Essentials of Complementary and Alternative Medicine (June 1999)

A
CCEPTANCE OF
 T
REATMENTS WITHOUT
 S
CIENTIFIC
 P
ROOF
Acupuncture is also a good example of how a therapy becomes increasingly accepted despite lack of convincing evidence from randomized trials, which is a 
phenomenon that also frequently occurs in conventional medicine (
44
). Recently, a National Institutes of Health (NIH) consensus panel concluded that acupuncture is 
effective for treating some conditions and should be integrated into standard medical practice. Yet only two relatively minor conditions (postoperative and 
chemotherapy-associated nausea and vomiting, and acute, postoperative dental extraction pain) out of a dozen conditions evaluated were proven effective by 
acupuncture treatment. Nevertheless, insight into mechanisms of action, positive experiences by patients and by a growing number of providers and physicians, and 
interest from consumers and insurance companies are contributing to the acceptance and use of acupuncture even in the absence of proof for most conditions for 
which it is used. Thus, the simplicity and safety of acupuncture made the NIH panel willing to recommend that this treatment be accepted with less evidence than 
would other, higher-risk interventions. It seems reasonable, then, for initial risk stratification to be a strategic element in evaluating CAM before setting the type and 
level of evidence required for acceptance. The application of risk strategies in evidence-based CAM is illustrated in 
Chapter 5
.
More and better randomized clinical trials of acupuncture are clearly desirable. However, an effective strategy requires a number of preconditions for such trials:
1. The investigated treatment strategy should represent an actual practice of at least a defined group of acupuncturists. Representativeness should be shown 
empirically by observational studies. An alternative is to use a treatment approach recommended officially by a professional society.
2. Before starting the randomized trial, pilot studies are mandatory.
3. The exclusive use of placebo-controlled conditions for the purpose of determining what techniques are adopted in practice should be avoided.
4. Standard therapies of proven effectiveness should be used for direct comparison to acupuncture if acupuncture offers a potential advantage (e.g., lower cost or 
side effects) over the standard therapy.
In addition, acupuncture societies and their members should be encouraged to perform clinical audit and outcome studies to monitor their performance. There is a 
growing awareness of the need for evaluation as a precondition for more extensive, broadly based, high-quality research, like rats. In addition, audit and outcome 
studies might identify areas of both strength and weakness in acupuncture practices to better guide both practice and research.
Homeopathy
Research questions in acupuncture are usually narrowed to whether acupuncture is effective in treating certain conditions, but usually not narrowed so much as to 
ask whether a specific type of acupuncture is effective, as in phytotherapy. In the case of homeopathy, however, the questions usually asked by those unfamiliar with 
the practice are even more general than for acupuncture. In homeopathy, the most frequently asked question is:  Isn't ALL of homeopathy due to placebo effects?
Homeopathy is one of the most widespread and most controversial of CAM systems. The fundamental principle of homeopathy is the  simile principle, which states that 
patients who have particular signs and symptoms can be cured if given a drug that produces the same signs and symptoms in a healthy individual. The  simile principle 
is not accepted by conventional medicine, but the main reason for the often vigorous rejection of homeopathy is its second tenet: the idea that remedies retain 
biological activity if they are repeatedly diluted and agitated or shaken between dilution steps. These dilutions are said to produce effects even when diluted beyond 
Avogadro's number, for which no original molecules of the starting substance remain.
Many scientists think that homeopathy violates natural laws (
45
), and thus any effect must be a placebo effect (
46
, 
47
). Apart from some speculative hypotheses, there 
is no good theory for a possible mechanism of action. Academic institutions are reluctant to do any research on homeopathy. For example, the German Society for 
Pharmacology and Toxicology in 1993 considered such research a waste of time and money (
48
), and discussion of homeopathy in journals continues to revolve 
around the value of researching this therapy at all (
49
). At the same time, practicing homeopaths are convinced that they offer a highly effective therapy, and many 
consider rigorous clinical research inadequate, unethical, and unnecessary.
This climate has not been supportive for developing an effective and competent research infrastructure. Nevertheless, individuals and small groups have done a 
considerable number of clinical trials. Recent systematic reviews have identified approximately 190 controlled clinical trials, 120 of which were randomized (
50
, 
51
). 
Overall, the available evidence clearly suggests that homeopathy can have an effect over placebo. However, there is a lack of independent replication of study 
models (as is done with P6 acupuncture) that convincingly proves the effectiveness of a single homeopathic strategy in a defined condition.
B
ALANCING
 S
CIENTIFIC
 P
LAUSIBILITY AND
 C
LINICAL
 R
ELEVANCE
Given the implausibility of homeopathy, it is not surprising that clinical research focuses almost exclusively on the placebo question. But “placebo” in clinical trials of 
homeopathy has a more fundamental meaning than in conventional medicine. If, for example,  d-sotalol (an anti-arrhythmic) is tested in a placebo-controlled trial, no 
one has any doubt that it has—regardless of its clinical usefulness—strong biological effects. However, homeopathic remedies—particularly when delivered in high 
dilutions—are assumed, a priori, to be completely inactive. If a clinical trial showed that significantly more side effects occurred in the homeopathic group compared 
with placebo, this might be interpreted as evidence for biological activity (in fact, such a trial exists [
52
]). Clinical trials in homeopathy are not really true clinical trials 
(attempting to answer questions 1–4 in 
Table 4.1
); they often try to also answer what would normally be considered a basic science question that might only be 
answered in the laboratory (see 
Table 4.1
, question 5). Mixing these questions in a single trial or series of trials usually produces ambiguous answers for both 
questions and is not a reasonable strategy.
Not only do such studies not answer the placebo question, most current studies in homeopathy do not represent actual practice and so are largely irrelevant for 
everyday homeopathic practice. The two most frequently investigated study models—administration of  Galphimia glauca for treatment of hay fever (
53
) and 
administration of a complex of opium, Raphanus, arnica, or China for postoperative ileus (
51
)—illustrate this point. The remedy Galphimia is rarely used by 

homeopaths to treat hay fever, and postoperative ileus is hardly ever addressed in homeopathic daily practice.
These models are studied because they are easy to study. As in the case of acupuncture, the best scientific evidence for homeopathic medicine's effectiveness exists 
in areas that are simple to investigate but not necessarily useful for guiding treatment decisions. Thus, the pressure to answer the broad question of placebo effect 
with rigor results in neglect of research that would be the most relevant for clinical practice.
In recent years, the quality of research in homeopathy has improved considerably; a number of excellent studies are available that, in principle, seem more 
representative and relevant for actual practice (
54
, 
55
 and 
56
). Many homeopaths practice a form of homeopathy (classical homeopathy) in which patients who have 
the same conventional diagnosis (e.g., migraine) receive different homeopathic remedies that fit their individual subjective symptom picture. Also, classical 
homeopathy involves extensive case-taking and poses considerable problems for clinical trial methodology. In recent studies of classical homeopathy, all included 
patients went through this case-taking procedure and then were prescribed their individual remedies. Only after that were these patients randomized to receive the 
true treatment or placebo by a third party. This method allows classical homeopathy to be studied more closely. However, it also brings up new problems. As with 
acupuncture, the intervention is no longer well defined (i.e., the remedy process is quite individualized), so possible placebo effects induced by the intense 
homeopathic case-taking might lead to underestimating the complete intervention's clinical effectiveness (
56
). Furthermore, such a design is associated with a number 
of logistic and ethical problems in long-term trials with patients who have chronic disease. Again, in such situations, direct comparisons of homeopathic treatment 
approaches to standard therapies of proven effectiveness appear more useful than do placebo-controlled trials.
Unless a breakthrough in basic research provides a plausible and reproducible mechanism for the action of high dilutions, scientific controversy about homeopathy 
will probably not be solved if the questions asked remain limited and dogmatic rather than pragmatic (see 
Table 4.1
, question 4). Because the use of homeopathy 
continues to grow, the inability of science to provide answers to the questions posed by society is a cause for concern. Therefore, a variety of research methods must 
be applied to get a better understanding of what is going on in homeopathic practice: that is, determining whether its observed effects are caused by placebo or by a 
process outside of the current biological paradigm. As with acupuncture, research in homeopathy needs a broader base and more systematic strategy. Homeopaths 
must learn to evaluate their performance and use clinical research as a tool for improvement. Data collected in everyday practice might then contribute to planning 
randomized studies that evaluate the usefulness of homeopathy beyond the placebo question.
Complex Naturopathic Interventions
The prevalence of chronic diseases is increasing, especially in Western countries. The management of chronic diseases is considered a cornerstone of 
complementary medicine. A number of treatment centers offer complex life-style and naturopathic programs for the management of a variety of chronic conditions. 
These programs are rarely restricted to one complementary therapy; they consist of a mixture of different treatment modalities compiled according to both the 
complaints of the individual patient and the skills or experiences of the providers. Besides acupuncture, treatments such as aromatherapy, or herbs, counseling, 
behavioral therapies, and nutritional and life-style changes are central components of such programs.
With a few exceptions (
57
, 
58
), there are no randomized clinical trials of such complex naturopathic systems. Doing good research on such programs is difficult for a 
variety of reasons, including lack of funding for such research and difficulty in both recruiting patients and obtaining sufficiently long observational periods. In addition, 
generalizability of any findings is unlikely unless the program is well standardized and transferable to other facilities. Studies on isolated components are of little value 
for determining the whole program's effectiveness. A more promising strategy in such a situation might be to perform long-term outcome studies and clinical 
evaluation of centers providing such programs. The results of such nonexperimental observation will not allow the same scientific conclusions as would a randomized 
trial. However, it is unlikely that randomized trials will ever be done for many of these programs. Observational studies are feasible in many instances and could even 
be a precondition for reimbursement. Such studies might provide sufficient information to enable patients, health care providers, and policymakers to make rational, 
data-based choices.
DEVELOPING DECISION RULES FOR A STRATEGIC SCIENCE IN CAM
Balancing Relevance, Rigor, and Realism in Practice
As the four examples previously described have shown, evaluating the effectiveness of CAM practices is an extremely complex issue. A handful of rigorous, 
large-scale randomized trials will not solve the problem. The huge resources needed for systematic and extensive research will not be available in the next few years, 
even for the most prevalent interventions. At the same time, CAM use will likely increase. Given such a situation, the choice of an adequate research methodology 
should not be fixed a priori, but should reflect a balance among relevance, scientific rigor, and feasibility. Finally, we must keep in mind that there are several different 
public groups that the results of such research must serve, including patients, practitioners, the scientific community, and policymakers. Usually, these groups are 
each interested in different types of information that require different types of research methods. Considering how these groups plan to use the resulting information 
can also help guide the design of research on CAM.
When considering complementary treatments, the conventional physician will ask,  How should I advise or warn my patient about a given treatment? Should I consider 
using or recommending it myself? These questions can be answered relatively easily by checking the evidence in the medical literature and by using available 
readers' guidelines (see, for example, 
Chapter 5
, “How to Practice Evidence-Based Complementary and Alternative Medicine”). In the case of a clearly defined and 
characterized single intervention for a specific condition, such as giving  Hypericum to a patient who has depression, a “conventional” framework can be used. 
However, getting a rational answer becomes much more difficult if the questions deal with complex therapeutic systems, such as acupuncture, naturopathy, traditional 
Chinese medicine, or homeopathy. The physician has to consider that the research evidence in most cases will be scarce, and even good research may not be 
relevant for making clinical decisions. In addition, issues like plausibility; the specific circumstances of the patient; the cost, feasibility, and risk of the treatment; 
severity of the condition; and the physician's own experiences and confidence in the particular provider must all be considered. In 
Chapter 5
, the steps in developing 
an evidence-based approach to CAM are outlined.
Choosing Research Strategies in CAM
Basic decisions about choosing research methods and the interpretation of existing research may be approached in flowchart fashion from the framework of the types 
of research and use of research information previously described (see 
Figure 4.1
). The decision to pursue a particular approach depends on a number of factors, 
including the following:
Simplicity or complexity of the therapy being investigated
Type of information sought
Purpose or planned use for the information found
Methods of investigation available and whether feasible, ethically acceptable, and affordable
By determining the main use for which information from a research project is to be put, the appropriate corresponding method can be determined (see 
Figure 4.1
). For 
complex practices that are not well described, observational data and outcomes research or pilot trials may be the best initial approach (e.g., naturopathy). For 
well-described CAM practices, outcomes data coupled with decision analysis may provide the best strategic approach (e.g., defined acupuncture techniques). This 
may or may not be followed by selective application of randomized controlled trials, depending on the need for and ability to obtain information about specific effects. 
For CAM products whose constituents are unknown (e.g., complex herbal combinations), consultation with expert practitioners, followed by basic laboratory 
characterization of the products, may be needed before clinical research is undertaken. For well-characterized CAM products (e.g., standardized plant extracts), 
randomized controlled trials are appropriate and feasible provided their likely cost-risk-benefit ratios and potential public health impact warrant such an investment. 
The results of placebo studies may be more useful for making policy decisions (e.g., public benefit plans) than for individual decision making. The United States 
National Institutes of Health study of the efficacy of the herb St. John's Wort for depression using a large, three-armed, multicentered, placebo-controlled trial is an 
example of this latter approach.
For a physician who is considering referring a patient for a CAM intervention such as acupuncture, it might be more valuable to know which patients are seen in the 
acupuncture practice, how they are treated, whether they are satisfied with treatment, and what their outcomes are rather than to rely on the results of small-scale, 
placebo-controlled randomized trials done in another continent with practitioners and populations quite different from those in the patient's community. Unfortunately, 
the methods of simple observational studies have not been used by biostatisticians and clinical epidemiologists who are under the dominance of industry-sponsored 
randomized trials for more easily tested and profitable products. Thus, the methodologies of observational studies may need to be developed further in ways 

applicable to CAM. Data collection and monitoring in observational studies must be performed at least as carefully as in experimental studies. The interpretation of 
such data must also be done carefully. Efficient systems of quality assurance should at least allow us to identify areas of particular risk and clinically significant 
benefits. Straightforward regulations requiring a certain level of quality would increase the probability that a treatment provided has at least limited risk.
Finally, for empirical observations that do not fit into our current assumptions about the nature of reality (e.g., psychic healing, homeopathy) but are of high public use, 
a carefully thought-out strategy with a basic science component is needed. Given the high public interest in some of these areas, it seems irresponsible for science to 
ignore studying these phenomena.
CAM AND THE EVOLUTION OF SCIENTIFIC MEDICINE
It is likely that only a small proportion of most therapies, whether conventional or complementary, will ever be established as fully evidence-based (i.e., answering all 
five questions in 
Table 4.1
). Thus, practical methods for collecting information relevant for patient and practitioner decisions should be developed and implemented. In 
addition, a more careful examination of what role science should play in providing information for the management of chronic disease and investigating anomalous 
findings is needed. Because only incremental, answerable questions can be addressed with science, the public must understand that research can never answer all 
questions of public interest. Skepticism among conventional physicians about unorthodox practices is often higher than for conventional practices, so a demand for 
data is often required before CAM practices are accepted. The continuing interface between orthodox and unorthodox medicine today provides the opportunity for 
new research strategies and methodologies to arise. By purposefully maintaining a creative tension between the established and the frontier, we can advance 
scientific methods and more clearly define the boundaries and purpose of the scientific process for medicine.
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CHAPTER 5. H
OW TO
 P
RACTICE
 E
VIDENCED
-B
ASED
 C
OMPLEMENTARY AND
 A
LTERNATIVE
 M
EDICINE
Essentials of Complementary and Alternative Medicine