process (if violations are deliberate or planned, a
case of fraud should be considered!).
Reporting and recording safety events
An issue over which site personnel and monitors
will be particularly watchful is the observation and
recording of safety information. In many studies,
safety information is under-reported because of the
tendency to make judgments that are often based
on subjective and biased clinical opinion. It seems
difficult to teach clinical researchers to operate as
‘scientists’: that is, to observe and record all obser-
vations before making judgments. The monitor and
all clinical research personnel must ensure that all
safety information is documented. This means that
all AEs occurring in clinical studies must be
recorded in CRFs, their significance must be
assessed and other information must be provided
for reporting AEs externally (e.g. to regulatory
authorities and ethics committees/IRBs). This
applies to any study treatment (including compara-
tor agents, placebo and nonmedical therapy) and
any stage of the study (e.g. run-in, washout, active
treatment, follow-up).
All research personnel must search for clues
about safety events from many sources, such as
information in clinical records at the study sites;
information in data collection forms (e.g. CRFs,
diary cards, quality-of-life forms, psychiatric
rating scales, etc.), occurrence of missed and/or
unscheduled visits, dropouts and withdrawals;
use of any concomitant medications/devices; and
abnormal laboratory data. AEs may also occur
simply as a result of study procedures and study
participation. Information about definitions of AEs
and requirements for reporting AEs must be clearly
stated in the protocol and explained to the site staff,
who must also be educated in the correct procedure
and immediate requirement for reporting any AE
suspected to be serious or unexpected as per the
regulatory definitions.
All investigators and other study site personnel,
ethics committees/IRBs and possibly study sub-
jects must be informed of all new significant safety
information, including all events occurring with
any treatment (e.g. washout, investigational pro-
duct, comparator, placebo, etc.) in the study, even if
these occurred in another study with the same
treatment or in another country. Significant safety
information includes all SAEs and any other eventsTable 12.7 (Contd.)
4.Other items:
Ethics committee/IRB approval obtained (some debate about this)
Name of ethics committee/IRB (if applicable by local and/or national requirements) and details of contact person
on the ethics committee/IRB (if applicable by local and/or national requirements)
Explanation that participation is confidential, but records (which divulge study subject names) may be reviewed by
authorized sponsor/CRO representatives and may be disclosed to a regulatory authority
Name, address and telephone number (24 h availability) of contact person at study site for information or in the
event of an emergency (this information may be provided on a separate card)
Requirement to disclose details of medical history, any medicines (or alcohol) currently being taken, changes in
any other medication/device use and details of participation in other clinical studies
Medical records will clearly identify study participation
Conditions as they apply to women of child-bearing potential
Primary care physician (or general practitioner or family doctor) and/or referring physician will be informed of
study participation and any significant problems arising during the study. Some subjects may not be comfortable with
this requirement, for example in a study of sexually transmitted diseases, they may not wish the doctor, perhaps a
family friend, to be aware of their situation. If this is the case, the subject is not eligible for the study as it is vital to
confirm history with the primary care physician
The information sheet must be written in language which is understandable, for example technically simple and in
the appropriate national language, to the study subject
148 CH12 GOOD CLINICAL PRACTICES