摘要：Many contraceptives are encumbered with potentially unnecessary restrictions on their use. Indeed, fear of side effects, fostered by alarmist labeling, is a leading reason that women do not use contraceptives. In the United States, hormonal methods currently require a prescription, although research suggests that women can adequately screen themselves for contraindications, manage side effects, and determine an appropriate initiation date, leaving little need for routine direct physician involvement. Sizing, spermicidal use, and length-of-wear limits burden users of cervical barriers and may be unnecessary. Despite recent changes in the labeling of intrauterine devices, clinicians commonly restrict use of this method and in some countries may limit the types of providers authorized to insert them. Although in some cases additional research is necessary, existing data indicate that evidence-based demedicalization of contraceptive provision could reduce costs and improve access. Both in the United States and globally, significant unmet need for contraception remains. Difficulty of use, concerns about side effects or long-term health effects, and barriers to access may deter use of contraceptives. 1 – 6 New contraceptives under development may be easier to use with fewer side effects. In the interim, however, it may be possible to increase initiation and continuation of use of existing methods by simplifying product labeling and updating practice guidelines. Two sources provide clinicians and consumers with information and regulations about appropriate contraceptive use: product labeling (the information that the US Food and Drug Administration [FDA] officially permits drug companies to use in their packaging and marketing) and practice guidelines (typically set forth by public sector groups such as the International Planned Parenthood Federation and the World Health Organization [WHO]). Sometimes labeling and practice guidelines are in consonance; however, they often differ. Frequently, product labeling is based on outdated data, potentially misinforming both the public and health care providers. In many cases, this misinformation hinders direct consumer access to contraceptives. FDA regulations mandate specific requirements on the content and format of labeling for prescription drugs. Regulations are intended to ensure that prescribing physicians and patients are aware of the scientific information and potential risks associated with new drugs, but concerns about product liability litigation may encourage manufacturers to add otherwise unwarranted warnings. The process of determining the prescribing information to include in labeling does not involve objective reviews by researchers or clinical experts. Consumers play no role in the FDA labeling approval process other than taking part in committee hearings (when such hearings are held at all). The Code of Federal Regulations governs labeling changes and generally requires that a supplement to the New Drug Application or Investigational Device Exemption be submitted to the FDA before labeling changes can be made. However, a manufacturer can add or strengthen warning information without first obtaining FDA approval. 7 Likewise, adverse experience reports, which manufacturers must file to comply with FDA regulations, 8 may lead to stronger labeling changes even when such changes are not strictly warranted by the available evidence. 9 – 11 It is difficult, however, to reduce the amount of safety information included or to add indications for use. The latter change generally requires that the manufacturer support the proposed change with at least 2 adequate, well-controlled studies. 12 Yet, as a result of the cost of conducting such clinical studies, there are few incentives for manufacturers to submit the additional paperwork necessary to simplify labeling unless there is a potentially significant increase in market share to be derived from the changes made. In the case of oral contraceptives, manufacturers are generally proscribed from distinguishing products through promotional campaigns or labeling, because oral contraceptives are regulated under class labeling guidelines. Therefore, it is unlikely that a reduction in amount of safety information included will be initiated by manufacturers. As a result, labeling often includes unnecessary and outdated information, much of which was grandfathered in when regulations were established. One study found that overdose management in the labeling of 80% of drugs reviewed involved at least 1 deficiency in terms of advice, and nearly half contained ineffective or harmful information. 13 All of these factors may result in more alarmist warnings being added to labeling information, with very little pressure to counter this effect. In addition, inaccurate labeling information may lead to overestimation of the dangers associated with a given contraceptive 14 and thus deter eligible women from using what are in fact widely studied, safe, and effective methods. Indeed, research has shown that misinformation included in oral contraceptive labeling leads women to believe that there are medical contraindications to the use of these pills or that they entail health risks so grave as to render their use unsafe. 15 Similarly, a review of studies that evaluated the European Commission guideline descriptors, phrases used to describe the risk of a given side effect, revealed that people significantly overestimated the likelihood of adverse effects. This resulted in higher ratings of perceived health risks and lower ratings of likelihood of taking the medicine. 16 Perhaps most important, labeling that focuses primarily on liability obfuscates particularly valuable information. Valid concerns regarding legitimate potential complications are overshadowed by a medically unwarranted emphasis on extremely rare complications (e.g., hepatic cancer in the case of oral contraceptives). 17 The 1951 Durham-Humphrey amendment to the original federal Food, Drug, and Cosmetic Act of 1938 requires that “a drug be made available without a prescription if, by following the labeling, consumers can use it safely and effectively without professional guidance.” 18 The Durham-Humphrey amendment suggests that over-the-counter status will result by default once these criteria are achieved, but in reality this legislation is not enforced. Given that FDA-approved labeling is often out of date or not based on current scientific evidence, physicians often use medications and devices in ways not listed in their labeling, so-called “off-label” use. Off-label use is common, and even the FDA recognizes that advances in medicine often precede changes to labeling. 19 Physicians prescribing a drug or device off label are assumed to be well informed and to base their decision to do so on sound medical evidence. 20 Off-label use is helpful in that it allows physicians to use medications in innovative ways, but the practice transfers liability risk to the provider, and some clinicians may be reluctant to use drugs in this manner. Women without access to clinicians who are knowledgeable about the latest research, particularly women in developing countries, are at a disadvantage because their providers are less likely to be aware of new or less restrictive uses of drugs or devices. As a consequence of the dearth of clinical trials including pregnant women and children, off-label use is extremely common among pediatricians and obstetricians. In 1 study, physicians prescribed medications for an off-label indication to 23% of women attending prenatal clinics. 21 When physicians prescribe off label, they often look to the other main source of information: expert recommendations or practice guidelines. Clinical guidelines have become increasingly common over the past several years, as more emphasis has been placed on evidence-based medicine and managed care and as research emerges highlighting variations in physician practices. 22 At their best, practice guidelines are systematically developed statements intended to help clinicians make decisions about specific patient circumstances. These guidelines are often developed by experts brought together by professional organizations, such as the Royal College of Obstetricians and Gynaecologists (RCOG) or WHO, and published either by the organization or in peer-reviewed journals. We reviewed the labeling of the major contraceptives available on the market worldwide, as well as the contraceptive practice guidelines of the leading professional and public sector organizations active in family planning. Our hypothesis was that both labeling and practice guidelines create barriers to access that, if removed, could increase the number of contraceptive users. We identified research priorities to help solidify the evidence supporting simplifying the provision of contraceptives.
