2024
Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH)
Do A, Zahrawi F, Mehal W. Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH). Nature Reviews Drug Discovery 2024, 24: 171-189. PMID: 39609545, DOI: 10.1038/s41573-024-01084-2.Peer-Reviewed Original ResearchSide effect profileTrial end pointsCombination of therapeuticsReverse many aspectsFatty acid synthase inhibitorGenetic susceptibility factorsPlacebo responseEffect profileFibrosis reversalTreated patientsClinical studiesLiver inflammationSynthase inhibitorLiver diseaseTherapeutic approachesClinical useEnd pointsSteatotic liver diseaseTherapeutic landscapeMetabolic environmentHepatocyte deathSusceptibility factorsChronic overnutritionGlobal epidemicLiverPremarket 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 AdministrationTherapyPeripheral blood cytokines and outcomes with immune checkpoint blockade: a systematic review and meta-analysis
Karol A, Fujiwara Y, D'Ovidio T, Baldwin E, Joshi H, Doroshow D, Galsky M. Peripheral blood cytokines and outcomes with immune checkpoint blockade: a systematic review and meta-analysis. Immunotherapy 2024, 16: 829-840. PMID: 39155854, PMCID: PMC11457654, DOI: 10.1080/1750743x.2024.2379230.Peer-Reviewed Original ResearchImmune checkpoint blockadeProgression-free survivalC-reactive proteinPeripheral blood cytokinesOverall survivalTumor-promoting inflammationCheckpoint blockadeInterleukin-6Interleukin-8Blood cytokinesOn-treatment declineIL-8 levelsTrial end pointsIL-6 levelsPharmacodynamic biomarkersInflammatory cytokinesEnd pointsResponse rateCytokinesMeta-analysisSystematic reviewBlockadeInflammationORRSurvival
2023
Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer
Kyalwazi B, Yau C, Campbell M, Yoshimatsu T, Chien A, Wallace A, Forero-Torres A, Pusztai L, Ellis E, Albain K, Blaes A, Haley B, Boughey J, Elias A, Clark A, Isaacs C, Nanda R, Han H, Yung R, Tripathy D, Edmiston K, Viscusi R, Northfelt D, Khan Q, Asare S, Wilson A, Hirst G, Lu R, Symmans W, Yee D, DeMichele A, van ’t Veer L, Esserman L, Olopade O. Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer. JAMA Network Open 2023, 6: e2349646. PMID: 38153734, PMCID: PMC10755617, DOI: 10.1001/jamanetworkopen.2023.49646.Peer-Reviewed Original ResearchConceptsDistant recurrence-free survivalPathologic complete responseErbB2-negative tumorsWorse distant recurrence-free survivalEarly breast cancerWhite patientsBreast cancerBlack patientsGene expression signaturesReceptor subtypesStage II/III breast cancerHigh-risk early breast cancerCox proportional hazards regression modelHigh-risk breast cancerClinical trial end pointsProportional hazards regression modelsTumor receptor subtypeRetrospective cohort studyPrimary tumor sizeRecurrence-free survivalTrial end pointsBreast cancer outcomesLong-term outcomesHazards regression modelsExpression signaturesInternational Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy
Dacic S, Travis W, Redman M, Saqi A, Cooper W, Borczuk A, Chung J, Glass C, Lopez J, Roden A, Sholl L, Weissferdt A, Posadas J, Walker A, Zhu H, Wijeratne M, Connolly C, Wynes M, Bota-Rabassedas N, Sanchez-Espiridion B, Lee J, Berezowska S, Chou T, Kerr K, Nicholson A, Poleri C, Schalper K, Tsao M, Carbone D, Ready N, Cascone T, Heymach J, Sepesi B, Shu C, Rizvi N, Sonett J, Altorki N, Provencio M, Bunn P, Kris M, Belani C, Kelly K, Wistuba I, Committee I. International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy. Journal Of Thoracic Oncology 2023, 18: 1290-1302. PMID: 37702631, DOI: 10.1016/j.jtho.2023.07.017.Peer-Reviewed Original ResearchConceptsPathologic responseViable tumorNeoadjuvant therapyLung cancerClinical trialsInter-rater agreementNeoadjuvant immune checkpoint inhibitorsClinical trial end pointsResected Lung CancerImmune checkpoint inhibitorsTrial end pointsInvasive mucinous adenocarcinomaResidual viable tumorTumor bed areaEosin-stained slidesLung cancer studiesCheckpoint inhibitorsNeoadjuvant treatmentMucinous adenocarcinomaPathologic evaluationStromal inflammationPulmonary pathologistsTumor bedLung tumorsCommon reasonStandardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP
Litton J, Regan M, Pusztai L, Rugo H, Tolaney S, Garrett-Mayer E, Amiri-Kordestani L, Basho R, Best A, Boileau J, Denkert C, Foster J, Harbeck N, Jacene H, King T, Mason G, O'Sullivan C, Prowell T, Richardson A, Sepulveda K, Smith M, Tjoe J, Turashvili G, Woodward W, Butler L, Schwartz E, Korde L. Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP. Journal Of Clinical Oncology 2023, 41: 4433-4442. PMID: 37433103, PMCID: PMC10522109, DOI: 10.1200/jco.23.00435.Peer-Reviewed Original ResearchConceptsSecondary end pointsPathologic complete responseClinical trialsEnd pointStandardized definitionsHormone receptor-positive diseaseCurative-intent surgeryNeoadjuvant clinical trialsPathologic nodal evaluationResidual invasive cancerEfficacy end pointReceptor-positive diseaseBreast cancer clinical trialsResidual cancer burdenAlternative end pointsTrial end pointsRegional lymph nodesCancer end pointsCross-trial comparisonsSurvival end pointsEnd point definitionsCancer clinical trialsDrug Administration (FDA) regulatory considerationsEfficacy outcomesComplete response
2022
Spending by the Centers for Medicare & Medicaid Services Before and After Confirmation of Benefit for Drugs Granted US Food and Drug Administration Accelerated Approval, 2012 to 2017
Skydel JJ, Egilman AC, Wallach JD, Ramachandran R, Gupta R, Ross JS. Spending by the Centers for Medicare & Medicaid Services Before and After Confirmation of Benefit for Drugs Granted US Food and Drug Administration Accelerated Approval, 2012 to 2017. JAMA Health Forum 2022, 3: e221158. PMID: 35977252, PMCID: PMC9142876, DOI: 10.1001/jamahealthforum.2022.1158.Peer-Reviewed Original ResearchConceptsSurrogate end pointsCross-sectional studyClinical benefitConfirmation of benefitEnd pointOriginal indicationClinical outcomesUS FoodConfirmatory trialsMedicaid ServicesPrimary end pointUnproven clinical benefitsTrial end pointsClinical trial resultsTypes of drugsPostapproval trialsAccelerated approvalClinical trialsMAIN OUTCOMEDrug AdministrationMedicare Part BStandard approvalConversion statusSupplemental indicationsTrial results
2021
Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0
Tolaney SM, Garrett-Mayer E, White J, Blinder VS, Foster JC, Amiri-Kordestani L, Hwang ES, Bliss JM, Rakovitch E, Perlmutter J, Spears PA, Frank E, Tung NM, Elias AD, Cameron D, Denduluri N, Best AF, DiLeo A, Baizer L, Butler LP, Schwartz E, Winer EP, Korde LA. Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0. Journal Of Clinical Oncology 2021, 39: 2720-2731. PMID: 34003702, PMCID: PMC10166345, DOI: 10.1200/jco.20.03613.Peer-Reviewed Original ResearchConceptsEfficacy end pointPrimary end pointBreast cancer clinical trialsPrimary cancerCancer clinical trialsEnd pointStandardized definitionsRecurrence rateClinical trialsInvasive disease-free survival eventsTherapy trialsBreast cancer-free survivalDisease-free survival eventsNon-breast cancer deathPrimary efficacy end pointClinical trial end pointsPhase III breast cancer trialsCancer-free survivalSecond primary cancerTrial end pointsAdditional end pointsBreast cancer trialsLow-risk populationPatient-reported outcomesSurvival end pointsComparability of Event Adjudication Versus Administrative Billing Claims for Outcome Ascertainment in the DAPT Study
Faridi KF, Tamez H, Butala NM, Song Y, Shen C, Secemsky EA, Mauri L, Curtis JP, Strom JB, Yeh RW. Comparability of Event Adjudication Versus Administrative Billing Claims for Outcome Ascertainment in the DAPT Study. Circulation Cardiovascular Quality And Outcomes 2021, 14: e006589. PMID: 33435731, PMCID: PMC7855905, DOI: 10.1161/circoutcomes.120.006589.Peer-Reviewed Original ResearchConceptsNegative predictive valuePositive predictive valueMyocardial infarctionPredictive valueDAPT studyClinical trialsAdjudicated eventsClaims dataNational Cardiovascular Data Registry CathPCI RegistryClinical events committeeTrial of patientsPercutaneous coronary interventionTrial end pointsKappa statisticsAdjudicated deathCathPCI RegistryCerebrovascular eventsCoronary interventionCumulative incidenceEvents committeeOutcome ascertainmentBilling claimsInpatient hospitalizationBleeding rateCardiovascular disease
2020
Use of Administrative Claims to Assess Outcomes and Treatment Effect in Randomized Clinical Trials for Transcatheter Aortic Valve Replacement
Strom JB, Faridi KF, Butala NM, Zhao Y, Tamez H, Valsdottir LR, Brennan JM, Shen C, Popma JJ, Kazi DS, Yeh RW. Use of Administrative Claims to Assess Outcomes and Treatment Effect in Randomized Clinical Trials for Transcatheter Aortic Valve Replacement. Circulation 2020, 142: 203-213. PMID: 32436390, PMCID: PMC7672506, DOI: 10.1161/circulationaha.120.046159.Peer-Reviewed Original ResearchConceptsTrial primary end pointPrimary end pointEnd pointSURTAVI trialCause mortalitySecondary outcomesAdjudicated outcomesClinical trialsTrial dataSecondary trial end pointsTranscatheter aortic valve replacementTreatment effectsClaims-based outcomesAortic valve replacementTrial end pointsRandomized clinical trialsMedicare inpatient claimsCardiovascular clinical trialsYears of ageSAVR patientsValve replacementTreatment armsInpatient claimsProcedural outcomesAdministrative claims
2019
End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings
Farrell A, Panepinto J, Desai A, Kassim A, Lebensburger J, Walters M, Bauer D, Blaylark R, DiMichele D, Gladwin M, Green N, Hassell K, Kato G, Klings E, Kohn D, Krishnamurti L, Little J, Makani J, Malik P, McGann P, Minniti C, Morris C, Odame I, Oneal P, Setse R, Sharma P, Shenoy S. End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings. Blood Advances 2019, 3: 4002-4020. PMID: 31809537, PMCID: PMC6963248, DOI: 10.1182/bloodadvances.2019000883.Peer-Reviewed Original ResearchConceptsLow-resource settingsEnd pointClinical trial end pointsTrial end pointsPatient-reported outcomesSickle cell disease clinical trialsPanel of cliniciansSickle cell diseaseMeasurement of cureClinical trialsNovel therapiesCell diseaseConsensus recommendationsGlobal burdenUS FoodBiomarker panelDrug AdministrationAvailable evidenceAmerican SocietyCureRelevant findingsLiterature reviewPainPatientsTherapy
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
2008
Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer
Wolff AC, Berry D, Carey LA, Colleoni M, Dowsett M, Ellis M, Garber JE, Mankoff D, Paik S, Pusztai L, Smith ML, Zujewski J. Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer. Journal Of Clinical Oncology 2008, 26: 806-813. PMID: 18258990, DOI: 10.1200/jco.2007.15.2983.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntineoplastic AgentsApoptosisBiomarkersBiomedical ResearchBreast NeoplasmsCell ProliferationEpidemiologic Research DesignErbB ReceptorsEthics, ClinicalFemaleGene Expression ProfilingHumansMastectomy, SegmentalNeoadjuvant TherapyPatient AdvocacyPreoperative CarePrognosisReceptors, SteroidTreatment OutcomeConceptsPreoperative systemic therapyOperable breast cancerSystemic therapyBreast cancerTrial designEnd pointCohesive multidisciplinary teamBreast conservation ratesEffective alternative therapyTrial end pointsLong-term outcomesSpecific breast cancer subtypesPredictors of responseNovel trial designsIntermediate end pointsBreast cancer subtypesIndividual patient subgroupsAdjuvant trialsPatient subgroupsSmall trialsAlternative therapiesMAIN OUTCOMEClinical careCancer subtypesMultidisciplinary team
2000
Southwest Oncology Group Study of paclitaxel and carboplatin for advanced transitional-cell carcinoma: the importance of survival as a clinical trial end point.
Small E, Lew D, Redman B, Petrylak D, Hammond N, Gross H, Eastham J, Crawford E. Southwest Oncology Group Study of paclitaxel and carboplatin for advanced transitional-cell carcinoma: the importance of survival as a clinical trial end point. Journal Of Clinical Oncology 2000, 18: 2537-44. PMID: 10893284, DOI: 10.1200/jco.2000.18.13.2537.Peer-Reviewed Original ResearchConceptsAdvanced transitional cell carcinomaTransitional cell carcinomaCombination of paclitaxelSurvival timeMedian progression-free survival timeNeoadjuvant platinum-based therapySouthwest Oncology Group studyProgression-free survival timeClinical trial end pointsGrade 4 toxicityPoor prognostic featuresTrial end pointsEnrollment of patientsMedian survival timeOverall survival timeCooperative group settingPlatinum-based therapyResponse proportionsAcceptable toxicityExtranodal diseaseNeoadjuvant therapyNeurologic toxicityComplete responsePartial responsePrognostic features
1992
Estramustine and Vinblastine: Use of Prostate Specific Antigen as a Clinical Trial End Point for Hormone Refractory Prostatic Cancer
Seidman A, Scher H, Petrylak D, Dershaw D, Curley T. Estramustine and Vinblastine: Use of Prostate Specific Antigen as a Clinical Trial End Point for Hormone Refractory Prostatic Cancer. Journal Of Urology 1992, 147: 931-934. PMID: 1371564, DOI: 10.1016/s0022-5347(17)37426-8.Peer-Reviewed Original ResearchConceptsHormone-refractory prostatic cancerProstatic cancerProgressive hormone-refractory prostate cancerElevated prostate-specific antigen levelsProstate-specific antigen levelHormone-refractory prostate cancerClinical trial end pointsOutpatient treatment regimenRefractory prostate cancerSpecific antigen levelsTrial end pointsProstate-specific antigenManageable toxicityMedian durationPartial responsePSA levelsTreatment regimenEstramustine phosphateAntigen levelsProstate cancerAdditive cytotoxicityMedian decreasePatientsSpecific antigenHuman prostate
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