CAM and Research
It is important to remember that many new innovations in medicine may originally be classified as CAM. 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 vivo studies 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.