FII AIC 2013 Hygiene2014 BremenBrussels20152015 · 2020-02-18 · FII AIC 2013 Hygiene2014 Arten von klinischen Studien Wegscheider K. 2. Wissenschaftliches Diskussionsforum zur Nutzenbewertung

FII 2013 HygieneAIC 2014

Univ.‐ Prof.Dr.med.FrankM.BrunkhorstCenterforClinicalStudies(CCS)

JenaUniversityHospital

Bremen 2015Brussels 2015


Arten von klinischen Studien

Wegscheider K. 2. Wissenschaftliches Diskussionsforum zur Nutzenbewertung im Gesundheitswesen, Berlin, 21. Oktober 2008

Ways to find “truth” …


CenterforClinicalStudies(CCS)JenaUniversityHospital


Statisticalconclusions,notindividual Statisticalconclusionsarenotpreciseinnature

(„Confidenceintervalsvsp‐values“).

Studyconclusions may notbe validinother settings(external validity)

Studyconclusions may notbe validincertain subgroups

Studyconclusionsnotvalidforever(„creeping“)

Limitations of clinical studies

Wegscheider K. 2. Wissenschaftliches Diskussionsforum zur Nutzenbewertung im Gesundheitswesen, Berlin, 21. Oktober 2008Bremen 2015Brussels 2015


Limitations of clinical studies

Wegscheider K. 2. Wissenschaftliches Diskussionsforum zur Nutzenbewertung im Gesundheitswesen, Berlin, 21. Oktober 2008Bremen 2015

Chance

Heterogenicity

Unsuitable outcome

External validity

Differentialmissings

Lackof blinding

Hiddenbias

Overt bias

unknown

Meta‐Analysis RCT

Cohort‐study

Case‐controlstudy Registry

Qualitativestudy

‐

‐

‐

‐

Brussels 2015

Source


Randomizedcontrolledtrialsdeliveronlyapartofinformation,whichpatientsandphysiciansneedfordecisionmaking OtherstudytypesmustbeaddedandmaybemoreimportantfortheindividualdecisionthanquantifyingefficacybyRCTs

Conclusions

Wegscheider K. 2. Wissenschaftliches Diskussionsforum zur Nutzenbewertung im Gesundheitswesen, Berlin, 21. Oktober 2008Bremen 2015Brussels 2015


Register

6

Nogivenintervention(non‐interventionalstudy)

Norandomization

Precisedefinedtargetpopulation

Representativeortotalinclusionofthetargetpopulation

Active,standardizeddataassessment

Registrys

AG Memorandum Register für die Versorgungsforschung Gesundheitswesen 2010; 72(11): 824-839Bremen 2015Brussels 2015

FII 2013 HygieneAIC 2014 7

Notprimarilydesignedforproofofefficacy,

Descriptionofepidemiologicalinteractionsanddifferences Supportofqualityassessmentand–improvementmeasures Supportoffurtherandnewclinicalresearchprojects Evaluationandmonitoringofpatientsafety Evaluationofefficacyunderreal–lifeconditions Oeconomicevaluation Minimumquantityresearch Supportinhealthcareservicesresearch

Registrys

Brussels 2015


„Sciencetellsuswhatwecando;Guidelineswhatweshoulddo;

Registrieswhatweareactuallydoing.„

LukasKappenbergerMDHeartRhythmSocietyPolicyConference

WashingtonDC2005

8

Take home message



Australian Clinical Quality Registers

http://www.registries.org.au/Bremen 2015Brussels 2015

FII 2013 HygieneAIC 2014 10* AAgency for Healthcare Research and Quality; U.S. Department of Health and Human Services, www.ahrq.gov

CytoSorb Registry – fulfils operatingprinciples of clinical quality registries *

Cleardefinition of purposes aiming atimproving thequality of health care

Datacollection focussed onessentialfeatures ofmedicinal product use

Datacomprise objective,reliable and reproducibleitems

Datacontribution by individualparticipants employsstandardized procedures

Datacover alargeproportion of the eligible population Bremen 2015Brussels 2015

FII 2013 HygieneAIC 2014 11* AAgency for Healthcare Research and Quality; U.S. Department of Health and Human Services, www.ahrq.gov

CytoSorb Registry – fulfils operatingprinciples of clinical quality registries *

Datacapture is performed closely to the place andtimeof product use

Dataare uniformly specified and readily comparable

Health careprocedures of product use have establishedlinksto outcomes

Registryincorporates in‐built data validation andmanagement processes

Arobustquality assurance planwarrants continuousdata accuracy control



Registrycustodianship and ownership is contractuallystipulated

Thirdparty access to data requires Steering Committeeand IRBapproval

Investigators are obliged to adhere to ethic standards

Dataacquisition complies with nationalregulations onprivacy protection

CytoSorb Registry – complies with ethics and privacy protection standards*

* Agency for Healthcare Research and Quality; U.S. Department of Health and Human Services, www.ahrq.govBremen 2015Brussels 2015


http://www.cytosorb-registry.orgBremen 2015Brussels 2015


Principal Investigator Prof.Dr.FrankM.Brunkhorst,JenaUniversityHospital,CenterforClinicalStudies

Projectmanagement

Manja Schein, Jena University Hospital, Center for Clinical Studies

BiometryDr.UlrikeSchumacherJenaUniversityHospital,CenterforClinicalStudies

Datamanagement

ViolaBahr,JenaUniversityHospital,CenterforClinicalStudies

SteeringCommittee Prof.Dr.FrankM.Brunkhorst,JenaUniversityHospitalProf.Dr.JanKielstein,HannoverMedicalSchoolProf.Dr.AndreasMeier‐Hellmann,HeliosClinic ErfurtProf.KarlTräger,UlmUniversityHospitalFrankBorn,Munich UniversityHospitalN.N.

ScientificAdvisoryBoardProf.MervinSinger,LondonProf.JohnKellum,Pittsburgh

CytoSorb Registry - Responsibilities



Title Registry on CytoSorb Use in Intensive Care Unit Patients

Shorttitle CytoSorb Registry

Population Patients subject to extracorporeal blood purification with CytoSorb®

Indications 1.) Severe sepsis / septic shock2.)Scheduledcardiovascularsurgerywithcardiopulmonarybypass2a.)preemptiveapplicationduringsurgery2b.)postoperativeapplicationinICU3.) Other conditions (e.g. liver failure, acute pancreatitis, major trauma, burns,ARDS)

Design Prospective multi‐center registry, based on systematic data acquisition

Aim Collection,evaluation,anddisseminationofdataonCytoSorbuseunderreal‐lifeconditions

Endpoints Effects of CytoSorb use on:‐ Organintegrity and function (SOFA‐ Score)‐Mechanical ventilation (days)‐ Biomarkersof inflammation ‐ ICUand hospital stay‐ ICUand in‐hospitalmortality ‐ Renalreplacement therapy (days)‐ Safety ‐ Vasopressor use (days)

15

Synopsis (1)CytoSorb Registry – Synopis 1



Inclusioncriteria ‐ CytoSorb use‐ Age ≥ 18

Exclusioncriteria ‐ none

Participatingcenters ‐ ca.30atinception‐ IncreasingrecruitmentinGermany,AustriaandSwitzerlandduringthe

study‐ Possibleexpansiontoothercountries

Timelines Start 01.01.2015

Duration 3 years, with an option of extension

Tentativerecruitment Approx. 1,000 new patients per year

Intermediateassessment Semi‐annually

Evaluation annually

16

CytoSorb Registry – Synopis 2



Baseline Visit1 Treatment Visit2 FollowupInclusion criteria xIndication xDemographics xOriginandlocalizationofinfection xCo‐morbiditiesaffectingAPACHEII/SAPSII xAPACHEII/SAPSIIscore xSOFAscore x xRelevantdiagnostictests x xCytoSorb®applicationdata(duration,anticoagulation,bloodpumpflowrate,vasopressors,corticoids)

x

Renalreplacementtherapy x x xComplications xDaysinICUandhospital xMortalityinICUandhospital xDaysonmechanicalventilation xDaysonrenalreplacementtherapy xDaysonvasopressors xAssessmentoftherapeuticeffect(Likert‐scale) x

17Visit 1: up to 24h before CytoSorb® application; Visit 2: 24h after end of CytoSorb® application; Follow up: Discharge from hospital

CytoSorb Registry (1) – severe sepsis


FII 2013 HygieneAIC 2014Brussels 2015


Baseline Visit 1 Treatment Visit 2 Follow upInclusion criteria check xIndication check xDemographics xCo‐morbidities affecting APACHE II / SAPS II xEuroSCORE xRelevant diagnostic tests x xCytoSorb® application data (duration, anticoagulation, blood pump flow rate, vasopressors, corticoids)

x

Renal replacement therapy (type, filter) xSurgery report xSOFA score xAPACHE II / SAPS II score xComplications xDays in ICU and hospital xMortality in ICU and hospital xDays on mechanical ventilation xDays on renal replacement therapy xDays on vasopressors xAssessment of therapeutic effect (Likert‐scale) x

19

Visit 1: up to 24h before CytoSorb® application; Visit 2:24h over the second postoperative day; Follow‐up: Discharge from hospital

CytoSorb Registry (2) – preemptive use in elective cardiovascular surgery



Baseline Visit 1 Treatment Visit 2 Follow upInclusion criteria xIndication xDemographics xCo‐morbidities affecting APACHE II / SAPS II xAPACHE II / SAPS II score xSOFA score x xEuroSCORE xSurgery report xRelevant diagnostic tests x xCytoSorb® application data (duration, anticoagulation, blood pump flow rate, vasopressors, corticoids)

x

Renal replacement therapy (type, filter) xComplications xDays in ICU and hospital xMortality in ICU and hospital xDays on mechanical ventilation xDays on renal replacement therapy xDays on vasopressors xAssessment of therapeutic effect (Likert‐scale) x

20

Visit 1: 24h before CytoSorb® application; Visit 2: 24h after end of CytoSorb® application; Follow up: Discharge from hospital

CytoSorb Registry (3) – after cardiovascular surgery



Baseline Visit 1 Treatment Visit 2 Follow upInclusion criteria xIndication xDemographics xCo‐morbidities affecting APACHE II / SAPS II xAPACHE II / SAPS II score xSOFA score x xRelevant diagnostic tests x xCytoSorb® application data (duration, anticoagulation, blood pump flow rate, vasopressors, corticoids)

x

Renal replacement therapy (type, filter) xComplications xDays in ICU and hospital xMortality in ICU and hospital xDays on mechanical ventilation xDays on renal replacement therapy xDays on vasopressors xAssessment of therapeutic effect (Likert scale) x

21Visit 1:up to 24h before CytoSorb® application; Visit 2: 24h after end of CytoSorb® application; Follow up: Discharge from hospital

CytoSorb Registry (4) – use in other indications



MainAnalysisPopulation:useinseveresepsisandsepticshock/postoperativeuseincardiovascularsurgery

22

24hpre 24hpost…CytoSorbapplication(s)…

SOFApre

Observedin‐hospitalmortality

SOFApost

APACHEII/SAPSII‐predicted

in‐hospitalmortality

Comparisonwitht‐test,linear/quadratic

modelling

Comparisonwithlogisticregressionmodel

time

discharge

Allowanceforcovariatesasforinstance:baselineSOFA;daysonmechanicalventilation;daysonrenalreplacementtherapy;daysonvasopressors

Subgroupanalysisforusageindicationgroups

Descriptiveanalysisofallvariables

CytoSorb Registry – Primary analysis



DataManagementwith OpenClinica (https://www.openclinica.com/)OpenClinica istheworldwidefastestgrowingclinicaltrialsoftware,usedfordatacapture,validationandquerymanagement

DataisenteredincentersviaRDE(RemoteDataEntry)andtransferredtotheCenterforClinicalStudiesinJenaviaasecurecommunicationprotocol(https)

OpenClinica supportsGoodClinicalPractice(GCP)andregulatoryguidelinessuchas21CFRPart11(electronicrecordsandelectronicsignatures)

Thesoftwareenablesdifferentiateduserrolesandprivileges Thesoftwarepermitscomprehensiveaudittrailstorecords,aswellasmonitoraccess

anddatachanges

AnalysiswithSASSAS(StatisticalAnalysisSystem)Instituteworksextensivelywithgovernmentagencies Meetsaccessibilitystandardsandcomplieswithallrelevantregulationsforsoftware

anddatasubmissions

23

CytoSorb Registry – Data management & analysis



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Ethics&informedconsentformsContractsPasswordandaccesstoe‐CRF

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Thank you for your attention !

http://www.zks.uniklinikum-jena.de/

Jena Center of Clinical StudiesBremen 2015Brussels 2015

Documents

FII AIC 2013 Hygiene2014 BremenBrussels20152015 · 2020-02-18 · FII AIC 2013 Hygiene2014 Arten von klinischen Studien Wegscheider K. 2. Wissenschaftliches Diskussionsforum zur Nutzenbewertung