and these hormone concentrations (10–20 times
higher than the natural hormone levels) may
cause drug interactions which cannot occur during
ordinary menstrual cycling. Intrauterine devices
are currently regaining popularity, subdermal
implants have had little influence on contraceptive
practice at the epidemiological level.
Liabilities for fetal damage
Given all of the above reasons for including women
of childbearing potential, the issue of the chilling
effect of legal liability for fetal damage on firms
and institutions is still present, and the necessary
addition to the patient’s informed consent does not
help. The Supreme Court in 1992 rejected an
attempt to cap the amount juries could award in
damages as ‘unconstitutional’, that is would
require a constitutional amendment. This is highly
unlikely to occur. The consequences of litigation,
particularly in obstetrics, were dramatic increases
in C section from 18 to 29.1% of all live births;
(2005 Center for Disease control) resignations
from this specialty, and a broader rejection of
‘high-risk’ or Medicaid patients (O’Reillyet al.,
1986; Bello, 1989). A possible solution might be
to follow the example of the National Vaccine
Injury Act of October 1988, where a trust fund
was set up derived from an excise tax imposed on
each vaccine. The funds, through an arbitration
panel, are used to compensate persons injured by
vaccination. It should be noted that a Drugs in
Pregnancy Registry has been set up to follow up
early embryonic exposure to the anticonvulsants
and antiviral drugs acyclovir and retrovir. This is
administered by the American Social Health Asso-
ciation (ASHA), Center for Disease Control (CDC)
and GlaxoSmithkline. One wonders if it could be
expanded (with suitable support) to cover addi-
tional agents.
Current enrollment
The use of double barrier contraceptive require-
ments in many clinical studies in women of child-
bearing potential has resulted in better recruitment.
Analysis of regulatory applications by the health
authorities in Europe, Japan and United States
reported (2003 ICH Working Report) that near
equal representation of both women and men
were observed.
As a result of this the ICH declined to issue a
separate guideline on women as a special popula-
tion (ICH, 2004). The Office of Research on
Women Health (ORWH), National Institute of
Health, in February 2005, reported in its monitor-
ing that both NIH recruitment of women and mino-
rities, in the clinical studies, were now reaching
substantial proportions. Even in industry-based
studies, by 2000, 22% of subjects were female in
early-stage studies.Data gathering
Gender data are collected by major pharmaceutical
companies; few, however, record the menstrual
dates. Frequently, no drug-handling differences
betweenthesexesisdetected;muchlesscommonly
is the absence commented upon in reports or pub-
lications. It is suggested that LMP dates could be
included in case report forms, and that publications
and reports should contain statements on the pre-
sence or absence of gender differences, also giving
the patient gender numbers andp-values. This
would allow for later meta-analysis. Both of these
suggestions would be inexpensive to implement.
Gender-related data from the FDA are more
readily available as the FDA continues to increase
its computer ability, and pharmaceutical firms uti-
lize computer-assisted NDAs and increase their
efforts to adequately power the studies to find
differences. Unified systems and formats would
enhance this. The information is included in the
Summary Basis for Approval or in the Medical
Reviewer’s Report. Either should be available
through the Internet at http://www.fda.gov./cder under
‘New Approvals’.16.8 Conclusion
Gender-related differences do exist in drug
handling, but in general are relatively clinically16.8 CONCLUSION 217