identifying primary efficacy and safety para-
meters;
determiningappropriatesubjectselectioncriteria;
identifying correct dosages and route.
This could be a two-step process where the proto-
col summary containing all the key elements is
prepared and approved, triggering key operational
activities such as case report form (CRF) and data-
base design, manufacturing and packaging of
investigational product supply. While these activ-
ities are being carried out, the full protocol text can
be refined to meet regulatory requirements and
investigator needs.
To prepare appropriate protocols, staff must
understand research design and statistical infer-
ence for clinical research, state-of-the-art research
designs (e.g. adaptive designs, futility analyses)
and trials, therapeutic area guidelines, good clin-
ical practice, regulatory requirements, guidelines
and country-specific issues, national and interna-
tional medical practices, sponsor protocol review
and approval procedures and possess in-depth
investigational product–disease knowledge.
Clinical protocols are the building blocks of the
CDP and the NDA/BLA/MAA. Protocols specify
the conditions that permit and lead to meaningful
and credible results in clinical programs. Opera-
tionally, protocols provide a written agreement
between the sponsor and the investigator on how
the trial is going to be conducted. This agreement
allows the sponsor to ensure that the study will be
done to the highest ethical and medical standards
and that the quality of the data can be relied upon as
credible and accurate.
All clinical protocols and supporting documents
are reviewed and approved internally by a group of
senior Clinical Research & Development managers.
This group assesses the overall study design and
ability of the study to meet its objectives, as well
as the quantity and quality of the data. In addition,
the group reviews the procedures for the safety and
welfareofthe subjectstoensure compliance togood
clinical practices and ethical principles.
The quality of a clinical protocol can be assessed
by how well the elements of the protocol are
prepared. The elements of clinical protocols are
described in Table 3.1.
The extent of a Background section will vary
with the drug’s stage of development. New clinical
data not already included in the IB should be
emphasized. The Rationale provides a concise
statement of the reasons for conducting the study
and the basis for the dosage selection and duration
that will be used in the trial. Quality protocols
should target relevant information in the Back-
ground and convincing rationale for the study.
Every protocol must state a primary, quantifiable
study objective. Secondary objectives should be
limited in scope and related to the primary ques-
tion. Objectives must be specific and capable of
answering a key clinical question required by the
CDP.
The study design is an important element
in assessment of quality protocols. The overall
purpose of the study design is to reduce the varia-
bility or bias inherent in all research. Good study
design will always address control methods that
reduce experimental bias. These control methods
will often include treatment blinding, randomiza-
tion and between- or within-patient study designs.
The Schedule of Assessments describes a sche-
dule of time and events and provides a completeTable 3.1 Elements of clinical protocols
Background and rationale
Study objectives
Experimental design and methods
Schedule of assessments
Subject selection criteria
Trial procedures (screening, trial period, follow-up,
assessments)
Adverse event reporting
Trial medication
Premature withdrawal
Subject replacement policy
Criteria for excluding data
Data analysis/statistical methods
Quality control/assurance
Data handling and record keeping
Ethics (e.g. IRB/IEC approval)
Definition of end of trial
Sponsor discontinuation criteria
Signatures3.3 COMPETENCY-BASED TRAINING PROGRAM FOR STAFF ASSOCIATED WITH CONDUCTING CLINICAL TRIALS 29