2025
Differences Between Trial Populations and Approved Label Populations of New Drugs in the United States and Europe (2012 to 2023) : A Cross-Sectional Study.
Vokinger K, Serra-Burriel M, Glaus C, Welti L, Ross J, Kesselheim A. Differences Between Trial Populations and Approved Label Populations of New Drugs in the United States and Europe (2012 to 2023) : A Cross-Sectional Study. Annals Of Internal Medicine 2025, 178: 1127-1137. PMID: 40623311, DOI: 10.7326/annals-24-03242.Peer-Reviewed Original ResearchConceptsTrial populationPatient fitnessResults of clinical trialsDisease severityEligibility criteriaLabeled populationEuropean UnionPostapproval trialsCross-sectional studyStudy cohortClinical trialsPatient subpopulationsPatientsDisease subtypesTrial dataNew drugsUnited StatesDrugTrialsPatient dataDiseaseLinear regression modelsSeverityRegression modelsApprovalChapter 49 Phase 0 & window of opportunity clinical trials
Reddy A, Bansal U, Lerner S. Chapter 49 Phase 0 & window of opportunity clinical trials. 2025, 249-253. DOI: 10.1016/b978-0-323-90186-4.00009-2.Peer-Reviewed Original ResearchExploratory investigational new drugClinical trialsPhase 1 clinical trialPreclinical animal studiesFood and Drug AdministrationInvestigational new drugOn-target effectsPhase 0 studiesDrug pharmacokineticsDrug efficacyDrug AdministrationAnimal studiesOncology drugsDrug trialsSuboptimal pharmacological propertiesNew drugsDrug approvalDrugDrug approval processCosts associated with drug developmentPharmacological propertiesDrug safetyTrialsDrug developmentTherapeutic areas
2023
Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution
Santinelli E, Pascale M, Xie Z, Badar T, Stahl M, Bewersdorf J, Gurnari C, Zeidan A. Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution. Blood Reviews 2023, 62: 101130. PMID: 37679263, DOI: 10.1016/j.blre.2023.101130.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid malignanciesLeukemia cell survivalBcl-2 signalingPro-apoptotic agentsClinical studiesMyeloid leukemiaMyeloid neoplasmsTherapeutic revolutionMolecular alterationsMyeloid neoplasiaTherapeutic landscapeSpecific drugsApoptosis dysregulationSynergistic efficacyNew drugsMechanism of apoptosisDrugsMalignancyCombination strategiesCell survivalAttractive targetApoptotic pathwayTreatmentApoptosisUse of Real‐World Evidence in Neuroscience‐Related New Drug and Biologics License Applications for Novel Therapeutics
Bloomfield‐Clagett B, Rahman M, Smith K, Concato J. Use of Real‐World Evidence in Neuroscience‐Related New Drug and Biologics License Applications for Novel Therapeutics. Clinical Pharmacology & Therapeutics 2023, 114: 1002-1005. PMID: 37548904, DOI: 10.1002/cpt.3018.Peer-Reviewed Original ResearchUse of Expedited Regulatory Programs and Clinical Development Times for FDA-Approved Novel Therapeutics
Wong A, Mooghali M, Ramachandran R, Ross J, Wallach J. Use of Expedited Regulatory Programs and Clinical Development Times for FDA-Approved Novel Therapeutics. JAMA Network Open 2023, 6: e2331753. PMID: 37651145, PMCID: PMC10472182, DOI: 10.1001/jamanetworkopen.2023.31753.Peer-Reviewed Original ResearchHuman TRPV1 structure and inhibition by the analgesic SB-366791
Neuberger A, Oda M, Nikolaev Y, Nadezhdin K, Gracheva E, Bagriantsev S, Sobolevsky A. Human TRPV1 structure and inhibition by the analgesic SB-366791. Nature Communications 2023, 14: 2451. PMID: 37117175, PMCID: PMC10147690, DOI: 10.1038/s41467-023-38162-9.Peer-Reviewed Original ResearchConceptsSB-366791Transient receptor potential (TRP) ion channelsPotential ion channelsPain pathwaysPain therapyPain treatmentPsychiatric disordersOpioid crisisTherapy targetTRPV1 inhibitorElectrophysiological recordingsHuman TRPV1TRP channelsTRPV1New drugsDisease conditionsVanilloid subfamilyIon channelsTreatmentInhibitorsOpioidsPainTherapyDiseaseCryo-electron microscopy structureThe Difficult Path to the Discovery of Novel Treatments in Psychiatric Disorders
Gribkoff V, Kaczmarek L. The Difficult Path to the Discovery of Novel Treatments in Psychiatric Disorders. Advances In Neurobiology 2023, 30: 255-285. PMID: 36928854, PMCID: PMC10599454, DOI: 10.1007/978-3-031-21054-9_11.Peer-Reviewed Original ResearchConceptsNervous system diseasesSystem diseasesPsychiatric disordersPsychiatric patientsNew drugsDetermination of efficacyDiseases/disordersNovel therapiesNovel treatmentsPsychiatric diseasesDiscovery effortsNew therapeuticsDisordersDiseaseDrugsPatientsFace validityPredictive validityTreatmentDiscoveryPresent particular challengesHuman healthRecent advancesTherapyClinicians
2022
Drug Design Strategies: Role of Structural Modifications of Drug Candidates to Improve PK Parameters of New Drugs
NASSAR A. Drug Design Strategies: Role of Structural Modifications of Drug Candidates to Improve PK Parameters of New Drugs. 2022, 323-343. DOI: 10.1002/9781119851042.ch10.Peer-Reviewed Original ResearchDrug candidatesSuccessful drug designDrug metabolism scientistsDrug designDrug discoveryStructural modificationsMetabolic stabilityDiverse propertiesActive metabolitePass metabolismToxicity relationshipsSoft drugsReactive metabolitesInhibition/inductionMetabolism studiesPharmacokinetic issuesRenal clearanceSafe drugPK parametersMetabolic clearanceMetabolic inactivationNew drugsDrugsMetabolitesClearanceFulfillment of Postmarket Commitments and Requirements for New Drugs Approved by the FDA, 2013-2016
Brown B, Mitra-Majumdar M, Darrow J, Moneer O, Pham C, Avorn J, Kesselheim A. Fulfillment of Postmarket Commitments and Requirements for New Drugs Approved by the FDA, 2013-2016. JAMA Internal Medicine 2022, 182: 1223-1226. PMID: 36190713, PMCID: PMC9531062, DOI: 10.1001/jamainternmed.2022.4226.Peer-Reviewed Original ResearchNew Drug Postmarketing Requirements and Commitments in the US: A Systematic Review of the Evidence
Moneer O, Brown BL, Avorn J, Darrow JJ, Mitra-Majumdar M, Joyce KW, Ross M, Pham C, Kesselheim AS. New Drug Postmarketing Requirements and Commitments in the US: A Systematic Review of the Evidence. Drug Safety 2022, 45: 305-318. PMID: 35182362, DOI: 10.1007/s40264-022-01152-9.Peer-Reviewed Original ResearchHeart Failure Spending Function: An Investment Framework for Sequencing and Intensification of Guideline-Directed Medical Therapies
Allen LA, Teerlink JR, Gottlieb SS, Ahmad T, Lam CSP, Psotka MA. Heart Failure Spending Function: An Investment Framework for Sequencing and Intensification of Guideline-Directed Medical Therapies. Circulation Heart Failure 2022, 15: e008594. PMID: 35000432, DOI: 10.1161/circheartfailure.121.008594.Peer-Reviewed Original ResearchConceptsGuideline-directed medical therapyMedical therapyReduced ejection fractionHealth care delivery researchAdverse eventsCardiac benefitsSerum creatinineBlood pressureEjection fractionHeart failureRoutine carePatient burdenHeart rateNew therapiesPatient harmHigh dosesPatientsPsychosocial domainsPocket costsTherapeutic opportunitiesClinical useTherapyNew drugsPhysiological domainsSpending function
2021
Direct antiviral agents for chronic hepatitis C virus infection improve health-related quality of life significantly in the long term
Atamla M, Khoury J, Dabbah I, Kramsky R, Yaacob A, Veitsman E, Saadi T. Direct antiviral agents for chronic hepatitis C virus infection improve health-related quality of life significantly in the long term. Clinical And Experimental Hepatology 2021, 7: 258-263. PMID: 34712826, PMCID: PMC8527337, DOI: 10.5114/ceh.2021.109192.Peer-Reviewed Original ResearchDirect antiviral agentsChronic hepatitis C virus (HCV) infectionHepatitis C virus infectionQuality of lifeC virus infectionHealth-related qualitySuccessful treatmentVirus infectionAntiviral agentsChronic HCV infectionDAA treatmentExtrahepatic manifestationsHCV infectionLiver diseaseLong termLiver fibrosisObservational studyProfound negative impactNew drugsInfectionHRQLTreatmentAverage timePatientsDrugsDopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia
Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME, Cho YT, Fonteneau C, Gil R, Girgis R, Gur RE, Gur RC, Grinband J, Kantrowitz J, Kohler C, Krystal J, Murray J, Ranganathan M, Santamauro N, Van Snellenberg J, Tamayo Z, Wolf D, D’Souza D, Srihari V, Gueorguieva R, Patel P, Forselius-Bielen K, Lu J, Butler A, Fram G, Afriyie-Agyemang Y, Selloni A, Cadavid L, Gomez-Luna S, Gupta A, Radhakrishnan R, Rashid A, Aker R, Abrahim P, Nia A, Surti T, Kegeles L, Carlson M, Goldberg T, Gangwisch J, Benedict E, Govil P, Brazis S, Mayer M, de la Garrigue N, Fallon N, Baumvoll T, Abeykoon S, Perlman G, Bobchin K, Elliott M, Schmidt L, Rush S, Port A, Heffernan Z, Laney N, Kantor J, Hohing T, Gray D, Lieberman J. Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia Bulletin 2021, 48: 199-210. PMID: 34423843, PMCID: PMC8781338, DOI: 10.1093/schbul/sbab095.Peer-Reviewed Original ResearchConceptsCortical dopamine neurotransmissionPositive allosteric modulationImportant therapeutic targetPF-06412562Dopaminergic receptorsD1R stimulationDA levelsTolerable dosesLevel of stimulationDopamine neurotransmissionReceptor stimulationTherapeutic targetPartial agonistCognitive deficitsBiased agonismFull agonismTarget engagementAllosteric modulationNew drugsStimulationPoor bioavailabilitySchizophreniaOptimal stimulationDrugsExpression levelsLong‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls HIV‐1 infection in a humanized mouse model
Beloor J, Kudalkar SN, Buzzelli G, Yang F, Mandl HK, Rajashekar JK, Spasov KA, Jorgensen WL, Saltzman WM, Anderson KS, Kumar P. Long‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls HIV‐1 infection in a humanized mouse model. Bioengineering & Translational Medicine 2021, 7: e10237. PMID: 35079625, PMCID: PMC8780078, DOI: 10.1002/btm2.10237.Peer-Reviewed Original ResearchNucleoside reverse transcriptase inhibitorHIV-1 infectionAntiretroviral therapyHIV-1-infected humanized miceTwo-drug combinationsHumanized mouse modelLong-term treatmentReverse transcriptase inhibitorMaintenance of CD4Nonnucleoside reverseHumanized miceAntiretroviral formulationsAdherence issuesARV combinationsTranscriptase inhibitorHIV pandemicT cellsMouse modelInjectable nanoformulationsTherapeutic indexNew drugsSustained levelsInfectionDrugsInterventionCurrent Treatment of Pediatric Type 2 Diabetes
Samuels S, Van Name M, Guandalini C, Tamborlane W, Caprio S. Current Treatment of Pediatric Type 2 Diabetes. Contemporary Endocrinology 2021, 191-202. DOI: 10.1007/978-3-030-64133-7_18.ChaptersPatterns of Care for Older Patients With Myelofibrosis: A Population-based Study
Meckstroth S, Wang R, Ma X, Podoltsev N. Patterns of Care for Older Patients With Myelofibrosis: A Population-based Study. Clinical Lymphoma Myeloma & Leukemia 2021, 21: e551-e558. PMID: 33648884, DOI: 10.1016/j.clml.2021.01.025.Peer-Reviewed Original ResearchConceptsPatterns of careOlder patientsEnd Results-Medicare databaseJAK inhibitor eraHigh-risk patientsPopulation-based studyUse of ruxolitinibJAK inhibitor ruxolitinibUnited States FoodRuxolitinib approvalMedian ageMedian timeTreatment patternsD claimsCurrent treatmentInhibitor ruxolitinibPatientsBetter outcomesClinical experienceDrug AdministrationMedicare Part BMyelofibrosisRuxolitinibStates FoodNew drugsAdvances in Treatments in Muscular Dystrophies and Motor Neuron Disorders
Roy B, Griggs R. Advances in Treatments in Muscular Dystrophies and Motor Neuron Disorders. Neurologic Clinics 2021, 39: 87-112. PMID: 33223091, DOI: 10.1016/j.ncl.2020.09.005.Peer-Reviewed Original ResearchConceptsMotor neuron disordersMuscular dystrophyGene therapyTreatment of muscular dystrophiesNeuronal disordersDuchenne muscular dystrophySpinal muscular atrophyClinical trialsTherapyDystrophyTherapeutic promiseMuscular atrophyDisease pathophysiologyAmyotrophic lateral sclerosisNew drugsDrugLateral sclerosisDiseaseTreatmentCost burdenDisordersDrug technologyReview advancesIncreased understandingPathophysiology
2020
Association between FDA and EMA expedited approval programs and therapeutic value of new medicines: retrospective cohort study
Hwang TJ, Ross JS, Vokinger KN, Kesselheim AS. Association between FDA and EMA expedited approval programs and therapeutic value of new medicines: retrospective cohort study. The BMJ 2020, 371: m3434. PMID: 33028575, PMCID: PMC7537471, DOI: 10.1136/bmj.m3434.Peer-Reviewed Original ResearchConceptsEuropean Medicines AgencyRetrospective cohort studyTherapeutic valueHigh therapeutic valueNew drugsCohort studyLow therapeutic valueEMA approvalUS FoodDrug AdministrationMedicines AgencyFDA approvalDrugsFDARegulatory approvalApproval programsNew medicinesAssociationGreater proportionApprovalProportionAdministrationBlutaparon portulacoides ethanolic extract reduced IL-1β and inflammatory parameters induced by the Mycobacterium complex and carrageenan in mice
Kassuya R, Radai J, Macorini L, Nunes V, Salvador M, Leite P, Oliveira R, Croda J, Arena A, Kassuya C. Blutaparon portulacoides ethanolic extract reduced IL-1β and inflammatory parameters induced by the Mycobacterium complex and carrageenan in mice. Inflammopharmacology 2020, 29: 439-450. PMID: 32910315, DOI: 10.1007/s10787-020-00752-0.Peer-Reviewed Original ResearchMeSH KeywordsAmaranthaceaeAnimalsAnti-Inflammatory AgentsAntitubercular AgentsCarrageenanDisease Models, AnimalDose-Response Relationship, DrugEdemaFemaleInflammationInterleukin-1betaMaleMiceMice, Inbred C57BLMicrobial Sensitivity TestsMycobacterium tuberculosisPlant ExtractsPleurisyRatsRats, WistarConceptsSwiss miceIL-1β levelsC57BL-6 miceEthanolic extractInflammation/infectionSafe new drugsM. tuberculosis growthMechanical hyperalgesiaInflammatory parametersOral treatmentIL-1βPleurisy modelMinimum inhibitory concentrationPharmacoeconomic perspectiveC57BL6 miceComplete adjuvantSubcutaneous injectionOral administrationWistar ratsMiceMycobacterium tuberculosisNew drugsHealth benefitsTuberculosis growthInhibitory concentrationTrends in FDA cancer registration trial design over time, 1969-2020.
Warner J, Sethi T, Rivera D, Venepalli N, Osterman T, Khaki A, Rubinstein S. Trends in FDA cancer registration trial design over time, 1969-2020. Journal Of Clinical Oncology 2020, 38: 2060-2060. DOI: 10.1200/jco.2020.38.15_suppl.2060.Peer-Reviewed Original ResearchTrial designFDA approvalImmunotherapy trialsRegistration trialsCommon trial designOverall survival endpointOncology drug approvalsClass switchFDA package insertsCancer drug indicationsStudy drugCytotoxic therapyControl armTherapeutic approachesPackage insertsRCTsRCT designIndication approvalsOncology drugsLog-linear regressionSurvival endpointsTherapyTrialsDrug approvalNew drugs
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