will not be harmed. Some companies report that, in
practice, they have little choice in this process, as
the marketing department has already selected the
investigators. Another rationale for apparent lack
of choice is that there are too few patients or
investigators in a particular therapeutic area.
None of these reasons is as important as compli-
ance with the basic GCP principle, which requires
the sponsor/CRO to assess, select and choose safe
settings for research.
Setting up clinical studies is alengthy process, as
there are many documents to prepare [e.g. proto-
cols and case report forms (CRFs)], study facilities
to be assessed (e.g. study sites, CROs, clinical
laboratories, phase I units), regulatory review to
be considered and negotiations and agreements
with study sites (e.g. contracts, finances, confiden-
tiality, indemnity, insurance) to be undertaken. In
addition, as will be dealt with in subsequent sec-
tions, ethical aspects of the study must be consid-
ered (e.g. ethics committee and IRB review
and informed consent requirements), and study
medications/devices must be organized.
Protocols and CRFs
The protocol, with the accompanying CRF, is the
key document governing a clinical study. It for-
mally describes how a clinical study will be con-
ducted and how the data will be evaluated, and it
must include all the information that an investiga-
tor should know in order to properly select sub-
jects, collect safety and efficacy data and prescribe
the correct study medication/device. Protocols
must be prepared in accordance with a specified
and standardized format that is described in guide-
lines and regulations (the reader is particularly
advised to refer to the ICH GCP document). Pro-
tocols are usually prepared, at least initially, by the
sponsor or the delegated CRO, although investiga-
tor input is obviously necessary.
Any document used to collect research data on
clinical study subjects may be generically classed
as a data collection form. These completed forms
provide evidence of the research conducted. The
most common type of data collection form is the
CRF. Other types of data collection forms includeTable 12.1 General systems and procedures for implementation of GCP
The following systems and procedures must be established by clinical researchers to ensure compliance
with GCP requirements:
Quality assurance: Systems for assuring quality and for checking quality must be established and followed
at all stages
Planning: Studies must be conducted for valid (ethical and scientific) reasons
Standard operating procedures(SOPs): Research procedures must be declared in writing so that reviewers
can determine the standards which are being applied and so that users have a reference point
Well-designed study: All studies must have a valid study design, documented in a protocol, so that it can be
fully reviewed by all interested parties. The data collection plans, as described in the CRF, are part of the protocol
Qualified personnel: All personnel (sponsor/CRO and study site) must be experienced and qualified
to undertake assigned tasks. Documentation of qualifications and training must be evident
Ethics committee review and approval: All studies must be independently reviewed by ethics committees/IRBs,
to assess the risk for study subjects, before clinical studies begin. Review must continue throughout the study
Informed consent: All study subjects must be given the opportunity to personally assess the risk of study
participation by being provided with certain information. Their assent to participate must be documented
Monitoring: A primary means of quality control of clinical studies involves frequent and thorough
monitoring by sponsor/CRO personnel
Data processing for integrity of data: data must be honest. Data must be reviewed by site personnel, monitors
and data processing personnel
Control of study medications/devices: The product being studied must be managed so that study
subjects ultimately receive a safe product and full accountability can be documented
Archives: Documentation of research activities must be securely retained to provide evidence of activities
12.2 SETTING UP CLINICAL STUDIES 141