2024
Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials
Zou H, Stebbins G, Simuni T, Luo S, Cedarbaum J. Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials. Parkinsonism & Related Disorders 2024, 128: 107118. PMID: 39353265, DOI: 10.1016/j.parkreldis.2024.107118.Peer-Reviewed Original ResearchPD clinical trialsClinical trialsEmergent symptomsPhase 3 clinical trialsPhase 3 studySlowing of disease progressionOutcome measuresParkinson's diseaseDe novo Parkinson's diseaseMDS-UPDRSItem-level dataFrequency of ESSymptomatic medicationsFrequent administrationMonths of observationEfficacy assessmentDisease progressionSymptom emergenceRating ScaleItem responsesIb and IIUrate elevationTrialsThe ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials
Genge A, Cedarbaum J, Shefner J, Chio A, Al-Chalabi A, Van Damme P, McDermott C, Glass J, Berry J, van Eijk R, Fournier C, Grosskreutz J, Andrews J, Bertone V, Bunte T, Couillard M, Cummings C, Kittle G, Polzer J, Salmon K, Straub C, van den Berg L. The ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials. Amyotrophic Lateral Sclerosis And Frontotemporal Degeneration 2024, 25: 382-387. PMID: 38396337, DOI: 10.1080/21678421.2024.2320880.Peer-Reviewed Original ResearchAmyotrophic Lateral Sclerosis Functional Rating ScaleALSFRS-RClinical trialsStatistical analysis planMonitor functional changesRating ScaleOutcome measuresFunctional Rating ScalePrimary outcome measureClinical trial designALS clinical trialsFunctional changesTrial designTrialsClinical trialistsScaleALS trialsCinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial.
Hutchison R, Fraser K, Yang M, Fox T, Hirschhorn E, Njingti E, Scott D, Bedell B, Kistner K, Cedarbaum J, Evans K, Graham D, Martarello L, Mollenhauer B, Lang A, Dam T, Beaver J. Cinpanemab in Early Parkinson Disease: Evaluation of Biomarker Results From the Phase 2 SPARK Clinical Trial. Neurology 2024, 102: e209137. PMID: 38315945, DOI: 10.1212/wnl.0000000000209137.Peer-Reviewed Original ResearchConceptsDisease progressionDopaminergic deficitNeurofilament light chain levelsNigrostriatal dopamine pathwayDopamine transporter SPECTTerminated due to lackStriatal dopaminergic deficitsLight chain levelsClinical disease progressionEvidence of dopaminergic deficitParkinson's diseaseEvaluate disease severityBiomarker measurementsEarly Parkinson's diseaseStriatal binding ratiosDevelopment of therapiesStatistically significant differenceScale total scoreBiomarker resultsDouble-blindPlacebo-controlledUnified Parkinson's Disease Rating Scale total scoreDopamine pathwayClinical trialsPrimary outcome
2022
Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort
Siderowf A, Seibyl J, Coffey C, Tosun-Turgut D, Shaw L, Trojanowski J, Singleton A, Kieburtz K, Toga A, Mollenhauer B, Galasko D, Poewe W, Foroud T, Poston K, Bressman S, Reimer A, Arnedo V, Clark A, Frasier M, Kopil C, Chowdhury S, Casaceli C, Dorsey R, Wilson R, Mahes S, Seibyl J, Salerno C, Ahrens M, Brumm M, Cho H, Fedler J, LaFontant D, Kurth R, Crawford K, Casalin P, Malferrari G, Weisz M, Orr-Urtreger A, Trojanowski J, Shaw L, Montine T, Baglieri C, Christini A, Russell D, Dahodwala N, Giladi N, Factor S, Hogarth P, Standaert D, Hauser R, Jankovic J, Saint-Hilaire M, Richard I, Shprecher D, Fernandez H, Brockmann K, Rosenthal L, Barone P, Espayc A, Rowe D, Marder K, Santiago A, Bressman S, Hu S, Isaacson S, Corvol J, Martinez J, Tolosa E, Tai Y, Politis M, Smejdir D, Rees L, Williams K, Kausar F, Williams K, Richardson W, Willeke D, Peacock S, Sommerfeld B, Freed A, Wakeman K, Blair C, Guthrie S, Harrell L, Hunter C, Thomas C, James R, Zimmerman G, Brown V, Mule J, Hilt E, Ribb K, Ainscough S, Wethington M, Ranola M, Santana H, Moreno J, Raymond D, Speketer K, Carvajal L, Carvalo S, Croitoru I, Garrido A, Payne L, Viswanth V, Severt L, Facheris M, Soares H, Mintun M, Cedarbaum J, Taylor P, Biglan K, Vandenbroucke E, Sheikh Z, Bingol B, Fischer T, Sardi P, Forrat R, Reith A, Egebjerg J, Hillert G, Saba B, Min C, Umek R, Mather J, De Santi S, Post A, Boess F, Taylor K, Grachev I, Avbersek A, Muglia P, Merchant K, Tauscher J. Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort. Npj Parkinson's Disease 2022, 8: 140. PMID: 36273008, PMCID: PMC9588016, DOI: 10.1038/s41531-022-00404-w.Peer-Reviewed Original ResearchNon-manifesting carriersParkinson's Progression Markers InitiativeHealthy controlsDAT deficitProgression Markers InitiativeLongitudinal changesBiofluid biomarkersCerebrospinal fluid AbetaNon-motor scalesDopamine transporter imagingPrevention clinical trialsNeurofilament light chainLRRK2 G2019S carriersClinical featuresClinical outcomesPhospho-tauTransporter imagingPPMI cohortTotal tauDAT bindingMean ageSerum biomarkersClinical trialsClinical measuresComprehensive motorTracking Emergence of New Motor and Non-Motor Symptoms Using the MDS-UPDRS: A Novel Outcome Measure for Early Parkinson’s Disease?
Tosin M, Simuni T, Stebbins G, Cedarbaum J. Tracking Emergence of New Motor and Non-Motor Symptoms Using the MDS-UPDRS: A Novel Outcome Measure for Early Parkinson’s Disease? Journal Of Parkinson's Disease 2022, 12: 1345-1351. PMID: 35466955, PMCID: PMC9198734, DOI: 10.3233/jpd-223170.Peer-Reviewed Original ResearchConceptsEmergent symptomsDisease progressionOutcome measuresParkinson's disease clinical trialsNon-motor symptomsEarly Parkinson's diseaseDaily Living ScalePatient-reported experiencesClinical rating scalesNovel outcome measuresSymptomatic treatmentPD progressionClinical trialsMedian numberDaily livingLiving ScaleParkinson's diseaseSummary scoresMDS-UPDRSUseful markerRating ScaleSTX groupProgressionStxSymptoms
2021
Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
Hutchison R, Evans K, Fox T, Yang M, Barakos J, Bedell B, Cedarbaum J, Brys M, Siderowf A, Lang A. Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial. BMC Neurology 2021, 21: 459. PMID: 34814867, PMCID: PMC8609885, DOI: 10.1186/s12883-021-02470-8.Peer-Reviewed Original ResearchConceptsDAT-SPECTParkinson's diseaseClinical trialsDisease trialsPhase 2 trialDopaminergic nerve terminalsEarly Parkinson's diseaseDisease-modifying therapiesIdiopathic Parkinson's diseaseMulticenter clinical trialParkinson's disease trialStudy design aspectsSingle photon emissionStages of progressionDegenerative parkinsonismEnrichment biomarkerResultsIn totalClinical assessmentNerve terminalsBlinded neuroradiologistsClinical diagnosisDopamine transporterMonoclonal antibodiesCentral laboratoryTrialsDetecting Sensitive Mobility Features for Parkinson's Disease Stages Via Machine Learning
Mirelman A, Frank M, Melamed M, Granovsky L, Nieuwboer A, Rochester L, Del Din S, Avanzino L, Pelosin E, Bloem B, Della Croce U, Cereatti A, Bonato P, Camicioli R, Ellis T, Hamilton J, Hass C, Almeida Q, Inbal M, Thaler A, Shirvan J, Cedarbaum J, Giladi N, Hausdorff J. Detecting Sensitive Mobility Features for Parkinson's Disease Stages Via Machine Learning. Movement Disorders 2021, 36: 2144-2155. PMID: 33955603, DOI: 10.1002/mds.28631.Peer-Reviewed Original ResearchConceptsParkinson's diseaseDisease stageMid-stage Parkinson's diseaseAge-matched healthy controlsEarly Parkinson's diseaseHigh discriminatory valueBilateral anklesDisease progressionClinical trialsHealthy controlsDisease spectrumGait measuresSeverity stagesAdvanced stageTrunk sensorDisease severityStride timingStudy participantsDiscriminatory valueObjective monitoringMobility measuresDiseaseCohort selectionMean sensitivity
2020
Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science
Stephenson D, Alexander R, Aggarwal V, Badawy R, Bain L, Bhatnagar R, Bloem B, Boroojerdi B, Burton J, Cedarbaum J, Cosman J, Dexter D, Dockendorf M, Dorsey E, Dowling A, Evers L, Fisher K, Frasier M, Garcia-Gancedo L, Goldsack J, Hill D, Hitchcock J, Hu M, Lawton M, Lee S, Lindemann M, Marek K, Mehrotra N, Meinders M, Minchik M, Oliva L, Romero K, Roussos G, Rubens R, Sadar S, Scheeren J, Sengoku E, Simuni T, Stebbins G, Taylor K, Yang B, Zach N. Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science. Digital Biomarkers 2020, 4: 28-49. PMID: 33442579, PMCID: PMC7768153, DOI: 10.1159/000512500.Peer-Reviewed Original ResearchPD clinical trialsParkinson's diseaseDigital health technologiesClinical trialsUse of DHTParkinson’s Disease Drug DevelopmentSymptoms of PDEuropean Medicines AgencyCritical Path InstituteHealth technologiesDrug development studiesClinical manifestationsPD signsRelentless progressionDisease continuumNew therapiesDrug development pipelineNovel treatmentsUS FoodDrug AdministrationMedicines AgencySubsequent approvalDrug developmentCOVID-19 pandemicTherapyLow cerebrospinal fluid volume and the risk for post-lumbar puncture headaches
Droby A, Omer N, Gurevich T, Kestenbaum M, Mina Y, Cedarbaum JM, Aizenstein O, Giladi N, Mirelman A, Thaler A. Low cerebrospinal fluid volume and the risk for post-lumbar puncture headaches. Journal Of The Neurological Sciences 2020, 417: 117059. PMID: 32739500, DOI: 10.1016/j.jns.2020.117059.Peer-Reviewed Original ResearchConceptsPost-LP headachePost-lumbar puncture headacheLow CSF volumeT1-weighted imagesCerebrospinal fluidCSF volumePuncture headacheDisease-modifying clinical trialsLow cerebrospinal fluid (CSF) volumePatient-related factorsGradient-echo T1-weighted imagesCerebrospinal fluid volumeLP headacheAdverse eventsMedical workupClinical trialsBrain MRINeurological conditionsHeadacheMRI scansT MR scannerWhite matterCSF collectionGray matterPilot studyDisease modification and biomarker development in Parkinson disease: Revision or reconstruction?
Espay A, Kalia L, Gan-Or Z, Williams-Gray C, Bedard P, Rowe S, Morgante F, Fasano A, Stecher B, Kauffman M, Farrer M, Coffey C, Schwarzschild M, Sherer T, Postuma R, Strafella A, Singleton A, Barker R, Kieburtz K, Olanow C, Lozano A, Kordower J, Cedarbaum J, Brundin P, Standaert D, Lang A. Disease modification and biomarker development in Parkinson disease: Revision or reconstruction? Neurology 2020, 94: 481-494. PMID: 32102975, PMCID: PMC7220234, DOI: 10.1212/wnl.0000000000009107.Peer-Reviewed Original ResearchConceptsClinicopathologic modelDisease modificationDisease-modifying interventionsParkinson's disease researchCommon pathobiologyLewy neuritesLewy bodiesIdiopathic formClinical trialsPostmortem studiesBreast cancerParkinson's diseaseCystic fibrosisSingle disorderΑ-synucleinBiomarker developmentSmall subgroupGenetic PDDiseaseTrial effortsBiomarkersUnique entityCohortTrue failuresDisease research
2019
The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease
Stephenson D, Hill D, Cedarbaum JM, Tome M, Vamvakas S, Romero K, Conrado DJ, Dexter DT, Seibyl J, Jennings D, Nicholas T, Matthews D, Xie Z, Imam S, Maguire P, Russell D, Gordon MF, Stebbins GT, Somer E, Gallagher J, Roach A, Basseches P, Grosset D, Marek K, Consortium O. The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease. Journal Of Parkinson's Disease 2019, 9: 825-825. PMID: 31524182, PMCID: PMC6878913, DOI: 10.3233/jpd-199003.Peer-Reviewed Original ResearchThe Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease
Stephenson D, Hill D, Cedarbaum JM, Tome M, Vamvakas S, Romero K, Conrado DJ, Dexter DT, Seibyl J, Jennings D, Nicholas T, Matthews D, Xie Z, Imam S, Maguire P, Russell D, Gordon MF, Stebbins GT, Somer E, Gallagher J, Roach A, Basseches P, Grosset D, Marek K, Consortium O. The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease. Journal Of Parkinson's Disease 2019, 9: 553-563. PMID: 31306141, PMCID: PMC6700608, DOI: 10.3233/jpd-191648.Peer-Reviewed Original ResearchConceptsEuropean Medicines AgencyParkinson's diseaseDopamine transporterEnrichment biomarkerClinical trialsPD subjectsParkinson's Progression Markers Initiative (PPMI) studyMotor Parkinson's diseaseParkinson Research ExaminationStriatal DAT bindingUPDRS part IISingle photon emission tomographyAppropriate patient selectionEarly Parkinson's diseaseIdiopathic PD patientsClinical trial populationsFuture clinical trialsClinical trial dataPhoton emission tomographyEarly motor symptomsTest therapeuticsIndependent predictorsTherapeutic trialsDopaminergic deficitMotor symptomsMolecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease
Romero K, Conrado D, Burton J, Nicholas T, Sinha V, Macha S, Ahamadi M, Cedarbaum J, Seibyl J, Marek K, Basseches P, Hill D, Somer E, Gallagher J, Dexter DT, Roach A, Stephenson D, Consortium F, Initiative T. Molecular Neuroimaging of the Dopamine Transporter as a Patient Enrichment Biomarker for Clinical Trials for Early Parkinson's Disease. Clinical And Translational Science 2019, 12: 240-246. PMID: 30706986, PMCID: PMC6510371, DOI: 10.1111/cts.12619.Peer-Reviewed Original ResearchConceptsClinical trialsImaging biomarkersDopamine transporterEuropean Medicines Agency's CommitteeParkinson's disease clinical trialsEarly Parkinson's diseaseCritical Path InstitutePatient selectionEnrichment biomarkerParkinson's diseaseMolecular neuroimagingPharmaceutical partnersDiseaseBiomarkersTrialsQualification opinionHuman useInternational ConsortiumTransportersMedical productsNeuroimagingA Proposed Roadmap for Parkinson’s Disease Proof of Concept Clinical Trials Investigating Compounds Targeting Alpha-Synuclein
Merchant KM, Cedarbaum JM, Brundin P, Dave KD, Eberling J, Espay AJ, Hutten SJ, Javidnia M, Luthman J, Maetzler W, Menalled L, Reimer AN, Stoessl AJ, Weiner DM, . A Proposed Roadmap for Parkinson’s Disease Proof of Concept Clinical Trials Investigating Compounds Targeting Alpha-Synuclein. Journal Of Parkinson's Disease 2019, Preprint: 1-31. PMID: 30400107, PMCID: PMC6398545, DOI: 10.3233/jpd-181471.Peer-Reviewed Original ResearchConceptsParkinson's diseaseProgression of PDDisease-modifying therapiesConcept clinical trialMichael J. Fox FoundationDisease-modifying therapeuticsLewy pathologyClinical outcomesClinical trialsTargeting therapyAnimal modelsClinical proofAlpha-synucleinBiomarker toolkitΑ-synClinical researchInvestigational moleculesTherapyPD researchTranslational frameworkParkinson's ResearchDiseaseBiomarkersConcept studyMeaningful strides
2018
Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models
Weihofen A, Liu Y, Arndt JW, Huy C, Quan C, Smith BA, Baeriswyl JL, Cavegn N, Senn L, Su L, Marsh G, Auluck P, Montrasio F, Nitsch RM, Hirst WD, Cedarbaum JM, Pepinsky R, Grimm J, Weinreb PH. Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models. Neurobiology Of Disease 2018, 124: 276-288. PMID: 30381260, DOI: 10.1016/j.nbd.2018.10.016.Peer-Reviewed Original ResearchConceptsΑ-Syn pathologyParkinson's diseaseΑ-synDisease progressionMouse modelPrevention of PDPhase 2 clinical trialPD mouse modelPD brain tissueDisease modelsDopamine transporter densityParkinson's disease modelΑ-synuclein antibodyPromising therapeutic approachDifferent mouse modelsHealthy elderly individualsΑ-syn fibrilsEpitope mapping studiesDopaminergic terminalsRecombinant α-synPreclinical dataClinical trialsTherapeutic approachesMotor impairmentElderly individualsFDG PET Parkinson’s disease-related pattern as a biomarker for clinical trials in early stage disease
Matthews DC, Lerman H, Lukic A, Andrews RD, Mirelman A, Wernick MN, Giladi N, Strother SC, Evans KC, Cedarbaum JM, Even-Sapir E. FDG PET Parkinson’s disease-related pattern as a biomarker for clinical trials in early stage disease. NeuroImage Clinical 2018, 20: 572-579. PMID: 30186761, PMCID: PMC6120603, DOI: 10.1016/j.nicl.2018.08.006.Peer-Reviewed Original ResearchConceptsHealthy controlsDisease-related patternsParkinson's diseaseYahr stagePD patientsClinical trialsParkinson's disease-related patternFluorodeoxyglucose positron emission tomographyGender-matched healthy controlsEarly-stage Parkinson's diseaseMild PD patientsEarly-stage diseaseFDG-PET scansMotor symptom scoresPositron emission tomographyStage diseaseMotor symptomsSymptom scoresFDG-PETDisease stagePD progressionLentiform nucleusParacentral gyrusSymptom evaluationPD subjectsTargeted Therapies for Parkinson's Disease: From Genetics to the Clinic
Sardi SP, Cedarbaum JM, Brundin P. Targeted Therapies for Parkinson's Disease: From Genetics to the Clinic. Movement Disorders 2018, 33: 684-696. PMID: 29704272, PMCID: PMC6282975, DOI: 10.1002/mds.27414.Peer-Reviewed Original ResearchConceptsParkinson's diseaseGreat unmet medical needDisease-modifying treatmentsNew therapeutic approachesUnmet medical needClinical stageClinical trialsRelentless progressionTherapeutic approachesPotential therapyClinical developmentTherapeutic paradigmMedical needDiseaseGenetic variantsPD geneticsNew arsenalTreatmentGenetic discoveriesKey outstanding questionsTherapySymptomsPathologyProgressionTrials
2015
Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial
Coric V, Salloway S, van Dyck CH, Dubois B, Andreasen N, Brody M, Curtis C, Soininen H, Thein S, Shiovitz T, Pilcher G, Ferris S, Colby S, Kerselaers W, Dockens R, Soares H, Kaplita S, Luo F, Pachai C, Bracoud L, Mintun M, Grill JD, Marek K, Seibyl J, Cedarbaum JM, Albright C, Feldman HH, Berman RM. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial. JAMA Neurology 2015, 72: 1324-1333. PMID: 26414022, DOI: 10.1001/jamaneurol.2015.0607.Peer-Reviewed Original ResearchConceptsNonmelanoma skin cancerObservational cohortProdromal Alzheimer's diseaseProdromal ADClinical trialsPositron emission tomographyAlzheimer's diseaseDiscontinuation ratesCSF biomarkersBiomarker criteriaTreatment phasePlacebo-controlled phase 2 clinical trialSkin cancerGastrointestinal tract adverse eventsKey clinical outcome measuresSerious adverse event ratesΓ-Secretase Inhibitor AvagacestatEmission tomographyPhase 2 clinical trialPotential disease-modifying agentsBrain atrophy ratesLow discontinuation rateAdverse event ratesDisease-modifying agentsGreater brain atrophyImpact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014
Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Cedarbaum J, Donohue MC, Green RC, Harvey D, Jack CR, Jagust W, Morris JC, Petersen RC, Saykin AJ, Shaw L, Thompson PM, Toga AW, Trojanowski JQ, Initiative A. Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014. Alzheimer's & Dementia 2015, 11: 865-884. PMID: 26194320, PMCID: PMC4659407, DOI: 10.1016/j.jalz.2015.04.005.Peer-Reviewed Original ResearchConceptsAlzheimer's Disease Neuroimaging InitiativeClinical trialsDisease Neuroimaging InitiativeAlzheimer's diseaseAD clinical trialsSurrogate outcome measureAD risk factorsTraumatic brain injuryPost-traumatic stress disorderAD risk allelesMultiple sclerosisRisk factorsBrain injuryAD progressionOutcome measuresEffective treatmentParkinson's diseaseImaging ligandsMilitary populationStress disorderRisk allelesDiseaseMultiple centersBiomarkersStandardized biomarkers
2012
BIOMARKERS OF SARCOPENIA IN CLINICAL TRIALS RECOMMENDATIONS FROM THE INTERNATIONAL WORKING GROUP ON SARCOPENIA
CESARI M, FIELDING R, PAHOR M, GOODPASTER B, HELLERSTEIN M, ABELLAN VAN KAN G, ANKER S, RUTKOVE S, VRIJBLOED J, ISAAC M, ROLLAND Y, M’RINI C, AUBERTIN-LEHEUDRE M, CEDARBAUM J, ZAMBONI M, SIEBER C, LAURENT D, EVANS W, ROUBENOFF R, MORLEY J, VELLAS B. BIOMARKERS OF SARCOPENIA IN CLINICAL TRIALS RECOMMENDATIONS FROM THE INTERNATIONAL WORKING GROUP ON SARCOPENIA. The Journal Of Frailty & Aging 2012, 1-9. DOI: 10.14283/jfa.2012.17.Peer-Reviewed Original ResearchSkeletal muscle declineInternational Working GroupMuscle declineAge-related skeletal muscle declineBiomarkers of sarcopeniaClinical trial recommendationsSkeletal musclePublic health priorityAvailable biomarkersPotential great benefitAge-related modificationsClinical trialsTrial recommendationsHealth prioritySarcopeniaTherapeutic strategiesOlder personsWorking GroupOlder peopleBiomarkersMuscleSpecific recommendationsNegative outcomesGreat benefitGroup