study medication/device. At the beginning of a
study, monitoring may be even more frequent.
The most time-consuming task at the study site is
the review of source documents to confirm entries
in CRFs and compliance with the protocol.
The monitor will be ever-vigilant for protocol
violations which can occur during a study and
which can have a serious impact on eligibility
and evaluability. Many researchers confuse the
terms ‘protocol violations’ and ‘protocol amend-
ments’. It is important to appreciate the differences
between these terms and understand how to
avoid protocol violations and how to manage pro-
tocol amendments. Perhaps the easiest way to
explain the difference is to stress that violations
are not planned changes (hopefully) to the proto-
col, whereas protocol amendments are planned
changes and are enacted through a formal approvalTable 12.5 Review by ethics committees/IRBs during and after clinical studies
The following items should be reviewed by ethics committees/IRBs during and after clinical studies:
Serious and/or unexpected AEs, if any occur during the study, including the follow-up period
Protocol amendments, if any, and reasons for amendments
Protocol violations which impact on subject safety, if any
Discontinuation of study, if applicable, and any reasons for premature discontinuation
Any new significant information, for example information arising from other studies, results of interim analyses,
marketing approvals, changes in local procedures, updated investigator brochure, supply problems, during study,
if any
Amendments to consent forms/information sheets, if any
Annual reports of the study. More frequent review may be necessary, depending on the working procedures
of each individual ethics committee
Final clinical report/summary of study. Some ethics committees/IRBs also review publications, if any
Table 12.6 Principles for the conduct of informed consent
The following principles for conducting informed consent should be implemented for all clinical studies:
Informed consent must be obtained from each study subject. The person receiving the information and giving
consent must sign the consent form. This is usually the study subject, but may be the study subject’s legally
acceptable representative (depending on national regulations) in the event that the study subject is incapable of
providing informed consent, for example the subject is unable to write or understand the consent documents, or
the study subject is in a ‘vulnerable’ population, for example children, elderly. Informed consent must be obtained
before the start of the study
The person providing the information and obtaining consent must sign the consent form. This person should be an
investigator who must be qualified to adequately inform the study subject, and her/his signature also indicates
personal involvement in the consent process. If other personnel, for example study nurses assist in providing
information or obtaining consent, they should also sign the consent form, clearly describing their role in the
consent procedure
A witness or patient advocate should be present during the consent procedure at the times of providing information
and giving consent, and should sign the consent form. The witness will ensure that there was no coercion in the
obtaining of informed consent and that the study subject was given adequate time to consider participation in the
study. The witness must be able to confirm that the consent procedure was adequate and must have no vested interest in
the clinical study, that is the witness should be impartial, independent, or neutral, as far as this can be achieved. The
relationship of the witness to the study subject and to the investigator and the study should be documented
All participants should personally date their signatures and all dates should precede the start of the study
(for each subject)
146 CH12 GOOD CLINICAL PRACTICES