amount of data and the number of visits. Generally,
most investigators should be monitored every four
to six weeks. The monitors should anticipate suffi-
cient time for good monitoring practices.
Following a monitoring visit, the monitor will
prepare a monitoring report for sponsor records
and follow up correspondence to the trial site.
The monitor may need to plan intervention and
possible replacement of nonperforming or non-
compliant trial centers.
Managing drug accountability
The sponsor is responsible for providing the investi-
gator with investigational product. Both the sponsor
and investigator have a role in drug accountability.
The sponsor’s representative inspects storage of
investigational product supplies, checks study site
investigational product dispensing records, checks
randomization and blinding and maintains records
of investigational product shipments.
The monitor reconciles investigational product
shipped, dispensed and returned, arranges for ship-
ment of investigational product to core country or
investigative sites, checks investigational product
supplies at site against enrollment and withdra-
wals, maintains investigational product account-
ability records, resolves investigational product
inventory problems, implements tracking system
for investigational product management on a study
and project level, arranges for the return and/or
destruction of unused or expired investigational
product supplies and ensures final reconciliation
of investigational product supplies.
Good clinical practices require sponsors to be
able to account for the drug supplies prepared and
shipped to the investigator, the investigator’s use of
those supplies and the return and destruction of
remaining drug supplies. Planning drug supplies
is a detailed and complex activity. Bulk and for-
mulated drug requests must be made at least six
months in advance of the need for those supplies.
This is to account for the ordering of intermediates
or finished drug, purchasing of comparator agents
and for quality control testing.
Drug packaging should follow as consistent a
format as possible within a project, and must be
identical within multicenter trials. Regulatory
documents required for investigational drug use
in the core countries must be anticipated and
made available when needed, for example meth-
ods/certificates of analysis, stability data and cus-
toms declarations.
The typical requirements for drug labels are
described in Table 3.5.
Once the study is underway, the investigator’s
staff must account for the use of the investigational
drug. Subjects should return unused medication
and empty containers to the investigator. The
amount of drug dispensed and the amount used
by the patients are compared for discrepancies.
This provides a measure of compliance by the
study subjects. Monitors must also check that
drug supplies are being kept under the required
storage conditions.
Study drug must be dispensed according to the
randomization schedule. Failure to do so can result
in some of the data having to be discarded during
statistical analysis. This issue can prove to be
problematic when a single site is studying patients
at different locations. Finally, the double-blind
code must not be broken except when essential
for the management of adverse events. The break-
ing of treatment codes can make that patient’s data
unusable for efficacy analyses.Handling adverse drug events (ADEs)Safety concerns are present throughout the drug
development process. From the filing of INDs/
CTAs through the conduct of clinical trials to theTable 3.5 Typical labeling requirements
for investigational drug
Local language Route of administration
Name of investigator Dosage
Study number Dosage form
Bottle number Quantity or volume
Lot number Storage precautions
Drug name or code Directions for use
Manufacturer name Note: ‘For Clinical Trial’
Manufacturer address Caution statement
Local affiliate name Expiry date3.3 COMPETENCY-BASED TRAINING PROGRAM FOR STAFF ASSOCIATED WITH CONDUCTING CLINICAL TRIALS 35