    URL https://journals.lww.com/10.1097/ACM.0000000000004021
    Accessed 12/28/2025, 9:59:30 AM
    Volume 96
    Pages 1291-1299
    Publication Academic Medicine
    DOI 10.1097/ACM.0000000000004021
    Issue 9
    ISSN 1040-2446
    Date Added 12/28/2025, 9:59:30 AM
    Modified 12/28/2025, 9:59:30 AM
  • Model‐assisted analyses of longitudinal, ordinal outcomes with absorbing states

    Item Type Journal Article
    Author Jonathan S. Schildcrout
    Author Frank E. Harrell
    Author Patrick J. Heagerty
    Author Sebastien Haneuse
    Author Chiara Di Gravio
    Author Shawn P. Garbett
    Author Paul J. Rathouz
    Author Bryan E. Shepherd
    Abstract Studies of critically ill, hospitalized patients often follow participants and characterize daily health status using an ordinal outcome variable. Statistically, longitudinal proportional odds models are a natural choice in these settings since such models can parsimoniously summarize differences across patient groups and over time. However, when one or more of the outcome states is absorbing, the proportional odds assumption for the follow‐up time parameter will likely be violated, and more flexible longitudinal models are needed. Motivated by the VIOLET Study (Ginde et al), a parallel‐arm, randomized clinical trial of Vitamin in critically ill patients, we discuss and contrast several treatment effect estimands based on time‐dependent odds ratio parameters, and we detail contemporary modeling approaches. In VIOLET, the outcome is a four‐level ordinal variable where the lowest ”not alive” state is absorbing and the highest ”at‐home” state is nearly absorbing. We discuss flexible extensions of the proportional odds model for longitudinal data that can be used for either model‐based inference, where the odds ratio estimator is taken directly from the model fit, or for model‐assisted inferences, where heterogeneity across cumulative log odds dichotomizations is modeled and results are summarized to obtain an overall odds ratio estimator. We focus on direct estimation of cumulative probability model (CPM) parameters using likelihood‐based analysis procedures that naturally handle absorbing states. We illustrate the modeling procedures, the relative precision of model‐based and model‐assisted estimators, and the possible differences in the values for which the estimators are consistent through simulations and analysis of the VIOLET Study data.
    Date 2022-06-30
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://onlinelibrary.wiley.com/doi/10.1002/sim.9366
    Accessed 12/28/2025, 10:08:05 AM
    Volume 41
    Pages 2497-2512
    Publication Statistics in Medicine
    DOI 10.1002/sim.9366
    Issue 14
    Journal Abbr Statistics in Medicine
    ISSN 0277-6715, 1097-0258
    Date Added 12/28/2025, 10:08:05 AM
    Modified 12/28/2025, 10:08:05 AM
  • Motivating Sample Sizes in Adaptive Phase I Trials Via Bayesian Posterior Credible Intervals

    Item Type Journal Article
    Author Thomas M. Braun
    Abstract Summary In contrast with typical Phase III clinical trials, there is little existing methodology for determining the appropriate numbers of patients to enroll in adaptive Phase I trials. And, as stated by Dennis Lindley in a more general context, “[t]he simple practical question of ‘What size of sample should I take’ is often posed to a statistician, and it is a question that is embarrassingly difficult to answer.” Historically, simulation has been the primary option for determining sample sizes for adaptive Phase I trials, and although useful, can be problematic and time-consuming when a sample size is needed relatively quickly. We propose a computationally fast and simple approach that uses Beta distributions to approximate the posterior distributions of DLT rates of each dose and determines an appropriate sample size through posterior coverage rates. We provide sample sizes produced by our methods for a vast number of realistic Phase I trial settings and demonstrate that our sample sizes are generally larger than those produced by a competing approach that is based upon the nonparametric optimal design.
    Date 2018-09-01
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://academic.oup.com/biometrics/article/74/3/1065-1071/7525822
    Accessed 12/11/2025, 4:35:46 PM
    Rights https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
    Volume 74
    Pages 1065-1071
    Publication Biometrics
    DOI 10.1111/biom.12872
    Issue 3
    ISSN 0006-341X, 1541-0420
    Date Added 12/11/2025, 4:35:46 PM
    Modified 12/11/2025, 4:37:26 PM

    Tags:

    • bayes
    • sample-size
    • drug-development
    • adaptive-design
  • N-of-1 Trial of Angina Verification Before Percutaneous Coronary Intervention

    Item Type Journal Article
    Author Christopher A. Rajkumar
    Author Michael J. Foley
    Author Fiyyaz Ahmed-Jushuf
    Author Florentina A. Simader
    Author Muhammad Mohsin
    Author Sashiananthan Ganesananthan
    Author Alexandra N. Nowbar
    Author Shayna Chotai
    Author Sayan Sen
    Author Ricardo Petraco
    Author Sukhjinder S. Nijjer
    Author Joban Sehmi
    Author Neil Ruparelia
    Author Jason N. Dungu
    Author Alamgir Kabir
    Author Kare Tang
    Author Reto Gamma
    Author John R. Davies
    Author Tushar Kotecha
    Author Graham D. Cole
    Author James P. Howard
    Author Thomas R. Keeble
    Author Gerald Clesham
    Author Peter D. O’Kane
    Author Frank E. Harrell
    Author Darrel P. Francis
    Author Matthew J. Shun-Shin
    Author Rasha K. Al-Lamee
    Date 07/2024
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0735109724068244
    Accessed 12/28/2025, 10:22:01 AM
    Volume 84
    Pages 1-12
    Publication Journal of the American College of Cardiology
    DOI 10.1016/j.jacc.2024.04.001
    Issue 1
    Journal Abbr Journal of the American College of Cardiology
    ISSN 07351097
    Date Added 12/28/2025, 10:22:01 AM
    Modified 12/28/2025, 10:22:01 AM
  • National Institutes of Health Stroke Scale as an Outcome in Stroke Research: Value of ANCOVA Over Analyzing Change From Baseline

    Item Type Journal Article
    Author Eva A. Mistry
    Author Sharon D. Yeatts
    Author Pooja Khatri
    Author Akshitkumar M. Mistry
    Author Michelle Detry
    Author Kert Viele
    Author Frank E. Harrell
    Author Roger J. Lewis
    Abstract National Institutes of Health Stroke Scale (NIHSS), measured a few hours to days after stroke onset, is an attractive outcome measure for stroke research. NIHSS at the time of presentation (baseline NIHSS) strongly predicts the follow-up NIHSS. Because of the need to account for the baseline NIHSS in the analysis of follow-up NIHSS as an outcome measure, a common and intuitive approach is to define study outcome as the change in NIHSS from baseline to follow-up (ΔNIHSS). However, this approach has important limitations. Analyzing ΔNIHSS implies a very strong assumption about the relationship between baseline and follow-up NIHSS that is unlikely to be satisfied, drawing into question the validity of the resulting statistical analysis. This reduces the precision of the estimates of treatment effects and the power of clinical trials that use this approach to analysis. ANCOVA allows for the analysis of follow-up NIHSS as the dependent variable while adjusting for baseline NIHSS as a covariate in the model and addresses several challenges of using ΔNIHSS outcome using simple bivariate comparisons (eg, a t test, Wilcoxon rank-sum, linear regression without adjustment for baseline) for stroke research. In this article, we use clinical trial simulations to illustrate that variability in NIHSS outcome is less when follow-up NIHSS is adjusted for baseline compared to ΔNIHSS and how a reduction in this variability improves the power. We outline additional, important clinical and statistical arguments to support the superiority of ANCOVA using the final measurement of the NIHSS adjusted for baseline over, and caution against using, the simple bivariate comparison of absolute NIHSS change (ie, delta).
    Date 04/2022
    Language en
    Short Title National Institutes of Health Stroke Scale as an Outcome in Stroke Research
    Library Catalog DOI.org (Crossref)
    URL https://www.ahajournals.org/doi/10.1161/STROKEAHA.121.034859
    Accessed 12/28/2025, 10:03:11 AM
    Volume 53
    Publication Stroke
    DOI 10.1161/STROKEAHA.121.034859
    Issue 4
    Journal Abbr Stroke
    ISSN 0039-2499, 1524-4628
    Date Added 12/28/2025, 10:03:11 AM
    Modified 12/28/2025, 10:03:11 AM
  • Nonparametric Assessment of Variable Selection and Ranking Algorithms

    Item Type Journal Article
    Author Zhou Tang
    Author Ted Westling
    Date 2025-10-13
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://www.tandfonline.com/doi/full/10.1080/10618600.2025.2547064
    Accessed 10/15/2025, 11:24:15 AM
    Pages 1-12
    Publication Journal of Computational and Graphical Statistics
    DOI 10.1080/10618600.2025.2547064
    Journal Abbr Journal of Computational and Graphical Statistics
    ISSN 1061-8600, 1537-2715
    Date Added 10/15/2025, 11:24:15 AM
    Modified 10/15/2025, 11:25:24 AM

    Tags:

    • variable-importance
    • ranking-selection
  • Novel Clinical Trial Design With Stratum‐Specific Endpoints and Global Test Methods for Rare Diseases With Heterogeneous Clinical Manifestations

    Item Type Journal Article
    Author Emily Shives
    Author Yared Gurmu
    Author Wonyul Lee
    Author Emily Morris
    Author Yan Wang
    Abstract ABSTRACT Many rare disease clinical trials are underpowered to detect a moderate treatment effect of an investigational product due to the limited number of participants available for the trials. In addition, given the complex, multisystemic nature of many rare diseases, it is challenging to confidently prespecify a single primary efficacy endpoint that is applicable to all trial participants with a heterogeneous clinical manifestation of their disease. Traditional trial designs and analysis methods often used in more common diseases to analyze the same endpoint(s) for all patients may be inefficient or impractical for a rare disease with heterogeneous clinical manifestations. To address these issues, we propose a novel trial design and analytic approach that allows for an evaluation of stratum‐specific efficacy endpoints in a broader population of participants. We develop several nonparametric global test methods that can accommodate the novel design and provide global evaluation of treatment effects. Using a case example in patients with Fabry disease, our simulation studies illustrate that the novel design evaluated using the global test methods may be more sensitive to detect a treatment effect compared to the traditional design that uses the same endpoint(s) for all patients.
    Date 08/2025
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://onlinelibrary.wiley.com/doi/10.1002/sim.70206
    Accessed 8/10/2025, 4:37:45 PM
    Volume 44
    Pages e70206
    Publication Statistics in Medicine
    DOI 10.1002/sim.70206
    Issue 18-19
    Journal Abbr Statistics in Medicine
    ISSN 0277-6715, 1097-0258
    Date Added 8/10/2025, 4:37:45 PM
    Modified 8/10/2025, 4:38:13 PM

    Tags:

    • multiple-endpoints
    • global-test
    • rare-disease
  • Performance of cardiac implantable electronic devices in detecting premature ventricular contraction burden

    Item Type Journal Article
    Author Matthew Elmo G. Gayoso
    Author Giovanni Davogustto
    Author Robert L. Abraham
    Author George H. Crossley
    Author Travis D. Richardson
    Author Quinn S. Wells
    Author Arvindh N. Kanagasundram
    Author Gregory F. Michaud
    Author William G. Stevenson
    Author Frank E. Harrell
    Author Yue Gao
    Author Jay A. Montgomery
    Date 12/2025
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S1547527125024294
    Accessed 12/28/2025, 10:48:35 AM
    Volume 22
    Pages 3231-3238
    Publication Heart Rhythm
    DOI 10.1016/j.hrthm.2025.05.006
    Issue 12
    Journal Abbr Heart Rhythm
    ISSN 15475271
    Date Added 12/28/2025, 10:48:35 AM
    Modified 12/28/2025, 10:48:35 AM
  • Predicting Residual Angina After Chronic Total Occlusion Percutaneous Coronary Intervention: Insights from the OPEN‐CTO Registry

    Item Type Journal Article
    Author Neel M. Butala
    Author Hector Tamez
    Author Eric A. Secemsky
    Author J. Aaron Grantham
    Author John A. Spertus
    Author David J. Cohen
    Author Philip Jones
    Author Adam C. Salisbury
    Author Suzanne V. Arnold
    Author Frank Harrell
    Author William Lombardi
    Author Dimitrios Karmpaliotis
    Author Jeffrey Moses
    Author James Sapontis
    Author Robert W. Yeh
    Abstract Background Given that percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) is indicated primarily for symptom relief, identifying patients most likely to benefit is critically important for patient selection and shared decision‐making. Therefore, we identified factors associated with residual angina frequency after CTO PCI and developed a model to predict postprocedure anginal burden. Methods and Results Among patients in the OPEN‐CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry, we evaluated the association between patient characteristics and residual angina frequency at 6 months, as assessed by the Seattle Angina Questionnaire Angina Frequency Scale. We then constructed a prediction model for angina status after CTO PCI using ordinal regression. Among 901 patients undergoing CTO PCI, 28% had no angina, 31% had monthly angina, 30% had weekly angina, and 12% had daily angina at baseline. Six months later, 53% of patients had a ≥20‐point increase in Seattle Angina Questionnaire Angina Frequency Scale score. The final model to predict residual angina after CTO PCI included baseline angina frequency, baseline nitroglycerin use frequency, dyspnea symptoms, depressive symptoms, number of antianginal medications, PCI indication, and presence of multiple CTO lesions and had a C index of 0.78. Baseline angina frequency and nitroglycerin use frequency explained 71% of the predictive power of the model, and the relationship between model components and angina improvement at 6 months varied by baseline angina status. Conclusions A 7‐component OPEN‐AP (OPEN‐CTO Angina Prediction) score can predict angina improvement and residual angina after CTO PCI using variables commonly available before intervention. These findings have implications for appropriate patient selection and counseling for CTO PCI.
    Date 2022-05-17
    Language en
    Short Title Predicting Residual Angina After Chronic Total Occlusion Percutaneous Coronary Intervention
    Library Catalog DOI.org (Crossref)
    URL https://www.ahajournals.org/doi/10.1161/JAHA.121.024056
    Accessed 12/28/2025, 10:05:45 AM
    Volume 11
    Pages e024056
    Publication Journal of the American Heart Association
    DOI 10.1161/JAHA.121.024056
    Issue 10
    Journal Abbr JAHA
    ISSN 2047-9980
    Date Added 12/28/2025, 10:05:45 AM
    Modified 12/28/2025, 10:05:45 AM
  • Predictive performance of machine and statistical learning methods: Impact of data-generating processes on external validity in the “large N, small p” setting

    Item Type Journal Article
    Author Peter C Austin
    Author Frank E Harrell
    Author Ewout W Steyerberg
    Abstract Machine learning approaches are increasingly suggested as tools to improve prediction of clinical outcomes. We aimed to identify when machine learning methods perform better than a classical learning method. We hereto examined the impact of the data-generating process on the relative predictive accuracy of six machine and statistical learning methods: bagged classification trees, stochastic gradient boosting machines using trees as the base learners, random forests, the lasso, ridge regression, and unpenalized logistic regression. We performed simulations in two large cardiovascular datasets which each comprised an independent derivation and validation sample collected from temporally distinct periods: patients hospitalized with acute myocardial infarction (AMI, n = 9484 vs. n = 7000) and patients hospitalized with congestive heart failure (CHF, n = 8240 vs. n = 7608). We used six data-generating processes based on each of the six learning methods to simulate outcomes in the derivation and validation samples based on 33 and 28 predictors in the AMI and CHF data sets, respectively. We applied six prediction methods in each of the simulated derivation samples and evaluated performance in the simulated validation samples according to c-statistic, generalized R 2 , Brier score, and calibration. While no method had uniformly superior performance across all six data-generating process and eight performance metrics, (un)penalized logistic regression and boosted trees tended to have superior performance to the other methods across a range of data-generating processes and performance metrics. This study confirms that classical statistical learning methods perform well in low-dimensional settings with large data sets.
    Date 06/2021
    Language en
    Short Title Predictive performance of machine and statistical learning methods
    Library Catalog DOI.org (Crossref)
    URL https://journals.sagepub.com/doi/10.1177/09622802211002867
    Accessed 12/28/2025, 9:58:39 AM
    Volume 30
    Pages 1465-1483
    Publication Statistical Methods in Medical Research
    DOI 10.1177/09622802211002867
    Issue 6
    Journal Abbr Stat Methods Med Res
    ISSN 0962-2802, 1477-0334
    Date Added 12/28/2025, 9:58:39 AM
    Modified 12/28/2025, 9:58:39 AM
  • Regression without regrets –initial data analysis is a prerequisite for multivariable regression

    Item Type Journal Article
    Author Georg Heinze
    Author Mark Baillie
    Author Lara Lusa
    Author Willi Sauerbrei
    Author Carsten Oliver Schmidt
    Author Frank E. Harrell
    Author Marianne Huebner
    Author on behalf of TG2 and TG3 of the STRATOS initiative
    Abstract Abstract Statistical regression models are used for predicting outcomes based on the values of some predictor variables or for describing the association of an outcome with predictors. With a data set at hand, a regression model can be easily fit with standard software packages. This bears the risk that data analysts may rush to perform sophisticated analyses without sufficient knowledge of basic properties, associations in and errors of their data, leading to wrong interpretation and presentation of the modeling results that lacks clarity. Ignorance about special features of the data such as redundancies or particular distributions may even invalidate the chosen analysis strategy. Initial data analysis (IDA) is prerequisite to regression analyses as it provides knowledge about the data needed to confirm the appropriateness of or to refine a chosen model building strategy, to interpret the modeling results correctly, and to guide the presentation of modeling results. In order to facilitate reproducibility, IDA needs to be preplanned, an IDA plan should be included in the general statistical analysis plan of a research project, and results should be well documented. Biased statistical inference of the final regression model can be minimized if IDA abstains from evaluating associations of outcome and predictors, a key principle of IDA. We give advice on which aspects to consider in an IDA plan for data screening in the context of regression modeling to supplement the statistical analysis plan. We illustrate this IDA plan for data screening in an example of a typical diagnostic modeling project and give recommendations for data visualizations.
    Date 2024-08-08
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-024-02294-3
    Accessed 12/28/2025, 10:23:48 AM
    Volume 24
    Pages 178
    Publication BMC Medical Research Methodology
    DOI 10.1186/s12874-024-02294-3
    Issue 1
    Journal Abbr BMC Med Res Methodol
    ISSN 1471-2288
    Date Added 12/28/2025, 10:23:48 AM
    Modified 12/28/2025, 10:23:48 AM
  • Resampling Methods with Multiply Imputed Data

    Item Type Journal Article
    Author Michael W Robbins
    Author Lane Burgette
    Abstract Abstract Resampling techniques have become increasingly popular for estimation of uncertainty. However, data are often fraught with missing values that are commonly imputed to facilitate analysis. This article addresses the issue of using resampling methods such as a jackknife or bootstrap in conjunction with imputations that have been sampled stochastically, in the vein of multiple imputation. We derive the theory needed to illustrate two key points regarding the use of resampling methods in lieu of traditional combining rules. First, imputations should be independently generated multiple times within each replicate group of a jackknife or bootstrap. Second, the number of multiply imputed datasets per replicate group must dramatically exceed the number of replicate groups for a jackknife; however, this is not the case in a bootstrap approach. We also discuss bias-adjusted analogues of the jackknife and bootstrap that are argued to require fewer imputed datasets. A simulation study is provided to support these theoretical conclusions.
    Date 2025-07-30
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://academic.oup.com/biomet/advance-article/doi/10.1093/biomet/asaf059/8219454
    Accessed 7/31/2025, 12:14:17 PM
    Rights https://creativecommons.org/licenses/by-nc-nd/4.0/
    Pages asaf059
    Publication Biometrika
    DOI 10.1093/biomet/asaf059
    ISSN 0006-3444, 1464-3510
    Date Added 7/31/2025, 12:14:17 PM
    Modified 7/31/2025, 12:14:46 PM

    Tags:

    • resampling
    • bootstrap
    • imputation
    • missing
    • jackknife
  • Second-generation p-values: Improved rigor, reproducibility, & transparency in statistical analyses

    Item Type Journal Article
    Author Jeffrey D. Blume
    Author Lucy D’Agostino McGowan
    Author William D. Dupont
    Author Robert A. Greevy
    Editor Neil R. Smalheiser
    Date 2018-3-22
    Language en
    Short Title Second-generation p-values
    Library Catalog DOI.org (Crossref)
    URL https://dx.plos.org/10.1371/journal.pone.0188299
    Accessed 9/4/2025, 8:51:13 AM
    Volume 13
    Pages e0188299
    Publication PLOS ONE
    DOI 10.1371/journal.pone.0188299
    Issue 3
    Journal Abbr PLoS ONE
    ISSN 1932-6203
    Date Added 9/4/2025, 8:51:13 AM
    Modified 9/4/2025, 8:51:41 AM

    Tags:

    • multiplicity
    • confidence-intervals
    • inference
  • Securely sharing DSMB reports to speed decision making from multiple, concurrent, independent studies of similar treatments in COVID-19

    Item Type Journal Article
    Author Natalie A. Dilts
    Author Frank E. Harrell
    Author Christopher J. Lindsell
    Author Samuel Nwosu
    Author Thomas G. Stewart
    Author Matthew S. Shotwell
    Author Jill M. Pulley
    Author Terri L. Edwards
    Author Emily Sheffer Serdoz
    Author Katelyn Benhoff
    Author Gordon R. Bernard
    Abstract Abstract Introduction: As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring. Methods: The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed. Results: Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial’s DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report. Conclusion: It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.
    Date 2022
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://www.cambridge.org/core/product/identifier/S2059866122003879/type/journal_article
    Accessed 12/28/2025, 10:03:52 AM
    Rights https://creativecommons.org/licenses/by/4.0/
    Volume 6
    Pages e49
    Publication Journal of Clinical and Translational Science
    DOI 10.1017/cts.2022.387
    Issue 1
    Journal Abbr J. Clin. Trans. Sci.
    ISSN 2059-8661
    Date Added 12/28/2025, 10:03:52 AM
    Modified 12/28/2025, 10:03:52 AM
  • Surrogate Perception of Disability after Hospitalization for Traumatic Brain Injury

    Item Type Journal Article
    Author Amelia W Maiga
    Author Madison Cook
    Author Mina F Nordness
    Author Yue Gao
    Author Shayan Rakhit
    Author Erika L Rivera
    Author Frank E Harrell
    Author Kenneth W Sharp
    Author Mayur B Patel
    Abstract BACKGROUND: The Glasgow Outcome Scale Extended (GOSE) is a measure of recovery after traumatic brain injury (TBI). Public surveys rate some GOSE states as worse than death. Direct family experience caring for patients with TBI may impact views of post-TBI disability. STUDY DESIGN: We conducted a national cross-sectional computer-adaptive survey of surrogates of TBI dependents incurring injury more than 1 year earlier. Using a standard gamble approach in randomized order, surrogates evaluated preferences for post-TBI GOSE states from GOSE 2 (bedridden, unaware) to GOSE 8 (good recovery). We calculated median (interquartile range [IQR]) health utilities for each post-TBI state, ranging from −1 to 1, with 0 as reference (death = GOSE 1), and assessed sociodemographic associations using proportional odds logistic regression modeling. RESULTS: Of 515 eligible surrogates, 298 (58%) completed scenarios. Surrogates were median aged 46 (IQR 35 to 60), 54% married, with Santa Clara strength of faith 14 (10 to 18). TBI dependents had a median GOSE5 (3 to 7). Median (IQR) health utility ratings for GOSE 2, GOSE 3, and GOSE 4 were −0.06 (−0.50 to −0.01), −0.01 (−0.30 to 0.45), and 0.30 (−0.01 to 0.80), rated worse than death by 91%, 65%, and 40%, respectively. Surrogates rated GOSE 4 (daily partial help) worse than the general population. Married surrogates rated GOSE 4 higher (p < 0.01). Higher strength of faith was associated with higher utility scores across GOSE states (p = 0.034). CONCLUSIONS: In this index study of surrogate perceptions about disability after TBI, poor neurologic outcomes—vegetative, needing all-day or partial daily assistance—were perceived as worse than death by at least 1 in 3 surrogates. Surrogate perceptions differed from the unexposed public. Long-term perceptions about post-TBI disability may inform earlier, tailored shared decision-making after neurotrauma.
    Date 04/2024
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://journals.lww.com/10.1097/XCS.0000000000000960
    Accessed 12/28/2025, 10:15:58 AM
    Volume 238
    Pages 589-597
    Publication Journal of the American College of Surgeons
    DOI 10.1097/XCS.0000000000000960
    Issue 4
    ISSN 1072-7515
    Date Added 12/28/2025, 10:15:58 AM
    Modified 12/28/2025, 10:15:58 AM
  • Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial

    Item Type Journal Article
    Author Jeffrey A. Freiberg
    Author Justin K. Siemann
    Author Edward T. Qian
    Author Benjamin J. Ereshefsky
    Author Cassandra Hennessy
    Author Joanna L. Stollings
    Author Taylor M. Rali
    Author Frank E. Harrell
    Author Cheryl L. Gatto
    Author Todd W. Rice
    Author George E. Nelson
    Author for the Vanderbilt Center for Learning Healthcare
    Abstract Abstract Background Vancomycin, an antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. Methods STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. The objective of this study is to test whether the use of MRSA PCR testing can safely reduce inappropriate vancomycin use in an intensive care setting. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the expected number of hours alive and free of the use of vancomycin within the first 7 days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. Discussion STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. Trial registration ClinicalTrials.gov NCT06272994. Registered on February 22, 2024.
    Date 2024-12-28
    Language en
    Short Title Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc)
    Library Catalog DOI.org (Crossref)
    URL https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08705-6
    Accessed 12/28/2025, 10:26:51 AM
    Volume 25
    Pages 854
    Publication Trials
    DOI 10.1186/s13063-024-08705-6
    Issue 1
    Journal Abbr Trials
    ISSN 1745-6215
    Date Added 12/28/2025, 10:26:51 AM
    Modified 12/28/2025, 10:26:51 AM
  • Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease

    Item Type Journal Article
    Author Florentina A. Simader
    Author Christopher A. Rajkumar
    Author Michael J. Foley
    Author Fiyyaz Ahmed-Jushuf
    Author Shayna Chotai
    Author Nina Bual
    Author Arif Khokhar
    Author Aisha Gohar
    Author Ioannis Lampadakis
    Author Sashiananthan Ganesananthan
    Author Rachel H. Pathimagaraj
    Author Alexandra Nowbar
    Author John R. Davies
    Author Tom R. Keeble
    Author Peter D. O’Kane
    Author Peter Haworth
    Author Helen Routledge
    Author Tushar Kotecha
    Author James C. Spratt
    Author Rupert Williams
    Author Sukhjinder S. Nijjer
    Author Sayan Sen
    Author Nick Curzen
    Author Manas Sinha
    Author James P. Howard
    Author Graham Cole
    Author Frank E. Harrell
    Author Darrel P. Francis
    Author Matthew J. Shun-Shin
    Author Rasha K. Al-Lamee
    Author Christopher Rajkumar
    Author Michael Foley
    Author Fiyyaz Ahmed-Jushuf
    Author Florentina Simader
    Author Sashiananthan Ganesananthan
    Author Danqi Wang
    Author Muhammad Mohsin
    Author Rachel Pathimagaraj
    Author Krzysztof Macierzanka
    Author Ricardo Petraco
    Author Ramzi Khamis
    Author Graham Cole
    Author James Howard
    Author Jamil Mayet
    Author Darrel Francis
    Author Arif Kokhar
    Author Aisha Gohar
    Author Ioannis Lampadakis
    Author Henry Seligman
    Author Amit Kaura
    Author Sukhjinder Nijjer
    Author Sayan Sen
    Author Punit Ramrakha
    Author Raffi Kaprielian
    Author Iqbal Malik
    Author Masood Khan
    Author Amarjit Sethi
    Author Rodney Foale
    Author Thomas Keeble
    Author Kare Tang
    Author John Davies
    Author Reto Gamma
    Author Gerald Clesham
    Author Jason Dungu
    Author Alamgir Kabir
    Author Shah Mohd Nazri
    Author Peter O’Kane
    Author Jonathan Hinton
    Author Jehangir Din
    Author Alexandra Nowbar
    Author Tushar Kotecha
    Author Peter Haworth
    Author James Spratt
    Author Rupert Williams
    Author Claudia Cosgrove
    Author Pitt Lim
    Author Helen Routledge
    Author Lal Mughal
    Author Jasper Trevelyan
    Author Manas Sinha
    Author Nick Curzen
    Author James Wilkinson
    Author Rohit Sirohi
    Author Alison Calver
    Author John Rawlins
    Author Richard Jabbour
    Author Neil Ruparelia
    Author Joban Sehmi
    Author Tim Kinnaird
    Author Fairoz Abdul
    Author Vasileios Panoulas
    Author David Collier
    Author George Thornton
    Author Afzal Sohaib
    Author Rasha K. Al-Lamee
    Date 07/2024
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0735109724069481
    Accessed 12/28/2025, 10:22:34 AM
    Volume 84
    Pages 13-24
    Publication Journal of the American College of Cardiology
    DOI 10.1016/j.jacc.2024.04.016
    Issue 1
    Journal Abbr Journal of the American College of Cardiology
    ISSN 07351097
    Date Added 12/28/2025, 10:22:34 AM
    Modified 12/28/2025, 10:22:34 AM
  • The Odds Ratio is “portable” across baseline risk but not the Relative Risk: Time to do away with the log link in binomial regression

    Item Type Journal Article
    Author Suhail A. Doi
    Author Luis Furuya-Kanamori
    Author Chang Xu
    Author Tawanda Chivese
    Author Lifeng Lin
    Author Omran A.H. Musa
    Author George Hindy
    Author Lukman Thalib
    Author Frank E. Harrell
    Date 02/2022
    Language en
    Short Title The Odds Ratio is “portable” across baseline risk but not the Relative Risk
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0895435621002419
    Accessed 12/28/2025, 10:01:01 AM
    Volume 142
    Pages 288-293
    Publication Journal of Clinical Epidemiology
    DOI 10.1016/j.jclinepi.2021.08.003
    Journal Abbr Journal of Clinical Epidemiology
    ISSN 08954356
    Date Added 12/28/2025, 10:01:01 AM
    Modified 12/28/2025, 10:01:01 AM
  • The Pragmatic Removal of Penicillin Allergy Electronic Health Record Labels (PROPEL) Trial: A Randomized Clinical Trial

    Item Type Journal Article
    Author Cosby A. Stone
    Author Heather L. Prigmore
    Author Allison B. McCoy
    Author Joanna L. Stollings
    Author Mary Lynn Dear
    Author William Hiser
    Author Grace Van Winkle
    Author Sunil Kripalani
    Author Adam Wright
    Author Frank E. Harrell
    Author Todd W. Rice
    Author Christopher J. Lindsell
    Author Elizabeth J. Phillips
    Date 10/2025
    Language en
    Short Title The Pragmatic Removal of Penicillin Allergy Electronic Health Record Labels (PROPEL) Trial
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S2213219825006385
    Accessed 12/28/2025, 10:47:36 AM
    Volume 13
    Pages 2747-2755
    Publication The Journal of Allergy and Clinical Immunology: In Practice
    DOI 10.1016/j.jaip.2025.07.006
    Issue 10
    Journal Abbr The Journal of Allergy and Clinical Immunology: In Practice
    ISSN 22132198
    Date Added 12/28/2025, 10:47:36 AM
    Modified 12/28/2025, 10:47:36 AM
  • The Role of the Collateral Circulation in Stable Angina: An Invasive Placebo-Controlled Study

    Item Type Journal Article
    Author Christopher A. Rajkumar
    Author Michael J. Foley
    Author Fiyyaz Ahmed-Jushuf
    Author Shayna Chotai
    Author Florentina A. Simader
    Author Muhammad Mohsin
    Author Ahmed Salih
    Author Sashiananthan Ganesananthan
    Author Nina Bual
    Author Ricardo Petraco
    Author Sukhjinder S. Nijjer
    Author Sayan Sen
    Author Joban Sehmi
    Author Neil Ruparelia
    Author Jason N. Dungu
    Author Alamgir Kabir
    Author Kare Tang
    Author Reto Gamma
    Author John R. Davies
    Author Tushar Kotecha
    Author Graham D. Cole
    Author James P. Howard
    Author Thomas R. Keeble
    Author Gerald J. Clesham
    Author Peter D. O’Kane
    Author Frank E. Harrell
    Author Darrel P. Francis
    Author Matthew J. Shun-Shin
    Author Rasha K. Al-Lamee
    Abstract BACKGROUND: Little correlation exists between the burden of ischemia and severity of angina in patients with stable coronary artery disease. This placebo-controlled, n-of-1 study investigated the relationship between ischemia, the collateral circulation, and symptoms in stable coronary artery disease. Additionally, it explored the association between progressive collateral recruitment and ischemic preconditioning. METHODS: Fifty-one participants with severe single-vessel coronary artery disease and angina were recruited. Antianginal medications were stopped, and daily angina symptoms were documented using a dedicated smartphone application (ORBITA [Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina] app) for 14 days before undergoing invasive pressure wire studies and coronary flow reserve assessment. Each participant then underwent four 60-s episodes of low-pressure balloon occlusion across their coronary stenosis. Each episode was paired with an audiovisually identical placebo inflation in a randomized order. After each episode, participants scored pain intensity on a 10-point scale, and a placebo-controlled pain intensity score was calculated. Collateral flow index was calculated from simultaneous measures of aortic, right atrial, and distal coronary wedge pressure during balloon occlusion. Higher Pr values from Bayesian models indicate a greater likelihood of association. RESULTS: The mean (±SD) age of participants was 63±9 years, and 78% were men. The median (interquartile range) fractional flow reserve was 0.68 (0.57–0.79), the median instantaneous wave-free ratio was 0.80 (0.48–0.89), and the median coronary flow reserve was 1.42 (1.08–1.85). Daily angina frequency showed little correlation with severity of ischemia, as assessed by fractional flow reserve (Somers’ D 0.124, Pr =0.057) or instantaneous wave-free ratio (Somers’ D 0.056, Pr =0.150). However, there was strong evidence of an association between lower fractional flow reserve and instantaneous wave-free ratio values and greater collateral flow (Somers’ D 0.302, Pr =0.998 and Somers’ D 0.316, Pr =0.999, respectively). There was also strong evidence of an association between more collateralization (higher collateral flow index) and lower pain intensity scores (Somers’ D 0.341, Pr =0.999). Finally, pain intensity scores and collateral flow index remained stable between sequential balloon occlusion episodes within individual patients, indicating little evidence of ischemic preconditioning. CONCLUSIONS: Coronary collateralization is associated with ischemic burden and may reduce the intensity of ischemic chest pain. This may explain the nonlinear relationship between stenosis, ischemia, and angina. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04280575.
    Date 2025-12-02
    Language en
    Short Title The Role of the Collateral Circulation in Stable Angina
    Library Catalog DOI.org (Crossref)
    URL https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074687
    Accessed 12/28/2025, 10:49:16 AM
    Volume 152
    Pages 1541-1551
    Publication Circulation
    DOI 10.1161/CIRCULATIONAHA.125.074687
    Issue 22
    Journal Abbr Circulation
    ISSN 0009-7322, 1524-4539
    Date Added 12/28/2025, 10:49:16 AM
    Modified 12/28/2025, 10:49:16 AM
  • The statistical design and analysis of pandemic platform trials: Implications for the future

    Item Type Journal Article
    Author Christopher J. Lindsell
    Author Matthew Shotwell
    Author Kevin J. Anstrom
    Author Scott Berry
    Author Erica Brittain
    Author Frank E. Harrell
    Author Nancy Geller
    Author Birgit Grund
    Author Michael D. Hughes
    Author Prasanna Jagannathan
    Author Eric Leifer
    Author Carlee B. Moser
    Author Karen L. Price
    Author Michael Proschan
    Author Thomas Stewart
    Author Sonia Thomas
    Author Giota Touloumi
    Author Lisa LaVange
    Abstract Abstract The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.
    Date 2024
    Language en
    Short Title The statistical design and analysis of pandemic platform trials
    Library Catalog DOI.org (Crossref)
    URL https://www.cambridge.org/core/product/identifier/S2059866124005144/type/journal_article
    Accessed 12/28/2025, 10:25:35 AM
    Rights http://creativecommons.org/licenses/by/4.0/
    Volume 8
    Pages e155
    Publication Journal of Clinical and Translational Science
    DOI 10.1017/cts.2024.514
    Issue 1
    Journal Abbr J. Clin. Trans. Sci.
    ISSN 2059-8661
    Date Added 12/28/2025, 10:25:35 AM
    Modified 12/28/2025, 10:25:35 AM
  • Trends in the Prevalence, Associated Risk Factors, and Health Burden of Heart Failure in the United States, 1988 to 2023

    Item Type Journal Article
    Author Ahmed Sayed
    Author Ramachandran S. Vasan
    Author Frank E. Harrell
    Author Javed Butler
    Date 12/2025
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://linkinghub.elsevier.com/retrieve/pii/S0735109725093118
    Accessed 12/28/2025, 10:49:54 AM
    Volume 86
    Pages 2542-2564
    Publication JACC
    DOI 10.1016/j.jacc.2025.09.1503
    Issue 25
    Journal Abbr JACC
    ISSN 07351097
    Date Added 12/28/2025, 10:49:54 AM
    Modified 12/28/2025, 10:49:54 AM
  • Uncertainty of risk estimates from clinical prediction models: rationale, challenges, and approaches

    Item Type Journal Article
    Author Richard D Riley
    Author Gary S Collins
    Author Laura Kirton
    Author Kym Ie Snell
    Author Joie Ensor
    Author Rebecca Whittle
    Author Paula Dhiman
    Author Maarten Van Smeden
    Author Xiaoxuan Liu
    Author Joseph Alderman
    Author Krishnarajah Nirantharakumar
    Author Jay Manson-Whitton
    Author Andrew J Westwood
    Author Jean-Baptiste Cazier
    Author Karel G M Moons
    Author Glen P Martin
    Author Matthew Sperrin
    Author Alastair K Denniston
    Author Frank E Harrell
    Author Lucinda Archer
    Date 2025-02-13
    Language en
    Short Title Uncertainty of risk estimates from clinical prediction models
    Library Catalog DOI.org (Crossref)
    URL https://www.bmj.com/lookup/doi/10.1136/bmj-2024-080749
    Accessed 12/28/2025, 10:41:31 AM
    Pages e080749
    Publication BMJ
    DOI 10.1136/bmj-2024-080749
    Journal Abbr BMJ
    ISSN 1756-1833
    Date Added 12/28/2025, 10:41:31 AM
    Modified 12/28/2025, 10:41:31 AM
  • Using Bayesian Methods to Augment the Interpretation of Critical Care Trials. An Overview of Theory and Example Reanalysis of the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial

    Item Type Journal Article
    Author Fernando G. Zampieri
    Author Jonathan D. Casey
    Author Manu Shankar-Hari
    Author Frank E. Harrell
    Author Michael O. Harhay
    Date 2021-03-01
    Language en
    Library Catalog DOI.org (Crossref)
    URL https://www.atsjournals.org/doi/10.1164/rccm.202006-2381CP
    Accessed 12/28/2025, 9:53:36 AM
    Volume 203
    Pages 543-552
    Publication American Journal of Respiratory and Critical Care Medicine
    DOI 10.1164/rccm.202006-2381CP
    Issue 5
    Journal Abbr Am J Respir Crit Care Med
    ISSN 1073-449X, 1535-4970
    Date Added 12/28/2025, 9:53:36 AM
    Modified 12/28/2025, 9:54:43 AM

    Tags:

    • rct
    • teaching-mds
    • bayes
    • basic
  • Why are not There More Bayesian Clinical Trials? Perceived Barriers and Educational Preferences Among Medical Researchers Involved in Drug Development

    Item Type Journal Article
    Author The Medical Outreach Subteam of the Drug Information Association Bayesian Scientific Working Group
    Author Jennifer Clark
    Author Natalia Muhlemann
    Author Fanni Natanegara
    Author Andrew Hartley
    Author Deborah Wenkert
    Author Fei Wang
    Author Frank E. Harrell
    Author Ross Bray
    Date 05/2023
    Language en
    Short Title Why are not There More Bayesian Clinical Trials?
    Library Catalog DOI.org (Crossref)
    URL https://link.springer.com/10.1007/s43441-021-00357-x
    Accessed 12/28/2025, 10:09:54 AM
    Volume 57
    Pages 417-425
    Publication Therapeutic Innovation & Regulatory Science
    DOI 10.1007/s43441-021-00357-x
    Issue 3
    Journal Abbr Ther Innov Regul Sci
    ISSN 2168-4790, 2168-4804
    Date Added 12/28/2025, 10:09:54 AM
    Modified 12/28/2025, 10:10:31 AM

    Tags:

    • teaching-mds
    • bayes
    • basic
  • Why are There not More Bayesian Clinical Trials? Ability to Interpret Bayesian and Conventional Statistics Among Medical Researchers

    Item Type Journal Article
    Author The Medical Outreach Team of the Drug Information Association Bayesian Scientific Working Group
    Author Ross Bray
    Author Andrew Hartley
    Author Deborah Wenkert
    Author Natalia Muehlemann
    Author Fanni Natanegara
    Author Frank E. Harrell
    Author Fei Wang
    Author Jennifer Clark
    Date 05/2023
    Language en
    Short Title Why are There not More Bayesian Clinical Trials?
    Library Catalog DOI.org (Crossref)
    URL https://link.springer.com/10.1007/s43441-022-00482-1
    Accessed 12/28/2025, 10:11:11 AM
    Volume 57
    Pages 426-435
    Publication Therapeutic Innovation & Regulatory Science
    DOI 10.1007/s43441-022-00482-1
    Issue 3
    Journal Abbr Ther Innov Regul Sci
    ISSN 2168-4790, 2168-4804
    Date Added 12/28/2025, 10:11:11 AM
    Modified 12/28/2025, 10:11:40 AM

    Tags:

    • teaching-mds
    • bayes
    • basic
  • Worse Than Death: Survey of Public Perceptions of Disability Outcomes After Hypothetical Traumatic Brain Injury

    Item Type Journal Article
    Author Jo Ellen Wilson
    Author Myrick C. Shinall
    Author Taylor C. Leath
    Author Li Wang
    Author Frank E. Harrell
    Author Laura D. Wilson
    Author Mina F. Nordness
    Author Shayan Rakhit
    Author Michael R. De Riesthal
    Author Melissa C. Duff
    Author Pratik P. Pandharipande
    Author Mayur B. Patel
    Abstract Objective: The aim of this study was to determine the health utility states of the most commonly used traumatic brain injury (TBI) clinical trial endpoint, the Extended Glasgow Outcome Scale (GOSE). Summary Background Data: Health utilities represent the strength of one's preferences under conditions of uncertainty. There are insufficient data to indicate how an individual would value levels of disability after a TBI. Methods: This was a cross-sectional web-based online convenience sampling adaptive survey. Using a standard gamble approach, participants evaluated their preferences for GOSE health states 1 year after a hypothetical TBI. The categorical GOSE was studied from vegetative state (GOSE2) to upper good recovery (GOSE8). Median (25th percentile, 75th percentile) health utility values for different GOSE states after TBI, ranging from −1 (worse than death) to 1 (full health), with 0 as reference (death). Results: Of 3508 eligible participants, 3235 (92.22%) completed the survey. Participants rated lower GOSE states as having lower utility, with some states rated as worse than death, though the relationship was nonlinear and intervals were unequal between health states. Over 75% of participants rated a vegetative state (GOSE2, absence of awareness and bedridden) and about 50% rated lower severe disability (GOSE3, housebound needing all-day assistance) as conditions worse than death. Conclusions: In the largest investigation of public perceptions about post-TBI disability, we demonstrate unequally rated health states, with some states perceived as worse than death. Although limited by selection bias, these results may guide future comparative-effectiveness research and shared medical decision-making after neurologic injury.
    Date 03/2021
    Language en
    Short Title Worse Than Death
    Library Catalog DOI.org (Crossref)
    URL https://journals.lww.com/10.1097/SLA.0000000000003389
    Accessed 12/28/2025, 9:52:19 AM
    Volume 273
    Pages 500-506
    Publication Annals of Surgery
    DOI 10.1097/SLA.0000000000003389
    Issue 3
    ISSN 0003-4932, 1528-1140
    Date Added 12/28/2025, 9:52:19 AM
    Modified 12/28/2025, 9:56:15 AM

    Tags:

    • collaboration
  • Would You Rather: Quantifying Traumatic Brain Injury Survivor Perceptions of Functional Status Through Their Surrogates

    Item Type Journal Article
    Author Amelia W. Maiga
    Author Madison R. Cook
    Author Mina F. Nordness
    Author Yue Gao
    Author Shayan Rakhit
    Author Erika L. Rivera
    Author Frank E. Harrell
    Author Mayur B. Patel
    Abstract Objective: To quantify health utilities of the Glasgow Outcome Scale–Extended (GOSE) states after actual traumatic brain injury (TBI). Background: Recovery after TBI is measured using the GOSE, a validated clinical trial endpoint. A recent public survey quantified the health utilities of some GOSE states after hypothetical TBI as worse than death. However, no health utilities exist for disability after actual TBI. Methods: This national computer-adaptive survey followed Enhancing the Quality and Transparency of Health Research-Checklist for Reporting Results of Internet E-Surveys guidelines and recruited adult TBI survivors (injury >1 year prior) through their available surrogates. Using a standard gamble approach in randomized order, participants gave preferences for post-TBI categorical health states ranging from GOSE 2 to GOSE 8. We calculated median (interquartile range) health utilities for each GOSE state, from −1 (worse than death) to 1 (full health), with 0 as reference (death, GOSE 1). Results: Of 515 eligible, 298 surrogates (58%) consented and completed the scenarios on TBI survivors’ behalf. TBI survivors had a current median GOSE 5 (3–7). GOSE 2, GOSE 3, and GOSE 4 were rated worse than death by 89%, 64%, and 38%, respectively. The relationship was nonlinear, and intervals were unequal between states, with a bimodal distribution for GOSE 4. Conclusions: In this index study of actual post-TBI disability, poor neurological outcomes represented by GOSE 2 to GOSE 4 were perceived as worse than death by at least one in 3 survivors. Similar to previously reported public perceptions after a hypothetical TBI, these long-term perceptions may inform earlier post-TBI shared decision-making, as well as help shape value-based research and quality of care. Level of Evidence: Level II—economic and value-based evaluations.
    Date 07/2024
    Language en
    Short Title Would You Rather
    Library Catalog DOI.org (Crossref)
    URL https://journals.lww.com/10.1097/SLA.0000000000006274
    Accessed 12/28/2025, 10:21:17 AM
    Volume 280
    Pages 144-149
    Publication Annals of Surgery
    DOI 10.1097/SLA.0000000000006274
    Issue 1
    ISSN 0003-4932
    Date Added 12/28/2025, 10:21:17 AM
    Modified 12/28/2025, 10:21:17 AM