AirProm Harmonisation and Statistical Analysis

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Presentation made during the EISBM workshop, 13-15 June 2012 by Chris Newby ( AirProm ).

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AirProm Harmonisation and Statistical Analysis

  1. 1. Supported byProminent international speakers from h"p://workshop.eisbm.eu1
  2. 2. AirPromHarmonisa,onand Sta,s,calAnalysis ChrisNewby ResearchAssociate Data2Knowledge HealthSciences&RespiratoryMedicine UniversityofLeicester UK
  3. 3. Harmonisa,onofBTSsevereasthma registryandUBioPred•  BTSsevereasthmaregistryvariablesbasedon informa,onobtainedfrompa,entrecords imputedbyresearchNurses•  Whatvariablescanbeobtainedfromboth cohortssothatvariabledefini,onsremainthe sameandpowerisincreased
  4. 4. DataShapermethodology Aim:% To%provide%a%template%to%facilitate% harmoniza;on%between%pre>exis;ng% Cohort%2% cohorts%and%support%the%design%of% emerging%ones.% Cohort%3%Cohort%1% common% Data% Cohort%4% Pool%% Cohort%5%
  5. 5. Threestepstoharmonisa,on Identify core sets of information to be shared (selection and definition of the variables) DATA SCHEMAAssess potential to share the core set of information between a group of cohorts HARMONIZATION PLATFORM Achieve processing and pooling of information (Real Data) Processing and pooling platform
  6. 6. DataSchemaStructure: a"nested"hierarchical"structure"Modules% M1%
  7. 7. DataSchemer Around80variablespoten,allycanbe harmonisedbetweenBTSdataandUBioPred HarmonisedVariableModule Theme Domain HarmonisedVariableName Descrip,onClinicalAssessment IndividualDiseaseHistory AsthmaDiseaseHistory Ageofonsetofsymptoms ageofonsetofsymptoms severitystagedeterminedbyClinicalAssessment IndividualDiseaseHistory AsthmaDiseaseHistory ATS/ERSseveritystage ATS/ERSguidelines severitystagedeterminedbyClinicalAssessment IndividualDiseaseHistory AsthmaDiseaseHistory GINAseveritystage GINAguidelinesPhysicalMeasures BodyComposi,onMeasures BodyMassIndex BMI height/weightPhysicalMeasures BodyComposi,onMeasures Obesity Obese BMI>=30PhysicalMeasures LungFunc,onMeasures Unstandardized PreBronchodilatorFEV1 PreBronchodilatorFev1PhysicalMeasures LungFunc,onMeasures Unstandardized PostBronchodilatorFEV1 PostBronchodilatorFev1
  8. 8. Threestepstoharmonisa,on Identify core sets of information to be shared (selection and definition of the variables) DATA SCHEMAAssess potential to share the core set of information between a group of cohorts HARMONIZATION PLATFORM Achieve processing and pooling of information (Real Data) Processing and pooling platform
  9. 9. BTSSevereasthmaanalysis•  ToexploretheheterogeneityofSevere asthmathroughdatacollectedinregistry•  Factoranalysiscarriedouttoexplorevariable heterogeneity•  Clusteranalysiscarriedouttoexplorepa,ent heterogeneity•  Clustersfollowedover,metodetermine medicaloutcomes
  10. 10. Factoranalysis Component 1 2 3 4 LungFunc,on BMI/Atopy Treatment Blood EosinophilBMI .045 .677 .215 .026Pre_bronchodilatorFVC% .767 _.340 .086 .246predictedPre_bronchodilatorFEV1(%) .986 .029 _.110 _.023predictedPre_bronchodilatorFEV1/FVC .674 .372 _.207 _.266Bloodeosinophilx109/L .010 .033 _.033 .907TotalIgEkU/L .030 _.520 _.137 .073BDPequivalent(mcg/day) _.070 .079 .710 .114Ageatonsetofsymptoms _.041 .593 _.397 .254OralSteroiddose(mg) _.059 .134 .641 _.130
  11. 11. 4Clustersfoundusingmixture modelling•  Cluster1,severeairflowobstruc,on•  Cluster2,non_obese,minimalairflow Obstruc,on•  Cluster3,obese,minimalairflowobstruc,on•  Cluster4,moderateairflowobstruc,onwith highernumberofexacerba,onsandonlarger amountsoftreatment
  12. 12. Variable% Cluster%1% Cluster%2% Cluster%3% Cluster%4% p> (N=106)% (N=129)% (N=80)% (N=34)% value% ‘Severe% ‘Non>obese% ‘Obese% ‘Moderate% airflow% minimal% minimal% airflow% obstruc;on’% airflow% airflow% obstruc;on’% obstruc;on’% obstruc;on’%BMI% 28.7(3.96) 24.7(3.76) 36.8(5.0) 29.2(6.44) <0.001Atopy%(%)%% 47 61 61 71 0.057Reflux%history%%(%%yes)% 56 67 48 35 0.001HAD%Anxiety%score%% 8(6) 7(5) 9(6.5) 8.5(5.75) 0.042Pre>bronchodilator%FEV1% 43.4(11.3) 78.4(20.5) 78.3(17.8) 62.8(23.3) <0.001Predicted%(%)%Pre%Bronchodilator%FVC% 67.2(17) 91.1(17.1) 88.4(16.8) 81.2(18.8) <0.001Predicted%(%)%FEV1%FVC%Pre%Bronchodilator% 52.6(13.9) 68.1(13.7) 69.5(10.3) 61.1(16.3) <0.001(%)%Blood%Eosinophil%count%109/l% 0.36(0.39) 0.29(0.50) 0.28(0.41) 0.42(0.28) 0.511Rescue%steroid%courses%in%last% 4(5) 3(4) 5(4) 5(6) 0.002year%(n)%BDP%equivalent%inhaled% 1650(501) 1540(647) 1640(541) 4050(1030) 0.011steroid%dose%(mcg)%Age%At%Onset%Of%Symptoms% 26(22) 26(20) 29(17) 19(17) 0.162(years)%
  13. 13. ClusterOutcomesover,me Cluster%1% Cluster%2% Cluster%3% Cluster%4% ‘Severe%airflow% ‘Non>Obese%minimal% ‘Obese%minimal% ‘Moderate%airflow% obstruc;on’% airflow%obstruc;on’% airflow%obstruc;on’% obstruc;on’% % Difference P_value Difference P_value Difference P_value Difference P_valueBMI% 0.65(2.34) 0.011 1.43(2.51) <0.001 0.59(3.44) 0.152 1.72(2.56) 0.001Pre%bronchodilator%%FEV1% 0.39(0.58) <0.001 0.08(0.60) 0.201 0.03(0.52) 0.628 0.10(0.72) 0.488Pre>bronchodilator%%FEV1%%%predicted% 15(22) <0.001 2(27) 0.593 3(21) 0.318 5(25) 0.308Blood%Eosinophil%count,%%x%109/l% _0.19(0.46) 0.001 _0.22(0.72) 0.011 _0.22(0.46) 0.004 _0.15(2.79) 0.11BDP%equivalent%(mcg/day)% 140(713) 0.051 276(839) 0.001 8(798) 0.931 _1576(1576) <0.001%%on%steroids%at%follow%up% 58% 0.071 50% 0.002 58% 0.064 74% 0.096Rescue%steroid%courses%in%last%year%% 0(5) 0.005 0(6) 0.021 _2(4) 0.001 _2(5) 0.004
  14. 14. ClusterClassifier•  Predictswhichclusterapa,entbelongstoata certainpointin,me•  Basedontheprobabilityofbeingin mul,variatenormaldistribu,onofsubsetof variablesforeachcluster•  97%correctclustermembership
  15. 15. ClusterClassifier•  Atfollowup54%ofpa,entsremainedinsamecluster %% Predicted%clusters%from%year%follow%up%data% Baseline%cluster%% Cluster1 Cluster2 Cluster3 Cluster4 1%% 34.6% 32.7% 23.1% 9.6% 2%%% 10.6% 66.7% 10.6% 12.1% 3%%% 11.4% 0.0% 80.0% 8.6% 4%%% 25.0% 35.0% 20.0% 20.0%
  16. 16. MedicalSystemsBiologyPreBron PreBron FEV1/% PreBron PostBron FVC/% FEV1/FVC FEV1/FVCPredicted Predicted Lung Mucus Plugging Bronchiectasis Lung Restric,on Obstruc,on Bronchiolewall NasalPolyps thickening %eosinophils Blood inSputum eosinophil TotalIgE Count bloodcount
  17. 17. BTS Cohort1 Cohort2 M PreBron PostBronPreBron PostBron FEV1/FVC FEV1/FVC PreBron PostBron EFEV1/FVC FEV1/FVC FEV1/FVC FEV1/FVC T A Lung Lung Lung Obstruc,on A Obstruc,on Obstruc,on N A L %eosinophilsin %eosinophilsin %eosinophilsin Y Sputum Sputum S Sputum I S Bloodeosinophil Bloodeosinophil Bloodeosinophil Count Count Count Bloodeosinophil Biomarker CountinTissue levels
  18. 18. linkingwithothercohorts•  Metaanalysisofmodelstoexpandandverify cohortspecificmodels•  Harmonisa,onofdatasoacombinedversion ofdataexistsandcanbeusedforfuture greaterpoweredanalysis•  Verifica,onofexis,ngmodelsinother cohorts

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