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 ResearchConceptsMeta-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
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
2018
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
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. FoodDisease
2017
Postapproval 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 approvalDiseaseTrialsDrugsFDAEndpointEfficacyMarkersTwo 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 journalsCohortClinical Evidence Supporting US Food and Drug Administration Approval of Otolaryngologic Prescription Drug Indications, 2005‐2014
Rathi VK, Wang B, Ross JS, Downing NS, Kesselheim AS, Gray ST. Clinical Evidence Supporting US Food and Drug Administration Approval of Otolaryngologic Prescription Drug Indications, 2005‐2014. Otolaryngology 2017, 156: 683-692. PMID: 28116974, DOI: 10.1177/0194599816689666.Peer-Reviewed Original ResearchConceptsPivotal studiesOriginal indicationPrimary endpointClinical evidenceDrug indicationsSupplemental indicationsUS FoodFDA approvalAvailable FDA documentsDouble-blinded studyDrug Administration approvalInformed treatment decisionsPivotal clinical studiesPremarket evidenceOtolaryngologic diseaseMedian enrollmentSurrogate markerAdministration approvalClinical studiesTreatment decisionsMost indicationsDrug AdministrationInitial approvalMultidisciplinary teamPrescription drugs