Principles and Practice of Pharmaceutical Medicine

subjects until the monitor has checked their condi-
tion. The monitor will verify that the amount
shipped matches the amount acknowledged as
received. If there is a lack of reconciliation, or if
the shipment is not intact, recruitment may be
delayed until the situation is resolved.

Control of study medications/devices
at study sites

Evidence of careful control at the study site is im-
perative, and naturally it is difficult to standardize
the situation across many study sites and many
countries. Security, correct storage and accurate
documentation of dispensing and inventory are
necessary. Systems to ensure and assess compli-
ance with the required use of the product being
studied must be established. Monitors must be
trained to check on these features and ensure that
all site personnel are fully briefed.
The expectations with regard to maintenance of
study medications/devices at study sites focus on
security and appropriate environmental conditions.
Concerns for security require that supplies be
maintained under locked conditions. All agree-
ments between the sponsor/CRO and the study
site must specify that supplies are only for clinical
study subjects – this information must also be
clearly stated on the labeling. The main concern
for appropriate environmental conditions is usually
temperature requirements, but other factors (e.g.
light, humidity) might also be important. Terms
such as ‘room temperature’ and ‘ambient tempera-
ture’, which have different meanings in different
countries, should always be avoided and specific
temperatures must be stated. At each monitoring
visit, the monitor will ensure that the correct pro-
cedures are being followed.
Compliance with medication/device use (by the
study subject) should be assessed in all studies.
If supplies are dispensed to subjects for self-
administration, methods to assure compliance
(e.g. diary cards, instructions on labeling, super-
vised administration) and methods to check com-
pliance (e.g. tablet counts, plasma/urine assays,
diary card review) must be in place. At each
study visit, the study subjects should be asked to

the investigator, who will check the supplies for

assessment of compliance and store them for return

to the sponsor/CRO. The monitor will review all

relevant documents (e.g. source documents, CRFs,

medication/device inventory, dispensing forms) to

ensure that the data in the CRFs reflect the subjects’

compliance with the study medications/devices.

Overall accountability of study

medications/devices

Overall accountability must documented and

reviewed. A reconciliation of the initial inventory

and the final returns must be undertaken and all

discrepancies must be explained. Final disposition

and destruction must be carefully documented

to also allow assessment of possible detrimental

environmental impact. All unused and returned

medications/devices, empty containers, devices,

equipment and so on, which are returned to the

investigator by the study subjects, must be stored

securely and under correct environmental con-

ditions at the study site until retrieved by the moni-

tor.Themonitorwillcheckthesuppliesreturnedand

verify that they reconcile with the written specifica-

tions. All discrepancies and the reasons for any non-

returns must be documented and explained.

Generally, destruction of returned study medica-

tions/devices by the sponsor/CRO may not take

place until the final report has been prepared and

until there is no further reason to question the

accountability of the study medication/device.

The actual destruction process must be documen-

ted in a manner which clearly details the final

disposition of the unused medications/devices

and the method of destruction. The information is

particularly necessary in case of any query regard-

ing environmental impact. In exceptional circum-

stances, unused study medications (e.g. cytotoxics,

radio-labeled products) may be destroyed at the

study site, with appropriate documentation.

Randomization and blinding

Randomization procedures are employed to ensure

that study subjects entered into a comparative

12.6 MANAGING STUDY MEDICATIONS/DEVICES 153