Principles and Practice of Pharmaceutical Medicine

dose-ranging studies;

dose-titration studies;

marketing and safety surveillance studies;

studies supporting over-the-counter switches
(see a separate chapter in this book).

Thegoal of these plans is to provide a lean, efficient
NDA/BLA/MAA with the minimum studies
needed for registration and approval in the world
markets. The medical, scientific, regulatory and
marketing opinions must be weighed and balanced
in the plans.

Understand and conceptualize clinical
study design

To create a CDP successfully, the individual must
know the basic concepts of research design and
statistics, the concepts of clinical research and
investigational drug development; possess an in-
depth understanding of the concepts of clinical
pharmacology, pharmacokinetics, pharmacody-
namics, toxicology, state-of-the-art therapeutic
medicine and methodology, FDA/EU/ICH thera-
peutic research guidelines and regulatory issues;
and understand basic concepts of project planning
and scheduling. Knowledge of new methodology
(e.g. better use of PK/PD modeling/simulations
and computer-assisted trial design), ‘right-sizing’
trials and alternative statistical designs (e.g. futility
analyses, adaptive designs) are becoming essential
as companies look to improve efficiency and
reduce costs of the clinical development process.

Preparation of the investigator’s brochure (IB)

The IB is a compilation of clinical and preclinical
data on the investigational product that is relevant
to the study of the investigational product in
human subjects and the investigator’s assessment
of risk in participating in the study. The sponsor
compiles clinical information for the preparation
of the IB.

Clinical staff or a medical writing group may

perform the preparation of an IB. The activities

included in preparing the IB include

coordination of the compilation of clinical and

preclinical data from contributing departments

(e.g. Clinical Pharmacology, Toxicology);

describing the physical, chemical and pharma-

ceutical properties and formulation;

preparing a clear, concise summary of the infor-

mation relating to the safety and effectiveness of

the investigational product;

providing a detailed description of possible risks

and benefits of the investigational product;

defining a clear rationale for the dosage and

dosing interval.

To prepare an IB, the sponsor’s representative must

understand the fundamental purpose and uses of

the IB, the basic format and content of sponsor IBs,

the clinical pharmacology and toxicology findings,

the investigational product–disease relationships,

the international regulatory requirements govern-

ing IBs and the indications and safety profile of the

investigational product.

Design and preparation of clinical protocols

The clinical protocol describes the objectives,

design, methodology, statistical considerations

and organization of the trial. The sponsor is usu-

ally responsible for developing the protocol in

industry-sponsored clinical trials. However, inter-

nal and external content experts (e.g. specialists,

key opinion leaders) are frequently consulted. Pro-

tocols must be written ensuring medical soundness

and clinical practicality.

Frequently, the sponsor uses a template to com-

plete the sections of the protocol. The tasks of

developing a protocol include

defining clear protocol objectives;

28 CH3 CLINICAL RESEARCH EDUCATION AND TRAINING FOR BIOPHARMACEUTICAL STAFF