2024
Premarket Pivotal Trial End Points and Postmarketing Requirements for FDA Breakthrough Therapies
Mooghali M, Wallach J, Ross J, Ramachandran R. Premarket Pivotal Trial End Points and Postmarketing Requirements for FDA Breakthrough Therapies. JAMA Network Open 2024, 7: e2430486. PMID: 39190303, PMCID: PMC11350476, DOI: 10.1001/jamanetworkopen.2024.30486.Peer-Reviewed Original ResearchConceptsFood and Drug Administration tableFood and Drug AdministrationSurrogate end pointsSurrogate markerPostmarketing studiesEnd pointsTraditional approvalCross-sectional studyClinical benefitAccelerated approvalTherapy designClinically significant end pointsReview of therapeuticsPrimary end pointUS Food and Drug AdministrationTrial end pointsSignificant end pointsPostmarketing requirementsPreliminary clinical evidenceApproval pathwayPivotal trialsClinical evidenceBreakthrough therapiesDrug AdministrationTherapyAssociations Between Surrogate Markers and Clinical Outcomes for Nononcologic Chronic Disease Treatments
Wallach J, Yoon S, Doernberg H, Glick L, Ciani O, Taylor R, Mooghali M, Ramachandran R, Ross J. Associations Between Surrogate Markers and Clinical Outcomes for Nononcologic Chronic Disease Treatments. JAMA 2024, 331: 1646-1654. PMID: 38648042, PMCID: PMC11036312, DOI: 10.1001/jama.2024.4175.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersChronic DiseaseClinical Trials as TopicHumansMeta-Analysis as TopicTreatment OutcomeConceptsMeta-analysesChronic diseasesFood and Drug AdministrationMeta-regression analysisMeta-analyses of observational studiesSurrogate markerClinical outcomesClinical trialsMeta-analysisEvidence of associationPublished meta-analysesStrength of associationMeta-analyses of clinical trialsChronic disease treatmentFood and Drug Administration tableResults of meta-regression analysisOutcome pairsFood and Drug Administration approvalMain OutcomesData extractionSystematic reviewStatistically significant resultsObservational studyPooled analysisDrug Administration
2023
Pivotal Trial Demographic Representation and Clinical Development Times for Oncology Therapeutics
Wong A, Miller J, Mooghali M, Ramachandran R, Ross J, Wallach J. Pivotal Trial Demographic Representation and Clinical Development Times for Oncology Therapeutics. JAMA 2023, 330: 2392-2394. PMID: 38079163, PMCID: PMC10714278, DOI: 10.1001/jama.2023.21958.Peer-Reviewed Original Research
2021
Strengthening the FDA’s Enforcement of ClinicalTrials.gov Reporting Requirements
Ramachandran R, Morten CJ, Ross JS. Strengthening the FDA’s Enforcement of ClinicalTrials.gov Reporting Requirements. JAMA 2021, 326: 2131-2132. PMID: 34766971, DOI: 10.1001/jama.2021.19773.Commentaries, Editorials and LettersMeSH KeywordsActivin Receptors, Type IIAntineoplastic AgentsAxitinibCarcinoma, Renal CellClinical Trials as TopicClinical Trials, Phase II as TopicDrug IndustryHumansImmunoglobulin Fc FragmentsKidney NeoplasmsLaw EnforcementMandatory ReportingNational Institutes of Health (U.S.)Recombinant Fusion ProteinsRegistriesUnited StatesUnited States Food and Drug AdministrationAccess to COVID-19 Vaccines in High-, Middle-, and Low-Income Countries Hosting Clinical Trials
Ramachandran R, Ross JS, Miller JE. Access to COVID-19 Vaccines in High-, Middle-, and Low-Income Countries Hosting Clinical Trials. JAMA Network Open 2021, 4: e2134233. PMID: 34792596, PMCID: PMC8603077, DOI: 10.1001/jamanetworkopen.2021.34233.Peer-Reviewed Original ResearchMeSH KeywordsClinical Trials as TopicCOVID-19COVID-19 VaccinesCross-Sectional StudiesDeveloped CountriesDeveloping CountriesHealth Services AccessibilityHumansIncomePovertyComparison of Duration of Postapproval vs Pivotal Trials for Therapeutic Agents Granted US Food and Drug Administration Accelerated Approval, 2009-2018
Wallach JD, Ramachandran R, Bruckner T, Ross JS. Comparison of Duration of Postapproval vs Pivotal Trials for Therapeutic Agents Granted US Food and Drug Administration Accelerated Approval, 2009-2018. JAMA Network Open 2021, 4: e2133601. PMID: 34751764, PMCID: PMC8579231, DOI: 10.1001/jamanetworkopen.2021.33601.Peer-Reviewed Original ResearchMeSH KeywordsClinical Trials as TopicDrug ApprovalDrug IndustryHumansProduct Surveillance, PostmarketingUnited StatesUnited States Food and Drug AdministrationFulfilling the Mandate of the US Food and Drug Administration’s Accelerated Approval Pathway
Gyawali B, Ross JS, Kesselheim AS. Fulfilling the Mandate of the US Food and Drug Administration’s Accelerated Approval Pathway. JAMA Internal Medicine 2021, 181: 1275-1276. PMID: 34254981, DOI: 10.1001/jamainternmed.2021.4604.Commentaries, Editorials and LettersEvaluation of Drug Trials in High-, Middle-, and Low-Income Countries and Local Commercial Availability of Newly Approved Drugs
Miller JE, Mello MM, Wallach JD, Gudbranson EM, Bohlig B, Ross JS, Gross CP, Bach PB. Evaluation of Drug Trials in High-, Middle-, and Low-Income Countries and Local Commercial Availability of Newly Approved Drugs. JAMA Network Open 2021, 4: e217075. PMID: 33950209, PMCID: PMC8100865, DOI: 10.1001/jamanetworkopen.2021.7075.Peer-Reviewed Original ResearchMeSH KeywordsAfricaClinical Trials as TopicCross-Sectional StudiesDeveloped CountriesDeveloping CountriesDrug ApprovalDrug CostsHumansMarketingPharmaceutical PreparationsUnited StatesConceptsFDA approvalHigh-income countriesDrug approvalIncome countriesNovel drugsDrug Administration (FDA) drug approvalsRegulatory agency websitesCross-sectional analysisProportion of drugPrimary outcomeFDA drug approvalsProportion of countriesDrug trialsMAIN OUTCOMEUS FoodClinical researchCountry income levelLow-income countriesMarketing approvalTrialsGoogle ScholarDrugsDrug companiesApprovalMedianLeveraging Open Science to Accelerate Research
Kadakia KT, Beckman AL, Ross JS, Krumholz HM. Leveraging Open Science to Accelerate Research. New England Journal Of Medicine 2021, 384: e61. PMID: 33761227, DOI: 10.1056/nejmp2034518.Commentaries, Editorials and Letters
2020
Characteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov
Wallach JD, Krystal JH, Ross JS, O’Malley S. Characteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov. JAMA Psychiatry 2020, 77: 1081-1084. PMID: 32459295, PMCID: PMC7254444, DOI: 10.1001/jamapsychiatry.2020.1167.Peer-Reviewed Original ResearchMeSH KeywordsAcupuncture TherapyAlcohol DeterrentsAlcoholismChinaClinical Trials as TopicCross-Cultural ComparisonHerbal MedicineHumansPsychotropic DrugsRegistriesUnited StatesPostmarket Clinical Evidence for High-Risk Therapeutic Medical Devices Receiving Food and Drug Administration Premarket Approval in 2010 and 2011
Rathi VK, Krumholz HM, Masoudi FA, Ross JS. Postmarket Clinical Evidence for High-Risk Therapeutic Medical Devices Receiving Food and Drug Administration Premarket Approval in 2010 and 2011. JAMA Network Open 2020, 3: e2014496. PMID: 32857145, PMCID: PMC7455850, DOI: 10.1001/jamanetworkopen.2020.14496.Peer-Reviewed Original ResearchAssessment 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 ResearchMeSH KeywordsBiological ProductsClinical Trials as TopicCross-Sectional StudiesDrug ApprovalHumansPharmaceutical PreparationsUnited StatesUnited States Food and Drug AdministrationConceptsPivotal 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 approvalTime for NIH to lead on data sharing
Sim I, Stebbins M, Bierer BE, Butte AJ, Drazen J, Dzau V, Hernandez AF, Krumholz HM, Lo B, Munos B, Perakslis E, Rockhold F, Ross JS, Terry SF, Yamamoto KR, Zarin DA, Li R. Time for NIH to lead on data sharing. Science 2020, 367: 1308-1309. PMID: 32193313, DOI: 10.1126/science.aba4456.Commentaries, Editorials and Letters
2019
Feasibility of Using Real-World Data to Replicate Clinical Trial Evidence
Bartlett VL, Dhruva SS, Shah ND, Ryan P, Ross JS. Feasibility of Using Real-World Data to Replicate Clinical Trial Evidence. JAMA Network Open 2019, 2: e1912869. PMID: 31596493, PMCID: PMC6802419, DOI: 10.1001/jamanetworkopen.2019.12869.Peer-Reviewed Original ResearchConceptsPrimary end pointClinical trialsReal-world evidenceEnd pointElectronic health recordsEHR dataExclusion criteriaClinical trial evidenceRandomized clinical trialsHigh-impact general medical journalsReal-world populationInsurance claimsTraditional clinical trialsCross-sectional analysisSame clinical questionPercentage of trialsPrimary outcomeClinical outcomesClinical evidenceTrial evidenceTrial populationTrial inclusionObservational studyAdministrative claimsMAIN OUTCOMESharing of clinical trial data and results reporting practices among large pharmaceutical companies: cross sectional descriptive study and pilot of a tool to improve company practices
Miller J, Ross JS, Wilenzick M, Mello MM. Sharing of clinical trial data and results reporting practices among large pharmaceutical companies: cross sectional descriptive study and pilot of a tool to improve company practices. The BMJ 2019, 366: l4217. PMID: 31292127, PMCID: PMC6614834, DOI: 10.1136/bmj.l4217.Peer-Reviewed Original ResearchMeSH KeywordsClinical Trials as TopicCross-Sectional StudiesDrug ApprovalDrug IndustryHumansInformation DisseminationPilot ProjectsStakeholder ParticipationTime FactorsConceptsClinical trial dataTrial dataDrug approvalSectional descriptive studyPharmaceutical companiesFDA drug approvalsLarge pharmaceutical companiesClinical trialsDrug levelsNew drug approvalsUS FoodDrug AdministrationNew drug applicationsFDA approvalPatientsNovel drugsDescriptive studyDrug applicationTrialsDrugsExternal investigatorsSharing scoreDrug companiesTrial transparencyStudy measuresAnalysis of Postapproval Clinical Trials of Therapeutics Approved by the US Food and Drug Administration Without Clinical Postmarketing Requirements or Commitments
Skydel JJ, Luxkaranayagam AT, Dhruva SS, Ross JS, Wallach JD. Analysis of Postapproval Clinical Trials of Therapeutics Approved by the US Food and Drug Administration Without Clinical Postmarketing Requirements or Commitments. JAMA Network Open 2019, 2: e193410. PMID: 31074812, PMCID: PMC6512282, DOI: 10.1001/jamanetworkopen.2019.3410.Peer-Reviewed Original ResearchMeSH KeywordsClinical Trials as TopicCross-Sectional StudiesDrug ApprovalDrug IndustryHumansProduct Surveillance, PostmarketingUnited StatesUnited States Food and Drug AdministrationConceptsPostapproval clinical trialsClinical trialsPrimary completion datePostmarketing requirementsNovel therapeuticsDrug AdministrationUS FoodNew indicationsPharmaceutical companiesNew clinical studiesCross-sectional analysisClinical outcomesStudy design elementsPatient populationUnapproved indicationsEfficacy dataClinical studiesStudy completionMAIN OUTCOMEFirst approvalMost trialsTrialsFDATherapeutic approvalsTherapeuticsBiomarkers as Surrogate Endpoints: Ongoing Opportunities for Validation
Zhang AD, Ross JS. Biomarkers as Surrogate Endpoints: Ongoing Opportunities for Validation. The Journal Of Law, Medicine & Ethics 2019, 47: 393-395. PMID: 31560627, DOI: 10.1177/1073110519876170.Commentaries, Editorials and Letters
2018
Timeliness of Postmarket Studies for New Pharmaceuticals Approved Between 2009 and 2012: a Cross-Sectional Analysis
Wallach JD, Egilman AC, Ross JS, Woloshin S, Schwartz LM. Timeliness of Postmarket Studies for New Pharmaceuticals Approved Between 2009 and 2012: a Cross-Sectional Analysis. Journal Of General Internal Medicine 2018, 34: 492-495. PMID: 30543020, PMCID: PMC6445841, DOI: 10.1007/s11606-018-4779-x.Peer-Reviewed Original ResearchOverview and experience of the YODA Project with clinical trial data sharing after 5 years
Ross JS, Waldstreicher J, Bamford S, Berlin JA, Childers K, Desai NR, Gamble G, Gross CP, Kuntz R, Lehman R, Lins P, Morris SA, Ritchie JD, Krumholz HM. Overview and experience of the YODA Project with clinical trial data sharing after 5 years. Scientific Data 2018, 5: 180268. PMID: 30480665, PMCID: PMC6257043, DOI: 10.1038/sdata.2018.268.Peer-Reviewed Original ResearchRegistration, 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 drugsDrugs