Principles and Practice of Pharmaceutical Medicine

approval process of the NDA/BLA/MAA and
the marketing of the drug, safety is the primary
concern of any clinical program.
Management of safety is a principal responsi-
bility of the sponsor monitor. The monitor has
responsibility for informing the investigator
about the safety requirements of the study. This
will include a discussion of expected and unex-
pected adverse events, how to report adverse
events should they occur and how to characterize
the adverse events in terms of project-specific
definitions.
Monitors are expected to review CRFs and
source documents with particular attention to
potential safety problems. On the CRF, the adverse
event section and laboratory result section are
reviewed for important findings. Often, the inves-
tigator makes relevant notes in the comment sec-
tion of the CRF. In source documents, safety issues
may be uncovered in the progress notes of hospital
charts or the interpretative reports of various diag-
nostic tests, for example chest X-rays and EKGs.
Safety problems can manifest themselves in many
ways. Monitors must be alert to exaggerated
changes from baseline with expected pharmacolo-
gical effects, acute and chronic effects and multiple
drug treatment reactions.
Monitors are often the first company representa-
tives to learn about an adverse event. The timeliness
of reporting the event to sponsor safety group is
important in satisfying regulatory reporting require-
ments. In general, the expectation is that the sponsor
will learn of the event within 24 h of its occurrence.
The monitor should immediately notify appropriate
safety staff of serious ADEs that are unexpectedly
discovered. These strict timelines are designed to
keep us in compliance with the regulatory authori-
ties. Failure to adhere to the reporting timelines
required for regulatory authorities is evidence of
negligence on the part of the sponsor. The sponsor
monitor is responsible for assuring adherence to
reportingsystemsformanagingSAEsandforensur-
ing that the investigator’s staff is aware of these
requirements of being in compliance with the reg-
ulatory authorities.
The sponsor monitor is responsible for the
timely follow-up of all SAEs. The cases must be
followed to completion. The monitor needs to

collect all required follow-up information on

ADEs.

To be successful, monitors need to be com-

petent in

basic medicine and therapeutics;

recognizing clinical signs and symptoms;

interpretation of laboratory findings;

medical practice, nomenclature and terminol-

ogy;

relevant regulatory requirements;

protocol requirements.

The sponsor needs to provide ongoing review of

safety data for investigational products.

Closing down the center

Closing down a study is important because it may

represent the sponsor’s last best chance to obtain

the data required in the trial. The study closedown

(closeout) visit usually occurs after the last subject

has completed the trial including anyposttreatment

follow-up visits. Drug supplies should be recon-

ciled, and the integrity of the double-blind treat-

ment codes should be confirmed. Any outstanding

queries should be resolved and documented.

Arrangements for retaining source data should

be confirmed with the investigator. In addition, the

investigator should notify the IRB/IEC of the com-

pletion of the study. When the final draft of the

clinical study report is available, it should be given

to the investigator for signature. In multicenter

trials, a single lead investigator may sign a pooled

study report.

Reviewing, editing and verifying in-house

case report data and databases

While the goal of monitoring is to provide ‘clean’

CRFs, it is necessary to review CRFs for

36 CH3 CLINICAL RESEARCH EDUCATION AND TRAINING FOR BIOPHARMACEUTICAL STAFF