© NIHS2006
PublishedbyDesignersInk,Limerick
Allorpartofthispublicationmaybereproducedwithoutfurtherpermission,provided
thesourceisacknowledged.
22Charge
Section 1: introduction 01
¢ PurposeoftheGuide 01
¢ ResearchversusAudit 01
Section 2: reSearch concept and hypotheSiS 03
Section 3: Study deSign and protocol development 05
¢ 3.1 CategoriesofResearch 05
¢ 3.2 Randomisation 06
¢ 3.3 Blinding 06
¢ 3.4 Methodology 07
¨ 3.4.1 InformationSource 07
¨ 3.4.2 DataCollection 08
¨ 3.4.3 Sampling 09
¨ 3.4.3(a) Power 09
¨ 3.4.3(b) SampleSizeCalculation 09
¨ 3.4.4 DataManagement 10
¨ 3.4.5 DataAnalysis 11
¨ 3.4.6 DataPresentation 13
¢ 3.5 AssessmentofSubjectComplianceandWithdrawal 14
¢ 3.6 EthicalConsiderations 14
¢ 3.7 InterimReports 14
Section 4: ethicS and health reSearch 16
¢ 4.1 WhentoSeekEthicalApproval(Guideline) 16
¢ 4.2 EthicsCommitteesAuthorisedtoProvideApprovalfor 18
ClinicalTrialsonMedicinalProductsforHumanUse.
¢ 4.3 AdditionalLegalIssuestoConsider 19
Contents
i
Section 5: propoSal development 20
¢ 5.1 TitlePage 20
¢ 5.2 Introduction 20
¢ 5.3 BackgroundandRationale 20
¢ 5.4 Methodology 21
¢ 5.5 BudgetaryRequirements 21
¢ 5.6 Linkages 21
¢ 5.7 Dissemination 22
¢ 5.8 LiteratureReview/Bibliography 22
Section 6: publiShing 24
¢ 6.1 Abstract 24
¢ 6.2 Introduction 24
¢ 6.3 Materials/SubjectsandMethods 24
¢ 6.4 Results 25
¢ 6.5 Discussion 25
¢ 6.6 Bibliography 26
Section 7: reSearch and integrity 27
¢ 7.1 Plagiarism 27
Section 8: referenceS 28
¢ Appendix1 31
¢ Appendix2 35
¢ Appendix3 37
Contents
ii
01
1.1 purpoSe of the guide
Thegoal increatingthisdocument is tosupplyhealthcareworkerswithguidanceon
howtoplanandexecutetheirresearchprojectsinordertoproducegoodqualitydatafor
analysis.Theinformationsuppliedisintendedtoactasaguidethroughthekeystages
in conducting research and to provide some assistance to both the novice andmore
experiencedresearcheralike.
1.2 reSearch verSuS audit 26
Itisimportanttoensurethatyourinvestigationisactualresearchandnotanaudit.An
audit “determineswhetherexistingclinical knowledgeskills and resourcesarebeing
properlyused…andtheprimaryaimofaudit isto improvethedeliveryofhealthcare”.
Incontrast“research isconcernedwithgeneratingnewknowledgewhichwillhavea
generalapplication”and“seekstoinfluenceclinicalpracticeasawhole”.
Introduction 1sectionone
02
Beforeundertakingaresearchprojectitisessentialtodevelopaclearconceptanddefine
thehypothesisyouwanttotest.there are several sources of information available to
achieve this:
¢ Yourownorsupervisor’sknowledgeandexpertise
¢ Review current literature published on the topic. This information can be
accessedvialibraryorinternet:14
¨ Usefulinternetsitesinclude:
• IrishMedicalOrganisation(www.imo.ie)
• HealthDiscovery(www.healthdiscovery.com)
• NationalLibraryofMedicine(www.nlm.nih.gov)
• PubMed(www.PubMed.gov)
• HealthontheNet(www.hon.ch/)
• MedlinePlus(www.medlineplus.gov/)
• Sciseek(www.sciseek.com/)
• Biocrawler(www.biocrawler.com/)
• HSELibrariesOnline(www.hselibrary.ie)
¢ ConsultCochranereviewsonthetopicwww.thecochranelibrary.com
Althoughtheinternetcanbeaveryusefulresource,itisimportanttocriticallyevaluate
thequalityoftheinformationyouretrieve.Keepinmindtheaccuracy,reliability,relevance,
objectivityandauthorityoftheinformationyouaresourcing.
Onceyouhaveanalysedtheinformationrelevanttoyourtopicofresearchitisimportant
torefineyourresearchideaandclarifythespecificgoal(s)andobjective(s)ofthestudy.
consider whether you research is: 9
¢ Descriptive–whatishappening?
¢ Explanatory–howandwhyithappens?
¢ Predictive–whatorhowitwillhappen?
Alsoconsideriftheresearchisappliedorbasicandmakesuretoavoidlargescopethat
isvagueandnotclearlyspelledout.Keepinmind;Who?What?Where?When?Why?and
How?
ResearchConceptandHypothesis 2
03
sectiontwo
Once you have clarified your ideas, determine from whom/what you will get your
information, and if your sources of data will be from subjects directly or from the
recordsofsubjects.Itisimportantatthisstagetoconsidertheresearchtechniquesand
methodologiesyouwilluseandyourgeneralexperimentaldesign.
also consider the following:
¢ Wherewilltheresearchbeconducted?
¢ What resources are available in terms of equipment, people, funding
andfacilities?
04
2sectiontwo
Yourresearchprojectshouldbeconceived,designedandimplementedaccordingtothe
highestpossiblestandards.13, 18, 19Developmentofyourresearchprotocol isakeystep
andnormallyapre-requisiteforethicalapprovalandfundingapplications.Itformsthe
blueprintforhowthestudywillbeconducted.Itshoulddescribethedesign,methodology,
statisticalconsiderationsandorganisationofthestudy.
3.1 categorieS of reSearch:
Choosethetypeof researchyouwillbeconducting. the options include but are not
limited to: 1, 2
¢ obServational: analytic and deScriptive
Examplesinclude:
¨ caSe-control StudieS
• Investigational samples are chosen on the basis of their
diseaseoroutcomeofinterest
• Controls should be sourced from a similar population but not
havetheoutcomeofinterest
¨ cohort-StudieS
• The exposure of interest should be clearly described and
usedtoclassifytheexposedgroup
• Internal comparison group without exposure of interest will
beused
¨ croSS-Sectional StudieS
• Exposure status and disease status are assessed at a single
pointintime
• Provides useful data on the health status of the population at
agiventime
¨ caSe reportS
StudyDesignandProtocolDevelopment 3
05
sectionthree
sectionthree
¢ eXperimental (see Appendix 2)
examples include:
¨ ClinicalTrials
¨ Non-interventional trials (including randomised controlled trials)
asdefinedbyEUdirectiveMay20047
¨ Non-clinical trials (may involve physiological studies, development
of health and disability services and use of secondary data for
epidemiologystudies)
¨ Experimental studies can be designed in parallel, crossover and
factorialfashion
3.2 randomiSation 24
Inordertominimizebiassubjectsaregenerallyrandomisedtothevarioustreatmentor
testgroups.the randomisation can be:
¢ Stratified
¢ Blocked
¢ Systematic
¢ Clustered
3.3 blinding 20, 21
Blindingcanalsobe introducedtoreducebias.Theblindingapproachusedwillneed
EthicsCommittee(EC)approval.there are two types of blinding;
¢ Single blind:Eitherthepatient/subjectorinvestigatorisnotawareofthe
treatmentbeenadministered.
¢ double blind:boththepatient/subjectandinvestigatorarenotawareofthe
treatmentbeingadministered.
Doubleblinddesignmaynotalwaysbepossiblee.g.insurgicaltreatments
3
06
sectionthree
ItisadvisabletoinvolveaqualifiedBiostatisticianinordertoensurethattheappropriate
study design approach is used. the expertise of a biostatistician will facilitate the
following:
¢ Selectingasuitablesamplefromyourpopulationofinterest
¢ Ensuringthatthesamplesizewillgiveyouenoughpower
¢ Choosingthecorrectstatisticalapproachtodataanalysis
StatisticalsupportisfreelyavailabletoHSEemployeesintheMid-WestRegionthrough
theStatisticalConsultingUnitattheUniversityofLimerick.
¢ Statistical consulting unit
UniversityofLimerick
tel: +35361213471
mob: +353863866353
fax: +35361334927
email [email protected]
3.4 methodology
3.4.1 information Source 20
The protocolmust detail the source of your data/information. in the case of healthy
volunteers or patients, provide specific details on:
¢ Howindividualsaresourced
¨ Thepublicdomain
¨ Aclinic
¨ Aregister
¢ Whatinclusion/exclusioncriteriawereapplied
¢ Therecruitment/enrolmentprocess
¢ Iftherewaspayment/compensationinvolved
¢ Howpatientconsentwasobtainedanddetailsofinformationsheetssupplied
3
07
sectionthree
3.4.2 data collection
Datacollectionmethodsinclude:9
¢ Surveysandquestionnaires(usingscales,measuresandindices)
¢ Experimentaltests,proceduresandscreens
¢ Interviewsandfocusgroups
Ensurethatyouhaveconsideredwhatyourreferencepointorcontrolwillbe,i.e.thatwith
whichyoucancompareyourdata.Thedatayouneedtocollecttotestyourhypothesis
maybequantitative,qualitativeorboth.Qualitativedatacanbeobtainedfromstructured
or semi-structured interviews, focus groups, surveys, questionnaires, photographs,
videosandsoundrecordings.this type of data is useful for: 6, 15
¢ Describingcomplexsituations
¢ Providinganinsightintohowpeoplemakesenseofexperiences
¢ Intheinitialexploratoryphaseofathemeofinvestigation
¢ Tofurtherenhanceorexplainquantitativedata
Quantitativedataistypicallynumericalandcanbesourcedfromsurveys,questionnaires,
andarangeoflaboratoryandclinicalprocedures.2
group Sub-group examples
Categorical(Qualitative) Nominal Gender,bloodgroup
Ordinal Indicesassociatedwith
diseasegradese.g.
cancertumours
Numerical(Quantitative) Continuous Resultsfrommeasuring
thingse.g.weight,time
spentwaiting
Discrete Wholenumbersandarise
fromcountingthings
3
08
sectionthree
3.4.3 Sampling 9, 21, 24
Appropriate sampling is a critical part in the data collection process.representative
samples can be obtained from a target population in several ways:
¢ Systematicsampling-may be atypical
¢ Randomsampling-best option when trying to avoid bias
¢ Conveniencesampling-bias may be hidden
Itiscriticaltotheoutcomeoftheresearchthatasufficientsamplesizeisanalysedto
detectadifferencebetweencontrolandtestgroups.Ifastudyistoosmallitmaylack
powertopickupdifferences.Thesamplemustbe largeenoughtoavoidproducinga
falsenegativeresult.
3.4.3(a) power
Theprobabilityofdetectingatruedifferenceiscalledpower(1-β).
the power of a study is low when:
¢ Largevariabilityexistsbetweenthedataandthestandarddeviationislarge
¢ Smallsamplesize
¢ Tryingtodetectsubtledifferences
Themajority of studies seek to have a power of 80-90%. This can then be used to
calculatethenumberofsubjectsthatarerequiredtodetectaminimumclinicallyrelevant
difference
3.4.3(b) Sample size calculation(whenyouhavecontinuousdata–parametersknown)
Quantify the following:
¢ Power:(1-β);β=0.2to0.3
¢ SignificanceLevel(α):Thelevelbelowwhichthenullhypothesisisrejected
(seepage12)
¢ StandardDeviation(σ)
3
09
sectionthree
¢ Smallesteffectofinterest/clinicallyrelevant(δ)
¢ Standardiseddifference=(δ/σ)=Ds
RefertotheAltmanPowerPlotforf(α,β)
n*ineachgroup=f(α,β)x2σ2/(μ1–μ2)2=f(α,β)x2/Ds
2
Assumesequalnumbersineachgroup
Forsamplingandsamplesizecalculations(includingpowercalculations)aBiostatistician
shouldbeconsultedunlessyouhaveexperienceinthisarea.Samplesizingmethodology
dependsontheprimaryoutcomevariabletypeandisnotalwaysasstraightforwardas
examplegivenabove.
3.4.4 data management 20
Informationmustbeprovidedontheapproachusedtoobtainresearchdataintermsof
experiments,testsandprocedures.efficient and accurate data management in research
is key, and the following information should be stated:
¢ Thesourceofdata
¢ Whowillcollectthedata?
¢ Isthedataaccuratecompleteandunbiased?
¢ Thetimepointsforcollections
¢ Whythedataisbeingcollected(e.g.baselinecomparison,primary
outcomeetc)?
¢ Mentionuseofstandardisedtools
¢ Theforminwhichthedatawillbepresented.
¢ Methodofdatahandling,recoding(paper/electronicandback-ups)security
andretention
¢ Methodsused for data transfer, protection and storage–must adhere to the
DataProtectionAct5
¢ Patient/healthyvolunteerconfidentialitymustbemaintainedatallstages
oftheresearch
3
10
sectionthree
3.4.5 data analysis
analysis of Qualitative data 6, 9, 15
¢ Collect
¢ Reduce
¨ Usingnumberssuchaspercentages
¨ Identifyrecurringconcepts,themesandgroupings
¢ Drawconclusionsandverify
Thereareanumberofcomputerprogrammesavailableforqualitativeanalysisofdata
includingNUD*IST,ATLAS,QUALRUSandNVIVO.
analysis of Quantitative data 2, 12, 21, 23
basic characteristics of Quantitative data
As previously stated a Biostatistician should be consulted during the study design
andmethodologystage.Atthispointsuitableapproachestostatisticalanalysiscanbe
identifiedtosuitthetypeofdatacollected.
Summaries include:
¢ MeasuresofCentralTendency
¨ Mean;average
¨ Median;middlevalue
¨ Mode;mostcommonvalue
¢ MeasuresofVariability
¨ StandardDeviation;variationaboutthemean
¨ Inter-quartilerange
¨ Range
3
11
sectionthree
InferencescanbemadeaboutdatathroughconstructionofConfidenceintervalsand/or
Hypothesistesting.Theprotocolshouldprovideasummaryonthestatisticalanalysis
thatwillbeperformedandtheformatinwhichthedatawillbepresented.
Statistical inference:
ConfidenceIntervalEstimation(CI)
¢ Involvesusinganintervaltoestimatethepopulationparameter.Usuallysetat
95%andindicatesthataresearcheris95%confidentthatthedatarepresents
aplausiblerangeofvaluesforthetruepopulationvalue.ThenarrowertheCI
thebetter.
HypothesisTesting
¢ Theresearchobjectiveisoftenexpressedintheformofanullhypothesis.The
nullhypothesisstatesthatnodifferenceexistsbetweencontrolandtestgroups.
ThePvalueistheprobabilityofaresultoccurringbychance.
Ifthepvalue<0.05–thenullhypothesisisrejected,thisimpliessignificance
Ifthepvalue>0.05-donotrejectthenullhypothesis
Sufficientpowerisrequiredtoavoiderrors.
errors in hypothesis testing:
type i error
A difference is detected yet no difference exists - false positive. This probability is
denotedαisequaltothesignificancelevel(usually5%).Thistypeoferrorcanoccurif
thesampleisbiasedand/ortoosmall.
3
12
sectionthree
type ii error
No difference is detected but a difference exists - false negative. This probability is
denotedβand20%isusuallyanacceptablelevel.
Thetypesofhypothesistestsusedtocalculatethep-valueincludethechi-squaredtest
ofassociationandthet-testdependingonthetypeofvariabletobetestedandthenull
hypothesisstated.
3.4.6 data presentation
Datacanbepresentedasfractions,proportions,ratesandwholenumbers.Thedatacan
beformattedinseveralways. examples include:
¢ Tables–synopsisofrawdata,usuallyintheformofmeansandstandard
deviations
¢ Graphs–x-axisindependentvariable(treatment),y-axisdependentvariable
(totalsormeans)
¨ Histograms
¨ Boxplots
¨ Linegraphs
• Usefulinshowingdatapointsovertime
Thejuxtapositionoftwodifferentsetsofdatacancreategoodvisualeffect.
Inadditionerrorbarscanbeusedtoshowthelevelofvariabilityaboutthemean.
¢ Pie Charts – can be used to display the contribution of each treatment to
thewhole
for further information on graphing data visit:
www.bettycjung.net/Graphing.htm
www.scene.asu.edu/habitat/data_present.html
3
13
sectionthree
3.5 aSSeSSment of Subject compliance and WithdraWal 20
¢ Whatsystemswillbeusedtomonitorpatient/volunteercompliance?
¨ Howwillalapseincomplianceberecorded/andfollowed-up?
¢ Asubjectcanwithdrawfromastudyatanytimeandforanyreason
¨ Howwillawithdrawalbedocumented?
¨ Willthesubjectbefollowed-up?
3.6 ethical conSiderationS
TheresearcherneedstodetermineifapprovalfromanECisnecessarytoconductthe
research(seeSection4).IfECapprovalisdeemednecessarythenpatientconsentforms
andinformationsheetsmustbepreparedandthensuppliedtotheappropriateEC.
3.7 interim reportS
WhereappropriatethePrincipalResearchershouldcoordinatethegenerationofinterim
reportssummarisingtheprogressoftheresearch.
the production of interim reports would generally be necessary when conducting:
¢ Clinicaltrials(includingtrialsonmedicinalproductsasdefinedbyEUDirective,
May2004)7
¢ Non-interventionalandnon-clinicaltrials
¢ Longitudinalinvestigations
interim reports are generally not necessary for:
¢ Short-terminvestigationsusingsmallsamplesizes
¢ Cross-sectionalstudies
3
14
sectionthree
Interim reportsmaybe requestedby theECthatprovidedapproval for thestudy, the
instituteorhospitalhostingtheresearchorthefundingbodythatprovidedthefinancial
supporttoconducttheinvestigation.Theformatofthereportwillvarydependingonthe
bodythathasrequestedtheinformation.it may be in the form of:
¢ Anabstractorsummary
¢ Scientific/MedicalPaper
Details may be required on resource personnel, expenditure as well as significant
scientific andmedical output. In general, dissemination in science, health and public
domainsisalsorecommendedwhereappropriate.
3
15
Healthresearchersneedtoconsiderifethicalapprovalisarequirementtoconducttheir
specificinvestigation.ThedeclarationofHelsinkifromtheWorldMedicalAssociationin
June1963outlinedtheguidelinesthatmedicalpractitionersandresearchersmustfollow
when engaging in trials that involve human subjects. This declaration also provides
ethicscommitteeswithguidanceanddirectionwhenreviewingresearchorclinicaltrial
applicationsinvolvinghumansubjects.
PrinciplesofEthicalReview(AsoutlinedbytheIrishCouncilforBioethics,
websitewww.bioethics.ie):17
¢ Respectforpersons
¢ Privacyandconfidentiality
¢ Validityofresearchproposals
¢ Minimalrisktoparticipants
¢ Toneitherdiscriminateorneglectindividuals
Researchinvolvinghumanparticipantsincludesbutisnotlimitedtoclinicaltrials.EC’s
are located throughout Ireland in hospitals, universities and research institutions to
reviewapplicationstoconductresearchinvolvinghumanparticipation.
4.1 When to Seek ethical approval (guideline)
Researchproposalsthatinvolvehumanparticipationorthecollectionanduseofprimary
andsecondarydatamayrequirereviewbyanEC.the text below summarises when a
researcher may require ethical approval from and ec:
mayRequireECApproval:17
¢ Clinicaltrialsonmedicinalproducts/medicaldevicesinvolvinghumans
¢ Newtreatmentorinterventions
¢ Research involvinghumanremains,cadavers, tissues,discardedtissuesand
biologicalfluids
¢ PhysiologicalStudies
4 EthicsandHealthResearch
16
sectionfour
¢ Comparinganestablishedprocedure(therapeuticordiagnostic)withprocedures
notestablished
¢ Innovativepracticesinhealthanddisabilityservices
¢ Observationalclinicalresearch
¢ Researchconductedbystudentsthatinvolveshumanparticipants
¢ Surveysorquestionnairesusedtocollectpersonalinformationonindividuals
¢ Useofdataderivedfromindividualrecordswherepeoplemaybeidentified
¢ Casestudieswithaseriesofsubjectobservationstoextrapolategeneralisations
withtheintenttopublish/disseminatedata
may notRequireECApproval:
¢ Researchusingexistingpubliclyavailabledataordocuments
¢ QualityAssuranceStudies*
¢ Audit*
¢ Casestudyof1patientwheninformedconsenthasbeenobtained
¢ Observationalstudiesinpublicplaceswhentheidentityofthepersonsremains
anonymous
* This statement does NOT imply that all quality assurance studies and audits are exempt
from ethical approval. That will depend on the source on the information and whether
confidentiality of patients or participants may be compromised.
Whenindoubtastowhetheryourresearchproposalorprojectrequiresethicalapproval
thenanECshouldbeconsultedfortheiropinion.
the documentation required by the ec to consider an application for ethics approval
generally includes but is not limited to:
¢ Signedanddatedapplicationform
¢ Protocol
¢ If a product (e.g. Pharmaceutical) is being assessed then a summary of all
pharmacological, toxicological and clinical experience data on a product or
deviceunderinvestigation.
¢ Casereportforms,patientinformationsheet,diarycards,questionnairesand
consentforms.
4
17
sectionfour
¢ CurriculumVitaeofallinvestigators
¢ Processusedtoobtainconsent
¢ Arrangementsmadetoindemnifyvolunteersandinvestigators
¢ All otherECdecisionsmade in relation to theproposal andanysubsequent
amendmentsthatweremade
¢ Descriptionoftheethicalconsiderationsinvolvedintheproposal
4.2 ethicS committeeS authoriSed to provide approval for clinical trialS on medicinal productS for human uSe
Therearecurrently13ECsinIrelandthathavebeenauthorisedtoprovideapprovalforof
clinicaltrialsonmedicinalproductsasdefinedintheEuropeanDirectiveonClinicaltrials
onMedicinalProductsforHumanUse(May2004).7Whenconductingclinicaltrialson
medicinalproductsforhumanuseguidanceonapplicationsforrecognisedECopinion
maybefoundat:www.dohc.ie/issues/clinical_trials_2004/
TheECsalsofunctiontoprovideapprovalforthemanyotherformsofhealthresearch
includingnon-clinicaltrialsandobservationalstudies.
See Appendix 1 for details on each committee.
See Appendix 3 for additional information on ECs operating in the Mid-West Region.
4
18
sectionfour
4.3 additional legal iSSueS to conSider
¢ AllClinicalTrialsonMedicinalProductsmustbeapprovedbytheIrishMedicines
Board7
¢ WhenconductingClinicalTrialsonMedicinalProductstherecommendations
detailed in the EU Directive, May 2004 must be adhered to.7 In addition
investigatorsmustfollowtherecommendationsoutlinedintheEUDirectiveon
GoodClinicalPractice(GCPDirective2005/28/EC)8
¢ Incaseswhereuseandstorageofbiological tissue isnecessaryaspartof
a research protocol the principle investigator should insure that the
recommendations outlined by The Irish Council for Bioethics are followed
(HumanBiologicalMaterial:RecommendationsforCollectionUseandStorage
inResearch2005).16
¢ AwarenessofDataProtectionLaws(seeDataProtectionAct1988)5
¢ That appropriate insurance is in place at the study site and that individuals
conductingthestudyareindemnified
¢ TheControlofClinicalTrialsActs1987and1990shallapplytoclinicaltrialsnot
subjecttotheRegulationsoutlinedintheEUDirective,May2004
(www.dohc.ie)
¢ Inthecaseofresearchandtrialsinvolvingthedevelopmentofmedicaldevices
researchersshouldadheretoGoodManufacturingPractice(GMP),andcomply
with the EU Medical Device Directives (see www.ec.europa.eu/enterprise/
medical_devices/index_enhtml).Ifthedevicewillbetestedanddevelopedwith
aview tomarketing in theUnitedStates theFood andDrugAdministration
(FDA)hassetoutarangeofguidelinesthatmustbefollowed(seewww.fda.
gov/cdrh/devadvice/)
4
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sectionfour
5.1 title page 20
both a full title and short title are required:
¢ Thefulltitleshoulddetailasummaryofstudydesign,exposureandoutcomes
ofinterest,patientpopulationandsetting.
¢ Theshorttitleissummaryoftheabove.
also include details of:
¢ Authors,investigatorsexpertsandadvisorsinthestudy(includingCurriculum
Vitae)
¢ Studysite:Clinical laboratory,technicaldepartments,clinicsand institutions
involvedinthestudy
¢ Acontentspage
¢ Listanddefinitionofabbreviations
5.2 introduction
Stateclearlytheaimoftheproposedresearch.Thisisgenerallyabroadstatementof
intent. Subsequentlyelaborateonhowthegoal(s)willbeachieved.The introduction
shouldalsocontaindetailsonthestrategy(ies)youwillemploytoachieveyourgoals
andobjectives.
5.3 background and rationale
Summariseswhyyouareconductingtheresearch,referencingwhathasbeenpublished
thus far in the area, how you plan to add to the knowledge base, who will benefit
frompotential outcomes,will benefits includepotential discoveryof newprocedures,
treatmentsorhaveapositivefinancialoutcome?
5 ProposalDevelopment
20
sectionfive
5.4 methodology
include details of the following:
¢ Studydesignchosenandwhy
¨ RandomisedControlledTrials,observationalstudyetc.
¢ Datasource,collection,storageandprocessing
¢ Subjectsandsamplesize(astatementshowinghowsamplesizewascalculated
whenappropriate)
¢ Patientinformationsheetsandconsentforms
¢ Ethicalapproval(ifnecessaryforthestudy)
¢ Methodofstatisticalanalysis
5.5 budgetary reQuirementS
Supplyconcisedetailsofpredictedongoingrunningcostsincludingstaffandnon-staff
costs(equipment,transportetc).Ifrelevanttothefundingcallcapitalcostsshouldalso
beaddressed.
5.6 linkageS
describe linkages to other national and international research cohorts:
¢ Highlightanyrelevantcollaboratorsyouproposetoengagewithfortheduration
ofthestudy
¢ Highlight their specific areaof expertise andsuccessful outcomes fromany
previousworkthatyouhaveconductedwiththisgroup
¢ Mentiontheresources,techniquesandequipmenttheywillbringtothestudy
5
21
sectionfive
5.7 diSSemination
Describeyourplanstodisseminateinformation/resultsduringandattheconclusionof
yourresearchincludingmilestonesanddeliverables.consider the following:
¢ Howoftenandthroughwhatmediumdoyouplantopubliciseyour
researchdata?
¢ Considerusingseminars,conferences,researchpublications
¢ Whatisyourexpectedpublishingoutput?
¨ Willyoutargetlocal,regionalnationalandinternationalpeer
reviewjournals?
¢ Howwillyoumonitorthescientificandclinicalvalueofyourresearch?
5.8 literature revieW/bibliography
It is usual practice to use the Vancouver method when referencing journals and
texts. (International Committee of Medical Journal Editors Uniform Requirements
for Manuscripts Submitted to Biomedical Journals: www.nlm.nih.gov/bsd/uniform_
requirements.html)
¢ Standard journal article:e.g.
HalpernSD,UbelPA,CaplanAL.Solid-organtransplantation inHIV-infected
patients.NEnglJMed.2002Jul25;347(4):284-7.
¢ book or monograph: e.g.
MurrayPR,RosenthalKS,KobayashiGS,PfallerMA.Medicalmicrobiology.4th
ed.St.Louis:Mosby;2002.
¢ newspaper article:e.g.
TynanT.Medicalimprovementslowerhomiciderate:studyseesdropinassault
rate.TheWashingtonPost.2002Aug12;Sect.A:2(col.4).
5
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sectionfive
¢ World Wide Web page (no author):e.g.
Cancer-Pain.org[homepageontheInternet].NewYork:AssociationofCancer
OnlineResources, Inc.; c2000-01 [updated 2002May 16; cited 2002 Jul 9].
Availablefrom:www.cancer-pain.org
Pleasenotethateachfundinginstituteorbodywillusuallyhaveitsownspecifictemplate
intermsofdocumentlayoutandinformationrequested.Ingeneral,thedetailsrequired
willcoverthetopicsoutlinedabove.
national and international research funding bodies include:
HealthResearchBoard;www.hrb.ie
ScienceFoundationIreland;www.sfi.ie
EnterpriseIreland;www.enterprise-ireland.com
IrishResearchCouncilforScience,Engineering&Technology;www.ircset.ie
IrishCancerSociety;www.cancer.ie
IrishHeartFoundation;www.irishheart.ie
EuropeanUnion;www.welcomeeurope.com
WellcomeTrustFoundation;www.wellcome.ac.uk
5
23
sectionfive
the editorial committee of each journal has its own standards and guidelines that must
be adhered to for publication:
¢ Checkeachjournalspecificrequirementsbeforesubmission
¢ RefertotheGuidelinesonGoodPublicationPractice3
in general the basic sections of any journal will include most if not all of the following
topics;
6.1 abStract
This is a very short summary ofwhatwas investigated by the researcher andwhy.
It should summarise key results. In addition the key-words in the paper should be
highlightedundertheabstracttext.
6.2 introduction 4
This section should define the condition or problem being investigated and provide
background information and concept. These should then be linked to the hypothesis
beingtested.Theaimsandobjectivesoftheresearchmustbeclearlystatedatthispoint.
In addition, summarisewhat youhave foundandhow,describe the limitationsof the
studyandtheimportanceofyourfindings.
6.3 materialS/SubjectS and methodS
Provide details on the source of you data, ie patients, healthy volunteers, bio-banks,
records etc and detail your inclusion/exclusion criteria. State the study design, is it
experimentalorobservational?Supplyinformationonwhatwillbemeasuredandhow.
Will you be using gold standard approaches, if so, what are they? Also discuss the
6 Publishing22
24
sectionsix
statisticalmethods used to analyse your data, i.e. confidence intervals or hypothesis
tests.
6.4 reSultS
Datamaybepresentedintheform,oftables,chartshistograms,imagesetc.Eachfigure
detailing resultsmust have a legend underneath summarising the content. The body
oftext intheresultssectionshoulddescribeinamatteroffactwaythedataandnot
explainoraccountforthefindings.Thetextshoulddealwiththeeachfigureofdatain
chronologicalorder.
figures, tables and legends – critical for the paper’s success 4
¢ Mostimportantpartofpaper
¢ Mostneglectedpartofthepaper
¢ Shouldbethefirstparttobedesignedandwritten
¢ Partofthepaperthatdeterminessuccessorfailure
6.5 diScuSSion 4
Thissectionofthepaperallowstheauthortopresenthis/herinterpretationofthedata
anddiscussthelikelyimpactofthefindingsoncurrentbestpracticeinthespecificfield.
Italsoprovidestheauthorwiththeopportunitytonotethelimitationsofthestudyand
describefutureresearchthatmaybeconductedinthearea.
6
25
sectionsix
6.6 bibliography
Eachjournalwillspecifytheformatinwhichtopresentthebibliographythiswillusually
betheVancouvermethod(seesection5.8).
note:
in cases where the author plans to release the findings to the mass media all participants
in the study should be made aware of the findings in advance.
6
26
sectionsix
Aresearchermust conduct scientific/medical researchandpublish thefindings in an
ethicalmanner.Thefollowingactionsareconsideredunethicalpracticesinthescientific
andmedicalcommunities:3,10,11
¢ Piracy-exploitationofideasfromotherswithoutacknowledgement
¢ Plagiarism-copyingofideas,dataandtextwithoutacknowledgement
¢ Fraud-fabrication,falsification/inventionofdata
Beawarethatmultipleauthorshipdisputesarealsoverycommon.Thepracticeofgift
orguestauthorshipshouldbeavoided.Althoughthereisnouniversallyagreeddefinition
ofauthorshipitisessentialthatrolesinmatterofauthorshipandpublicationbeagreed
whenthestudyisbeingdesigned.Atthispointthelevelofcontributionandinputtothe
studydesignandexecutionthatisrequiredtowarrantauthorshipshouldbestated.
7.1 plagiariSm 25
ArecentarticleintheIrishExaminerhighlightstheproblemofplagiarismandthatthis
issueisnotconfinedtothosetryingtoestablishthemselvesearlyonintheircareers.The
authorcorrectlydescribesplagiarismastheblatant “disregard for the reputationand
hardworkofothers”
common unacceptable excuses include:
¢ Cutandpasteerrorononespersonalcomputerresultinginreferencesbeing
“inadvertentlyomitted”.
¢ Topleadignoranceasitisthefirstsubstantialworkonehaswritten.
Inordertoavoidtheinadvertentplagiarismpitfallandgeneralmisconductinscientific
andmedicalresearch,theCommitteeofPublicationEthics(COPE)hasproducedasetof
guidelinesprovidingadviceanddirection.3
7ResearchandIntegrity
27
sectionseven
1. Bland JM, Butland BK, Peackock JL, Poloniecki J, Reid F, Sedgewick P.
StatisticsGuide forResearchGrantApplicants [monographon the Internet].
No date [cited 2005Dec12]. Available from:www.sgul.ac.uk/depts/chs/chs_
research/stat_guide/guide.cfm#top
2. BowersD,HouseA,OwensD.UnderstandingClinicalPapers.JohnWiley&
Sons;2003.
3. Committee on Publication Ethics (COPE). Guidelines on Good Publication
Practice[monographonthe Internet].Nodate [cited2005Dec21].Available
from:www.publicationethics.org.uk/guidelines/reports/2003/2003pdf15.pdf
4. CostelloR.Gettingon:Asseenbysomeonewhoisgettingon[homepageonthe
Internet].c2000[cited2006Jan16].Availablefrom:www.nihs.ie
5. DataProtectionCommissioner.DataProtection(Amendment)Act2003[statute
ontheInternet].c2003[cited2006Oct17].Availablefrom:
www.dataprotection.ie/documents/guidance/New_Act_Summary_website_
version.pdf
6. Denzin,Lincoln.HandbookofQualitativeResearch.3rded.Sage;2005
7. DepartmentofHealth&Children. EuropeanCommunities (ClinicalTrialson
MedicinalProductsforHumanUse)Regulations,2004[statueontheInternet].
c2004[cited2005Nov25].Availablefrom:
www.dohc.ie/legislation/statutory_instruments/pdf/si20040190.pdf?direct=1
8. Department of Health & Children. European Communities (Clinical Trials on
Medicinal Products for Human Use) (Amendment no. 2) Regulations 2006
[statuteontheInternet].c2006[cited2006Sept3].Availablefrom:
www.dohc.ie/issues/consultation_good_clinical_practice_2006/Draft_
Regulations.pdf?direct=1
8
28
Referencessectioneight
9. Kane E. De- Bruin-O’ Reilly M. Doing Your Own Research. London: Marion
Boyars;2001
10. Fenton J. Integrity in Medical Research & Publication [homepage on the
Internet].c2005[cited2005Dec21].Availablefrom:www.nihs.ie
11. FentonJE,JonesAS. Integrity inMedicalResearchandPublication.Clinical
Otolaryngology.2002;27,436-439.
12. Gardner MJ, Altman Douglas G. Statistics with Confidence – Confidence
intervalsandstatisticalguidelines.London:BritishMedicalJournal,1994.
13. Wellcome Trust. Guidelines on Good Research Practice [monograph on the
Internet].c2002.[updated2005Nov;cited2005Dec6]Availablefrom:
www.wellcome.ac.uk/doc%5Fwtd002753.html
14. GuptaR.ConceptandIdea[homepageontheInternet].c2005[cited2005Dec
21].Availablefrom:www.nihs.ie
15. Houghton F. Qualitative Methodologies [homepage on the internet]. c2005
[cited2005Dec21].Availablefromwww.nihs.ie
16. IrishCouncil forBioethics.HumanBiologicalMaterial:Recommendationsfor
Collection,UseandStorageinResearch.Dublin: IrishCouncilforBioethics,
2005.
17. Irish Council for Bioethics. Operational Procedures for Research Ethics
Committees:Guidance2004.Dublin:IrishCouncilforBioethics,2004.
18. MedicalResearchCouncil;EthicsSeries.GoodResearchPractice[monograph
on the Internet]. c2000. [updated 2005Sept; cited 2006Nov 20]. Available
from:www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC002415
8
29
sectioneight
19. International Conference on Harmonisation of Technical Requirement for
Registration of Pharmaceuticals for Human Use (ICH). ICH Harmonised
Tripartite Guidelines; Guideline for Good Clinical Practice (GCP(E6.R1))
[monographontheInternet]c2002[cited2006Nov20]Availablefromwww.
emea.eu.int/pdfs/human/ich/013595.en.pdf
20. Medical Statistics Unit, UCLH R&D Directorate. Guidelines for Completing
aResearchProtocol forObservational Studies [monograph on the Internet].
c2006 [cited 2006 Sept 6]: Available from: www.uclh.nhs.uk/NR/rdonlyres/
066EBB58-BB0F-462A-908A-86DB5FB9216A/0/obs_protocol_guidelines_
2006.pdf
21. PetrieA,SabinC.MedicalStatisticsataGlance.BlackwellPublishing;2003.
22. BrownerW.Publishing andPresentingClinical Research. 2nd ed. Lippincott
Williams&Wilkins;2006.
23. SaundersJ,SCU,UniversityofLimerick.MedicalStatistics[homepageonthe
internet].2005[cited21December2005].Availablefrom:www.nihs.ie.
24. Saunders J, SCU, University of Limerick. Study Design & Methodology
[homepageonthe internet].2005 [cited18December2005].Available from:
www.nihs.ie
25. ProneT.CopyrightandCopyWrongs.IrishExaminer.2005Nov11.
26. CooperM,TurpinG,BucksR,KentG.GoodResearchPracticeGuidelinesforthe
ConductofPsychologicalResearchwithintheNHS.[monographontheInternet].
c2005 [cited 2006 Jan 17] Available from: www.bps.org.uk/downloadfile.
cfm?file_uuid=E615A15A-1143-DFD0-7E9F-60808ED2875D&ext=pdf
8
30
sectioneight
name of ethics address for date of area for description or class
committee correspondence recognition which of clinical trials
committee for which
may act committee may act
SJH/AMNCH TallaghtHospital, 13July Thewhole Clinicaltrialsof
ResearchEthics Dublin24 2004 State alldescriptions
Committee andclasses.
StVincent’s Administrator, 13Sep Thewhole Clinicaltrialsof
HealthcareGroup StVincent’s 2004 State alldescriptions
Ethicsand HealthcareGroup andclasses.
MedicalResearch Ethicsand
Committee MedicalResearch
Committee,
Educationand
ResearchCentre,
ElmPark,Dublin4.
ClinicalResearch Secretariat, 27Sep Thewhole Clinicaltrialsof
EthicsCommittee ClinicalResearch 2004 State alldescriptions
oftheCork EthicsCommittee andclasses.
Teaching ofTheCork
Hospitals TeachingHospitals,
2200CorkAirport
BusinessPark,
KinsaleRoad,Cork
HSENorthEast Secretary,HSE 26Jan Thewhole Clinicaltrialsof
AreaResearch NorthEastArea 2005 State alldescriptions
EthicsCommittee ResearchEthics andclasses.
Committee,Dublin
Rd,Kells,Co.Meath
Appendix1 8
31
sectioneight
name of ethics address for date of area for description or class
committee correspondence recognition which of clinical trials
committee for which
may act committee may act
ResearchEthics Administrator, 22Feb Thewhole Clinicaltrialsof
Committee,Mater ResearchEthics 2005 State alldescriptions
Misericordiae Committee,Mater andclasses.
UniversityHospitalMisericordiae
andMaterPrivate UniversityHospital,
Hospital EcclesStreet,
Dublin7
BeaumontHospitalGillianVale, 9March Thewhole Clinicaltrialsof
EthicsCommittee Administrator, 2005 State alldescriptions
EthicsCommittee, andclasses.
BeaumontHospital,
BeaumontRoad,
Dublin9
GalwayRegional SecretaryResearch 21April Thewhole Clinicaltrialsof
HospitalsResearchEthicsCommittee, 2005 State alldescriptions
EthicsCommittee Services andclasses.
Department,Block
2C,MainHospital,
UniversityCollege
Hospital,
NewcastleRoad,
Galway
8
32
sectioneight
name of ethics address for date of area for description or class
committee correspondence recognition which of clinical trials
committee for which
may act committee may act
ResearchEthics Secretary, 17May Thewhole Clinicaltrialsof
Committee, ResearchEthics 2005 State alldescriptions
OurLady’s Committee, andclasses.
HospitalforSick OurLady’s
Children HospitalforSick
Children,Crumlin,
Dublin12
IrishCollegeof Administrator, 17May Thewhole Clinicaltrialsof
General ICGPResearch 2005 State alldescriptions
Practitioners Committee,4/5 andclasses.
ResearchEthics LincolnPlace,
Committee Dublin2
EthicsResearch MsDeniseO’Brien, 20July Thewhole Clinicaltrialsof
Committee, Secretary, 2005 State alldescriptions
NationalMaternity EthicsResearch andclasses.
Hospital Committee,Masters
/CEOOffice,
NationalMaternity
Hospital,Holles
Street,Dublin2
8
33
sectioneight
name of ethics address for date of area for description or class
committee correspondence recognition which of clinical trials
committee for which
may act committee may act
HSESouth- Secretary, 30Aug Thewhole Clinicaltrialsof
EasternArea ResearchEthics 2005 State alldescriptions
ResearchEthics CommitteeOffice, andclasses.
Committee OldSchoolOf
Nursing,Waterford
RegionalHospital,
DunmoreRoad,
Waterford
ResearchEthics Administrator, 20Sep Thewhole TheCommitteeshall
CommitteeSligo ResearchEthics 2005 State actinrelationto
GeneralHospital Committee, clinicaltrialsofall
SligoGeneral descriptionsand
Hospital,TheMall, classesotherthan
Sligo thosetowhich
Regulation13(4)
refers(i.e.gene
therapy,somaticcell
therapyetc.).
EthicsResearch Secretary, 22March Thewhole Clinicaltrialsof
CommitteeHSE EthicsCommittee, 2006 State alldescriptions
Mid-WesternArea Mid-Western andclasses.
RegionalHospital,
Dooradoyle,
Limerick
8
34
sectioneight
a clinical trial
Any investigation in human subjects intended to discover or verify the clinical,
pharmacologicaland/orotherpharmacodynamiceffectsofaninvestigationalproducts(s)
and/or to identify anyadverse reactions to an investigational product and/or to study
absorption,distribution,metabolismandexcretionofaninvestigationalproduct(s)with
theobjectofascertainingsafetyandorefficacy.(ICHHarmonisedTripartiteGuidelines
forGoodClinicalPractice.19
also see:PocockSJ.ClinicalTrials:APracticalApproach.JohnWiley&Sons;1990.
a clinical trial (clinical trialS on medicinal productS for human uSe regulationS, may 2004) 7
any investigation in human subjects, other that a non-interventional trial intended:
A. Todiscoverorverifytheclinical,pharmacologicalorotherpharmacodynamic
effectsofoneormoreinvestigationalmedicinalproducts,or
B. Toidentifyanyadversereactionstooneormoresuchinvestigationalmedicinal
products,or
C. To study absorption, distribution,metabolism and excretion of one ormore
suchinvestigationalmedicinalproducts,or
D. Todiscover,verify,identifyorstudyanycombinationorthemattersreferredto
inA,B,orCwiththeobjectofascertainingsafetyorefficacyofsuchproducts
orboth.
non-interventional trial: (clinical trialS on medicinal productS for human uSe regulationS, may 2004) 7
is a trial involving the study of one or more medicinal products which have a marketing
authorisation where the following conditions are met:
Appendix2 8
35
sectioneight
A. Theproductsareprescribedintheusualmannerinaccordancewiththeterms
ofthatauthorisation.
B. Theassignmentofanypatientinvolvedinthestudytoaparticulartherapeutic
strategy isnotdecided inadvancebyaclinicaltrialprotocolbut fallswithin
currentpractice.
C. Thedecisiontoprescribeaparticularmedicinalproduct isclearlyseparated
fromthedecisiontoincludethepatientinthestudy.
D. Nodiagnosticormonitoringproceduresareappliedtothepatientsincludedin
thestudy,otherthanthosewhichareordinarilyapplied inthecourseofthe
particulartherapeuticstrategyinquestion
E. Epidemiologicalmethodsaretobeusedfortheanalysisofthedataarisingfrom
thestudy.
non-clinical trial
Canbedefinedasaninvestigationtoobtaininformation,advanceknowledgeandimprove
humanwell-being.Suchstudiesmayinvolvebutnotbelimitedtophysiologicalstudies,
developmentofhealthanddisabilityservicesanduseofsecondarydataforepidemiology
studies.
8
36
sectioneight
ethicS committeeS in the mid-WeSt region
university of limerick research ethics committee
applications to conduct research must be sought from the university rec by ul staff
and students in the following circumstances:
¢ Directexperimentationonindividuals
¢ Surveysorquestionnairesposedtoindividuals
¢ Useofdataderivedfromindividualrecordswherepeoplemaybeidentified
PleasenotethattheECattheUniversitydealswithinvestigationsinvolvingpublicand
communityparticipantsonlyandnotpatientsthatarereceivingtreatmentortherapyfor
an illness. Ifpatientsare involvedapprovalmustbesought fromtheEthicsResearch
CommitteeHSEMid-WesternArea
the operational procedures of this ec are as follows:
¢ FormalmeetingsareheldmonthlyduringtheAcademicYear(onepermonth
exceptAugust),andthedeadlineforreceiptofprotocolsisthelastworkingday
oftheprecedingmonth(allowancemustbemadeforbankholidaysetc.)
¢ Thereare15membersonthecommittee
¢ GuidelinesandapplicationformsforresearchbasedinScience&Technologies
orBusinessHumanities andEducationcanbedownloaded fromtheULREC
website www.ul.ie/researchethics. Receipt of the application form will be
acknowledgedandallocatedaULRECNumber.
¢ Themain REC approves doctorate and staff directed proposals that involve
membersofthecommunityasparticipants.Approvalmaybegivenimmediately
orpendingminorchanges.Approvalcanbegivenforupto3yearsandifthe
projecthasnotstartedwithinayearapprovalmayberescinded.
Appendix3 8
37
sectioneight
university of limerick research ethics committeeTheSecretary,
UniversityofLimerickResearchEthicsCommittee
C/oVicePresidentAcademicandRegistrar’sOffice,
UniversityofLimerick.
ethics research committee hSe mid-Western area
ApplicationforethicsapprovalmustbesenttothisECwhentheresearchinvolvesaccess
topatientsorclientsanddata/recordswithinthehealthservice.Thisethicscommittee
canprovideapprovalforClinicalTrialsonMedicinalProductsforHumanUseasdefined
bytheEUDirective.7ApplicationsmaybesenttothisoroneoftheothertwelveEthics
Committees which have been recognised under Regulation 7 of the EU Directive on
ClinicalTrialsonMedicinalProductsforHumanUse.
http://www.dohc.ie/issues/clinical_trials/ethics_committees.html
(seeAppendix1)
the operational procedures of this ec are as follows:
¢ MeetingstakeplaceonceamonthexceptinJuly,AugustandDecember.
¢ Applications and submissions to the ethics committee shall be received
nolessthanthreeweeksinadvanceofthemeetingatwhichtheapplicationis
tobeconsidered.
¢ MsBernadetteRyancanbecontactedforinformationonmeetingschedulesPh:
¢ One of the researchers involved in the proposed research must attend the
ECmeetingtopresenttheresearchandexplainanyethicalissues.
¢ The application form to apply for ethical approval can be obtained fromMs
BernadetteRyan(Ph:[email protected])
8
38
sectioneight
8
¢ The committeemembers receive proposals in advance of eachmeeting. At
this meeting the research proposal will then be; a) accepted, b) rejected
outright,orc)acceptedpendingamendments.Followingthemeetinga letter
will be sent to the applicant stating what changes must be made before
approvalcanbegiven.Initialapprovalisgrantedfora12monthperiod.Ifthe
study/project continues after 12months then the primary investigatormust
reapplyinwriting(letter).
¢ Allapplicationssubmittedmusthavetheproposedresearchprojectsupervised
byamedicalconsultantfromtheHSEintheMid-WestRegion.
ethics research committee hSe mid-Western areaSecretary,
EthicsCommittee
Mid-WesternRegionalHospital,
Dooradoyle,
Limerick
39
sectioneight
40
ethicS approval in the mid-WeSt region
use of:• healthy volunteers from the public and community by ul staff or students• data from the public or community by ul staff or students
use of:• patients• clients of hSe• patient data
apply to the university of limerick rec
apply to the ethics research committee hSe mid-Western area
complete the application form and Supply all relevant documentation
• approval• approval pending protocol amendments• rejection
8
health reSearch
sectioneight
if the reSearch comeS under:
clinical trials on medicinal products for human use
(AsdefinedbyEUDirective,May2004andauthorisedbytheIrishMedicinesBoard)
ThentheprincipalresearchermustapplytotheEthicsResearchCommitteeHSE
Mid-WesternAreaoroneoftheother12approvedEthicsCommitteesthathavebeen
recognisedbytheEthicsSupervisoryBodyunderregulation7oftheEUDirectiveto
approvesuchstudies(SeeAppendix1)
41
8sectioneight
42
Notes
National Institute of Health ScienceSt. Camillus Hospital
Shelbourne RoadLimerick, Ireland
T: 061 483929 F: 061 326670 E: [email protected] W: www.nihs.ie