2024
Recommendations to promote equity, diversity and inclusion in decentralized clinical trials
Aiyegbusi O, Cruz Rivera S, Kamudoni P, Anderson N, Collis P, Denniston A, Harding R, Hughes S, Khunti K, Kotecha D, Krumholz H, Liu X, McMullan C, Molony-Oates B, Monteiro J, Myles P, Rantell K, Soltys K, Verdi R, Wilson R, Calvert M. Recommendations to promote equity, diversity and inclusion in decentralized clinical trials. Nature Medicine 2024, 30: 3075-3084. PMID: 39472759, DOI: 10.1038/s41591-024-03323-w.Peer-Reviewed Original ResearchClinical trial participationDecentralized clinical trialsTrial participantsBarriers to clinical trial participationPromote equityGeneralizability of trial resultsClinical trial teamsHealth inequalitiesUnderserved groupsBarriers individualsTrial teamClinical trialsParticipantsElectronic dataTrial resultsEquitable mannerTrialsRecommendationsHealthInclusionRemote researchAssociated with several challengesAdvancing patient-centric care: integrating patient reported outcomes for tolerability assessment in early phase clinical trials – insights from an expert virtual roundtable
Yap C, Aiyegbusi O, Alger E, Basch E, Bell J, Bhatnagar V, Cella D, Collis P, Dueck A, Gilbert A, Gnanasakthy A, Greystoke A, Hansen A, Kamudoni P, Kholmanskikh O, King-Kallimanis B, Krumholz H, Minchom A, O'Connor D, Petrie J, Piccinin C, Rantell K, Rauz S, Retzer A, Rizk S, Wagner L, Sasseville M, Seymour L, Weber H, Wilson R, Calvert M, Peipert J. Advancing patient-centric care: integrating patient reported outcomes for tolerability assessment in early phase clinical trials – insights from an expert virtual roundtable. EClinicalMedicine 2024, 76: 102838. PMID: 39386161, PMCID: PMC11462221, DOI: 10.1016/j.eclinm.2024.102838.Peer-Reviewed Original ResearchEarly phase trialsPatient-reported outcomesPhase trialsInvestigator-reported adverse eventsEarly phase clinical trialsTolerability assessmentsPhase clinical trialsIntegration of patient-reported outcomesAdverse eventsClinical trialsPatient-centred careDosing decisionsDiverse clinical areasTherapy risksLaboratory assessmentPatientsTrialsPatient advocatesClinical areasOutcomesSafety alertsPharmaceutical representativesVirtual roundtableRiskIllusory generalizability of clinical prediction models
Chekroud A, Hawrilenko M, Loho H, Bondar J, Gueorguieva R, Hasan A, Kambeitz J, Corlett P, Koutsouleris N, Krumholz H, Krystal J, Paulus M. Illusory generalizability of clinical prediction models. Science 2024, 383: 164-167. PMID: 38207039, DOI: 10.1126/science.adg8538.Peer-Reviewed Original Research
2023
The Science of Precision Prevention Research Opportunities and Clinical Applications to Reduce Cardiovascular Health Disparities
Pearson T, Vitalis D, Pratt C, Campo R, Armoundas A, Au D, Beech B, Brazhnik O, Chute C, Davidson K, Diez-Roux A, Fine L, Gabriel D, Groenveld P, Hall J, Hamilton A, Hu H, Ji H, Kind A, Kraus W, Krumholz H, Mensah G, Merchant R, Mozaffarian D, Murray D, Neumark-Sztainer D, Petersen M, Goff D. The Science of Precision Prevention Research Opportunities and Clinical Applications to Reduce Cardiovascular Health Disparities. JACC Advances 2023, 3: 100759. PMID: 38375059, PMCID: PMC10876066, DOI: 10.1016/j.jacadv.2023.100759.Peer-Reviewed Original ResearchCardiovascular health disparitiesPrecision preventionHealth disparitiesHealth equity gapCardiovascular disease disparitiesPrevention intervention researchCardiovascular healthSocial determinantsDisease disparitiesPreventionClinical applicationImplementation scienceIntervention researchHealthDisparitiesCurrent gapsEquity gapIndividualsTrialsClinical trial data sharing: a cross-sectional study of outcomes associated with two U.S. National Institutes of Health models
Rowhani-Farid A, Grewal M, Solar S, Eghrari A, Zhang A, Gross C, Krumholz H, Ross J. Clinical trial data sharing: a cross-sectional study of outcomes associated with two U.S. National Institutes of Health models. Scientific Data 2023, 10: 529. PMID: 37553403, PMCID: PMC10409750, DOI: 10.1038/s41597-023-02436-0.Peer-Reviewed Original Research
2022
Effectiveness of a clinical decision support system for hypertension management in primary care: study protocol for a pragmatic cluster-randomized controlled trial
Song J, Wang X, Wang B, Gao Y, Liu J, Zhang H, Li X, Li J, Wang JG, Cai J, Herrin J, Armitage J, Krumholz HM, Zheng X. Effectiveness of a clinical decision support system for hypertension management in primary care: study protocol for a pragmatic cluster-randomized controlled trial. Trials 2022, 23: 412. PMID: 35578345, PMCID: PMC9109449, DOI: 10.1186/s13063-022-06374-x.Peer-Reviewed Original ResearchConceptsHypertension managementPrimary carePrimary outcomeDual antihypertensive therapyHypertension Treatment TrialBlood pressure managementGuideline-based treatmentPrimary care sitesCluster-randomized trialUnit of randomizationGuideline-based decision support systemClinical decision support systemAntihypertensive regimensAntihypertensive treatmentUsual careGuideline adherenceBlood pressureMiddle-income countriesTreatment trialsManagement visitsStudy protocolCare sitesPatientsTrialsPressure management
2021
Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19 JACC State-of-the-Art Review
Talasaz AH, Sadeghipour P, Aghakouchakzadeh M, Dreyfus I, Kakavand H, Ariannejad H, Gupta A, Madhavan MV, Van Tassell BW, Jimenez D, Monreal M, Vaduganathan M, Fanikos J, Dixon DL, Piazza G, Parikh SA, Bhatt DL, Lip GYH, Stone GW, Krumholz HM, Libby P, Goldhaber SZ, Bikdeli B. Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19 JACC State-of-the-Art Review. Journal Of The American College Of Cardiology 2021, 78: 1635-1654. PMID: 34649702, PMCID: PMC8504484, DOI: 10.1016/j.jacc.2021.08.021.Peer-Reviewed Original ResearchConceptsLipid-modulating agentsEndothelial activationLow high-density lipoprotein cholesterolCOVID-19High-density lipoprotein cholesterolLipid modulating agentsHigh triglyceride levelsMultiorgan manifestationsStatin trialsLipoprotein cholesterolSystemic inflammationTriglyceride levelsJACC StateWorse outcomesInflammatory responsePatient managementRCTsCoronavirus diseaseViral entrySystematic searchLipid raft disruptionTrialsPatientsRaft disruptionPreventionRecent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19 JACC State-of-the-Art Review
Talasaz AH, Sadeghipour P, Kakavand H, Aghakouchakzadeh M, Kordzadeh-Kermani E, Van Tassell BW, Gheymati A, Ariannejad H, Hosseini SH, Jamalkhani S, Sholzberg M, Monreal M, Jimenez D, Piazza G, Parikh SA, Kirtane AJ, Eikelboom JW, Connors JM, Hunt BJ, Konstantinides SV, Cushman M, Weitz JI, Stone GW, Krumholz HM, Lip GYH, Goldhaber SZ, Bikdeli B. Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19 JACC State-of-the-Art Review. Journal Of The American College Of Cardiology 2021, 77: 1903-1921. PMID: 33741176, PMCID: PMC7963001, DOI: 10.1016/j.jacc.2021.02.035.Peer-Reviewed Original ResearchConceptsCOVID-19Recent randomized trialsCommon pathophysiological featuresDuration of therapyClinical trial enterpriseMacrovascular thrombosisThromboprophylactic regimensAntithrombotic therapyAntithrombotic strategiesEndothelial injuryFuture RCTsMedical wardsIllness severityRandomized trialsPathophysiological featuresJACC StateAntithrombotic agentsCoronavirus diseasePatientsRCTsTherapyTrialsRegimensThrombosisOutpatients
2020
Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials
Bikdeli B, Caraballo C, Welsh J, Ross JS, Kaul S, Stone GW, Krumholz HM. Non-inferiority trials using a surrogate marker as the primary endpoint: An increasing phenotype in cardiovascular trials. Clinical Trials 2020, 17: 723-728. PMID: 32838556, PMCID: PMC8088773, DOI: 10.1177/1740774520949157.Peer-Reviewed Original ResearchConceptsNon-inferiority trialPrimary endpointClinical outcome trialsNon-inferiority marginSurrogate markerNon-inferiority designCardiovascular trialsOutcome trialsClinical outcomesDefinitive clinical outcome trialsNon-inferiority criteriaStudy protocolSurrogate outcomesBACKGROUND/Median numberSurrogate endpointsPrimary analysisCardiovascular interventionsCardiovascular medicineTrialsEndpointClinical interpretationOutcomesMarkersIntervention
2019
Noninferiority Designed Cardiovascular Trials in Highest-Impact Journals
Bikdeli B, Welsh JW, Akram Y, Punnanithinont N, Lee I, Desai NR, Kaul S, Stone G, Ross JS, Krumholz HM. Noninferiority Designed Cardiovascular Trials in Highest-Impact Journals. Circulation 2019, 140: 379-389. PMID: 31177811, PMCID: PMC8416048, DOI: 10.1161/circulationaha.119.040214.Peer-Reviewed Original ResearchConceptsNoninferiority marginNoninferiority trialCardiovascular trialsAllocation concealmentLower riskOpen labelHazard ratioRelative riskMethodological qualityProportion of trialsIndependent reviewersRisk differenceNew England JournalNoninferiorityHigh-impact journalsNew interventionsTrialsCohortDiscrepant resultsProtocol analysisTime trendsRiskTreatInterventionFactorsCARDIOVASCULAR EVENTS IN PATIENTS RECEIVING SULODEXIDE VERSUS CONTROL: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Bikdeli B, Chatterjee S, Kirtane A, Parikh S, Andreozzi G, Gibson C, Goldhaber S, Eikelboom J, Krumholz H, Stone G. CARDIOVASCULAR EVENTS IN PATIENTS RECEIVING SULODEXIDE VERSUS CONTROL: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS. Journal Of The American College Of Cardiology 2019, 73: 144. DOI: 10.1016/s0735-1097(19)30752-1.Peer-Reviewed Original Research
2018
Registration, results reporting, and publication bias of clinical trials supporting FDA approval of neuropsychiatric drugs before and after FDAAA: a retrospective cohort study
Zou CX, Becker JE, Phillips AT, Garritano JM, Krumholz HM, Miller JE, Ross JS. Registration, results reporting, and publication bias of clinical trials supporting FDA approval of neuropsychiatric drugs before and after FDAAA: a retrospective cohort study. Trials 2018, 19: 581. PMID: 30352601, PMCID: PMC6199729, DOI: 10.1186/s13063-018-2957-0.Peer-Reviewed Original ResearchConceptsRetrospective cohort studyPublication biasNeuropsychiatric indicationsCohort studyClinical trialsRelative riskEfficacy trialsFDA approvalPositive trialsFisher's exact testRecent FDA approvalDrug Administration Amendments ActClinical trial publicationsTRIAL REGISTRATIONMAIN OUTCOMEProportion of trialsNeuropsychiatric drugsNew drug approvalsTrial publicationsExact testMedical interventionsTrialsDrug approvalNew drugsDrugsAge of Data at the Time of Publication of Contemporary Clinical Trials
Welsh J, Lu Y, Dhruva SS, Bikdeli B, Desai NR, Benchetrit L, Zimmerman CO, Mu L, Ross JS, Krumholz HM. Age of Data at the Time of Publication of Contemporary Clinical Trials. JAMA Network Open 2018, 1: e181065-e181065. PMID: 30646100, PMCID: PMC6324269, DOI: 10.1001/jamanetworkopen.2018.1065.Peer-Reviewed Original ResearchConceptsClinical trialsFinal data collectionParticipant enrollmentInternal medicineMultivariable linear regression analysisFirst participant enrollmentPrimary end pointMultivariable regression analysisContemporary clinical trialsClinical trial dataJAMA Internal MedicineRegression analysisCross-sectional analysisTime of publicationMedian timeTrial characteristicsOutcome measuresMAIN OUTCOMENew England JournalClinical practiceLinear regression analysisTrial dataEnd pointTrial resultsTrialsAccurate estimation of cardiovascular risk in a non-diabetic adult: detecting and correcting the error in the reported Framingham Risk Score for the Systolic Blood Pressure Intervention Trial population
Warner F, Dhruva SS, Ross JS, Dey P, Murugiah K, Krumholz HM. Accurate estimation of cardiovascular risk in a non-diabetic adult: detecting and correcting the error in the reported Framingham Risk Score for the Systolic Blood Pressure Intervention Trial population. BMJ Open 2018, 8: e021685. PMID: 30037874, PMCID: PMC6059296, DOI: 10.1136/bmjopen-2018-021685.Peer-Reviewed Original ResearchConceptsSystolic Blood Pressure Intervention TrialFramingham risk scoreCardiovascular riskRisk scoreStudy populationStudy participantsNon-diabetic adultsTotal study populationHigh-risk populationClinical trial dataClinical trial sitesTrial populationIntervention trialsRisk populationsNew England JournalIndependent investigatorsTrial dataSecondary analysisSPRINT trialSPRINT dataTrialsRiskScoresParticipantsPopulation
2017
Systolic Blood Pressure Response in SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD (Action to Control Cardiovascular Risk in Diabetes): A Possible Explanation for Discordant Trial Results
Huang C, Dhruva SS, Coppi AC, Warner F, Li S, Lin H, Nasir K, Krumholz HM. Systolic Blood Pressure Response in SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD (Action to Control Cardiovascular Risk in Diabetes): A Possible Explanation for Discordant Trial Results. Journal Of The American Heart Association 2017, 6: e007509. PMID: 29133522, PMCID: PMC5721802, DOI: 10.1161/jaha.117.007509.Peer-Reviewed Original ResearchConceptsSystolic blood pressure responseBlood pressure responseTreatment groupsCause deathVisit variabilityDiscordant trialsBlood pressure trialStandard treatment groupPressure responseACCORD participantsPressure trialSBP responseHeart failureMean SBPPrimary outcomeSBPDiscordant resultsMean differenceSimilar interventionsTrial resultsTrialsSimilar mean differencesTreatment effectsSignificant differencesStrokeAssociation of the FDA Amendment Act with trial registration, publication, and outcome reporting
Phillips AT, Desai NR, Krumholz HM, Zou CX, Miller JE, Ross JS. Association of the FDA Amendment Act with trial registration, publication, and outcome reporting. Trials 2017, 18: 333. PMID: 28720112, PMCID: PMC5516301, DOI: 10.1186/s13063-017-2068-3.Peer-Reviewed Original ResearchConceptsCardiovascular diseaseTRIAL REGISTRATIONFDA approvalNew drugsClinical trial registrationFDA Amendments ActDrug Administration Amendments ActAccessible trial registryClinical trial publicationsTrials RegistryResultsBetween 2005Efficacy trialsFDA reviewersTrial publicationsOutcome reportingMedical literatureReviewer interpretationsTrialsReporting of findingsDiseaseFDA documentsDrugsDiabetesFDAAAReviewersPostapproval studies of drugs initially approved by the FDA on the basis of limited evidence: systematic review
Pease AM, Krumholz HM, Downing NS, Aminawung JA, Shah ND, Ross JS. Postapproval studies of drugs initially approved by the FDA on the basis of limited evidence: systematic review. The BMJ 2017, 357: j1680. PMID: 28468750, PMCID: PMC5421452, DOI: 10.1136/bmj.j1680.Peer-Reviewed Original ResearchConceptsSingle pivotal trialPivotal trialsPostapproval studiesSurrogate markerPrimary endpointNovel drugsClinical outcomesClinical studiesLimited evidenceSystematic reviewDouble-blind studyMedian total numberClinical evidenceSuperior efficacyBlind studyDrug AdministrationOriginal FDATrial approvalDiseaseTrialsDrugsFDAEndpointEfficacyMarkersAssessing the reliability of self-reported weight for the management of heart failure: application of fraud detection methods to a randomised trial of telemonitoring
Steventon A, Chaudhry SI, Lin Z, Mattera JA, Krumholz HM. Assessing the reliability of self-reported weight for the management of heart failure: application of fraud detection methods to a randomised trial of telemonitoring. BMC Medical Informatics And Decision Making 2017, 17: 43. PMID: 28420352, PMCID: PMC5395848, DOI: 10.1186/s12911-017-0426-4.Peer-Reviewed Original ResearchConceptsEnd-digit preferenceHeart failureHeart Failure Outcomes trialEffective preventive careCharacteristics of patientsSelf-reported weightHealth care professionalsSix-month trial periodIntervention patientsMore medicationsAccuracy of reportingOutcome trialsTrial enrollmentPreventive careClinical managementUnnecessary treatmentDesign of initiativesCare professionalsPatientsRegistration numberAlert fatigueElectronic medical dataTrial periodTrialsNumber of daysTwo Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011
Bikdeli B, Punnanithinont N, Akram Y, Lee I, Desai NR, Ross JS, Krumholz HM. Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011. Journal Of The American Heart Association 2017, 6: e005285. PMID: 28325713, PMCID: PMC5524035, DOI: 10.1161/jaha.116.005285.Peer-Reviewed Original ResearchConceptsClinical outcome trialsOutcome trialsEndpoint trialsPrimary endpointCardiovascular trialsClinical outcome studiesClinical outcomesSurrogate markerPatient's perspectiveSurrogate endpointsOutcome studiesNew England JournalSample cohortTrial resultsTrialsSurrogate trialsEndpointPositive resultsAmerican MedicalInterventionHigh-impact journalsCohort
2016
Commentary: Diagnostic devices in clinical trials have high stakes for patient care
Rathi VK, Krumholz HM, Ross JS. Commentary: Diagnostic devices in clinical trials have high stakes for patient care. The BMJ 2016, 354: i5197. PMID: 27681285, DOI: 10.1136/bmj.i5197.Commentaries, Editorials and Letters