These following critical changes are reflected in drug and biologic product protocols presented to IRBs:
- First, the restriction on participation by most women with childbearing potential from entering Phase 1 and early Phase 2 trials is lifted, encouraging their participation. FDA believes that early drug and biologic trials can be safely conducted in women even before completion of all animal reproduction studies through protocol designs that include monitoring for pregnancy as well as measures to prevent pregnancy during exposure to investigational agents. Pregnancy testing is recommended, and women must be counseled about the reliable use of contraception or abstinence from intercourse while participating in the clinical trial. The guideline does not, however, specify the type of contraception to be used because FDA believes that decisions of this nature are best left to the woman in consultation with her health care provider. It is important that investigators have access to gynecologic consultants who can provide information about contraceptives and advice for study participants.
- Second, sponsors should collect gender-related data during research and development and should analyze the data for gender effects in addition to other variables such as age and race. FDA requires sponsors to include a fair representation of both genders as participants in clinical trials so that clinically significant gender-related differences in response can be detected. The guideline also underscores the importance of collecting pharmacokinetics data on demographic differences beginning in the Phase 1 and 2 studies, so that relevant study designs are developed for later trials.
- Third, three specific pharmacokinetics issues should be considered when feasible: (1) effect of the stages of the menstrual cycle, (2) effect of exogenous hormonal therapy including oral contraceptives, and (3) effect of the drug or biologic on the pharmacokinetics of oral contraceptives.