Added: Deborah Kyser - Date: 11.09.2021 09:33 - Views: 49166 - Clicks: 959
Try out PMC Labs and tell us what you think. Learn More. This paper chronicles attempts in the United States over the past 20 years to fully represent women in clinical trials and ensure the study of sex and gender in biomedical research. We maintain that productive science with the aim of serving the public health requires examining the influence of sex and gender on health outcomes. We also cite all reports by the U. Institute of Medicine and the U. The key message of this paper is that it has been 20 years since the first requirements to include women as well as men in clinical trials and analyze by sex were mandated by a U.
Recent s of potential change in both policy and practice of scientific inquiry suggest much more progress may be within reach. However, awaiting a cultural shift to allow the study of sex and gender to be embraced is not seen as an effective strategy for change. Rather, specific instrumental recommendations are offered for how to include the study of sex and gender in research so as to increase our understanding and promotion of health for the benefit of all.
Now is the time to fully integrate the study of sex and gender into biomedical research — a goal that is essential to productive and reproducible scientific inquiry [ 1 ], and by so doing generate findings that advance the public health.
We focus on efforts to reach this goal in the United States over the past 20 years since the implementation of a U. This report chronicles the changes in recommendations and requirements of both the National Institutes of Health and the U. All U. Institute of Medicine and General ability Office reports on this topic from to the present are cited, as are selected high-impact, published studies to highlight the paucity of, yet the continued need for, inclusion of females and consideration of sex and gender in research across an array of biomedical disciplines.
These published studies are woven into the historical perspective to illustrate the impact of the legal milestones and policy initiatives. The scope of the report is from — the immediate prelude to the NIH Revitalization Act — to the present with an emphasis on recent developments through The position advanced by this report is that steps have been taken in the United States to remedy the underrepresentation of women and the inadequate attention to sex and gender differences in research and regulatory approvals.
However, progress has been painfully slow — stalling for long periods or sometimes reversing direction [ 2 ] — and, consequently, not nearly enough progress has been made. Even when women have been included as subjects in clinical research, the influence of sex or gender is not widely analyzed and reported for various health outcomes [ 5 ]. Most laboratory studies continue to use only male animals and do not take note of how cells differ on the basis of sex, yet these very studies form the biological basis for human health studies and derivative treatments [ 6 , 7 ].
We follow these definitions see Table 1 : Sex and Gender Definitions [ 8 ] in our narrative but recognize, as did the IOM report, that current available definitions of these terms are not unambiguous and cannot always be used in a mutually exclusive fashion due to the interaction of biological and social elements affecting health outcomes [ 8 ]. The current report concludes with recommendations regarding next steps in finally complying with the year-old requirements set by the NIH, and the inclusion of sex and gender in biomedical research in a comprehensive and meaningful way. It is our view that further operational changes are needed to create a scientific environment in which sex and gender-sensitive approaches to research are embraced, and result in greater understanding of how women and men are differentially affected by health conditions.
Importantly, we maintain that such change will result in findings for both women and men that can be translated into improved health and healthcare. Congress and can provide reports on issues of concern to the nation. Furthermore, the NIH had done little to encourage researchers to for sex or gender when analyzing study [ 9 ].
This set of studies using large samples of American women who had gone through menopause was begun to better understand treatment for cardiovascular disease, cancer, and osteoporosis — the major causes of death, disability and impairment in this population of women within the United States [ 11 ]. These studies represented the first nationally-representative clinical trials deed to study key health conditions affecting women. Hormone therapy was of particular interest as it was commonly prescribed and increasing in use. And population surveys in the s indicated that of 30 million postmenopausal women in the United States, one-third were receiving estrogens, often to prevent heart disease [ 13 ].
Yet, despite this practice, only observational data were available to support the use of hormones for the prevention of cardiovascular disease. This report highlighted that the use of prescription drugs was the most common form of medical treatment, and that available data showed sex differences in the metabolism of drugs as well as in drug interactions. When women were included, data were not analyzed for most drugs to determine whether responses differed between women and men. For the first time, NIH-funded investigators were to be required to include women as well as men in human subject research.
Cost was not allowed as an acceptable reason for exclusion of women and minorities. However, requiring the study of female animals and human tissues that cannot be linked to a living individual was not included in this legislation. These new regulations published in the U. Federal Register defined new drug application requirements pertaining to effectiveness and safety data for demographic subgroups, specifically gender, age and racial subgroups.
The rules did not impose any new mandates on the conduct of studies for new drug applications, requiring only safety and efficacy data that already had been collected be presented separately for these demographic subgroups, including men and women. The FDA did not require any discussion or analysis of these data [ 20 ]. This May report concluded that ificant progress was being made in increasing representation of women in clinical trials, spurred by the fact the inclusion of subgroup populations had become a matter of scientific merit when research grants were assessed for funding.
However, the report found that studies still were not routinely being deed to enable analyses by sex, and when researchers were analyzing outcomes by sex, these were not always published [ 21 ]. This continuing program is a collaborative effort to ensure that the influence of sex and gender on health is studied by the next generation of scientists. In June , the FDA issued a new regulation allowing the agency to halt research on drugs for life-threatening diseases and conditions if men or women who have the condition are excluded from study based on a perceived risk to their reproductive potential.
In a subsequent review, it was again demonstrated that women suffered more adverse effects from prescription drugs than men [ 25 ]. In addition, the GAO found that the FDA had not yet exercised its power to suspend research on life-threatening conditions if men or women were excluded based on their potential to reproduce, though the GAO report did not examine if such a sanction should have been used in any particular instance. In particular, the effects of hormone therapy on preventing cardiovascular disease, fractures, and breast and colorectal cancer were studied [ 26 ].
Both parts of these hormone therapy trials were halted early, in and , respectively, because investigators determined that estrogen did not appear to be protective against cardiovascular disease for which it was generally prescribed and that health risks outweighed benefits [ 27 ]. Despite subsequent controversy about the value versus adverse effects of estrogen use, this was the first attempt to investigate the benefits and risks of this widely prescribed hormone in a large nationally-representative longitudinal sample of women.
In , the first U. The findings in this study left women and their care providers uninformed as to whether this preventive strategy would help, harm or have no effect on women. Aspirin provided the same primary preventive benefit in women older than 65 as it did in men 50 years and over. Yet most clinicians are unaware that the sexual differences associated with these problems are the result of inherent differences in biology at the cellular and molecular level.
In a finding specific to the United States compared to Western Europe, Australia, New Zealand and Japan, life expectancy was found to be falling for a ificant of American women for the first time since the influenza epidemic of [ 31 ]. Census population data to estimate sex-specific life expectancy for U.
From the early s, life expectancy ificantly decreased in 11 U. Smoking, obesity and high blood pressure largely led to the higher rates of death for women. As concluded in this review in The Journal of Pain , recent findings demonstrate that women have a greater risk for many pain syndromes than do men, report greater pain after invasive procedures, and greater sensitivity to most forms of experimentally induced pain. In reviewing physiological and pharmacological differences between women and men relevant to general anesthesia and recovery after surgery, findings published in Anaesthesia and Intensive Care indicated that women awaken from anesthesia faster than men, suggesting less sensitivity to the hypnotic effects of anesthesia, but have slower recovery from anesthetic drugs due to higher rates of complications or adverse effects from general anesthesia [ 34 ].
Two years after publishing this review, the authors then confirmed their findings using a prospective, matched cohort de with patients women and men who received a general anesthetic for elective surgery. This study in the British Journal of Anaesthesia showed women to be less sensitive to the drugs used, to wake faster and to have poorer recovery than men.
These outcomes appeared to be due to sex differences in the pharmacodynamic effects of the anesthetic drugs. Subgroup differences were also noted in that premenopausal women compared to postmenopausal women had worse recovery [ 35 ]. Each of these prominent journals acknowledged the very important lack of information in many areas of health due to the absence of female subjects in studies using model systems [ 36 , 37 ].
The focus was on a of diseases or syndromes that are more common or serious for women, or have different treatments for women than men, or for which there was a clear unmet need for research regarding women. The report found major progress in breast cancer, cardiovascular disease CVD and cervical cancer. The report credited the translation of new research findings in the progress made in treating these illnesses.
In addition, consumer demand for were cited in the case of breast cancer, and behavioral changes such as decreased smoking in the case of CVD. In the case of cervical cancer, research-based improvements in diagnosis and screening were credited as well as the development of a vaccine to prevent human papillomavirus HPV , the cause of most cervical cancer [ 39 ]. Yet, the World Health Organization, which ranked depression as the leading cause of disability worldwide as of October , indicated that depression affects more women than men [ 41 ].
Published in Circulation, this review reiterated once again that more women than men die each year in the United States from cardiovascular disease — the greatest cause of mortality for both women and men. It pointed out that inclusion of women in clinical trials for cardiovascular disease remained controversial as some examinations of the data suggest an increase in the proportion of women while others do not. Nonetheless, parity in inclusion had not been achieved and analysis of outcomes by sex remained minimal with evidence of such analyses in about one-third of studies [ 42 ].
Presentations and discussions from an IOM workshop held in San Francisco March 8—9, focused on why it was important to study sex differences in neuroscience and the need to translate findings to advance the public health. The key roles of scientific journals in reporting sex differences, and of industry in ensuring that sex differences are evaluated in drug development were highlighted.
In fact, a quarter of these analyses 12 of 47 found differences by sex either in safety or effectiveness. The FDA also had convened workshops in to inform guidance on this matter and issued draft guidance in with recommendations for increasing the of women and conducting sex-specific analyses. Section of the law directed the FDA to review the inclusion and analysis of demographic subgroups in applications for drugs, biologics and devices by sex, race and ethnicity, and age [ 48 ].
The review was to take the form of a progress report of current practices and planning for further improvement, and a subsequent Action Plan with recommendations for enhanced enrollment and analysis of subgroups, and communication of data to health care professionals and the public. This suggests that although the FDA supplies the necessary information on how sponsors should provide subgroup data and analysis, there is not consistent reporting by sponsors. Published in Cancer, this study examined scientific publications reviewing both the diversity of and reporting on study participants in treatment trials and 27 prevention trials conducted in the decade between and The difference was noted in a study analysis years earlier but nothing was done about it before the drug went to market.
Although not as widely prescribed as Ambien, several other drugs have been identified by the FDA that require sex-sensitive prescribing [ 50 ]. Marking the 50th year since the U. However, in any given quit attempt, women are less successful than men, indicating that women have more difficulty quitting [ 52 ]. Women are also more likely than men to relapse to smoking after quitting [ 53 ]. Senators on April 30, A bipartisan group of U. Senators sent a letter to the FDA requesting that the agency include in its forthcoming Action Plan a requirement for proportional representation of women and minorities in clinical research, assurance that analyses of subgroups are conducted, and a process to ensure the progress of the plan is tracked and are made available to the public.
One month later, a bipartisan group of members of the U.Mature sex southern women
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