Bimal H. Ashar MD, FACP1
Adrian S. Dobs MD, MHS2
1Assistant Professor of Medicine, Johns Hopkins University School of Medicine
2Professor of Medicine and Oncology and Director, Clinical Trials Unit, Johns Hopkins University School of Medicine
The authors have no commercial relationships with manufacturers of products or providers of services discussed in this chapter.
The term alternative medicine encompasses a spectrum of approaches to medical conditions not routinely used by conventional practitioners. Historically, the term has been associated with negative conceptions about medical practices that did not conform to accepted standards of care. The term complementary medicine has since evolved to describe a more positive, symbiotic relationship between unconventional medicine and conventional medicine. The field of complementary and alternative medicine (CAM) now encompasses a multitude of different approaches and beliefs that are generally linked by their emphasis on so-called natural modalities of healing and wellness. More and more, the term integrative medicine is being used, suggesting that CAM should be integrated into conventional care. This chapter describes modalities that are complementary to conventional medicine in the United States; in other countries, many of these modalities are part of mainstream medical practice.
Patient demand, media attention, and the growth of an approximately $40 billion industry1 have stimulated leaders in governmental agencies and academic medicine to recognize and categorize CAM and to direct research initiatives on the subject. Although there is currently no universally accepted classification of CAM modalities, the National Center for Complementary and Alternative Medicine (NCCAM) has grouped CAM practices into five domains [see Table 1]. It should be recognized that these categories are not mutually exclusive. Certain practices will overlap (e.g., qigong is considered an energy therapy but is part of Chinese medicine, which is an alternative medical system). Also, as evidence emerges regarding mechanisms of action, safety, and efficacy, certain modalities will naturally move beyond the CAM label and become part of mainstream medicine.
Table 1 NIH/NCCAM Classification of Complementary and Alternative Medicine Practices
Use of CAM
PREVALENCE AND DEMOGRAPHICS
The widespread use of CAM by the public has been well documented. In 2002, about 62% of adults in the United States reported using at least one form of alternative medicine within the previous year.1 It has been estimated that 75% of people in the United States have used at least one CAM therapy over their lifetime.1 Public-opinion surveys have suggested similar overall patterns of use in European countries, although the popularity of specific CAM modalities varies greatly from country to country.2 Patients across all demographic groups use alternative medicine. However, some surveys have noted that predictors of CAM use may include female gender, white race (as opposed to African-American or Hispanic), higher socioeconomic status, and higher levels of education.3,4 Many CAM users have chronic, non-life-threatening medical conditions,3,5 and they may have an interest in spirituality.6 A number of diagnosis-based surveys suggested exceptionally high usage of alternative medicine in patients with cancer,7 HIV infection,8 fibromyalgia,9 and inflammatory bowel disease.10
The alternative-medicine movement has clearly been a public-driven process that has spanned decades. It was initially thought that this movement was primarily the result of dissatisfaction with conventional medicine.11 Subsequent studies have shown that this is not the case6,12 and that patients continue to see their conventional health care practitioners while using CAM therapies; however, about 27% of CAM users believe that conventional medicine will not help their health care problem.1 Two disturbing observations are that most patients do not disclose their use of alternative therapies to their physicians and that such patients are never asked about CAM use by their physicians.13 Furthermore, many patients feel no need to communicate their CAM use to their physicians because they believe that their physicians would be unable to understand and incorporate that information into their treatment plan.12,14 On the other hand, current data suggest that about one quarter of patients who use CAM do so on the advice of a conventional medical professional.1
A number of other factors have stimulated public use of alternative medical therapies. The fact that many CAM modalities emphasize natural forms of healing seems to form the fundamental basis for its use. Many patients desire a more holistic approach to their medical care.6 They may feel that conventional medicine focuses excessively on suppression of symptoms (e.g., pharmacologic lowering of elevated blood pressure) rather than addressing the root cause of symptoms. They believe that so-called natural products are better and safer than synthetic medications. In many cases, they may turn to alternative medical practices to get relief from chronic conditions that have not responded to conventional symptomatic therapy. Additionally, media hype, direct-to-consumer advertising, and the widespread availability of information over the Internet have all played a role in the popularity of CAM and have served to expand the public's health care choices. Of concern to many physicians is that these choices are frequently based on insufficient basic science or clinical evidence.
One of the defining characteristics of alternative medicine is the paucity of definitive evidence supporting mechanism of action, efficacy, and safety. Although a number of clinical trials on CAM have been published, the overall quality of those trials is quite poor, primarily because of inadequate sample size, randomization, and blinding.15,16 Additionally, publication bias may be common in the international literature. Critical reviews of published studies on CAM therapies from a number of countries have shown that the studies almost universally report positive findings pertaining to CAM. This suggests that studies reporting negative findings may never make it to press.17,18
There are a number of barriers to the proper evaluation of CAM studies. First, the establishment of adequate control groups is frequently very difficult. Studies on acupuncture, for example, have attempted to incorporate a placebo control by stimulating nonacupuncture points, stimulating actual points unrelated to the treated condition, or applying pressure instead of inserting needles. Some critics argue that so-called sham acupuncture is an inadequate placebo that does not preserve subject blinding. Proponents of acupuncture may argue that such control methods are still potentially therapeutic because of their possible positive effect on the flow of subtle energy through the body. Similar pitfalls are inherent in mind-body research. In the study of personal prayer, of prayer groups, or of intercessory prayer that occurs in the presence of the patient, the intervention group can be compared with those who do not partake in organized prayer. Such a design clearly does not lend itself to adequate blinding. Additionally, any positive results could reflect aspects of prayer that are unrelated to its spiritual qualities (e.g., relaxation), making definitive conclusions difficult.
Another major problem with interpreting CAM research stems from inconsistencies in the intervention groups. Drawing meaningful conclusions from herbal-medication studies is difficult because extracts are not standardized. For example, although positive effects have been seen in a number of published clinical trials with the plant genus Echinacea for treatment of upper respiratory tract infections, definitive conclusions cannot be drawn because of variation in the species of plant studied, the part of the plant utilized (root, leaf, or flower), and extraction methods.19 In addition, the manufacturing processes within and between companies vary widely, so that the concentration of active product in an over-the-counter preparation is rarely known.
Lack of standardization is also a flaw in acupuncture research. Many different types of acupuncture are practiced around the world, and each type may utilize a completely different set of points for the same condition. Even among providers who practice the same type of acupuncture, variation in point selection is common because approaches differ on the basis of the patient's history and physical examination and on the acupuncturist's personal style. This individualization of therapy is alluring to patients, but the unwillingness of practitioners to agree on what constitutes acceptable technique challenges conventional study methodology. CAM practitioners often criticize the typical scientific model that employs randomized clinical trials because in clinical practice, there are multiple interventions, such as mind-body and herbal treatments, that occur simultaneously. Thus, any research in the area may have to be multidimensional.
Unlike conventional pharmaceutical and medical-device research, large-scale studies in CAM derive their funding almost exclusively from government sources. Modalities such as prayer, acupuncture, and massage therapy are not lucrative enough endeavors to support large, privately funded trials. Dietary supplements, such as herbs, may have a significant profit potential, but the incentive for research is weakened by the fact that herbs, like other natural substances, cannot be patented. In addition, the rules and regulations under which foods and natural products are regulated differ from those for pharmaceuticals, which must meet stringent standards of efficacy and safety.
In an effort to boost CAM research, the United States Government set up NCCAM (http://www.nccam.nih.gov), under the National Institutes of Health (NIH). With an annual working budget of about $120 million, NCCAM has funded a number of individual projects, as well as specialty centers around the country [see Table 2].
Table 2 Government-Funded Specialty Centers for Research into Complementary and Alternative Medicine
Specific CAM Modalities
ALTERNATIVE MEDICAL SYSTEMS
Traditional Chinese Medicine
Acupuncture has been used for centuries as a component of traditional Chinese medicine (TCM). It involves the insertion of thin needles into specific points on the skin to facilitate the movement of energy (qi). Chinese medicine posits that qi (pronounced chee) flows along distinct channels (called meridians) in the body and that balanced circulation of qi is a prerequisite for good health. A block in the flow of qi can result in either a deficiency or an excess of qi along a meridian; those imbalances can be corrected by accurate needle placement (or pressure, in the case of acupressure) at specific points on the body. Acupuncture practitioners often enhance the effect of the needles by electrical stimulation; manual manipulation (e.g., twirling); or moxibustion, which involves burning mugwort (Artemisia vulgaris) on the acupuncture point or the end of the needle. Practitioners of TCM frequently combine acupuncture with other modalities, including herbal remedies, to achieve the desired physiologic response. Each treatment is individualized on the basis of the patient's history and physical examination, including pulse and tongue examinations. Many types of acupuncture are practiced today; a few examples are traditional Chinese acupuncture, five-elements acupuncture, and auricular acupuncture.
To date, no clear physical mechanism of action has emerged to explain the potential therapeutic response to acupuncture. Changes in blood flow and biologic mediators (e.g., hormones, neurotransmitters, and endorphins) have been shown to occur with needle manipulation.20,21,22,23 There are numerous published clinical studies on acupuncture treatment for a variety of ailments. Most are small in size and have methodologic flaws that make consensus difficult. Nevertheless, in 1997, an NIH consensus panel concluded that there is clear evidence to support the use of acupuncture for postoperative, chemotherapy-induced, and probably pregnancy-associated nausea and vomiting.23 Although the data are less compelling, evidence also suggests a positive effect of acupuncture on idiopathic headache,24fibromyalgia,25,26 and osteoarthritis of the knee.27 Current evidence does not support its use for smoking cessation,28 asthma,29 or low back pain.30
If done correctly, acupuncture is quite safe.31 Rare case reports of serious adverse events, including skin infections, hepatitis, pneumothorax, and cardiac tamponade, seem to stem from inadequate sterilization of needles and practitioner negligence.32,33 To prevent transmission of infection, most practitioners now use disposable needles. Minor side effects, including insertion-site pain or bleeding, fatigue, and vasovagal syncope, are probably more common.34
Homeopathy is one of the most controversial modalities in CAM, primarily because of its theoretical implausibility. The roots of homeopathy trace back to the 1700s, when it was first described by Samuel Hahnemann. Homeopathic principles revolve around two basic tenets: the law of similars and the principle of serial dilutions. According to the law of similars, substances that cause symptoms in healthy people can cure those same symptoms in people who are sick. A number of examples of this principle exist in conventional medicine. Digoxin is used to treat the same arrhythmias that it is capable of inducing. Similarly, methylphenidate, which is a stimulant, has been used to treat attention-deficit/hyperactivity disorder.35
The principle of serial dilutions (or the minute dose) is another controversial aspect of homeopathy. According to this principle, medications can have a biologic effect even if diluted to levels at which the original substance is undetectable (a so-called homeopathic dose).
A homeopath's approach to patients differs from that of the conventional physician. Homeopaths concentrate almost exclusively on subjective symptoms and sensations. They choose medications on the basis of the patient's symptomatology, rather than on the objective medical diagnosis. This results in the use of a wide array of different medications for any one conventionally diagnosed condition. A number of homeopathic encyclopedias (materia medica) are available that describe symptoms induced by different remedies when given to healthy individuals (provings). These provings are matched to a patient's symptoms to determine the therapeutic regimen. Patients are typically followed closely so that the homeopath can titrate dosing schedules.
Meta-analyses of a number of trials of homeopathic remedies have suggested an effect superior to placebo.36,37 However, many studies and reviews on specific medications have shown negative or inconclusive results.37,38,39 Given the conflicting clinical data and the lack of evidence regarding mechanism of action, it is difficult to support the general use of homeopathy until more high-quality research is available.
Because homeopathic remedies typically contain little or no detectable active ingredients, serious side effects are rare. Homeopathic preparations are generally marketed as over-the-counter remedies and are usually exempt from government requirements for finished product testing or expiration dating. In the United States, the Food and Drug Administration requires that all homeopathic remedies list the indications for their use, the ingredients, instructions for safe use, and dilutions. Dilutions in a ratio of 1:10 are labeled with an X, and dilutions in a ratio of 1:100 are labeled with a C. For example, a 3X product has been diluted 1:10 three times; a 3C product has been diluted 1:100 three times. It should also be noted that these remedies are not restricted to the 10% alcohol limit of conventional drugs.40
The relationship between psychological stress and physical health has been studied extensively over the past 30 years. Despite positive results from some trials, interventions designed to alter the stress response have not become part of mainstream medical practice. The reluctance of physicians to incorporate mind-body strategies into their therapeutic armamentarium likely stems from their unfamiliarity with such interventions; time constraints; and the lack of a clear mechanistic pathway to disease. Furthermore, many physicians may feel that these therapies need to be patient driven rather than physician driven, because they require significant changes in self-care.
The proposed theory of mind-body medicine stems from work done in the early 1900s. The fight-or-flight response was described as physiologic preparation for combating or fleeing an external threat.41 Stimulation of the hypothalamus and increased sympathetic nervous system activity lead to neurohormonal stimulation and increases in blood pressure, heart rate, respiratory rate, and muscle tension. This response has historically been protective, ensuring survival in the face of physical danger. In today's society, however, we are continually faced with innumerable stressors that can elicit the fight-or-flight response, yet fighting or running away is inappropriate or impossible. The body is primed for action but can take none. This chronic physiologic stimulation is thought to increase the likelihood of disease. Furthermore, the development of a chronic disease may stimulate the response through a feedback mechanism, potentially worsening the condition. The effect of the chronic fight-or-flight response on immunosuppression and cytokine and hormone production needs greater elucidation.
Mind-body interventions can elicit a relaxation response that may prevent or aid in the treatment of a number of medical ailments42 [seeFigure 1]. A number of modalities can be used for this purpose. Many people have incorporated yoga, meditation, or self-hypnosis into their daily self-care regimen. Several clinical studies have suggested that there are positive results from mind-body modalities for many conditions [see Table 3]. As with other CAM interventions, however, limitations in study methodology and sample size, as well as lack of an adequate control, make definitive conclusions difficult.
Figure 1. Possible Mechanism of Mind-Body Interventions
Possible mechanism of mind-body interventions. (CRF—corticotropin-releasing factor)
Table 3 Selected Mind-Body Interventions
The mind-body category also encompasses techniques for which a mechanism is not even remotely understood. No physical explanation for distant healing modalities—such as intercessory prayer, spiritual healing, and mental healing—is currently accepted, despite some evidence for positive treatment effects.43 No harmful effects are seen when most mind-body interventions are used as an adjunct to conventional care. However, there is concern that patients might choose exclusive use of one or more of these methods in lieu of appropriate diagnosis and therapy.
Biologic therapy is the most popular of all fields of CAM. Its popularity stems from its similarity to the process of using conventional medications. Some people consider biologics to be a possible quick fix for their ailments, without the need for physician visits or potentially harmful prescription medications. Others turn to biologics in the hope of preventing potentially serious diseases through the use of so-called natural substances.
Dietary supplements, including herbal and nonherbal products, make up the preponderance of medications in this category. The supplement industry has become a billion-dollar business, largely as a result of the loosening of federal regulations. The Dietary Supplement Health and Education Act (DSHEA) of 1994 expanded the definition of dietary supplements to include vitamins, amino acids, herbs, and other botanicals. Furthermore, under DSHEA, supplements no longer require premarket testing for safety and efficacy. Supplements are assumed to be safe unless proved otherwise by the FDA. Given the number and variety of products currently available, the FDA's ability to effectively regulate all products after they have been marketed is limited. An example of the regulatory process was the banning of products containing ephedra. The FDA first expressed concern over the herb in 1997, when it proposed limitations on its use. The General Accounting Office viewed these limitations as inappropriate, because of insufficient evidence proving harm. It took 7 years (and a few high-profile deaths) for the FDA to be able to effect a ban on ephedra.44 Although most dietary supplements are well tolerated and are associated with few adverse effects, the potential for harm from the lack of regulation can be seen from examples of misidentification of plant species,45 contamination with heavy metals, and addition of pharmaceutical agents.46,47
Overall, there is only limited evidence supporting the use of most dietary supplements. Most clinical trials have been small, nonrandomized, or unblinded. In general, physicians and patients should view herbs as medications. Physicians should advise patients to be wary of products for which grandiose claims are made, because misleading advertising is common.48 The potential for significant toxicity and drug interactions does exist. The list of currently used supplements is immense, and this chapter can touch on only the most popular [see Tables 4, 5, and 6]. More comprehensive resources for dietary supplements (and other CAM modalities) are now available [see Table 7].
Table 4 Commonly Used Herbal Dietary Supplements
Table 5 Commonly Used Nonherbal Dietary Supplements
Table 6 Popular Uses for Common Dietary Supplements*
Table 7 Sources of Information on Complementary and Alternative Medicine
MANIPULATIVE AND BODY-BASED THERAPIES
Many would argue that chiropractic medicine should not be considered alternative therapy. Patients, physicians, and insurance companies have all shown some degree of support for chiropractic care in recent years. Between 10% and 20% of the population have used chiropractors.6 Health care insurance plans, including Medicare, cover many of the services performed during chiropractic visits. Most chiropractor visits are for musculoskeletal problems, including low back pain, neck pain, and extremity pain. However, a small proportion of patients currently seek out chiropractic care for a variety of other conditions, as well as general health concerns.49 The tenets of chiropractic medicine place the spinal cord and nervous system at the center of a person's well-being. The nervous system is thought to control and influence all other bodily systems. Malalignments (subluxations) of the vertebrae are thought to cause or perpetuate disease. Once these subluxations are identified and corrected (via manipulation), the body uses its natural healing abilities to restore physiologic balance and health. Chiropractors typically look for spinal pain, asymmetry, impaired range of motion, or abnormalities in tone, texture, and temperature when evaluating patients.50 Laboratory testing, including x-rays, electromyography (EMG), and ultrasonography, may be used to aid in diagnosis. Actual spinal manipulation is performed by direct or indirect delivery of thrusts to the spine. Frequently, the patient will experience a cracking noise. Some chiropractors may use adjunctive therapies, including massage, heat, and trigger-point injections.50
Chiropractic manipulation has been touted as treatment for a number of conditions, including hypertension, asthma, pelvic pain, and fibromyalgia. Very little data exist to support its use for these conditions.51,52 Use of chiropractic therapy for neck pain and headaches is also weakly supported.53,54 Much of the current use of chiropractic care stems from its utility in cases of low back pain. A number of controlled trials on chiropractic treatment for low back pain have been done, with conflicting results. A meta-analysis concluded that spinal manipulation appears to be more effective than sham therapy or treatments previously judged to be ineffective, but not to be superior to other standard treatments for acute or chronic low back pain, such as analgesics, physical therapy, or exercises.55 Patient satisfaction also seems to be high with such therapy.56
Serious complications from lumbar spinal manipulation seem to be uncommon, although there are reports of cauda equina syndrome.57 Many patients, however, experience mild to moderate side effects, including localized discomfort, headache, or tiredness. These reactions usually disappear within 24 hours.58 Brain stem or cerebellar infarction, vertebral fracture, tracheal rupture, internal carotid artery dissection, and diaphragmatic paralysis are rare but have all been reported with cervical manipulation.59 Given the lack of efficacy data and the risk (although small) of catastrophic adverse events, it is difficult to advocate routine use of this technique for treatment of neck or headache disorders. Physicians should also recognize potential contraindications to chiropractic therapy. Patients with coagulopathy, osteoporosis, rheumatoid arthritis, spinal neoplasms, or spinal infections should be advised against such treatments.59
A number of different types of massage are in practice today. Many therapists combine aspects of Swedish massage (stroking and kneading), shiatsu (pressure-point manipulation), and neuromuscular massage (total body, deeper therapy) to relieve stress, anxiety, and muscle tension, as well as improve circulation. Frequently, aromatic oils are employed to enhance the relaxation response. A number of small studies have suggested a potential beneficial effect of massage on fibromyalgia, head aches, and anxiety,60 although the paucity of data precludes definitive conclusions. Massage therapy does seem to be effective for subacute and chronic back pain.30 No significant adverse effects are seen with properly performed massage, although caution must be advised for patients with coagulation disorders.
Structural integration (rolfing) is a system of deep-tissue manipulation that involves stretching of the fascial planes. In this system, the fascia is thought to be the key supporting structure for bones and muscles. When injury or stress occurs, the fascia tends to become shorter and thicker. Manipulation of the fascia with fingers, thumbs, and elbows is supposed to relieve tension, restore structural integrity, and improve physiologic and psychological function. Limited data exist to support the efficacy of rolfing for any particular condition.
Many traditional cultures describe the physical body as existing within a field of energy. Such energy is called prana by Indians and qi by the Chinese; English terms include subtle energy, vital energy, and life energy. Many ancient and modern CAM techniques involve the manipulation of this energy or the transfer of additional energy into the patient's field in an effort to restore or maintain balance. Because the field extends beyond the body, energy therapies do not always involve physical contact between practitioner and patient. Further, the presumed connection of these individual fields with a universal field is believed to permit the use of some of these therapies at a distance.
Qigong is a branch of traditional Chinese medicine designed to affect the flow of energy (qi) to preserve health. This system combines relaxation techniques with movement to achieve a meditative state designed to ensure mental and physical health. Tai chi (tai chi chuan) is a type of movement-oriented qigong that utilizes a sequence of slow, dancelike maneuvers to enhance the flow of qi through the body. In the course of a tai chi session, the person shifts body weight constantly from one foot to the other. Studies of tai chi in elderly persons have shown that long-term regular practice may improve balance, flexibility, and cardiovascular fitness and, possibly, decrease the risk of falls in older individuals.61,62 Meditative qigong is accomplished without movement and is intended to establish inner harmony. Breathing exercises can also be part of qigong. They are designed to enhance circulation of qi and expel negative energy. Qigong has been used extensively in China for a number of conditions, including hypertension, anxiety, asthma, and nausea and vomiting.63 Data to support use for any individual condition are lacking, despite historical successes. Although the principles of qigong seem simple, it involves a complex set of processes that are not clearly understood. Inappropriate training has reportedly been associated with physical and mental disturbances.64
Yoga is an ancient Indian philosophical practice that uses postures or stretching exercises (asanas), breathing exercises (prana- yama), and meditation to help unite the body and the mind. It was developed as a means of enlightenment through self-realization and self-mastery. Only recently, with its migration to the West, has yoga come to be seen as a means to heal illness or reduce anxiety. As with most CAM modalities, there are limited data for or against the use of yoga for particular conditions. Studies on the use of yoga in patients with carpal tunnel syndrome seem promising.65 Yogic breathing exercises may have some beneficial effect on the symptoms of asthma and may reduce bronchodilator use, but they do not decrease airway reactivity or improve lung function.66
Therapeutic touch is the use of the hands, without actual physical touching, to influence or direct life energy throughout the body in an effort to promote healing. Therapeutic touch was codeveloped by a nurse, Dolores Krieger,67 and many of its practitioners are nurses who use the technique for hospital inpatients.
In a therapeutic-touch session, which generally lasts 20 to 30 minutes, the practitioner enters a meditative state (centering) and then assesses the patient's energy field. To do so, the practitioner holds his or her hands a few inches from the patient's body and moves from head to foot. Downward sweeping movements are then used to remove any blockages of energy and correct any energy-field imbalances. The practitioner then transfers energy to the patient's field and finishes the session by smoothing the field.
A number of small trials have suggested a positive effect of thera peutic touch on conditions such as osteoarthritis, tension headache, and anxiety.43 However, most of these trials are quite small and suffer from methodologic weaknesses that make definitive conclusions difficult.68 A critical evaluation of relevant trials concluded that the data did not support the hypothesis that therapeutic touch promoted wound healing.69 More vigorous trials need to be performed to determine the true efficacy of this technique.
CAM and the Practicing Physician
The field of research in CAM is in its infancy. Current levels of evidence are insufficient to support or disprove a majority of CAM modalities. Despite these limitations, the public continues to embrace CAM therapies as alternatives or adjuncts to conventional care. Given that many patients currently do not inform their physician of their use of CAM, it is imperative that physicians take the lead in inquiring about such therapies. Open dialogue needs to be established to uncover the types of modalities being utilized, reasons for pursuing such therapy, and patient experiences. From there, a discussion of the current data on level of efficacy and toxicity can follow. Ultimately, primary care physicians may need to develop referral networks of trusted CAM practitioners who are open to reciprocal communication. These steps should serve to strengthen the physician-patient relationship while limiting the potential for adverse outcomes.
Specific emphasis should be placed on the role of dietary supplements, which pose a risk of significant toxicity and drug interactions. To ensure patient safety, the medication history should include specific questioning about what vitamins, herbs, or other supplements the person is taking. Unfortunately, supplements are often sold as combination products that are identified only by their catchy trade names. Patients should be encouraged to bring in all new medications and supplements at each visit. Depending on their side-effect profile or potential for drug interactions, certain supplements should be discontinued in the perioperative period.70 Finally, any suspected adverse reactions or drug-supplement reactions should be reported to the FDA's MedWatch program at their web site (http://www.fda.gov/medwatch) or by calling them at 1-800-FDA-1088.
Editors: Dale, David C.; Federman, Daniel D.