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
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 drugsDrugsComparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study
Wallach JD, Ciani O, Pease AM, Gonsalves GS, Krumholz HM, Taylor RS, Ross JS. Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study. BMC Medicine 2018, 16: 45. PMID: 29562926, PMCID: PMC5863466, DOI: 10.1186/s12916-018-1023-9.Peer-Reviewed Original ResearchConceptsPostapproval trialsPivotal trialsActual clinical effectSurrogate markerTrial endpointsLarge treatment effectsPrimary endpointNovel therapeuticsNovel drugsTreatment effectsFDA approvalPatient-relevant outcomesMeta-epidemiological studyStandardized mean differenceTreatment effect sizeClinical effectsResultsBetween 2005Odds ratioDrug trialsSame indicationDrug AdministrationEvidence of differencesMean differenceU.S. FoodDiseaseBringing Vioxx back to market
Ross JS, Krumholz HM. Bringing Vioxx back to market. The BMJ 2018, 360: k242. PMID: 29371221, DOI: 10.1136/bmj.k242.Commentaries, Editorials and Letters
2017
Association 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 documentsDrugsDiabetesFDAAAReviewersPostmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010
Downing NS, Shah ND, Aminawung JA, Pease AM, Zeitoun JD, Krumholz HM, Ross JS. Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010. JAMA 2017, 317: 1854-1863. PMID: 28492899, PMCID: PMC5815036, DOI: 10.1001/jama.2017.5150.Peer-Reviewed Original ResearchConceptsNovel therapeuticsSafety eventsAccelerated approvalTherapeutic characteristicsUS FoodDrug AdministrationFDA approvalInitial regulatory approvalClinician decision makingNew safety risksMedian followCohort studyMedian timeMultivariable analysisBoxed warningDrug classesMAIN OUTCOMEClinical practicePostmarket periodPsychiatric diseasesPriority reviewTherapeutic areasOrphan statusPsychiatric therapeuticsBiologicsPostapproval 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 approvalDiseaseTrialsDrugsFDAEndpointEfficacyMarkersIs Hemoglobin A1c the Right Outcome for Studies of Diabetes?
Lipska KJ, Krumholz HM. Is Hemoglobin A1c the Right Outcome for Studies of Diabetes? JAMA 2017, 317: 1017-1018. PMID: 28125758, PMCID: PMC5350060, DOI: 10.1001/jama.2017.0029.Commentaries, Editorials and Letters
2016
Participation of the elderly, women, and minorities in pivotal trials supporting 2011–2013 U.S. Food and Drug Administration approvals
Downing NS, Shah ND, Neiman JH, Aminawung JA, Krumholz HM, Ross JS. Participation of the elderly, women, and minorities in pivotal trials supporting 2011–2013 U.S. Food and Drug Administration approvals. Trials 2016, 17: 199. PMID: 27079511, PMCID: PMC4832528, DOI: 10.1186/s13063-016-1322-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedClinical Trials as TopicCross-Sectional StudiesDatabases, FactualDrug ApprovalEthnicityFemaleHealth Status DisparitiesHealthcare DisparitiesHumansMaleMiddle AgedMinority GroupsPatient SelectionSex FactorsTime FactorsUnited StatesUnited States Food and Drug AdministrationConceptsSubgroup efficacy analysesPivotal trialsEfficacy analysisNovel therapeuticsSubgroup analysisTrial participantsU.S. FoodMean proportionAvailable FDA documentsCross-sectional studyDrug Administration approvalBasis of approvalYears of ageTrial patientsElderly patientsMedian ageBlack patientsAsian patientsAdministration approvalClinical studiesFDA reviewersPatientsHispanic participantsTrialsDemographic characteristics
2015
Characterizing the US FDA's approach to promoting transformative innovation
Downing NS, Krumholz HM, Ross JS, Shah ND. Characterizing the US FDA's approach to promoting transformative innovation. Nature Reviews Drug Discovery 2015, 14: 740-741. PMID: 26435528, DOI: 10.1038/nrd4734.Peer-Reviewed Original Research
2014
Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012
Downing NS, Aminawung JA, Shah ND, Krumholz HM, Ross JS. Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012. JAMA 2014, 311: 368-377. PMID: 24449315, PMCID: PMC4144867, DOI: 10.1001/jama.2013.282034.Peer-Reviewed Original ResearchConceptsPivotal efficacy trialsNovel therapeutic agentsClinical trial evidencePivotal trialsEfficacy trialsTherapeutic agentsEnd pointTrial evidenceMedian numberAvailable FDA documentsSingle pivotal trialTrial end pointsSurrogate end pointsNumber of patientsLength of treatmentCross-sectional analysisPrimary outcomeClinical outcomesTrial completion ratesClinical benefitPlacebo comparatorSurrogate outcomesMAIN OUTCOMEDrug AdministrationUS Food
2012
Regulatory Review of Novel Therapeutics — Comparison of Three Regulatory Agencies
Downing NS, Aminawung JA, Shah ND, Braunstein JB, Krumholz HM, Ross JS. Regulatory Review of Novel Therapeutics — Comparison of Three Regulatory Agencies. New England Journal Of Medicine 2012, 366: 2284-2293. PMID: 22591257, PMCID: PMC3504361, DOI: 10.1056/nejmsa1200223.Peer-Reviewed Original ResearchConceptsNovel therapeutic agentsEuropean Medicines AgencyHealth CanadaTherapeutic agentsNew therapeutic agentsMedian lengthTherapeutic comparisonsDrug AdministrationMedicines AgencyNew drug applicationsPrescription Drug User Fee ActNovel therapeuticsDrug applicationFDAUnique agentUnited StatesTotal review timeFirst reviewRegulatory agenciesReview timeDaysAgentsReviewRegulatory reviewVast majority
2010
Licensing drugs for diabetes
Lehman R, Yudkin JS, Krumholz H. Licensing drugs for diabetes. The BMJ 2010, 341: c4805. PMID: 20819887, DOI: 10.1136/bmj.c4805.Peer-Reviewed Original Research