2024
Advancing 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
2022
Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High–risk Pulmonary Embolism
Sadeghipour P, Jenab Y, Moosavi J, Hosseini K, Mohebbi B, Hosseinsabet A, Chatterjee S, Pouraliakbar H, Shirani S, Shishehbor MH, Alizadehasl A, Farrashi M, Rezvani MA, Rafiee F, Jalali A, Rashedi S, Shafe O, Giri J, Monreal M, Jimenez D, Lang I, Maleki M, Goldhaber SZ, Krumholz HM, Piazza G, Bikdeli B. Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High–risk Pulmonary Embolism. JAMA Cardiology 2022, 7: 1189-1197. PMID: 36260302, PMCID: PMC9582964, DOI: 10.1001/jamacardio.2022.3591.Peer-Reviewed Original ResearchConceptsConventional catheter-directed thrombolysisRV/LV ratioRisk pulmonary embolismCatheter-directed thrombolysisProportion of patientsPulmonary embolismLV ratioMajor bleedingPrimary outcomeRight ventricleClinical trialsIntermediate-high risk pulmonary embolismDefinitive clinical outcome trialsMain safety outcomeMajor gastrointestinal bleedingRV/LVClinical events committeeClinical outcome trialsLarge cardiovascular centresCause mortalityEfficacy outcomesGastrointestinal bleedingMonotherapy groupOutcome trialsSecondary outcomesDurable functional limitation in patients with coronavirus disease-2019 admitted to intensive care and the effect of intermediate-dose vs standard-dose anticoagulation on functional outcomes
INVESTIGATORS I, Sadeghipour P, Talasaz A, Barco S, Bakhshandeh H, Rashidi F, Rafiee F, Rezaeifar P, Jamalkhani S, Matin S, Baghizadeh E, Tahamtan O, Sharif-Kashani B, Beigmohammadi M, Farrokhpour M, Sezavar S, Payandemehr P, Dabbagh A, Moghadam K, Jimenez D, Monreal M, Maleki M, Siegerink B, Spatz E, Piazza G, Parikh S, Kirtane A, Van Tassell B, Lip G, Goldhaber S, Klok F, Krumholz H, Bikdeli B. Durable functional limitation in patients with coronavirus disease-2019 admitted to intensive care and the effect of intermediate-dose vs standard-dose anticoagulation on functional outcomes. European Journal Of Internal Medicine 2022, 103: 76-83. PMID: 35879217, PMCID: PMC9212871, DOI: 10.1016/j.ejim.2022.06.014.Peer-Reviewed Original ResearchConceptsStandard-dose prophylactic anticoagulationPatient Health Questionnaire-2Proportion of patientsProphylactic anticoagulationIntermediate doseFunctional limitationsDepressive symptomsFunctional outcomeCOVID-19Intensive care unit hospitalizationCritically Ill PatientsMultiple organ failureSevere functional limitationsFunctional Status ScaleCoronavirus disease 2019Open labelExercise limitationAirway diseaseICU patientsOrgan failureIntensive careStatus ScaleClinical trialsGrade 3Anticoagulation
2021
Patterns of Prescribing Sodium-Glucose Cotransporter-2 Inhibitors for Medicare Beneficiaries in the United States
Sangha V, Lipska K, Lin Z, Inzucchi SE, McGuire DK, Krumholz HM, Khera R. Patterns of Prescribing Sodium-Glucose Cotransporter-2 Inhibitors for Medicare Beneficiaries in the United States. Circulation Cardiovascular Quality And Outcomes 2021, 14: e008381. PMID: 34779654, PMCID: PMC9022137, DOI: 10.1161/circoutcomes.121.008381.Peer-Reviewed Original ResearchConceptsType 2 diabetesMedicare beneficiariesSodium-glucose cotransporter 2 inhibitorsLarge randomized clinical trialsMedicare Part D prescriber dataChronic kidney diseaseCotransporter 2 inhibitorsAtherosclerotic cardiovascular diseasePercent of cliniciansRandomized clinical trialsUS Medicare beneficiariesAdvanced practice providersCross-sectional studyKidney outcomesSGLT2i useSulfonylurea prescriptionUnique cliniciansCardiovascular deathMedication classesKidney diseaseLabel indicationsClinical trialsSGLT2iCardiovascular diseasePractice providersContemporary National Patterns of Eligibility and Utilization of Novel Cardioprotective Anti‐hyperglycemic agents in Type 2 Diabetes
Nargesi AA, Jeyashanmugaraja GP, Desai N, Lipska K, Krumholz H, Khera R. Contemporary National Patterns of Eligibility and Utilization of Novel Cardioprotective Anti‐hyperglycemic agents in Type 2 Diabetes. Journal Of The American Heart Association 2021, 10: e021084. PMID: 33998258, PMCID: PMC8403287, DOI: 10.1161/jaha.121.021084.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkersBlood GlucoseCardiovascular DiseasesDiabetes Mellitus, Type 2Drug UtilizationEligibility DeterminationFemaleGlucagon-Like Peptide-1 ReceptorGuideline AdherenceHeart Disease Risk FactorsHumansIncretinsMaleMiddle AgedNutrition SurveysPractice Guidelines as TopicPractice Patterns, Physicians'Risk AssessmentSodium-Glucose Transporter 2 InhibitorsTime FactorsTreatment OutcomeUnited StatesConceptsSGLT-2 inhibitorsType 2 diabetes mellitusAtherosclerotic cardiovascular diseaseChronic kidney diseaseLarge clinical trialsGLP-1RAsDiabetes mellitusCardiovascular diseaseHeart failureKidney diseaseClinical trialsHigh-risk atherosclerotic cardiovascular diseaseGLP-1RA useAmerican Diabetes AssociationNutrition Examination SurveyAnti-hyperglycemic agentsPublic health benefitsComplex survey designCardiovascular riskGuideline recommendationsDiabetes AssociationExamination SurveyProtective therapyNational HealthAmerican College
2020
Assessment of Clinical Trials Supporting US Food and Drug Administration Approval of Novel Therapeutic Agents, 1995-2017
Zhang AD, Puthumana J, Downing NS, Shah ND, Krumholz HM, Ross JS. Assessment of Clinical Trials Supporting US Food and Drug Administration Approval of Novel Therapeutic Agents, 1995-2017. JAMA Network Open 2020, 3: e203284. PMID: 32315070, PMCID: PMC7175081, DOI: 10.1001/jamanetworkopen.2020.3284.Peer-Reviewed Original ResearchConceptsPivotal trialsProportion of indicationsIndication approvalsNew drugsUS FoodTrial durationPrimary end pointTherapeutic areasPivotal efficacy trialsCross-sectional studyDrug Administration approvalFast track designationCommon therapeutic areasRecent FDA approvalOrphan designationLonger trial durationAccelerated approvalAdministration approvalClinical trialsMonths durationEfficacy trialsMAIN OUTCOMETherapeutic safetyDrug AdministrationFDA approval
2019
P573Effects of mobile text messaging on glycemic control in patients with coronary heart disease and diabetes mellitus: a randomized controlled trial
Huo X, Krumholz H, Bai X, Spatz E, Ding Q, Horak P, Zhao W, Gong Q, Yan X, Wu X, Li J, Li X, Spertus J, Masoudi F, Zheng X. P573Effects of mobile text messaging on glycemic control in patients with coronary heart disease and diabetes mellitus: a randomized controlled trial. European Heart Journal 2019, 40: ehz747.0184. DOI: 10.1093/eurheartj/ehz747.0184.Peer-Reviewed Original ResearchCoronary heart diseaseIntervention groupPhysical activityControl groupGlycemic controlHeart diseaseBaseline 6 monthsHigh-risk patientsText messaging programsSecondary outcome analysisMobile health interventionsText message programMean change differenceBP controlGlycemic hemoglobinHbA1c levelsLifestyle modificationUsual careDiabetes mellitusFamily Planning CommissionPrimary outcomeLifestyle recommendationsMonth followRisk factorsClinical trials
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 resultsTrialsRationale, Design and Methodology of the Computerized Registry of Patients with Venous Thromboembolism (RIETE)
Bikdeli B, Jimenez D, Hawkins M, Ortíz S, Prandoni P, Brenner B, Decousus H, Masoudi FA, Trujillo-Santos J, Krumholz HM, Monreal M. Rationale, Design and Methodology of the Computerized Registry of Patients with Venous Thromboembolism (RIETE). Thrombosis And Haemostasis 2018, 118: 214-224. PMID: 29304541, PMCID: PMC5821113, DOI: 10.1160/th17-07-0511.Peer-Reviewed Original ResearchMeSH KeywordsAnticoagulantsCardiologyCause of DeathFemaleFollow-Up StudiesHemorrhageHumansInternational CooperationIschemiaPregnancyPregnancy Complications, CardiovascularProspective StudiesPuerperal DisordersPulmonary EmbolismRecurrenceRegistriesResearch DesignTreatment OutcomeVena Cava FiltersVenous ThromboembolismConceptsOutcomes of patientsVenous thromboembolismDeep vein thrombosisPulmonary embolismOngoing registryClinical trialsOutcomes of VTEPragmatic comparative effectiveness studyLong-term outcome dataUnstable pulmonary embolismPattern of presentationPatterns of carePrevalent vascular diseaseComparative effectiveness studiesHospital deathVein thrombosisVenous thrombosisPreventable causeComputerized registryVascular diseaseRIETEInclusion criteriaThrombotic conditionsOutcome dataPatients
2017
Impact of Telemonitoring on Health Status
Jayaram NM, Khariton Y, Krumholz HM, Chaudhry SI, Mattera J, Tang F, Herrin J, Hodshon B, Spertus JA. Impact of Telemonitoring on Health Status. Circulation Cardiovascular Quality And Outcomes 2017, 10: e004148. PMID: 29237746, PMCID: PMC5776725, DOI: 10.1161/circoutcomes.117.004148.Peer-Reviewed Original ResearchConceptsKansas City Cardiomyopathy QuestionnaireUsual careHealth statusHeart failureKCCQ overall summary scoreRecent heart failure hospitalizationDisease-specific health statusKCCQ overall summaryHeart failure hospitalizationWeeks of dischargeRandomized clinical trialsOverall summary scoreKCCQ scoresNoninvasive TelemonitoringFailure hospitalizationBaseline characteristicsSecondary outcomesTreatment armsClinical trialsSummary scoresPatientsSubscale scoresCareHospitalizationScoresComparison of two independent systematic reviews of trials of recombinant human bone morphogenetic protein-2 (rhBMP-2): the Yale Open Data Access Medtronic Project
Low J, Ross JS, Ritchie JD, Gross CP, Lehman R, Lin H, Fu R, Stewart LA, Krumholz HM. Comparison of two independent systematic reviews of trials of recombinant human bone morphogenetic protein-2 (rhBMP-2): the Yale Open Data Access Medtronic Project. Systematic Reviews 2017, 6: 28. PMID: 28196521, PMCID: PMC5310069, DOI: 10.1186/s13643-017-0422-x.Peer-Reviewed Original ResearchConceptsParticipant-level dataSystematic reviewSummary estimatesRecombinant human bone morphogenetic protein-2Inclusion criteriaCenter BIndividual participant-level dataMeta-analysis inclusion criteriaHuman bone morphogenetic protein-2Trial inclusion criteriaMulti-site clinical trialMain outcome measuresMost clinical outcomesStatistical methodsConcurrent systematic reviewIndependent systematic reviewsProtein 2Bone morphogenetic protein-2Summary efficacyMorphogenetic protein-2Adverse eventsClinical outcomesSurgical approachTrial inclusionClinical trials
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 LettersAvailability of Clinical Trial Data From Industry‐Sponsored Cardiovascular Trials
Murugiah K, Ritchie JD, Desai NR, Ross JS, Krumholz HM. Availability of Clinical Trial Data From Industry‐Sponsored Cardiovascular Trials. Journal Of The American Heart Association 2016, 5: e003307. PMID: 27098969, PMCID: PMC4859296, DOI: 10.1161/jaha.116.003307.Peer-Reviewed Original ResearchConceptsIndividual participant-level dataLarge cardiovascular trialsCardiovascular trialsParticipant-level dataClinical trial dataPharmaceutical companiesMajor pharmaceutical companiesIndustry-sponsored clinical trialsInterventional trialsAvailable trialsClinical trialsTrial dataTrialsPatientsSpecific reasonsPolypharmacy in the Aging Patient: A Review of Glycemic Control in Older Adults With Type 2 Diabetes
Lipska KJ, Krumholz H, Soones T, Lee SJ. Polypharmacy in the Aging Patient: A Review of Glycemic Control in Older Adults With Type 2 Diabetes. JAMA 2016, 315: 1034-1045. PMID: 26954412, PMCID: PMC4823136, DOI: 10.1001/jama.2016.0299.BooksConceptsRandomized clinical trialsIntensive glycemic controlGlycemic controlClinical trialsOlder adultsMicrovascular outcomesTreatment burdenPatient preferencesMost RCTsLarge randomized clinical trialsType 2 diabetes mellitusMajor macrovascular eventsStandard glycemic controlOptimal glycemic controlLower treatment burdenSurrogate end pointsHigh-quality evidenceType 2 diabetesLikelihood of benefitMajority of adultsGlycemic treatmentMacrovascular eventsDiabetes mellitusPatient factorsAging PatientPublication and reporting of clinical trial results: cross sectional analysis across academic medical centers
Chen R, Desai NR, Ross JS, Zhang W, Chau KH, Wayda B, Murugiah K, Lu DY, Mittal A, Krumholz HM. Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers. The BMJ 2016, 352: i637. PMID: 26888209, PMCID: PMC4768882, DOI: 10.1136/bmj.i637.Peer-Reviewed Original ResearchConceptsAcademic medical centerInterventional clinical trialsClinical trialsMedical CenterStudy completionPrimary completion dateClinical trial resultsReporting of resultsSectional analysisInterventional trialsProportion of trialsTrial resultsTrialsMonthsPhase IIManual reviewLead investigatorUnited StatesProportionRate of publicationReportingCompletionPatientsCenter
2014
Predictors of clinical trial data sharing: exploratory analysis of a cross-sectional survey
Rathi VK, Strait KM, Gross CP, Hrynaszkiewicz I, Joffe S, Krumholz HM, Dzara K, Ross JS. Predictors of clinical trial data sharing: exploratory analysis of a cross-sectional survey. Trials 2014, 15: 384. PMID: 25277128, PMCID: PMC4192345, DOI: 10.1186/1745-6215-15-384.Peer-Reviewed Original ResearchMeSH KeywordsAccess to InformationAgedAttitude of Health PersonnelChi-Square DistributionClinical Trials as TopicCooperative BehaviorCross-Sectional StudiesDatabases, FactualFemaleHealth Knowledge, Attitudes, PracticeHumansInformation DisseminationInternetMaleMiddle AgedPerceptionRegistriesResearch PersonnelSurveys and QuestionnairesConceptsTrial funding sourceExact testMain outcome measuresFisher's exact testCross-sectional surveyChi-square testClinical trialsTrial characteristicsOutcome measuresGeneral medical journalsClinical trialistsWeb-based surveyTrialistsExploratory analysisBackgroundA numberStatistical significanceSignificant differencesExternal investigatorsClinical trial data sharingTrialsMedical journalsPharmaceutical companiesFunding sourcesIndustry fundingPotential respondents
2012
Sharing of clinical trial data among trialists: a cross sectional survey
Rathi V, Dzara K, Gross CP, Hrynaszkiewicz I, Joffe S, Krumholz HM, Strait KM, Ross JS. Sharing of clinical trial data among trialists: a cross sectional survey. The BMJ 2012, 345: e7570. PMID: 23169870, PMCID: PMC3502744, DOI: 10.1136/bmj.e7570.Peer-Reviewed Original ResearchConceptsClinical trial dataTrial dataGeneral medical journalsHigh-impact general medical journalsCross-sectional surveyDe-identified dataMedical journalsClinical trialsTrial fundersClinical trialistsSectional surveyTrialistsTrialsInvestigatorsExperiences of sharingPrevalence of dataPotential respondentsHigh impact factorAppropriate data usePrevalenceRespondentsPublication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis
Ross JS, Tse T, Zarin DA, Xu H, Zhou L, Krumholz HM. Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis. The BMJ 2012, 344: d7292. PMID: 22214755, PMCID: PMC3623605, DOI: 10.1136/bmj.d7292.Peer-Reviewed Original Research