dr siddharth jain critical path

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Planning andPlanning and

Management of Management of

Clinical TrialsClinical Trials

A PHASE II, A PHASE II, RANDOMIZED, DOUBLE- RANDOMIZED, DOUBLE-BLIND, PLACEBO-BLIND, PLACEBO-

CONTROLLED, 12 WEEK CONTROLLED, 12 WEEK STUDY OF THE EFFICACY STUDY OF THE EFFICACY AND SAFETY OF ZX-125 AND SAFETY OF ZX-125 FOR INHALATION IN FOR INHALATION IN ADULTS WITH ADULTS WITH

PERSISTENT ASTHMA PERSISTENT ASTHMA

Dr Siddharth Jain

M.D(Pharmacology)[email protected]



What isWhat is

SuccessfulSuccessful

Management ??Management ????

--Defined as meeting clinicalDefined as meeting clinicaltrial objectives in terms of trial objectives in terms of

timelines, quality andtimelines, quality andbudget.budget.

-Develop a-Develop aCOMPREHENSIVECOMPREHENSIVEPROJECT PLAN PROJECT PLAN beforebeforestarting the trial.starting the trial.



Flowchart of Flowchart of

Clinical trialClinical trial

Protocol, CRF’s Informed Consent Investigator

AgreementCenter SelectionSite Visits

Monitoring PlanPrepare

Regulatory

Dossier Order IP’s

Regulatory

Approval IRB/IEC Approval Initiation visitsSigned

Agreements

Investigator Meeting

Site Staff

Training

Patient Enrollment Informed ConsentRecords KeepingDevice/Supplies

AccountabilitySource Docs

CRF ReviewData QueriesMonitoringReporting

Conduct Close Out Post StudyDesign Initiation

Database LockRecords

Retention Investigator

PaymentsUnused

Product Return

Clinical Report Internal ReportsRegulatory

SubmissionsPromotional

Materials



Jan 09-Jul 09 Aug 09 ….....Oct 09 Nov 09 Dec 09 Jan 10 Feb 10.................Jun 10.……….…Sep 10

Planning

Writing Protocol, IB,

ICD, & CRF

Review & Approval from

Regulatory & IEC/IRB

Selection

of PI

Site selection &

assessment

IP

FPFV

IM Planning

Study

initiation

meeting

IM

Recruitment Period

Treatment Period

LPLV

Cont….

ASSESSING TIMELINES FOR PROJECT

LPFV

Jan 09-Jul 09 Aug 09 ….....Oct 09 Nov 09 Dec 09 Jan 10 Feb 10.................Jun 10.……….…Sep 10

Initial

Monitoringvisit



Sep 10………..…Nov 10..………..Mar 11 Apr 11………………Oct 11 Nov 11…………………May 12

Final

Monitoring

DataEntry

Db Lock

Publication

StatisticalAnalysis

Study

Termination &

Close-out

Final Report

Periodic Monitoring

ASSESSING TIMELINES FOR PROJECT

Sep 10………..…Nov 10..………..Mar 11 Apr 11…………..…Oct 11 Nov 11………….……...May 12



Critical PathCritical Path

MethodMethod • The Critical Path is theThe Critical Path is the

longest sequencelongest sequenceof sequential activitiesof sequential activitiesleading to theleading to thecompletion of the plancompletion of the plan..

• Any delay of in the Any delay of in thecommencement or commencement or

completion of an activitycompletion of an activity

on the critical path willon the critical path willdelay the completion of delay the completion of the whole plan.the whole plan.



Critical PathCritical Path

MethodMethod

• Identification of necessaryIdentification of necessaryresourcesresources

• Effective method of analyzing aEffective method of analyzing a

complex projectcomplex project• Calculates the minimum timeCalculates the minimum time

for completionfor completion

• Prioritizes activities to bePrioritizes activities to be

completed by that datecompleted by that date• Effective scheduling andEffective scheduling and

monitoring of progressmonitoring of progress

• Focuses on the essentialFocuses on the essential

activitiesactivities• Provides a graphic view of theProvides a graphic view of the

planplan



Critical PathPlanning

Writing protocol ,IB,ICF,CRF

Review & Approval

Investigator Meeting &

Study initiation meeting

FPFV

LPLV & Study

termination close out

Database lock

Final Report

Publication

Selection of PI and siteassesment and selection IM Planning

Shipping of IP’s

Periodic MonitoringTreatment Period

Data entry

Statistical analysis

Float Tasks Float Tasks06

03

03

01

03

04

07

09 Duration in Months

Total : 36 months



OrganizationalOrganizational

Structure of Structure of

MulticentreMulticentreTrialsTrials

• Oversight levelOversight level

• Co-ordination levelCo-ordination level

• Conduct LevelConduct Level






• Oversight levelOversight level Steering CommitteeSteering Committee

Composed of PI’s of eachComposed of PI’s of each participating centre. participating centre. Responsible for overall guidance,Responsible for overall guidance,

setting policies and for setting policies and for dissemination of study results.dissemination of study results.

Overseeing the design and conductOverseeing the design and conductof the trialof the trial

Implementation of SOPs and goodImplementation of SOPs and goodclinical practicesclinical practices

Compliance with international andCompliance with international andlocal regulations.local regulations.

C di iC i i






• Co-ordinationCo-or inationlevellevel

Administrative co-ordination of the Administrative co-ordination of thestudystudy

Essential member – Project Co-Essential member – Project Co-ordinator (PC)ordinator (PC)

Responsible for protocol development,Responsible for protocol development,development of study materials,development of study materials,training, communication, laboratorytraining, communication, laboratory

determinations, data processing anddeterminations, data processing andmanagement, report generation,management, report generation,statistical analysis and manuscriptstatistical analysis and manuscriptdevelopment.development.

Second major responsibility of the CC Second major responsibility of the CC is ensuring the quality of the data inis ensuring the quality of the data in

all its aspects: design of data collectionall its aspects: design of data collection forms, field work procedures, data forms, field work procedures, dataentry management systems, qualityentry management systems, qualityassurance procedures, data processingassurance procedures, data processingand editing, and analysis andand editing, and analysis andinterpretation of datainterpretation of data






• Conduct levelConduct level Responsible for direct interaction withResponsible for direct interaction with

the study participants, identifying andthe study participants, identifying and

screening potential study participants,screening potential study participants,obtaining informed consent, enrollingobtaining informed consent, enrollingeligible study participants, collectingeligible study participants, collectingdata (interviews), schedulingdata (interviews), scheduling

participant visits, maximizing patients’ participant visits, maximizing patients’compliance, and minimizing loss tocompliance, and minimizing loss to

follow up. follow up.

CRA (clinical research associate) beingCRA (clinical research associate) beingthe person responsible for monitoringthe person responsible for monitoringthe activities at the sitethe activities at the site

The site data coordinator is responsibleThe site data coordinator is responsible for collection, quality, and management for collection, quality, and managementof data from the site.of data from the site.

The data coordinator is the contactThe data coordinator is the contact person for the coordination with person for the coordination withcenter’s project coordinator (PC).center’s project coordinator (PC).



Other MajorOther Major

PersonnelPersonnel • Trial statisticianTrial statistician

• Data managerData manager• Randomization specialistRandomization specialist

• Quality assurance officerQuality assurance officer

• Computer support personnelComputer support personnel• Resource Centre DirectorsResource Centre Directors

• Training directorsTraining directors

• Field site personnelField site personnel• Independent DataIndependent Data

Monitoring CommitteeMonitoring Committee



RISK RISK

MANAGEMENTMANAGEMENT• Identification, assessment, andIdentification, assessment, and

prioritization of risks followed by prioritization of risks followed by

co-ordinated and economicalco-ordinated and economicalapplication of resources toapplication of resources tominimize, monitor, and control theminimize, monitor, and control the

probability and/or impact of probability and/or impact of unfortunate events.unfortunate events.

• All research and development All research and developmentactivities involve some risk.activities involve some risk.

• Some of the risks are typicallySome of the risks are typicallyencountered in the main stages of aencountered in the main stages of aclinical trial described further inclinical trial described further inslides.slides.



RISK RISK

MANAGEMENTMANAGEMENT

• Approval delay byApproval delay byregulatoryregulatoryagencies(DCGI) & Ethicsagencies(DCGI) & Ethics

CommitteeCommittee Ensure that the dossier submitted is time.Ensure that the dossier submitted is time. Ensure that the selected sites have an ECEnsure that the selected sites have an EC

which meets regularly.which meets regularly. Address EC queries immediately andAddress EC queries immediately and

review the EC/RA status weeklyreview the EC/RA status weekly

• Recruitment problemsRecruitment problems Prepare recruitment planPrepare recruitment plan Open back-up sitesOpen back-up sites

CRA to help the investigator to get accessCRA to help the investigator to get accessto patientsto patients Keep sufficient recruitment periodKeep sufficient recruitment period

D i i kD i i k



RISK RISK


• Documentation risksDocumentation risks This involves loss of any documentationThis involves loss of any documentation

done during the entire process of CT.Todone during the entire process of CT.Toavoid this make multiple copies of sourceavoid this make multiple copies of sourcedocuments.documents.

Make the CRF’s as simple and legible asMake the CRF’s as simple and legible aspossible to avoid generation of Datapossible to avoid generation of DataClarification Forms later.Clarification Forms later.

• Contract issuesContract issues Contracts negotiated well in advanceContracts negotiated well in advancewith the budget and should be forwardedwith the budget and should be forwarded

immediately to the clinical team leader.immediately to the clinical team leader.

• Drug supply problemsDrug supply problems

Correctly prepare a study drugCorrectly prepare a study drugassignment and re-assignment planassignment and re-assignment plan Ensure sufficient quantity of IP(s) sent toEnsure sufficient quantity of IP(s) sent to

the sitethe site Maintain proper accountability of studyMaintain proper accountability of study

drugdrugss



RISK RISK


• Delays due to site specificDelays due to site specificproblemsproblems

Ensure a good feasibility study done priorEnsure a good feasibility study done priorto start of the trial to avoid infrastructureto start of the trial to avoid infrastructureproblems.problems.

Ensure that the selected investigator hasEnsure that the selected investigator hassufficient staff.sufficient staff. Logistic requirements (InternetLogistic requirements (Internet

connection, telephone lines, freezer,connection, telephone lines, freezer,Centrifuge) are met well in advance.Centrifuge) are met well in advance.

Ensure a good Pharmacy set up whichEnsure a good Pharmacy set up whichmeetsmeets the requirements of the Study drug.the requirements of the Study drug.

• Training issuesTraining issues Ensure that the site is properly trained inEnsure that the site is properly trained in

regards to the activities of the trial and aregards to the activities of the trial and aproper and uniform implementation of theproper and uniform implementation of theSOP’s is achieved.SOP’s is achieved.

Edc training at the IM and also for the siteEdc training at the IM and also for the site

staffstaff Sufficient training for handlingSufficient training for handlinginstruments (eg.Spirometer)instruments (eg.Spirometer)

Ensure an elaborate TOM is preparedEnsure an elaborate TOM is preparedindicating the responsibility of everyindicating the responsibility of everyperson involved in the trial.person involved in the trial.



THANK YOUTHANK YOU

dr siddharth jain critical path

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