Childbearing population

It has been stated that large numbers of mature women are volunteering for the new lipid, heart risk, osteoporosis and arthritis phase 3 studies, due to their concern that women have been represented so poorly as subjects in the past. Phase I studies are of short duration (one to two weeks) but usually require confinement of the volunteers. Because of this time commitment, far fewer mature women volunteer, due to career conflicts or because they are often burdened unequally with family management. Those that do volunteer are generally unattached young female students. Thus, most female volunteers may not be typical of a representative , mature, childbearing population (if this can ever be defined). 

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),... 

Please describe planned study population. Choice of participants should be appropriate for the indication proposed. Subjects should not have enrolled in a clinical trial during the preceding 12 weeks. Please describe how special populations such as women of childbearing age, children and the elderly will be handled in this study. Please comment on the special need for close monitoring due to safety considerations. 

Adverse Effects Adverse effects are seen regularly in patients given mitoxantrone (see Table 26-3). Patients often experience bluish discoloration of the sclera and the urine for 24 hours after infusion.46 Transient leukopenia and neutropenia are common with a nadir 10 to 14 days after the infusion. Patients should avoid exposure to infectious individuals during this time.46 Patients taking mitoxantrone should not receive live virus vaccines other vaccines should be held for 4 to 6 weeks after a mitoxantrone dose.46 Amenorrhea, caused by a direct toxic effect on the ovary, may be permanent, an important consideration because the MS population includes women of childbearing potential.27... 

Phase I dosing of females if childbearing potential requires a Segment II study in at least one species Phase III dosing of this population requires a Segment I study and both Segment II studies. 

The primary human exposure to methyl mercury is from consumption of contaminated fish. The most sensitive population is the developing fetus or infant due to the effects of methyl mercury on the nervous system (neurotoxic) and developmental effects. Exposure limits and fish consumption advisories are directed at pregnant women, women of childbearing age, and children. All agencies also recognize that fish consumption has many nutritional benefits and is an important part of many people s diet. Nevertheless, the widespread distribution of mercury and subsequent bioaccumulation of methyl mercury requires that many agencies have developed recommendation for levels of mercury in fish. Below is a list of some of these recommendations, but it is very important to consult the local fish consumption advisories. 

Seventh, patients in trials often are carefully selected. If a study sample has a mean patient age of 45 years, the result of the trial may not be readily generalizable to substantially older or younger populations. Similarly, exclusion criteria in clinical protocols may rule out patients with specific clinical syndromes (e.g., diabetes mellitus), women of childbearing potential, or patients of advanced age. These patients may require additional resources or may receive less benefit from therapy because their life span is shorter. These exclusions further limit the generalizability of the findings of efficacy studies. 

A predominance of women of childbearing potential in the patient population... 

Although this topic is important for all classes of psychiatric medications, it may be particularly important for antidepressants, because they are the most commonly prescribed class of psychiatric medications. Furthermore, they are disproportionately prescribed to women of childbearing potential because major depression is more likely to be diagnosed and treated in this population. 

The first National Report on Human Exposure to Environmental Chemicals was initially released in 2001 and is based on analyses of NHANES biomonitoring data on exposure to chemicals. The data have various uses to determine which chemicals people are exposed to and at what concentrations to establish reference ranges for assessing whether an individual or group has an unusually high exposure, including susceptible populations, such as children, the elderly, and women of childbearing age to track exposure trends to assess the effectiveness of public-health efforts to reduce exposure of Americans to specific chemicals and to set priorities for research on human health effects (CDC 2005). 

Stroke is a very uncommon event in childbearing women, occurring in approximately 11 per 100,000 women over a 1-year period of time. Therefore, even a doubling of this risk with oral contraceptive pills would have minimal effect on attributable risk. The estimated risk of myocardial infarction associated with oral contraceptive pill use in nonsmokers is 3 per million women over 1 year. The estimated risk of venous thromboembolism attributable to oral contraceptive pills is less than 3 per 10,000 women per year. However, the risk may be increased in women who smoke or have other predisposing factors to thrombosis or thromboembolism. In fact, it should be emphasized that the risk of serious cardiovascular side effects is particularly marked in women over 35 years of age who are heavy smokers (e.g., more than 15 cigarettes per day). Additionally, the literature suggests that there may be an increased risk of breast cancer associated with long-term oral contraceptive pill use in women under the age of 35. However, because the incidence of breast cancer is so relatively low in this population, the attributable risk of breast cancer from birth control pill use is small. 

Reproductive and Developmental Toxicity Studies The requirement for reproductive and developmental toxicity studies depends on the clinical indication and intended patient population. For example, when (1) no relevant animal species exists, (2) a biopharmaceutical is not used for pregnant women or women of child-bearing potential (3) there is a structurally comparable natural biopharmaceutical for which there is much experience in clinical practice, or (4) a biopharmaceutical is indicated for patients with minimal childbearing potential and indicated for those with serious diseases, reproductive, and developmental toxicity studies could be obviated. 

This type of hADME study will always have an explorative character, and typically comprises less than the normal minimum of 12 subjects for a PK study. If the compound is expected to show different and unpredictable ADME characteristics in special populations, then it might be necessary to include these populations in addition to normal, healthy subjects. Or, if other conditions might influence ADME in an unpredictable manner (e.g. food effects), then it might even be necessary to run the study in a cross-over design. The inclusion of females (being not of childbearing potential) was discussed several times, but it seems to be a rare exception for hADME studies. 

ICH/M3 provides information about which studies -and of what duration - are needed before the different clinical phases of development can be started. In addition to this, timing of preclinical studies in dependence of clinical development plans, there are recommendations under which conditions different population can be included into clinical trials, populations such as men, women of childbearing potential or pregnant women and finally pediatric populations. 

This can be based on the incidence of disease proportional to gender distribution and can be studied 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 undertaken in older patients. 

Premarketing studies generally do not include special populations, such as children, women of childbearing age, or the elderly... 

Percentiles of the Population General Population Women of Childbearing Age ... 

Assuming body weight of 70 kg for the general population and 60 kg for women of childbearing age. 

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