The Federal Food, Drug, and Cosmetic Act and related regulations (21 U.S.C. 301 et seq.) give FDA staff the legal authority and responsibility to review the safety and effectiveness of drugs and biological products (including products used in cancer treatment), from preclinical testing through all phases of clinical research and marketing. FDA review activities in the oncology arena can be divided into five major categories: (1) initial review of investigational new drug (IND) applications; (2) ongoing review of premarketing research (including new research protocols submitted to existing INDs and IND safety reports describing adverse events with the new drug); (3) discussions with commercial sponsors regarding their clinical development plans, including the design and conduct of key studies that are intended to support initial marketing approval for a new product or to support the addition of new indications to the prescribing information for currently marketed products; (4) review of submitted new drug applications (NDAs) or biological licensing applications (BLAs); and (5) continuing review of the safety and effectiveness of marketed products. Through these review activities, FDA staff work to ensure that products approved for marketing for cancer treatment are effective and adequately safe for their intended uses and to ensure that the quality, effectiveness, and safety of products on the market are preserved or enhanced, so patients and physicians may use these products with confidence and with adequate safety. Because these review activities generally fall into a chronologic sequence, the following discussion parallels the development course of a typical new drug.
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PMID 11795373 11795373 DOI 10.1111/j.1749-6632.2001.tb04042.x 10.1111/j.1749-6632.2001.tb04042.x
Cite this article
Kobayashi K, & DeLap RJ (2001). FDA review practices and priorities for drugs used in cancer treatment. Annals of the New York Academy of Sciences, 949(1), 341-344. https://doi.org/10.1111/j.1749-6632.2001.tb04042.x
Kobayashi K, DeLap RJ. FDA review practices and priorities for drugs used in cancer treatment. Annals of the New York Academy of Sciences. 2001;949(1):341-344. doi:10.1111/j.1749-6632.2001.tb04042.x
Kobayashi K, and DeLap RJ. "FDA review practices and priorities for drugs used in cancer treatment." Annals of the New York Academy of Sciences, vol. 949, no. 1, 2001, pp. 341-344.
Menstruation is the cyclic, orderly sloughing of the uterine lining on account of the interactions of hormones produced by the hypothalamus, pituitary, and ovaries. There is a tendency among parents and clinicians to view oligo-amenorrhea as a normal variant in the teen years. In fact, the 95th percentile for the time interval between cycles is 90 days. Thus, it is abnormal for an adolescent to be amenorrheic for greater than 3 months, even in the early gynecologic years. Identification of abnormal menstrual patterns throughout adolescence may permit early identification of potential health concerns for adulthood. Few problems in gynecologic endocrinology are as complex or challenging to the clinician as amenorrhea. However, thorough evaluation of menstrual cycle disorders in adolescence provides a window of opportunity for early diagnosis and treatment of conditions affecting the hypothalamic-pituitary-ovarian (HPO) axis. Here we discuss a systematic approach to the evaluation and treatment of amenorrhea in adolescents who do not have androgen excess. There is strong evidence that estrogen deficiency is a risk factor for later development of osteoporosis and hip fracture. Delay in the evaluation and treatment of disordered menses in some cases may contribute to reduced bone density. Both patients and clinicians need to view the ovary as an important endocrine organ that helps maintain health, especially bone health.
Stubbs ML, 2008·Annals of the New York Academy of Sciences
This overview details the persistence of negative characterizations of the menstrual cycle as a feature of the current cultural context in which girls begin menstrual life in the United States. In addition, research on girls' current menstrual attitudes and experiences within this context are reviewed. Current research suggests that girls are not very knowledgeable about menstruation, and that menstrual education continues to provide girls with mixed messages, menstruation is a normal, natural event, but it should be hidden. Girls' attitudes and expectations about menstruation are negatively biased and have been found to contribute to self-objectification, body shame, and lack of agency in sexual decision-making. Although preparation has been found to be associated with more positive menarcheal and menstrual experiences, specificity about what constitutes "good" preparation has not been well articulated. Implications for promoting the menstrual cycle among young girls as a vital sign in service of monitoring their health are discussed.
Golden NH et al., 2008·Annals of the New York Academy of Sciences
Menstrual irregularity is a common occurrence during adolescence, especially within the first 2-3 years after menarche. Prolonged amenorrhea, however, is not normal and can be associated with significant medical morbidity, which differs depending on whether the adolescent is estrogen-deficient or estrogen-replete. Estrogen-deficient amenorrhea is associated with reduced bone mineral density and increased fracture risk, while estrogen-replete amenorrhea can lead to dysfunctional uterine bleeding in the short term and predispose to endometrial carcinoma in the long term. In both situations, appropriate intervention can reduce morbidity. Old paradigms of whom to evaluate for amenorrhea have been challenged by recent research that provides a better understanding of the normal menstrual cycle and its variability. Hypothalamic amenorrhea is the most prevalent cause of amenorrhea in the adolescent age group, followed by polycystic ovary syndrome. In anorexia nervosa, exercise-induced amenorrhea, and amenorrhea associated with chronic illness, an energy deficit results in suppression of hypothalamic secretion of GnRH, mediated in part by leptin. Administration of recombinant leptin to women with hypothalamic amenorrhea has been shown to restore LH pulsatility and ovulatory menstrual cycles. The use of recombinant leptin may improve our understanding of the pathophysiology of hypothalamic amenorrhea in adolescents and may also have therapeutic possibilities.
EndometriosisEstrogen Production and MetabolismAromatase ActivityAromatase Inhibitors
Bulun SE et al., 2002·Annals of the New York Academy of Sciences
Aromatase activity is absent in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis, which gives rise to strikingly high levels of aromatase activity in this tissue. Both aromatase expression and activity are stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, that is, deficient 17beta-HSD type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.