Principles and Practice of Pharmaceutical Medicine

The section will also detail the requireme-
nts for obtaining informed consent from trial sub-
jects.
For trials conducted in the EU, the protocol
must include a definition of the end to the trial
(in an EU member state or in all participating
countries).
The Sponsor Discontinuation section of the pro-
tocol provides a reminder to the investigator that
the trial may be terminated prematurely as a result
of a regulatory authority decision, a change in
opinion of the IRB/IEC, drug safety problems or
at the discretion of the sponsor. In addition,
most sponsors will reserve the right to discontinue
development of the investigational product at
any time.

Design of the format and content
of Case Report Forms CRFs

The CRF is the document used to record all of the
protocol-specified data to describe individual sub-
ject results. Many sponsors use standard modules
to prepare the CRF and are increasingly using
electronic data capture technology.
To prepare successful CRFs, the sponsor’s staff
must know typical clinical practices, therapeutic
conventions, investigator and staff needs, data
management and analysis plans, project-specific
definitions and procedures, CRF completion pro-
blem areas, remote data/electronic entry and
review and approval procedures for CRFs. Ideally,
CRFs should be pretested with internal and exter-
nal experts (e.g. investigational sites).
The quality of a clinical trial can be influenced
by how well the CRF is designed. If the investiga-
tor’s staff cannot enter the protocol data as
required, the sponsor will have a considerable
challenge in trying to interpret the results. There
are a number of design principles that facilitate
the use of CRFs in clinical trials. These principles
include the concepts of standardization and mini-
mization. The sponsor standardizes the design of
CRFs in one consistent international format. This
permits uniform databases, consistency in collec-
tion and more rapid data entry/capture. In addition,
standardization facilitates the monitoring process

and therefore increases accuracy of the data.

Although efficiency is an important variable in

the design process, the systems must also be suffi-

ciently flexible to account for the variances

between projects. Finally, an important principle

of both protocol and CRF design is to collect only

the data needed to satisfy the objectives of the

protocol. The inherent temptation to collect more

data must be resisted.

There are several CRF design characteristics

that define quality CRFs. Some of these

include

limiting the amount of space or blank fields for

free text;

providing instructions on the CRF or within the

electronic tool for its completion;

consistent layout of information within the CRF;

simple, unambiguous language, particularly for

multinational trials;

collecting only raw data, letting the computer do

transformation calculations;

intensive monitor training in the use of the CRFs.

High-quality CRF design is probably the cheapest

investment in big returns on a clinical trial.

Packaging and labeling of investigational

product

The investigational product is the active ingredient

or placebo being tested in a clinical trial. Forecast-

ing investigational drug supplies is important in

that it must be done well in advance of the start date

of the clinical trial. To make this forecast, it is

necessary to estimate, from the CDP, the bulk

investigational product supply needs. Oftentimes,

the protocol summary provides the trigger to begin

packaging and labeling of investigational supplies

for the trial.

To successfully handle drug supplies, the spon-

sor’s representative must know

3.3 COMPETENCY-BASED TRAINING PROGRAM FOR STAFF ASSOCIATED WITH CONDUCTING CLINICAL TRIALS 31