INTRODUCTION

Prior to the third quarter of the 20^thcentury, the Food and Drug Administration’s (FDA’s) guidelines for the inclusion of women in clinical studies for all types of illnesses were limited. The FDA barred women of childbearing age from all phase I trials (safety studies) and from all other studies until animal teratology and fetal toxicity studies could be completed and analyzed.

After the U.S. Public Health Service Task Force on Health deemed that excluding women from clinical research was detrimental to women’s health, guidelines from the National Institutes of Health (NIH) urged the inclusion of women in NIH-sponsored research. The NIH Revitalization Act mandated that the NIH ensure that women and members of minority groups be included in all research on humans. The U.S. General Accounting Office (GAO), however, stated that the FDA was not thoroughly monitoring research data to determine how sex differences were affecting the safety and effectiveness of medicine. generic prescription drugs

Although it was slow at first, progress in including women in clinical trials has followed the changes in health care policies and regulations over the past quarter century. Many drug therapies and their effects on women need to be reassessed. Although the regulatory agencies did adopt some important federal rules and regulations, it was not until late in the 20^th century that study protocols included women in a meaningful way.

CHRONOLOGICAL PERSPECTIVE

I960-I970s

In the early and middle 20^th century, women’s participation in clinical studies of new drugs was minimal. Their under-representation stemmed from the belief in the federal government and its agencies that it was not safe to study the safety and efficacy of new drugs in women. It was their way of protecting female subjects, especially those of childbearing age, from reproductive problems that might result from testing new chemical entities. Drug testing was encouraged in men, and it was assumed that whatever safe and effective doses were derived from clinical studies in men could be extrapolated for women.

Of course, the thinking was totally fallacious; it was not until the 1970s that the FDA realized that federal legislation, up to that decade, was not offering the same quality of drug care to women that was offered to men. The political climate, as a result of the women’s movement in the U.S., was beginning to change along with the realization that clinical research on the effects of new drugs on people was not being conducted in an ethical manner if at least half of the population was being excluded. cheap viagra uk

In 1964, the World Medical Association affirmed and adopted the Declaration of Helsinki as a statement of ethical principles to guide physicians and other participants in medical research involving humans. In medical research on human subjects, considerations related to their well-being had to take precedence over the interests of science and society Medical research was subject to ethical standards that required respect for all people and that protected their health and rights. Healthy volunteers were precluded, and the research was to be conducted only if the importance of the objective outweighed the inherent risks and burdens to the patients. Every biomedical research project involving humans was to be preceded by careful assessment of predictable risks in comparison with foreseeable benefits to patients or to others. The Declaration of Helsinki contained no statement excluding women from bio-medical research.

In 1975 in the U.S., the National Commission for Protection of Human Subjects of Biomedical and Behavioral Research passed a special regulation, the Belmont Report, which described the principles of equitable selection of research subjects. Congress established the Commission (1974-1978) under the National Research Act: Public Law 93-348, Title II, Part A, on July 12, 1974. The Commission’s purpose was to conduct a comprehensive investigation and to identify the basic ethical principles that should underlie the conduct of bio-medical and behavioral research involving humans in the U.S. The Commission developed guidelines to ensure ethical research protocols.

The Commission undertook a comprehensive study of the ethical, social, and legal implications of advances in biomedical and behavioral research and technology. One of the principles was the justice involved in the selection of research subjects. Justice was considered to be relevant at both the individual level and the social level:

• Individual justice required that researchers exhibit fairness in (1) not offering potentially beneficial research to only some patients and (2) not selecting only “undesirable” persons for risky research. canadian cialis online
• Social justice required that a distinction be drawn between classes of subjects (e.g., adults and children) who should and should not participate in a particular kind of research, based on the ability of members of that class to bear burdens and on the appropriateness of placing further burdens on already troubled persons. Thus, it was considered a matter of social justice that there be an order of preference in selecting classes of subjects (e.g., adults before children) and that some classes of potential subjects (e.g., institutionalized mentally infirm patients or prisoners) might be research subjects only under certain conditions. The Commission did not distinguish, in patient selection, on the basis of sex.

This principle of distributive justice was applied to the equitable selection of research subjects. For example, if women were going to acquire the benefits of the particular research, such as the use of new drugs or devices, they had the right and the responsibility to participate in the research. Because of the sensitivity of clinical research in 1974 and 1975, however, the Commission members approved some special regulations that were promulgated in 1975 to provide extra protections for vulnerable subjects undergoing research,⁵ such as children, mentally disabled people, educationally disadvantaged persons, prisoners, and pregnant women. In regard to pregnant women, the fetus—not the mother—was considered to be the vulnerable subject. Unfortunately, the only definite way to protect fetuses was to exclude all women from research.

In 1977, the FDA recommended that premenopausal women who were capable of becoming pregnant be excluded from early drug studies. Even though the FDA guidelines referred to early phases of drug development, the Pregnancy Discrimination Act of 1978 affected the participation of women in all phases of trials. The Act stated that women who were pregnant or who had pregnancy-related conditions had to be treated the same as other applicants and employees with regard to their ability or inability to work. However, following the tragedies caused by the use of thalidomide and diethyl-stilbestrol in pregnant women, the FDA’s guidance in 1977 recommended against including women of childbearing age in the early phases of drug testing unless the study concerned life-threatening illnesses. viagra soft