significant percentage loss or enhancement of effi-
cacy, for example 30%, dependent on the disease or
symptoms.
Representative population of women
This can be based on the incidence of disease
proportional to gender distribution and can be stu-
died when drug development and toxicity are well-
enough advanced, usually by phase III. Women of
childbearing age must be represented if the disease
is prevalent in the age group of 15–50 years.
Indeed, diseases such as endometriosis can only
be studied in such a population, whereas drugs to
treat urinary incontinence would be better under-
taken in older patients.
In some diseases, such as hypertension, where
both sexes are similarly affected, balanced num-
bers of male and female patients in phase III would
not seem out of place, although many investigators
are finding recruitment of sufficient numbers of
female patients increasingly difficult.
In diseases such as osteoarthritis, where women
patients outnumber males (80%), a legitimate case
can be made for a ‘female-weighted database’, and
also when women are the majorityusersfor med-
icines, such as psychotropic agents (although they
are not necessarily the majority of sufferers). Pro-
vision and timing of adequate animal toxicology
and fertility data are critical to avoid expensive
delays and to allow adequate female recruitment,
so these animal data may be advanced onan ‘at-risk
basis’, depending on the drug’s clinical signifi-
cance and its market potential. A list of diseases
more prevalent in women is provided inMedicines
in Development for Women(Holmer, 2004).
The potential childbearing population
The probability of potential early embryonic expo-
sure occurring in a drug development program
must be expected and confronted because, despite
careful pregnancy testing and adequate contracep-
tive precautions being undertaken, it happens.
Levine (1975) in his book suggested that, in the
consent form, there should be ‘a statement that the
particular treatment or procedure may involve risks
to the subject (or to the embryo or fetus if the
subject is or may become pregnant) which are
currently unforeseeable’.
When a woman of childbearing age participates
in a research procedure in which there is a risk to
the fetus, the nature of the risk being either known
or unknown, she should be advised that, if she
wishes to be a subject, she should avoid becoming
pregnant. Her plans for avoiding conception should
be reviewed during consent negotiations. At times,
if her plans seem inadequate and she does not
consent to the investigator’s suggestions, it will
be necessary to exclude her from the research.
She should be further advised that if she deviates
from the plans discussed at the outset, she should
advise the investigators immediately.
Halbreich and Carson (1989) made the point that
not to include women of childbearing age could
even increase liability.
The general policy of an academic institution
should be to favor the conduct of research invol-
ving women and children in testing of new drugs
with potential for major therapeutic value to those
populations. Such research may expose the institu-
tion to risk of liability for damage to subjects;
however, that is inherent in research involving
human subjects anyway, and there are many ways
of minimizing such risks. Not to do such research,
while it may serve to protect the interests of the
institution as narrowly conceived, would involve a
failure to serve the public interest in a much more
serious manner by exposing classes of persons to
knowable but unknown risks, through the practice
of clinical medicines using drugs not thoroughly
tested and understood, and withholding drugs that
may be of benefit.
It has been suggested that members of female
religious orders, women who have had tubal liga-
tion or lesbians could provide a ‘no-risk preg-
nancy’ pool of volunteers. Although possible, this
is not generally a widely applicable solution,
because geographic, environmental and volunteer
numbers now become added variables.
Should women on OCs enter studies, could the
high level of artificial hormones confound the
results? Female OC users make up 28% of the
potential childbearing population (Ortho, 1991),216 CH16 DRUG DEVELOPMENT RESEARCH IN WOMEN