chronic otitis media · 2019-05-02 · chronic otitis media scoping document (abbreviated version)...
TRANSCRIPT
Chronicotitismediascopingdocument(abbreviatedversion)30thJanuary2017
Chronic Otitis Media
Ascopingexerciseforareasofpriorityforsystematicreview
Projectlead:ChrisBrennan-Jones(TelethonKidsInstitute,UniversityofWesternAustralia&PrincessMargaretHospital)Projectclinicians:MahmoodBhutta(TheUniversityofWesternAustraliaandRoyalPerthHospital)MartinBurton(CochraneENT,Oxford)AnneSchilder(CochraneENT,evidENT)ShyanVijayasekaran(PrincessMargaretHospitalandTheUniversityofWesternAustralia)Systematicreviewers/methodologists:Lee-YeeChong(AteimedConsultingLtd)KarenHead(KarenHeadFreelanceLtd)InformationScientist:SamanthaFaulkner(CochraneENT)PatientRepresentative:CourtneyMcMahen Editor:JennyBellorini(CochraneENT)Funders&collaborators
CONFIDENTIAL-Chronicotitismediascopingdocument 2
Summary of the scoping process for proposed reviews BackgroundTheaimofthisscopingexerciseistoidentifypriorityareasfornewandupdatedevidencesummariesinpatientswithchronicotitismedia(COM).COMinthisdocumentisdefinedaschronicinflammationofthemiddleearandmastoidcavitywithpersistentorrecurrenteardischargethroughatympanicmembrane(eardrum)perforation.
COMisestimatedtohaveanincidencerateof31millionepisodesperyear,or4.8newepisodesper1,000people(allages).Childrenareparticularlyaffected,with22%ofallcasesaffectingchildren<5yearsofage.TheprevalenceofCOMvarieswidelybetweencountries,butitdisproportionatelyaffectspeopleinlow-incomeandmiddle-incomecountries,resourcelimitedareas,certainindigenousgroupsandpeoplewithspecificconditionssuchascleftpalateandDownSyndrome.ManypeoplewhoareaffectedbyCOMdonothavegoodaccesstomodernprimaryhealthcare,letalonespecialisedear,noseandthroat(ENT)care.Therefore,itiscrucialthattheevidenceispresentedinawaythatcouldsupportthedevelopmentandupdatingofguidelinesaffectingthesesettings.
TerminologyOtitismedia(OM)orinflammationofthemiddleearisabroadtermthatincludesacuteOM(AOM),OMwitheffusion(OME;‘glueear’)andchronicsuppurativeOM(CSOM).Theseconditionsarecloselyrelatedandcanoverlap.Oneofthechallengesofresearchinthisareaisthevariationinterminologyusedacrossstudiesandregions,andbetweenclinicians.Thefocusofthisworkistoexaminetheinterventionsusedinthemanagementofpatientswithchroniceardischargeduetochronicotitismedia(COM),whichistypicallyreferredtoaschronicsuppurativeotitismedia(CSOM)oractivechronicmucosalotitismedia.However,chronicdischargefromtheearcanalsobeasymptomofinflammationoftheexternalear(chronicotitisexterna)andthedifferentiationbetweeneardischargeduetoCOMandeardischargeduetochronicotitisexternamaynotalwaysbeclear.Therefore,forthepurposesofthisdocumentwewillrefertopatientsashavingchroniceardischarge(CED)ifthecauseofthedischargeisunknownandthedurationisatleasttwoweeks,andwewillusethetermchronicotitismedia(COM)todescribechronicorpersistenteardischargeforatleasttwoweekswithaperforatedtympanicmembrane,whichreflectsthemoretraditionaldefinitionassociatedwithCSOM.Cholesteatomaisanabnormalaccumulationofsquamousepitheliumthatisusuallyfoundinthemiddleearcavityandmastoidprocessofthetemporalbone.Mostcliniciansconsider‘cholesteatoma’tobeavariantofCSOM.Itisunclearwhethertheresponsetonon-surgicaltreatmentsinpatientswithcholesteatomatonon-surgicaltreatmentswillbeidenticaltotheresponseinpatientswhohaveCOMwithoutcholesteatoma.Managementofpatientswithacuteotitismedia(AOM)andotitismediawitheffusion(OME)willnotbeconsideredinthisproject.MethodsandfindingsofourscopingexerciseThisdocumentprovidesanoverviewofthemethodsweplantousetoconductthereviewofCOMevidence.Thisdocumentisnowcirculatedtocliniciansaroundtheworldaspartofourconsultationprocess(inwhichyouareparticipating).Patientrepresentativeswillalsoprovideinputintotheproposedscope.
CONFIDENTIAL-Chronicotitismediascopingdocument 3
Thisdocumenthasbeendevelopedbygatheringpreliminaryinputfromcliniciansanditisinfluencedbyliteraturesearchesandreviewsofcurrentclinicalguidelinesandkeypapers,especiallytheCochranedatabaseandmajorsystematicreviews.Wealsoconductedsearchestoidentifythenumberofnewtrialabstracts,inordertoestimatetheamountofnewevidenceavailable.Thenumberofpotentialrandomisedcontrolledtrialsinthisareaissmall,asreflectedbytherelativelysmallnumbersofabstractsfound.
ExistingguidelinesidentifiedOursearchesidentifiedonemajorinternationalguideline:thecurrentWorldHealthOrganization(WHO)guideline,publishedin2004(CSOM–burdenofillnessandmanagementoptions).PartoftheevidencebasethatwasusedtosupportthisguidelinewaspublishedastwoCochranesystematicreviewsontheuseofantibiotics1.Wefoundonlytwonational-levelguidelines(fromIndonesiaandAustralia).Wenoticedmajorvariationsinpractice,especiallyaroundtheuseoftopicalantibiotics,topicalantisepticsandauraltoileting.
TopicsofpriorityforevidencereviewThelistofproposedreviewsispresentedinthefollowingsections(Section2:Reviewquestions).Thereisalsoanaccompanyingdocumentdetailingthescopingprocessanditsfindings.
Webelievethatreviewsonthreegroupsofinterventionswillpotentiallyhavethehighestimpact.Thistakesintoconsiderationtheuncertaintyandvariationincurrentclinicalpractice,thecurrentevidencebase,thepotentialeconomicimpactandtheareasintheworldwhereCOMismostprevalent.Thethreegroupsofinterventionsofpriorityare:
1. Topicalantiseptics2. Antibiotics(systemicandtopical)3. Auraltoileting
Therationaleforfocusingontheabovetopicsincludestheconsiderationthattheseareinterventionsthataremostusedandthereislargevariationinpracticeinthisarea.Thediseasedisproportionatelyaffectspeoplefromresource-limitedcountries,thereforetopicalantiseptics(whichareoftencheaperthantopicalantibiotics)andalternativeformsof‘auraltoileting’(ratherthanmicro-suctionmethods,whicharesometimesonlyavailableinmorespecialisedcaresettings)areoftenusedduetocostandotherlimitations.Thepotentialeconomicimpactandtheissueofaccesstocaremeanthattheseinterventionsareimportant.
Weconsideredtheroleoftopicalsteroidstobeimportantbecausesteroidsareoftenaddedtotopicalantibiotics.However,weareunclearwhetherthisinterventioncouldberegardedasmoreimportantthattheotherthreeinterventiongroups.AreviewoftheevidenceforsurgicalinterventionsisoflowerprioritybecauseonlyasmallproportionofpatientsarereferredtoanENTspecialistsettingandrequiresurgery.Intheliteraturewefoundmentionsofotherclassesofdrugsbeingused,suchasantifungals,antihistaminesanddecongestants,buttheseinterventionsareuncommonandthereisnostrongbiologicalbasisfortheiruse.Thereis,therefore,unlikelytobehigh-levelevidencefromRCTsinthesethreeclasses.
OutcomesusedtoassesstheeffectsofinterventionsWewilluseacommonsetofoutcomemeasuresthatareimportanttopatientstoassesseffectivenessacrossallthereviews.Qualityoflifeisthemostimportantoutcomeandwillbea
1CD005608:Systemicantibioticsversustopicaltreatmentsforchronicallydischargingearswithunderlyingeardrumperforations;CD004618:Topicalantibioticswithoutsteroidsforchronicallydischargingearswithunderlyingeardrumperforations
CONFIDENTIAL-Chronicotitismediascopingdocument 4
primaryoutcomeinthereviews.However,wehavefoundneitherwell-validatedpatient-reportedsymptomscoresnordisease-specificqualityoflifeinstrumentsbeingusedinclinicaltrialsofnon-surgicalinterventions.Therefore,wealsosuggestmeasuringresolutionofdischarge(dryear)asaprimaryoutcome.Forthesecondaryoutcomes,wesuggestmeasuringrecurrenceofeardischarge,hearinglossandcomplicationsfromCSOM(includingintracranialcomplications,extracranialcomplicationsanddeath).Wewillalsoassessthepotentialharmsofallinterventionsreviewedbasedonthecharacteristicsoftheinterventionsconsidered.
CONFIDENTIAL-Chronicotitismediascopingdocument 5
1 PROPOSED SCOPE OF REVIEWS Thefollowingsectionssetoutthescopeandprioritiesoftheproposedreviewsbasedonthefindingsofthescopingexercisethusfar.Figure1presentsaflowchartofthepatientjourneywiththeboxesinbluerepresentingtheareasproposedforevidencereviewinthecurrentscope.
1.1 SETTING Wewillincludeevidencefromallhealthcaresettings.Therewillbenolimitsonthelanguageoryearofpublicationorthecountrywheretheresearchwasconducted.
1.2 POPULATION
1.2.1 Populat ions that wi l l be included: Wewillincludestudiesthatincludedpatients(adultsandchildren)whohad:
• chroniceardischargeofunknowncause;or• chronicotitismedia.
Patientswithchroniceardischarge(CED)willbedefinedaspatientswithatleasttwoweeksofeardischarge,wherethecauseofthedischargewasunknown.
Patientswithchronicotitismedia(COM)willbedefinedaspatientswith:
• chronicorpersistenteardischargeforatleasttwoweeks;and• aperforatedtympanicmembrane.
Wewillnotexcludeanypopulationsbasedonage,riskfactors(cleftpalate,Downsyndrome),ethnicity(e.g.AustralianAboriginalorTorresStraitIslanders)orthepresenceofgrommets.AlthoughtheincidenceandriskofdevelopingCOMarehigherinthesesubgroupsofpatients,wehavenotfoundevidencethatthesepatientsresponddifferentlytotreatment(i.e.thereisdifferentrelativeeffectiveness)comparedtopatientswhodonothavethesecharacteristics.Whereavailable,wewillrecordthesefactorsinthepatientcharacteristicssectionduringdataextractionfromthetrials.Ifanyoftheincludedstudiesmostlyrecruitthesepatients,wewillanalysetheminasubgroupanalysis(see‘Analysis,subgroupsandpoolingofevidence’).
1.2.2 Populat ions that wi l l not be included: WewillexcludestudiesthatspecificallyrecruitedpopulationswithoutCOMandstudieswithparticipantswhereanalternativediagnosistoCOM(e.g.otitisexterna)formedthemajority(morethan50%)ofparticipants.
StudieswithinclusioncriteriaofpatientswithCEDorCOMmayincludepeoplewithunderlyingcholesteatoma.Giventhatcholesteatomadoesnotrespond,orwillrespondonlytemporarilytonon-surgicaltreatment,wewillexcludethosestudieswheremorethan50%oftheparticipantswerediagnosedwithcholesteatoma.
CONFIDENTIAL-Chronicotitismediascopingdocument 6
Figure1:Areasinchronicotitismediacoveredinproposedscope
Note:boxesinblueareincludedintheproposedscope;boxesinorangeareoutsidetheproposedscope.
CONFIDENTIAL-Chronicotitismediascopingdocument 7
1.3 INTERVENTIONS Takingintoconsiderationtheuncertaintiesincurrentpractice,theamountofpotentialevidenceavailableandtheageandrelevanceofrecentreviews,wehaveprioritisedthereviewsofinterventionsthatarelikelytomakethemostimpact.
1.3.1 Types of intervention to be included in reviews 1. Topicalantibiotics2. Systemicantibiotics3. Topicalantiseptics4. Auraltoileting
Wewillincludeallmethodsofauraltoileting.Thetopicalantisepticsusedwillincludeagentssuchaspovidone-iodine(i.e.Betadine),aceticacid,boricacidandhydrogenperoxide.
1.3.2 Types of interventions to be excluded from the reviews 1. Topicalsteroids,whetherasanadd-ontherapy(e.g.toantibiotics)oralone2. Antifungals3. Decongestants4. Antihistamines5. Surgery(mastoidectomy,and/ormyringoplastyortympanoplasty)
1.4 MAIN OUTCOMES Weplantousetwoeffectivenessoutcomesacrossallthereviews(coreoutcomes)toallowforcomparabilityacrossreviews:
1. Completeresolutionofeardischarge,measuredatbetween1weekandtoupto2weeks,2to4weeksandafter4weeks(measuredasproportionofpeople)
2. Health-relatedqualityoflife(e.g.COMOT-12,COMOT-15,CES)
Wewillchoosetheotheroutcomesbasedontheinterventionandcomparisonsassessed.Dependingonthesefactors,theseoutcomesmayinclude:
1. Recurrence(durationoftimeeardischargefree/timetorecurrence)2. Hearingloss(e.g.forchildrenahearinglossof≥30dBaveragedacrossfrequencies0.5,1,2
and4kHz)3. ComplicationsfromCOM–extracranial4. ComplicationsfromCOM–intracranial5. Death6. Adverseeffectsfromtreatment(thiswillbedependentonthetypeoftreatmentreviewed)
Adverseevents:differentadverseeventswillbemeasureddependingontheinterventionassessedbutmayinclude:
• Pain• Ototoxicity• Fungalinfection
Wedidconsiderotheroutcomesbutthoughtthatthesemightbeoflowerpriority.Weconsidereddiseaseseveritymeasuredusingsymptomscores,butdecidedthatthiswaslessimportant,ontheassumptionthatpatientswishtoachieveadryearratherthanjustsymptomimprovement.Moreover,wearenotawareofanyvalidatedscores.Wealsoconsideredsmell(ofthedischarge)asanimportant,potentiallybothersomesymptom.However,thisoutcomedidnotappeartobe
CONFIDENTIAL-Chronicotitismediascopingdocument 8
capturedinclinicaltrialsandshouldinanycaseresolvewithadryear,whichisalreadymeasuredasaprimaryoutcome.
CONFIDENTIAL-Chronicotitismediascopingdocument 9
2 REVIEW QUESTIONS
Table1liststhereviewstobeconducted,withdetailsofthetypesofpatient(population),interventionandcomparisontobeincluded.Wewillprioritisereviews1to6inthisprojectandwewilldeliverthesewithinthetimelinestipulatedandwithinthegrantprovided.
Table1:Listofpopulations,interventionsandcomparisonsforthesuiteofreviewsandwithinwhichreviewsthesearelikelytobepresented.Key: COM Chronicotitismedia CEDChroniceardischarge(Tentative)Reviewshortname2
Pair Population3
Intervention4
Comparison
Comments5 Mainclinicalquestions
1. Antibiotics–topical
1. CED Antibiotics–topical
Placeboornointervention
Thiswillincludestudieswhereanotherinterventionisusedasanadjuvanttreatmentinbotharms(e.g.topicalantiseptics,topicalcorticosteroids).
1. Aretopicalantibioticseffective?
2. Aretopicalantibioticseffectivewhenaddedtootherinterventions(e.g.auraltoileting)?
2. CED Antibiotics-topical
Antibiotics-topical(otherclasses)
ThecurrentCochranereviewincludesninestudies.
3. Whichtopicalantibioticismoreeffective(whentheyarecomparedtoeachother)?
4. Whichtopicalantibioticismoreeffectivewhenaddedtootherinterventions?
2. Antibiotics–systemic
3. CED Antibiotics-systemic
Placeboornotreatment
Thiswillincludestudieswhereanotherinterventionis
5. Aresystemicantibioticseffective?
6. Aresystemicantibioticseffectivewhenaddedonto
2Thisreflectsthetentativeorganisationofdifferentcomparisonpairsinthereviews.Theorganisationofinformationintodifferentreviewsmayneedtobechanged,dependingonthenumberofstudieseventuallyincludedandtheclinicalrelevanceoftheavailablecomparisons.3Characteristicsofpopulationstobeexploredassubgroupsare:whethermostofthepatientshaveadefiniteCOMdiagnosisandagegroup.4Wewillexploretheeffectsofthetypeofactiveintervention(withinaclass),methodofdelivery,doseanddurationofintervention,andcomparisonsusingsubgroupanalysiswhereappropriate.Ifauraltoiletinghasbeenused,wewillalsoreportthis.5Whencombinationsoftreatmentsarecompared,thereviewinwhichtheevidenceislocatedwillbebasedonthecomparisonused.Forexample,wewillanalyseauraltoileting+topicalantibioticsversusauraltoiletingastopicalantibioticsversusnointervention(withauraltoiletingasanadjuncttreatment)inReview1:Antibiotics-topical)
CONFIDENTIAL-Chronicotitismediascopingdocument 10
(Tentative)Reviewshortname2
Pair Population3
Intervention4
Comparison
Comments5 Mainclinicalquestions
usedasanadjuvanttreatmentinbotharms(e.g.topicalantiseptics).
otherinterventions(e.g.topicalantibiotics)?
4. CED Antibiotics-systemic
Systemicantibiotics(otherclasses)
7. Whichtypeofsystemicantibioticismoreeffective(whentheyarecomparedtoeachother)?
8. Whichsystemicantibioticismoreeffectivewhenaddedtootherinterventions?
3. Antibiotics-topicalversussystemic
5. CED Antibiotics-topical
Antibioticssystemic
ThisisthemaincomparisoncoveredbythecurrentCochranereviewofsystemicversustopicaltreatment,whichincludesninestudies.
9. Whataretherelativeeffectsoftopicalantibioticscomparedwithsystemicantibiotics(forthesameantibiotic)?
10. Whataretherelativeeffectsoftopicalantibioticscomparedwithsystematicantibiotics(fordifferentantibiotics)?
4. Topicalantibioticversustopicalantiseptic
6. CED Antibiotics-topical
Antiseptics
Thismayinvolvemanycomparisonpairsofdifferentclassesofantibioticcomparisons.
11. Whataretherelativeeffectsoftopicalantibioticscomparedwithantiseptics?
12. Whataretherelativeeffectsoftopicalantibioticscomparedwithantisepticswhenaddedontodifferentinterventions?
5. Auraltoileting
7. CED Auraltoileting
Noauraltoileting
13. Areauraltoiletingmethodseffective(comparedtonotreatment)?
14. Areauraltoiletingmethodseffectivewhenaddedtootherinterventions(e.g.auraltoileting,systemicantibiotics)?
8. CED Auraltoileting
Auraltoileting(anothe
Thisincludescomparingthevariousdifferentauraltoileting
15. Whataretherelativeeffectsofdifferentauraltoiletingmethods?
CONFIDENTIAL-Chronicotitismediascopingdocument 11
(Tentative)Reviewshortname2
Pair Population3
Intervention4
Comparison
Comments5 Mainclinicalquestions
rmethod)
methodsandwhetherantisepticswereusedduringorimmediatelyaftertheauraltoiletingsession.
16. Whataretherelativeeffectsofdifferentauraltoiletingmethodswhenaddedontootherinterventions(e.g.topicalantibiotics)?
6. Antiseptics
9. CED Antiseptics
Placeboornointervention
Thiswillincludestudieswhereanotherinterventionisusedasatreatmentinbotharms(e.g.auraltoileting).
Inthiscaseauraltoiletingversusauraltoiletingwithantisepticsrelatestothedailyuseofantisepticsaftertheauraltoileting
17. Aretopicalantisepticseffective(comparedwithnotreatment)?
18. Aretopicalantisepticseffectivewhenaddedtootherinterventions(e.g.auraltoileting,systemicantibiotics)?
10. CED Antiseptic Otherantiseptics
19. Whataretherelativeeffectsofdifferentantiseptics?
20. Whataretherelativeeffectsofdifferentantisepticswhenaddedontootherinterventions(e.g.topicalantibiotics)?
7. Topicalcorticosteroids
11. CED Topicalcorticosteroids
Placeboornointervention
Thiswillincludestudiesthatlookattheimpactofaddingatopicalcorticosteroid(e.g.topicalcorticosteroidsplustopicalantibioticsversusanidenticaltopicalantibiotic).
21. Aretopicalsteroidseffective?
22. Aretopicalsteroidseffectivewhenaddedtootherinterventions(e.g.topicalantibiotics)?
12. CED Topicalcorticosteroids
Othertopicalsteroids
Thiswilllookatstudiesinvestigating
23. Whataretherelativeeffectsofdifferenttopicalsteroidpreparations?
CONFIDENTIAL-Chronicotitismediascopingdocument 12
(Tentative)Reviewshortname2
Pair Population3
Intervention4
Comparison
Comments5 Mainclinicalquestions
differenttypesofcorticosteroids(e.g.AntibioticAplustopicalsteroidBversusantibioticAplustopicalsteroidC)
24. Whataretherelativeeffectsofdifferenttopicalsteroidswhenaddedtootherinterventions?
13. CED Topicalcorticosteroids+otherinterventions
Placeboornointervention
25. Isacombinationoftopicalsteroidsplustopicalantibioticeffective?
26. Isacombinationoftopicalsteroidsplusantibioticseffectivewhenaddedtootherinterventions?
14. CED Topicalcorticosteroids+otherinterventions
Otherinterventions
E.g.Topicalcorticosteroidsplustopicalantibioticsversusanothertopicalantibiotic
27. Whataretherelativeeffectsofacombinationoftopicalantibioticsplustopicalsteroidswhencomparedtootherinterventions?
28. Whataretherelativeeffectsofacombinationoftopicalantibioticsplustopicalsteroidswhencomparedotherinterventionswhenbothgroupsalsoreceiveanotherintervention?
8. Antifungals
15. CED Antifungals
Placebo
16. CED Antifungalsplusotherinterventions
Otherinterventions4
9. Decongestants
17. CED Decongestants
Placebo
18. Decongestants
Otherinterventions4
10. Antihistami 19. CED Antihista Placebo
CONFIDENTIAL-Chronicotitismediascopingdocument 13
(Tentative)Reviewshortname2
Pair Population3
Intervention4
Comparison
Comments5 Mainclinicalquestions
nes
mines
20. Antihistamines
Otherinterventions4
11. Surgery
21. CSOM–specificdiagnoses
Surgery Nosurgery
22. Specificdiagnoses
Surgery Astep-upinconservativetherapy
23. CSOM-diagnoses
Surgery Anothersurgicalmethod
14
3 REVIEW METHODS
WewillusestandardCochranesystematicreviewmethodology.Inaddition,wewillalsoensurethattheformulationofreviewquestionsandinterpretationofeffectsareinlinewiththerecommendationsofGRADEandwiththeNICEguidelinesmanual.Fullprotocolswillbepublishedbeforethereviewsareconducted.Onlythemethodsthatarespecifictothesereviewsarehighlightedhere.
3.1 SEARCHES Systematicsearchesforrandomisedcontrolledtrials(RCTs)andcontrolledclinicaltrialswillbeconductedusingthestandardCochranemethods.
3.2 TYPES OF RESEARCH DESIGNS CONSIDERED FOR REVIEW Wewillincluderandomisedcontrolledtrials,includingcluster-randomisedtrialsandquasi-randomisedtrials.
Wewillnotincludecross-overtrialsforpharmacologicalinterventions,sinceCSOMisnotexpectedtobeastablechronicconditioniftreatmentiseffective.
Wewillnotexcludestudiesthatrandomisedpatientsbyear(within-patientcontrolled).Thesestudieswillonlybeincludedifdataarepresentedinawaythatallowsanalysisaspairwisedataandiftheinterventionsstudieddonothavespecificpropertiesthatmakethemunsuitableforrandomisationbyear(e.g.systemictreatments).
Wewillonlyincludestudieswherepatientswerefollowedupforatleast1week.
3.3 DATA EXTRACTION, RISK OF BIAS ASSESSMENT WewillusethecurrentstandardsforCochraneReviewprocess.
Allthereviewswillshareacommonsetofoutcomemeasuresofeffectivenesstoensurecomparabilitybetweenreviews.Thetypeofadverseeffectsforeachreviewwillbedependentontheinterventionsevaluated.
3.4 ANALYSIS, SUBGROUPS AND POOLING OF EVIDENCE
3.4.1 Subgroup analys is Subgroupsareusedtoinvestigatefactorsthatcanaffecttherelativeeffectivenessofinterventions.
3.4.1.1 We wil l consider the fol lowing POPULATION subgroups in the meta-analysis : 1. DiagnosisofCOM:itislikelythatsomestudieswillincludepatientswithchronicear
dischargebutwhohavenothadadiagnosisofCOM.Therefore,wewillsubgroupstudieswheremostpatients(80%ormore)metthecriteriaforCOMdiagnosisinordertodeterminewhethertheeffectoftheinterventionisdifferentcomparedtopatientswheretheprecisediagnosisisunknownandinclusionintothestudyisbasedpurelyonchroniceardischargesymptoms.
2. Patientage(veryyoungpatientsversusyoungpatientsversusadults16yearsandabove).3. Durationofeardischarge(morethansixweeks’versuslessthansixweeks)
15
4. Othersubgroups–cleftpalate,DownSyndromeandspecificethicgroupsknowntohavepotentialanatomicaldifferences,suchasIndigenousAustralians.
3.4.1.2 We wil l consider the fol lowing INTERVENTION subgroups in the meta-analysis :
WewillusethefollowingconsiderationsfortheanalysisofeachINTERVENTIONgroup:
Antibioticclass:Wewillanalyseeachantibioticclassassubgroups.Forsystemicantibiotics,wewillconsiderthebioavailabilitypriortopooling.Wewillincludemoredetailedanalysisplansinthereviewprotocolandtheywillbesetoutaprioribeforethereviewscommence.
Auraltoileting:Wewillconsiderthevariousmethodsofauraltoiletingassubgroupsandpoolthemifthereisnoevidenceofadifferenceineffects.Thetypeofsolutionusedduringauraltoiletingwillalsobeconsideredwhensubgroupingtheinterventions.
Antisepticagent:Wewilltreateachtypeofantisepticasaseparatesubgroupunlessthereisinformationthattheysharethesamemechanismofactionandareusedinthesameway(e.g.thesameeffectiveconcentrationlevelsandwhethertheyareusedasstand-alonedropsoraspartofanauraltoiletingprocedure).
3.4.2 Time points of outcomes measurement Toavoidmultiplicityofanalysisorreviewerbias,wewillpredeterminethetimepointsforanalysisforeachoutcome,andwewillonlyusethelongestavailabledatafromthestudywithinthespecifiedperiodintheanalysis.Wewillspecifythetimepointsfordataanalysisintheprotocolforeachinterventionreviewandtakeintoconsiderationboththemechanismsofactionoftheintervention-comparisonpairinvolvedandthenaturalhistoryofCOM.
3.5 RATING OF QUALITY OF EVIDENCE WewillratethequalityofevidenceusingtheGRADEcriteriaforsystematicreviews.