Clinical protocol

Clinical Research

1. Protocol Writing in Clinical Research
SreenuThalla
Clinical Pharmacologist

2. •Writingaresearchproposalisprobablyoneofthemostchallenging
anddifficulttaskasresearchisanewareaforthemajorityof
postgraduatesandnewresearchers.
•Thisistosummarizethemostimportantstepsandnecessary
guidelinesforproducingastandardresearchprotocol.
•Academicandadministrativesuccessofanyprojectisusually
determinedbyacquiringagrantfortherelatedfieldofresearch.
•Hence,thequalityofaprotocolisprimarilyrequiredtoachievesuccess
inthisscientificcompetition.

3. WhatisaProtocol?
•Clinicalresearchisconductedaccordingtoaplan(aprotocol)oran
actionplan.
•Theprotocoldemonstratestheguidelinesforconductingthetrial.
•Itillustrateswhatwillbemadeinthestudybyexplainingeach
essentialpartofitandhowitiscarriedout.
•Italsodescribestheeligibilityoftheparticipants,thelengthofthe
study,themedicationsandtherelatedtests.
•Aprotocolisdirectedbyachiefresearcher.
•Thehealthoftheparticipants’willberegularlycheckedby
membersoftheresearchteamtoultimatelyensurethestudy’s
safetyandeffectiveness

4. Purpose of a Research Proposal
Toraisethequestiontoberesearchedandclarifyitsimportance.
Tocollectexistingknowledgeanddiscusstheeffortsofother
researcherswhohaveworkedontherelatedquestions
(Literaturereview).
Toformulateahypothesisandobjectives.
Toclarifyethicalconsiderations.
Tosuggestthemethodologyrequiredforsolvingthequestion
andachievingtheobjectives.
Todiscusstherequirementsandlimitationsinachievingthe
objectives.

5. Benefits of the Proposal to a Researcher
•Allowstheresearchertoplanandreviewtheproject'ssteps.
•Servesasaguidethroughouttheresearch.
•Forcestimeandbudgetestimates.
Whyisthestudyimportant?(Significance)
Whereandwhenitwilltakeplace?
Whatisthemethodology?(Proceduresandmethodstobe
used).
Howareyougoingtodoit?(Researchdesign)
Proposedtimetableandbudget.
Resourcesrequired(technical,scientific,andfinancial).

6. WhatisaProtocolReview?
•ClinicaltrialsmustbeapprovedandmonitoredbyanInstitutional
ReviewBoardthatensuresthattherisksarenegligibleandare
worthanypotentialbenefits.
•Itisanindependentcommitteethatconsistsofphysicians,
dentists,statisticiansandmembersofthecommunity.
•Thecommitteeensuresthatclinicaltrialsareethicalandthatthe
rightsofallparticipantsareprotected.
•Theboardmustinitiallyapproveandperiodicallyreviewthe
research.

7. Components of a Research Protocol
1.Titleofthestudy
2.Administrativedetails
3.Projectsummary
4.Introductiontotheresearchtopic,background(Literaturereview)
5.Preliminarystudies
6.Studyobjectivesand/orquestions.Statementoftheproblem.
7.Methodology:Studydesign,studypopulationandmethodsof
recruitment,variableslist,samplesize,methodsofdatacollection,
datacollectiontools,planofanalysis(analysisofdata)
8.Projectmanagement:Workplan(Timeline-proposedschedule)
9.Strengthsandlimitationsofthestudy
10.Issuesforethicalreviewandapprovals

8. Title of the Study
•Titleofproposalshouldbeaccurate,short,conciseandidentify
•Whatisthestudyabout,Whoarethetargets,Whereisthesetting
ofthestudyandwhenitislaunched,ifapplicable-
•Itshouldmakethemainobjectiveclear,conveythemainpurpose
oftheresearchandmentionthetargetpopulation.
•Carrymaximuminformationaboutthetopicinafewwords;itisa
goodpracticetokeepthetitletowithin12-15words.
•Itshouldconveytheideaabouttheareaofresearchandwhat
methodsaregoingtobeusedinacompact,relevant,accurate,
attractive,easytounderstand,andinformativeway

9. AdministrativeDetails
Thefollowingadministrativedetailsandaprotocolcontentsummary
shouldfollowthetitlepage
•Contentspagelistofrelevantsectionsandsub-sectionswith
correspondingpagenumber.
•Signaturepageissignedbyseniormembersoftheresearchteam
anddatedtoconfirmthattheversionconcernedhasbeen
approvedbythem.
•Contactdetailsfortheresearchteammemberslistingpostaland
e-mailaddressesandtelephonenumbersformembersofthe
researchteam

10. ProjectSummary
•Thesummaryshouldbedistinctive,conciseandshouldsumupall
theessentialsoftheprotocol.

11. Introduction (Background)
•Thebackgroundtotheprojectshouldbeconciseandrefertothe
subjectstraightforwardly.
•Inwritingthereview,attentionshouldbedrawntothepositives,
negativesandlimitationsofthestudiesquoted.
•Introductionisconcludedbyexplaininghowthepresentstudy
willbenefitthecommunity.
•Theliteraturereviewshouldlogicallyleadtothestatementofthe
aimsoftheproposedprojectandendwiththeaimsandobjectives
ofthestudy.
•Thereviewshouldincludethemostrecentpublicationsinthe
fieldandthetopicoftheresearchisselectedonlyaftercompleting
theliteraturereviewandfindingsomegapsinit.

12. •Introductionshouldbrieflyanswertheimportanceofthetopic,the
gaps/lacunaeintheliterature,thepurposeofthestudyand
benefitsforthesociety,fromthestudy.
•Theresearchquestionshouldbedescribedpreciselyandconcisely.
•Itisgoingtobethebasisofdesigningtheproject.
•Thedefinitionoftheproblemshouldbeclearsothatareadercan
straightforwardlyrecognizetherealmeaningofit.

13. •TheobjectivesshouldbeSMART
Specific
Measurable
Achievable
Relevant
Timebased
StudyObjectives(Aims)
•Theaimsshouldbeexplicitlystated.
•Theseshouldbeconfinedtotheintentionoftheprojectandthey
shouldarisefromtheliteraturereview.
•Statethegoalyouneedtoachieve.
•Thestudyaimsorobjectivesemergefromthestudyquestions/
hypothesis.

14. •Thestatementoftheproblemshouldprovideasummaryofexactly
whattheprojectistryingtoachieve.
Whatexactlydoyouwanttostudy?
Whyisitworthstudying?
Doestheproposedstudyhavetheoreticaland/orpractical
significance?
Doesitcontributetoanewunderstandingofaphenomenon?
(i.e.,Doesitaddressneworlittleknownmaterialordoesit
treatfamiliarmaterialinanewwayordoesitchallengean
existingunderstandingorextendexistingknowledge?)

15. •Thejustificationoftheresearchshouldbeaconvincingstatementfor
theneedtodoit:
Howdoestheresearchrelatetotheprioritiesoftheregion
andthecountry?
Whatknowledgeandinformationwillbeobtained?
Whatistheultimatepurposethattheknowledgeobtained
fromthestudywillserve?
Howwilltheresultsbedisseminated?
Howwilltheresultsbeused,andwhowillbethe
beneficiaries?

16. Materials and Methods
a)Studydesign(cross-sectional,case-control,interventionstudy,RCT
b)Studypopulation(Studysubjects)
c)Samplesize
d)Proposedintervention
e)Datacollectionmethods,instrumentsused
Retrospectivedata(medicalrecords)
Questionnaires
Interviews(Structured,Semi-Structured)
LaboratorytestClinicalexaminations
Descriptionofinstruments,toolsusedfordatacollection,aswellas
themethodsusedtotestthevalidityandreliabilityofthe
instrumentshouldbeprovided

18. DataManagementsandAnalysisPlan
•Thissectionshouldbewrittenfollowingstatisticaladvicefroma
statistician.
•Theanalysisplanandwhichstatisticaltestswillbeusedtocheck
thesignificancetotheresearchquestion/hypothesiswith
appropriatereferencesshouldbedescribed.
•Namesofvariablesthatwillbeusedintheanalysesandthename
ofstatisticalanalysisthatwillbeperformedtoassesstheoutcome
shouldbelisted.
•Ifcomputerprogramsaretobeapplied,itisimportanttomention
thesoftwareusedanditsversion.

19. ProjectManagement
•Workplan-Aworkplanisanoutlineofactivitiesofallthephases
oftheresearchtobecarriedoutaccordingtoananticipatedtime
schedule.
•Propertimetableforaccomplishingeachmajorstepofthestudy
shouldbedefined.
•Assigningtimeframetoeachstepinthetrialwillbehelpfulin
organizingthestructureoftheresearchtrial.
•Thepersonnel(investigators,assistants,laboratorytechniciansetc.)
involvedinthestudyordatacollectionshouldbeproperlytrained.

20. StrengthsandLimitations
•Itisimportanttomentionthestrengthsorlimitationsofthestudy,
i.e.,whatstudycanachieveorcannotachieveisimportant,soas
topreventwastefulallocationofresources.

21. Ethical Considerations
(Issues for Ethical Review and Approvals)
•Thebenefitsandrisksforthesubjectsinvolved.
•Thephysical,socialandpsychologicalimplicationsofthe
research.
•Detailsoftheinformationtobegiventothestudypatients
includingalternativetreatments/approaches.
•Informationshouldbeprovidedonthefreeinformedconsentof
theparticipants.
•Justificationforresearch
•Confidentiality

22. Operational Planning and Budgeting
(Budget Summary)
•Outlinethebudgetrequirementshowingheadwiseexpenditurefor
thestudy-manpower,transportation,instruments,laboratorytests,
andcostofthedrug.
•Budgetestimateistobeattachedintheannexure.
•Allcostsincludingpersonnel,consumables,equipment,supplies,
communication,andfundsforpatientsanddataprocessingareall
includedinthebudget.
•Eachitemshouldbejustified.

23. Reference System
•Referencingistheregularmethodofrecognizinginformationtaken
fromotherresearchers’work.
•Apropercitationwillenablethereaderstofollow-upanyreferenceof
interest.
•Plagiarismreferstoclaimingandacquiringsomeoneelse’sideas,an
actionthatisconsideredacriminalaction
•Failuretoreferenceanideathatyouhavefoundinyourresearch,or
toacknowledgetheworkofotherteammembersinateam
assignmentfallsunderthecategoryofplagiarism.
•Thereforereferencingisanextremelyimportantaspectoftheresearch
protocol.
•Thetwomostcommonlyusedcitationsystemsinclinicalwritingare
theVancouversystemandtheHarvardsystem

24. Annexure
Thefollowingannexesaretobeattachedattheendoftheprotocol
1.Informedconsentform.
2.Lettersfromethicscommittees.
3.Studyquestionnaire
4.CaseRecordForms(CRFs).
5.Budgetdetails.
6.CurriculumVitae(CV)ofthechiefinvestigatorandco-
investigatorandtheirroleinthestudy.Itwillensurethatthe
roleofeachinvestigatoriswelldefined.

25. Howtojudgeagoodprotocol?
•Theprotocolshouldadequatelyanswertheresearchquestion.
•Theresearchdesignmustbesoundenoughtoyieldtheexpected
knowledge.
•Itshouldprovideenoughdetail(methodology)thatcanallow
anotherinvestigatortodothestudyandarriveatcomparable
conclusions.
•Here,theproposednumberofparticipantsisreasonablyjustified
andthescientificdesignisadequatelydescribed.

26. Common mistakes
(Common pitfalls to avoid)
•Incorporatinginsufficientelementsregardingproposedstudies
andinadequateexplanationfortheimplicationoftheproblem
mustbeshunnedaswellassuggestingfarmoreworkthancanbe
practicallydoneduringthestudyperiod.
•Furthermore,underpoweredsamplesizeshouldbejustified,
invalidorunreliableinstrumentationshouldbetestedand
improperstatisticsshouldbeadequatelyanalyzed