Complimentary - Alternative Medicine (CAM) and Research
Medically reviewed by C.H. Weaver M.D. Medical editor
Chemotherapy and radiation were once considered unconventional and questioned by the mainstream medical community. Likewise, CAM dietary supplements may have active ingredients that demonstrate anti-cancer activity and eventually become used as conventional cancer drugs. One example is the Pacific yew tree. Its bark contains active ingredients that prevent cancer cells from replicating rapidly. These constituents have been isolated and are now used as the chemotherapy drug paclitaxel. This example demonstrates how a particular CAM therapy, or its active ingredients, can become part of conventional medicine after demonstrating safety and efficacy in scientific studies. For this reason, therapies defined as CAM are constantly evolving, with successful therapies eventually integrated into conventional medicine.
Integrating successful CAM into conventional medicine may be delayed, however, by one or more of the following factors:
- the amount of funds available for research
- philosophical and political issues that affect which therapies receive funding
- our current scientific understanding of how the body works
- methodologies available to investigate novel therapeutic approaches that may or may not be appropriate for CAM therapies
- regulatory issues
- economic and business issues regarding patents, or the lack thereof, for natural substances
- current patient usage of CAM therapies, which is rapidly increasing even without research, thereby eliminating incentives for manufacturers to conduct expensive scientific studies
The landscape of medicine has been dramatically changing over the past several decades. A survey published in 1994 revealed that over 60% of medical doctors from a variety of specialties recommended CAM to their patients at least once. In addition, 47% of the same doctors reported using CAM themselves. In 1997, Americans spent more than $27 billion on CAM therapies, exceeding out-of-pocket spending for all U.S. hospitalizations. In 1998, the Journal of the American Medical Association published an article in which CAM use by the general public was found to have increased from 34% in 1990 to 42% in 1997. A small study published in the February 2000 issue of Cancer indicated that of 46 patients with prostate cancer, 37% used one or more CAM therapies as part of their cancer treatment. The Journal of Clinical Oncology followed in July 2000 with an article noting that 83% of 453 cancer patients with different types of cancer used at least one CAM therapy as part of their cancer treatment. Even excluding spiritual or psychotherapy practices, 69% of patients reported using at least one CAM therapy in their cancer treatment. That same year, the Journal of Clinical Oncology published another study finding that 67% of over 400 breast cancer survivors reported using one or more CAM therapies.
Even prior to the 1990s, the increased use of unconventional therapies led the U.S. Congress to direct the Office of Technology Assessment to investigate alternative cancer therapies. The resulting report, Unconventional Cancer Treatments, recommended that funding be made available to alternative therapies that preliminary investigation suggested may be beneficial. This led to the formation of the Office of Alternative Medicine. Today, there are two main government agencies whose directives include funding CAM research: OCCAM and NCCAM. OCCAM is the Office of Cancer Complementary and Alternative Medicine, a division of the National Cancer Institute, and its research focuses on CAM for cancer. NCCAM is the National Center for Complementary and Alternative Medicine and is part of the National Institutes of Health; it has a wider focus of all CAM. Together, these agencies are responsible for funding CAM research that investigates whether specific CAM therapies are systematically effective and safe.
To determine which CAM therapies receive funding for cancer research, the National Cancer Institute created the Best Case Series Program in 1991. This program provides an independent review of medical records and primary source materials (e.g., medical imaging and surgical tissue samples) and overall assessment of evidence demonstrating therapeutic effect. In 1999, NCCAM created the Cancer Advisory Panel for Complementary and Alternative Medicine (CAPCAM). CAPCAM reviews Best Case Series submissions and based on its findings, advises NCCAM on which CAM therapies appear promising for the treatment of cancer and should receive funding.
Evaluating CAM Research
There are many different CAM therapies being used by cancer patients to improve wellness, ameliorate side effects of conventional cancer treatment and/or treat cancer. However, until recently, most of these therapies had never undergone rigorous scientific analysis. As a result, if CAM therapies do have evidence of their effectiveness, it is usually empirical, speculative, based on human case studies or from laboratory studies.
Most of the recent research on CAM therapies is done in the laboratory, either in vitro (on cell or tissue samples from animals or humans) or in vivo (in live animals). Laboratory research that demonstrates anti-cancer effects often does not produce clinical effects in humans. Many conventional in vitro or in vivostudies that produced significant results have failed to produce significant results in subsequent human clinical trials. There are many possible reasons for the poor crossover rate of success. Laboratory studies often use extremely high doses to achieve anti-cancer effects in vitro or in vivo. Additionally, the physiological processing of substances within a test tube or in animals is not the same as in humans. As a result, laboratory research findings usually only describe proposed mechanisms of action. Any extrapolation of such research to its potential effect on humans, while critical to directing future courses of inquiry, is usually regarded as speculative. Speculative evidence is indirect and may also include inferences from empirical scientific studies.
Empirical evidence rests on traditional knowledge (also known as folk medicine) or on results obtained from years of extensive use. Empirical evidence provides the best historical information on the effectiveness and safety of a therapy’s use in humans. Human case studies are records of one individual’s responses to a specific treatment or combination of treatments and provide unique insights into the possible effects of a therapy. However, the only current tools researchers have to ascertain whether a CAM therapy systematically produces anti-cancer results are human clinical trials. A human clinical trial is a scientific study specifically undertaken to examine the safety and/or efficacy of a certain type of therapy on humans with a specific type of disease.
The gold standard in clinical trials is a randomized, controlled clinical trial. In these kinds of trials, patients with similar types of cancer and other common factors are randomly divided into two or more groups, one receiving the standard therapy or, if none exists, a placebo (an inactive substance) and the other group(s) receiving the treatment(s) in question. These kinds of trials are considered the most objective for two reasons: 1) observer bias is limited by randomizing which treatments are given to which patients, and 2) the effect of the treatment(s) in question is compared against the standard therapy or a placebo to determine whether the medicine contributed to healing.
Randomized, controlled clinical trials are difficult to conduct on CAM therapies and few have been performed. One main difficulty is that most people use many different CAM therapies concurrently. Clinical trials are designed to compare one, or at most two, variables at a given time. Another concern is whether it is ethical to give a placebo to a patient with cancer. In some situations, CAM practitioners and physicians may feel that it is inappropriate to give a patient a placebo when a promising new medicine could be given instead. In addition, most CAM practitioners are not familiar with experimental design and have difficulty designing high-quality clinical studies.
In spite of an increase in funding, there is still very little money available for research on CAM compared to conventional medicine. In part, this can be attributed to the funding sources for medical research. A significant portion of the cost of conventional medicine research is borne by the pharmaceutical or medical equipment industry. Costs incurred during research are recouped through the patent process, which gives exclusive rights of the treatment to the company for several years. Many CAM therapies cannot be patented, whether they are mind-body interventions or substances like herbs and vitamins. In addition, the current success of the CAM industry suggests that consumers are not hesitant to use CAM therapies lacking scientific evidence. This removes the incentive for most manufacturers of CAM therapies (e.g., dietary supplements) to pay for expensive and time-consuming research. As a result, CAM research is largely dependent on government funding.
Another pertinent question is whether clinical trials are the most appropriate means of evaluating CAM therapies. Several studies in recent years have revealed limitations of the randomized, controlled clinical trial. In addition, clinical trials make several assumptions that may be inconsistent with some CAM approaches. CAM therapies are tailored to the unique needs of each individual. In contrast, clinical trials focus on the sameness of a group of individuals and draw blanket conclusions on what works for a group with certain factors in common. This assumption rests on two additional suppositions: 1) that we are identifying the correct similarities relevant to the therapy in question, and 2) that we are able to treat and control a group of individuals in exactly the same way, even when they are only in the treatment setting for an hour a day. One last issue to consider is how to determine the appropriate measure of an anti-cancer effect.
While the above issues merit consideration, human clinical trials still represent the best method available for investigating the reliability, efficacy and safety of medical treatments.
Does CAM cure cancer?
What does it mean to cure cancer? Most people would agree that cancer is cured when it is no longer detectable on a molecular or clinical (i.e., not showing up on scans) level. Historically, a person who remained cancer-free for five years was considered “cured”; today, few studies use this term. Instead, most studies measure factors such as disease-free survival as indicators of the probability that cancer has been eradicated. Some conventional cancer treatments have fairly high cure rates, like surgery, radiation and/or chemotherapy for early-stage breast cancer. However, the stage (how much the cancer has spread) and grade (aggressiveness) of a cancer determine how difficult it is to treat. In early stage or low-grade cancers, conventional medicine may produce relatively high cure rates.
Many patients turn to CAM therapies after conventional medicine has declared them incurable. Some patients may experience a spontaneous remission, which is attributed to the CAM treatment. These stories inspire hope; however, it is not clear in these cases whether CAM therapies, individually or collectively, were responsible for recovery. While this issue is irrelevant to the individual experiencing the remission, it is of great importance to other patients with cancer. Moreover, there are also many case reports of spontaneous remission in patients undergoing conventional therapies, as high as 5% for some types of kidney cancer or melanoma.
A CAM therapy that has not undergone a clinical trial, or that has failed to produce significant results, may still be helpful to certain patients if it has demonstrated safety. However, it is impossible to ascertain which patients, if any, may experience benefits from that CAM therapy. The failure to produce significant clinical effects, unless due to problems with design or implementation of the study, suggest that particular CAM therapy is unable to consistently produce anti-cancer effects throughout a population of patients afflicted with a specific cancer. Such CAM therapies cannot be said to cure cancer because they do not reliably do so.
There is, however, an inherent flaw within this system of defining CAM and conventional medicine. A CAM therapy that does demonstrate systematic efficacy in treating certain types of cancer, managing side effects, stimulating the immune system or promoting wellness can become accepted as conventional medicine. As a result, successful CAM therapies may no longer be recognized as CAM. More attention might be given to crossover therapies, acknowledging their origin so that the general population might understand the nature of this evolution.
Using CAM Therapies
With the myriad of CAM therapies available, it is often difficult and overwhelming to determine which, if any, may be appropriate. Because of the potential for interaction between CAM therapies and conventional medical treatments, it is extremely important for a patient to consult with their oncologist and other attendant health care professionals about CAM therapies they currently use or are considering using. While information regarding interactions is limited, it is crucial that the information available be utilized. For example, some data suggest that certain CAM therapies may interfere with specific chemotherapy agents or cause dangerous side effects when used concurrently.
Another benefit of discussing CAM therapies with one’s conventional medical provider is that it promotes a health care team approach in which appropriate information may be shared for optimal treatment. In China, for example, a cancer patient often has an oncologist and an acupuncturist working together. This structure assists health care providers in developing comprehensive treatment plans.
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As a patient interested in CAM therapies, several steps can taken to make informed decisions. First, research CAM therapies. Make sure that health claims are supported by scientific studies, recognizing that results in laboratory or animal studies often do not translate to the same benefits in humans. Also look for evidence that the CAM therapy is safe. An oncologist or other health care professional may be able to help interpret these scientific studies.
Most medical doctors have not received training in CAM and therefore do not offer CAM treatments. However, a physician or other health professionals may be able to recommend a CAM practitioner. Sometimes local hospitals, medical schools, or area clinics maintain a list of local CAM practitioners and may offer recommendations. It may also be helpful to contact a professional organization or regulatory agency regarding the type of CAM therapy in question.
When considering a prospective practitioner, it is important to understand his or her qualifications and the CAM therapy itself. To this end, the following questions may be helpful during an initial consultation:
- What are the training requirements and credentials for this type of CAM therapy?
- Does the treatment intend to promote wellness, manage symptoms and/or treat cancer?
- Have any scientific studies been published on this CAM therapy in peer-reviewed medical journals?
- Do patients with similar illnesses commonly use this CAM therapy? Can the practitioner provide references of patients for whom the treatments have proven successful?
- How does one know whether the treatment is working? What are indications of benefit?
- Can the CAM therapy be used concurrently with conventional medical treatments? Does it increase the efficacy of the conventional treatment? Are they any known contraindications?
- What are the potential side effects? How safe is the treatment?
- What does the treatment consist of? How long does a treatment session last? How often is it required?
- How much does treatment cost? Do insurance companies usually cover these costs?
- Is the practitioner willing to communicate with other health care providers, particularly conventional physicians and oncologists, regarding the CAM therapy?
Use care when choosing a CAM practitioner. Patients should be comfortable with any CAM therapy they choose to undergo and the practitioner they select. They should be equally at ease in discontinuing treatment if they choose to or in not using any CAM therapy at all. The ultimate decision about health care strategies lay in the hands of the person most affected: the patient.
CAM Safety and Regulations
All medical treatments entail some degree of risk and CAM therapies are no different. CAM therapies can be divided into two groups when examining safety concerns and regulatory issues. The first group contains products that a patient typically uses either internally or externally. These CAM therapies, such as Echinacea capsules or colloidal silver salve, are regulated as dietary supplements in the United States. The second group of CAM therapies consists of therapeutic processes a patient undergoes with a practitioner. Examples of these CAM therapies include reiki, massage and chiropractic medicine. When therapeutic processes are regulated, it is usually by state agencies or licensing boards. There are some practitioners, such as naturopaths, which utilize dietary supplements in addition to therapeutic processes and are affected by both categories.
Most herbs, vitamins, minerals, amino acids and other “natural” substances sold over the counter are designated as “dietary supplements” in the United States (the main exception being homeopathic drugs which are regulated separately; see Homeopathy for additional information). These products are considered dietary supplements because their use is intended to “supplement” a person’s diet; because of this distinction, they are regulated as food and not as drugs.
The Dietary Supplement Health and Education Act (DSHEA) passed by the United States Congress in 1994 formally defined “dietary supplements”, outlined guidelines for literature displayed where supplements are sold, established a new framework for safety, required ingredient and nutrition labeling, provided for “use of” claims and nutritional support statements and granted the FDA authority to establish good manufacturing practice (GMP) regulations. The law also required the formation of an executive level Commission on Dietary Supplement Labels and led to the establishment of the Office of Dietary Supplements within the National Institutes of Health.
According to the this law, the dietary supplement manufacturer is responsible for ensuring that a dietary supplement is safe before it is marketed, while the FDA is responsible for taking action against a product if it appears unsafe after introduction to the market. Manufacturers do not usually need to get FDA approval prior to selling a dietary supplement nor do they need to register with the FDA. The FDA only reviews safety and efficacy data prior to allowing a new product to be sold when it contains a new dietary ingredient (i.e., those not marketed in the United States prior to October 15, 1994). However, manufacturers must ensure that their statements are not misleading and have sufficient evidence to substantiate their product claims. A product is considered unsafe when it appears to cause acute or chronic toxicity, has interactions with medications or is contaminated with pesticides, heavy metals or prescription drugs. The FDA may issue a warning or recall for such supplements.
The FDA does not monitor manufacturing practices. It is the responsibility of the manufacturer to maintain safe production procedures in accordance with GMP and ensure that the label information is accurate. Several concerns have arisen from this lack of regulation. Some herbal products, particularly those manufactured in China, may contain pesticides, heavy metals, prescription medications and other herbs that are not listed on the products’ labels. In addition, research comparing several different brands of DHEA and ginseng products have found labeling discrepancies. One study found that few dietary supplement labels correctly identified the amount of DHEA in the supplement, ranging from no or trace amounts of DHEA to 150% of the labeled amount. Another study noted that many ginseng supplements contain the incorrect species of ginseng (e.g., American ginseng rather than Siberian ginseng). To address these concerns, the National Center for Complementary and Alternative Medicine (NCCAM) has started funding Centers for Dietary Supplement Research. Four centers will conduct research on dietary supplements and investigate manufacturing procedures that enable production of purer, more standardized products.
Many people believe that dietary supplements are safe because they are sold in health food stores and are more ”natural” than conventional pharmaceuticals. However, this is not necessarily the case. Many pharmaceutical drugs were originally derived from natural, plant sources. Hence, the active ingredients in plant or herbal sources are potentially powerful medicines that may have drug-like effects in therapeutic doses. Many natural substances such as the herb Belladonna or certain mushrooms are natural and yet poisonous enough to cause acute toxicity when eaten. Even dietary supplements that appear to be relatively safe for short-term use may be dangerous when used for extended periods of time (i.e., chronic toxicity).
Each individual may have different responses to dietary supplements. Known or unknown allergies, pre-existing conditions, diseases or organ dysfunctions may make it dangerous to take certain products (e.g., cat’s claw and autoimmune diseases). Another concern is that a patient may be taking medications (prescription or over-the-counter) that have harmful interactions with certain natural products (e.g., Gingko biloba and warafin). As with many prescription and over-the-counter medications, many dietary supplements are not safe for pregnant or breastfeeding women or young children.
Little research is available on the safety of dietary supplements. Case reports, rather than clinical studies, are usually all that are available. Physicians use these case reports, combined with inferences from folk traditions and our understanding of how the dietary supplement may work, to develop a picture of the relative safety of a dietary supplement and its contraindications. Contraindications are circumstances, either illnesses, medications, etc., in which the dietary supplement should not be taken. Some contraindications are rooted in evidence, while others are speculative.
If a product demonstrates dangerous side effects or interactions, the FDA will usually issue a warning or recall.
CAM Therapies Involving Therapeutic Processes
Practitioner certification, accreditation or licensing is generally regulated by states. Many states have regulatory agencies or licensing boards for practitioners of specific types of CAM (e.g., chiropractors, massage therapists, counselors). However, most CAM practitioners are not regulated at the state level at this time. This is changing as CAM therapies gain increasing popularity and standards are sought to ensure practitioners’ competency.
Even without formal state licensing or accreditation, many practitioners have graduated from accredited institutions (e.g., chiropractic, naturopathic, or acupuncture schools) or are members of organizations that practice self-regulation (i.e., must meet certain training requirements).
The safety of CAM therapies involving therapeutic processes depends on the CAM therapy itself and on the individual CAM practitioner. Little research has been done on the safety of most CAM therapies. Nonetheless, it is advisable for a patient to examine the scientific evidence available with regard to safety of a specific CAM therapy. An oncologist or other health care professional may be able to help interpret any scientific studies or case reports that are available.
When considering a prospective practitioner, it is important to consider their knowledge, skill and experience to minimize risk. For more information on choosing a CAM practitioner, please refer to the section Using CAM Therapies.