The Drug development process - Pharmaceutical Biotechnology: Concepts and Aapplications - page 91

Box 4.3

Randomized control clinical trial studies

This trial design, which is the most scientifi cally desirable, involves randomly assigning partic-
ipants into either control or test groups, with concurrent testing of both groups. (Randomness
means that each participant has an equal chance of being assigned to one or the other group.
This can be achieved by, for example, fl ipping a coin or drawing names from a hat). Random-
ness is important as it:

• removes the potential for bias (conscious or subconscious) and, thus, will produce compara-

ble groups in most cases;

• guarantees the validity of subsequent statistical analysis of trial results.

The trial may also be unblinded or blinded. In an unblinded ('open') trial, both the investiga-
tors and participants know to which group any individual has been assigned. In a single blind
trial, only the investigator is privy to this information, whereas neither the investigator nor the
participants in double blind trials know to which group any individual is assigned. Obviously,
the more blind the trial, the less scope for systematic error introduced by bias.
The most signifi cant objection to the randomized control design is an ethical one. If a new
drug is believed to be benefi cial, then many feel it is ethically unsound to effectively deprive up
to half the trial participants from receiving the drug.
One modifi cation that overcomes the ethical diffi culties is the use of historical control trials.
In this instance, all the trial participants are administered the new drug and the results are
compared with previously run trials in which a comparable group of participants was used.
The control data are thus obtained from previously published or unpublished trial results. This
trial design is non-randomized and non-concurrent. Although it bypasses ethical diffi culties
associated with withholding the new drug from any participant, it is vulnerable to bias. The
trial designers have no infl uence over the criteria set for their control group. Furthermore,
historical data can distort the result, as benefi cial responses in the test subjects may be due
not only to the therapeutic intervention, but generally improved patient management practices.
This can be particularly serious if the control data are old (in some trials it was obtained 10-20
years previously).

4.14 The role and remit of regulatory authorities

The pharmaceutical industry is one of the most highly regulated industries known. Governments
in virtually all world regions continue to pass tough laws to ensure that every aspect of pharma-
ceutical activity is tightly controlled. All regulations pertaining to the pharmaceutical industry are
enforced by government-established regulatory agencies. The role and remit of some of the major
world regulatory authorities is outlined below. In the context of this chapter, particular emphasis
is placed upon their role with regard to the drug development process.