Table 12.8 Objectives of monitoring visits
The following tasks should be undertaken by the sponsor/CRO monitor at each study site visit:
Verify accuracy and completeness of recorded data in CRFs, including diary cards, quality of life
forms, registration forms, consent forms, etc., by comparing with the original source documents
(clinic or hospital records). Where discrepancies are found, arrangements must be made for
corrections and resolution. Resolve any outstanding
queries, ensuring completion of any issued data queries, since the last monitoring visit
Verify compliance with entry criteria and procedures, for all study subjects, as specified in the protocol.
If subjects are found to be ineligible or unevaluable, these events must be immediately brought to the attention
of the investigator. There may also be implications for payment to the study site and requirements for
reporting to ethics
committees/IRBs. Finally, and most seriously, there could be implications for subject safety
Review all AEs, including clinically significant laboratory abnormalities, that have occurred since the
previous visit. If a serious or unexpected AE has occurred, which was not correctly reported by the investigator,
the monitor must ensure that the correct reporting procedure is followed immediately
Evaluate the subject recruitment and withdrawal/dropout rate. If recruitment is less than optimal, suggest
ways in which it can be increased. In particular, query the reasons for withdrawals/dropouts, or unscheduled
visits, in case these are related to AEs
Confirm that all source documents will be retained in a secure location. Source documents must be legible
and properly indexed for ease of retrieval. Check the study site file to ensure that all appropriate documents are
suitably archived. Check that the investigator files are secure and stored in a separate area which is not
accessible to individuals not involved in the study
Conduct an inventory and account for study medications/devices and arrange for extra supplies, including
other items, such as CRFs, blank forms and so on, if necessary. Resolve discrepancies between inventory and
accountability records, and medication/device use, as recorded in the CRFs. If a pharmacy is involved in the
study, the pharmacy and pharmacist must be visited. Check that the medication/device is being dispensed
in accordance with the protocol. Check that the medication/device is being stored under appropriate
environmental conditions and that the expiry dates are still valid. Check that the medication/device is securely
stored in a separate area that is not accessible to individuals not involved in the study. Check that any
supplies shipped to the site since the last visit were received in good condition and are properly stored.
If applicable, ensure that randomization procedures are being followed, blind is being maintained,
randomization codebreak envelopes are intact (sealed and stored properly) and a chronological
sequence of allocation to treatment is being followed
Verify correct biological sample collection (especially number, type, and timing), correct procedures for assays
(if applicable), and labeling, storage and transportation of specimens or samples. All clinical laboratory reports
should be checked for identification details, validity and continued applicability of reference ranges, accuracy of
transcription to CRFs (if any), comments on all out-of-range data, and investigator signatures and dates.
The dates of sample collection, receipt, analysis and reporting should be checked to ensure that samples are
analyzed promptly, and that investigators are informed of results and review them promptly
Ensure continued acceptability of facilities, staff and equipment. Ensure that the reference range,
documentation of certification and proficiency testing, licensing, and accreditation, for the clinical laboratory are
still current. Document any changes in clinical site personnel and, if changes have occurred, collect
evidence of suitability of new personnel. Ensure that new staff are fully briefed on the requirements of the
protocol and study procedures and arrange any training of new personnel, if necessary. Document any
changes in overall facilities and equipment and if changes have occurred, collect new evidence of
suitability, maintenance, calibration and reason for change of new equipment
Advise the investigator and other site personnel of any new developments, for example protocol amendments,
AEs, which may affect the conduct of the study
12.4 MONITORING AND SAFETY ASSESSMENT 149