The monitoring process

Author: Esther Kivaya, KEMRI-Wellcome Trust Research Programme

Version: 3-Nov-2008

The monitoring process


Version: 3-Nov-2008

Stages of a monitoring visit

• Before the visit

• During the visit

• After the visit


Version: 3-Nov-2008

During the visit

• The monitor will assess or discuss:Site, staffing, research labs or other facilitiesRegulatory file and study recordsClinical procedures if possible or appropriateAny problems and issues identifiedDebrief at end of visit


Version: 3-Nov-2008

After the visit

• The monitor willComplete site visit reportSubmit the report to the sponsor

• The sponsor will:• Distribute site visit report to the site


Version: 3-Nov-2008

4 types of monitoring visits:

• Site assessment(pre trial)

• Site initiation

• Routine(interim) visits)

• Close out visit


Version: 3-Nov-2008

Pre study visit

Purpose :It’s a face to face meeting with the

investigator to explore the overall feasibility of the site and the investigator to participate into the study.

May be combined with the study initiation visit.


Version: 3-Nov-2008

Site assessment


Version: 3-Nov-2008

Study initiation visit

• Purpose:

- to uniformly provide study specific information to investigator(s) and study staff prior to study start up.

- reassess resources and capability to conduct a research study.


Version: 3-Nov-2008

Study initiation(cont)

The monitor will meet with the study staff to discuss research obligations under GCP:

Investigator administrative responsibilitiesIRB approvals and communicationsRegulatory file requirements(ICH GCP E6 8.2)Informed consent forms and processProtocol and protocol amendmentsSource documentationStudy product handling and accountabilitySafety reportingProtocol specific trainingArchiving of study documents


Version: 3-Nov-2008

Study initiation (cont)• The monitor will

Review sponsor policies , standards and procedures for the conduct of clinical trials.

Reassess the site facilitiesProvide additional guidance to the site as

determined by his/her findings.

The better the site initiation, the better the site

performance.


Version: 3-Nov-2008

Interim monitoring visits Purpose:Protection of human subjects rights and wellbeing.

Accuracy, completeness and verification of reported trial data.

Trial conduct in compliance with protocol/amendments, GCP and regulatory requirements.


Version: 3-Nov-2008

Interim visit (cont)• Review /assess the following:

Enrollment status, rate and any drop outs.regulatory filesCRF’s, source documents, informed consents,

AEs/SAEs/SUSARsStudy productProtocol and regulatory compliancelaboratory reviewclinical operations

• Follow up on previously identified issues• Debrief


Version: 3-Nov-2008

Source data verification process

Source data: all information in original records and certified copies of original

records of clinical findings, observations or other activities in a clinical trial necessary for the reconstruction an evaluation of the trial. (ICH GCP1.51)

Source documents: original documents, data and records(e.g. hospital records, lab

notes, clinical charts, subjects diaries, pharmacy dispensing records, x-rays, subject files etc) (ICH GCP 1.52)


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SDV process(cont)

SDV: evaluation of the conformity of the data presented in CRFs with source data.

Main aim: confirm that the data collected is complete, accurate, reliable and verifiable so as to give confidence to sponsor and regulatory authorities in the data being used to support a marketing application.

Without SDV, no scientist can have confidence in data presented and conclusions derived.


Version: 3-Nov-2008

SDV process (cont)

Key data :10 efficacy dataInclusion/exclusion criteriaMedical/medication historyPhysical exam/vital signsvisit datesAdverse eventsConcomitant medicationRecord that patient entered clinical study and date of IC

Any gross errors in these might be detrimental to the scientific and

ethical quality of the clinical trial.


Version: 3-Nov-2008

SDV process(cont)Methods of SDV:

Back to backDirect method- monitor has direct access to

source data (ICH GCP E6 1.21,5.15)

Extent of SDV ??? Depends on: clinical trial phase, quantity of data,

time availability, man power availability, investigator research experience, company policy,


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SDV process (cont)Common approach:

Critical data: focal to aims and objectives of study and must be correct. Informed consent to participate Clinical notes Conformance to inclusion/exclusion criteria Primary efficacy endpoints Secondary efficacy endpoints Recording and reporting of SAEs Documentation that that study drug was prescribed and at the

specified dosage Visit dates as per protocol

Non-critical data e.g. very neat, high numbers of overwriting, rapid recruitment, lack of SAEs when they would be expected etc.


Version: 3-Nov-2008

SDV process(cont)

• CRF content review:Missing, incomplete or illegible entries, signatures

or datesData recorded in wrong fieldsIllogical, inconsistent or ambiguous dataData omissionsEntries demonstrating failure to follow protocolInaccurate calculationsInadequate documentation of corrections


Version: 3-Nov-2008

SDV process(cont)• Common problems

Data entered directly to CRFBrief medical history/ scanty clinical notesSeveral volumes of SDSD/CRF mismatchIllegible handwritingMaximum acceptable error rate

• Document the SDV processSD examinedCRFs checked and why they were selectedCritical and non-critical data items checkedNature and frequency of errorsAny corrective actions undertaken


Version: 3-Nov-2008

Informed consent documents

• What to check:Each participant has personally signed and dated ICD

prior to study procedures.Appropriate use of independent witnessCorrect version being usedNames of subjects/person giving consent, date and

timeInvestigator appropriately signed ICD and dated.All pages of ICD present

Documents

The monitoring process