Standardization

Replicability is a hallmark of the scientific method. Specifically what is tested (e.g., a substance, treatment procedure, or system of practice) must be defined, described, and stabilized so that it can be delivered reliably from patient to patient and study to study. Standardization is a great strength of modern medicine’s pharmacotherapeutics. Natural medicine does not have as definitive a codex. Rather, its practices evolve over time, with some areas highly dependent on current scientific discovery, whereas others are used empirically, rather than rationally, in procedures that are hundreds or thousands of years old.

The organized natural medical professions have variably definitive articulations of philosophy and clinical strategies. What constitutes a competent practitioner in a given discipline often remains uncertain,⁸ and many natural medicine approaches, like those of indigenous practices, are unlikely ever to be codified. Even with the licensed practices (e.g., naturopathic medicine, acupuncture, and chiropractic), health insurance coverage with regulation by practitioner-review panels is recent. It is only in the last two decades that coding systems for alternative practices have begun to describe the array of interventions available in the United States.⁹ The current emphasis on research in CAM practices calls for speeding up the process of standardization toward replicability.

Communication about natural medicine research issues can be problematic when using standard clinical practice and biomedical research metaphors. One way to understand the problem is to say that natural medicine’s critical practices lack articulation and operationalization of accepted and, within the respective practitioner groups, widely understood memes. Memes are collective concepts: ideas, behaviors, or skills that are transferred from one person to another by imitation and replicable on a population basis (see Richard Dawkins’ book The Selfish Gene, from 1976)^9a. A meme, as a phrase, invokes meaning beyond those of the words themselves, such as in the principle vis medicatrix naturae (the healing power of nature). Dictionaries of memes may be needed for the collective concepts of natural medicine practice that may be identified as the practices are investigated. The development of memes through which to express the syncretic concepts of natural medicine and which may have broad applicability is one of the benefits of researching the practices.⁵ The dearth of articulation of natural medicine’s concepts accounts in part for its remarkable variation among practitioners. Its transfer from mentor to student may be imprecise or misinterpreted even before practitioner preferences and personalities are brought into play. This is not to say that the concepts of natural medicine practice are not reliably transmitted from mentor to student, only that they are not yet always articulated in ways that have been operationalized for clinical trials.

Standardization of natural remedies is becoming better understood. To perform a single-agent controlled trial of herbs in a specific disease, numerous choices should be made about the intervention. The Policy Announcement on the Quality of Natural Products of the National Institutes of Health (NIH) National Center for Complementary and Alternative Medicine (NCCAM) has brought some clarity to the botanical standards for NIH sponsored trials (http://www.nccam.nih.gov/research/policies/naturalproducts.htm). Studies should begin with verification of plant species used, growth and harvesting conditions, and the stability of purported active compounds. Selections should be made among plant parts, various crude extracts, or specific chemical constituents that may be concentrated in various ways and to varying degrees of purity. Crude fresh extracts, which traditional herbalists prefer, are highly susceptible to deterioration. In more sophisticated systems of botanical medicine preparation, a product is standardized to guarantee the minimum or maximum concentration of a number of ingredients for a given period, for example, EGb 761 (Schwabe GmbH, Karlsruhe, Germany), the Ginkgo biloba, which has been the most researched botanical and is standardized on four constituents. Standardizing on particular constituents has its challenges. Active ingredients in plants are often classes of molecules (e.g., polysaccharides, saponins, terpenes) that are difficult to distinguish in biological activity. Different compounds in a single species may have similar, possibly complementary effects, such as the polysaccharides and isobutyramides in Echinacea species. During in vitro assays, which guide fractionation of the crude extract toward a single active molecule, it is not uncommon for activity to increase but then diminish as greater purity of an identified molecular species is reached, as was the case of the terpenes of Andrographis paniculata (AndroVir, Paracelsian, Inc., Ithaca, NY) in cell signaling. A few botanicals are standardized on an in vitro biological activity. The industry standard, porously applied, is chemical standardization on actives and certified Good Manufacturing Practices.

Nutrition can be divided into dietary practices and nutritional supplements. Studies in dietary interventions are demanding. The gold standard for dietary intervention is a residential facility to maintain adherence to the therapeutic regimen, but this solution is expensive and recruitment is difficult. A long observation time is frequently needed in dietary studies because diets are often intended as preventives or restoratives.

Some nutritional supplements are cultures, such as probiotics (live bacteria taken to normalize commensal bacterial populations) and algae. Studies in these types of interventions have some of the same complications as botanical medicine studies, as well as the issues of organism viability and interactivity with commensal microorganisms and the internal conditions for proliferation.

Homeopathy is a special case in standardization, in that chemical standards are largely irrelevant for remedies that rely on ultradilutional remedies that may contain no molecules of the material originally potentized. Biological testing of homeopathics is in its infancy, and reliability is not ensured. Thus, only the manufacturing process can be standardized at this time.

“Body, mind, spirit” is a leitmotif of natural medicine. The interplay of psychodynamic and spiritual phenomena and physical health are only partially encompassed by the behaviorist approach of most health psychology research, but this has been greatly augmented by recent studies in “mind–body” medicine with numerous reviews in various specialties in publication. Advances have been made in the neuroscience of expectancies in the placebo effect, with the size of the placebo effect recognized as different in different conditions, but despite the ubiquitous use of placebo in practice,¹⁰ operationalization and manipulation of placebo effects remain fraught methodologically and ethically. Placebo use in medical encounters continues to be explored, but raises more questions than answers;¹¹ however, hope remains for advances in future studies.¹²

While they represent a small proportion of all health studies, questions about spirituality remain of investigative interest, although with few authoritative and widely used research methods. Operationalization of spiritual experience is likely to be idiosyncratic or culture specific. The 4th edition of the Diagnostic and Statistical Manual (DSM-IV, 1995) reinstated the possibility of a religious or spiritual problem. Definitions of spirituality in the medical literature may refer to hope and meaning or to a personal relationship with God, serenity, or connectedness, all perhaps related to states of the patient’s consciousness.^13,14 A number of thinkers continue to bemoan the lack of definition in the area.¹⁵ Although efforts to present cogent, broadly acceptable definitions have been made, they have not been successful.^16,17 Better approaches to specifying spiritual interventions may be needed before they will be accessible to replicable research. Recent reviews of the health effects of intercessory prayer, an observable phenomenon, have been equivocal.¹⁸

Individualization of Treatment

Natural medicines’ disease taxonomies (classifications of human illness) are not always congruent with those of Western molecular biomedicine. Primary variance (differences in outcome) of efficacy is more likely to vary with the conditions of a practice’s native taxonomy than with a foreign one. For example, “strengthening the immune system,” “decreasing toxicity,” and “fortifying the will to health” are common goals in natural health therapeutics but are rare in conventional practice. Treatment response would be expected to have a different profile because different diseases are being treated. Thus, the speed to healing, as well as the disease being treated, may be confounded in the evaluation of one system by the other’s definitions and rules. These concepts are themes to be described more explicitly in natural medicine diagnosis.

Some natural medicine concepts may no longer have or may never have had a biomedical equivalent. An example is the concept of “constitution” used in naturopathy, homeopathy, and Asian medical systems. This is a patient’s given biological potential, tendencies, and patterns of long-standing psychophysical strengths and weaknesses that are genetically and embryologically determined. Others are the “biological terrain” (the background physical health and individual context for the immediate medical problem) and the “vital force” (the motive plan or spirit animating mind and body expressed as physiologic and psychological functionality and adaptability). Biomedical equivalents exist in some parameters for system control concepts; however, they are therapeutically exploited more thoroughly by holistic practitioners. Such concepts are balance (as in the immune system, among microbial symbionts, hormones, and neurotransmitters); deficiency (not just nutritional but organ deficiencies, such as hypochlorhydria and hypothyroidism); functional reserves; endogenous and exogenous toxicities; and dysmetabolisms (e.g., syndrome X). An important concept is that a disease syndrome may be an attempt by the body to adapt to ecologic stress and so should not be unnecessarily suppressed. This is of interest not only because it is an independent variable (baseline factor), but also because it influences the measurement of the dependent variable (outcome).

A skilled natural medicine practitioner necessarily expects success through individualization of treatment regimens. Individualization means that remedies are prescribed not solely on the basis of disease entities but also according to other characteristics of the patient. Such characteristics may be transient, constitutional, or representative of the entire constellation of the patient’s health problems, strengths, and his or her capacity for self-care. The lack of fit of a person’s health syndrome with a conventional disease model, expressed perhaps in the inability or reluctance of a conventional practitioner to diagnose a particular health problem, may be the very reason a patient turns to natural medicine. A medical system that does not recognize an entity is unlikely to have an effective therapy for it. The complaint will be managed as something else, resulting in ineffective treatment while exposing the patient to the side effects of the “remedy.” Conversely, a medical system that provides an adequate explanatory model for a patient’s symptoms—their origin, aggravators, and ameliorators—has a better chance of effective treatment or management of the condition. Thus, individualization of treatment is a strength of natural medicine rather than merely a research problem. Compromises may be made in practice to make a trial of specified therapy possible, such as by semi-protocolized treatments, but they may alter therapeutic effect. If the need for individualization is neglected in natural medicine research design, the design will fail to apply the medicine as practiced and thus to evaluate its potential benefit.