Wayne B. Jonas

Circular instead of hierarchical: methodological principles for the evaluation of complex interventions

BackgroundThe reasoning behind evaluating medical interventions is that a hierarchy of methods exists which successively produce improved and therefore more rigorous evidence based medicine upon which to make clinical decisions. At the foundation of this hierarchy are case studies, retrospective and prospective case series, followed by cohort studies with historical and concomitant non-randomized controls. Open-label randomized controlled studies (RCTs), and finally blinded, placebo-controlled RCTs, which offer most internal validity are considered the most reliable evidence. Rigorous RCTs remove bias. Evidence from RCTs forms the basis of meta-analyses and systematic reviews. This hierarchy, founded on a pharmacological model of therapy, is generalized to other interventions which may be complex and non-pharmacological (healing, acupuncture and surgery).DiscussionThe hierarchical model is valid for limited questions of efficacy, for instance for regulatory purposes and newly devised products and pharmacological preparations. It is inadequate for the evaluation of complex interventions such as physiotherapy, surgery and complementary and alternative medicine (CAM). This has to do with the essential tension between internal validity (rigor and the removal of bias) and external validity (generalizability).SummaryInstead of an Evidence Hierarchy, we propose a Circular Model. This would imply a multiplicity of methods, using different designs, counterbalancing their individual strengths and weaknesses to arrive at pragmatic but equally rigorous evidence which would provide significant assistance in clinical and health systems innovation. Such evidence would better inform national health care technology assessment agencies and promote evidence based health reform.

Auricular Acupuncture in the Treatment of Acute Pain Syndromes: A Pilot Study

This pilot study used a randomized controlled clinical trial design to compare the effects of standard emergency medical care to auricular acupuncture plus standard emergency medical care in patients with acute pain syndromes. Eighty-seven active duty military personnel and their dependents with a diagnosis of acute pain completed the study, which was conducted in the emergency room (ER) at Malcolm Grow Medical Center, Andrews Air Force Base, Maryland. The primary outcome measure was change in pain level from baseline, as measured by the Numerical Rating Scale. Participants in the acupuncture group experienced a 23% reduction in pain before leaving the ER, while average pain levels in participants in the standard medical care group remained basically unchanged. (p < 0.0005). However, both groups experienced a similar reduction in pain 24 hours following treatment in the ER. More research is needed to elucidate treatment effects and to determine mechanisms.

HOMEOPATHY AND RHEUMATIC DISEASE

Despite a growing interest in uncovering the basic mechanisms of arthritis, medical treatment remains symptomatic. Current medical treatments do not consistently halt the long-term progression of these diseases, and surgery may still be needed to restore mechanical function in large joints. Patients with rheumatic syndromes often seek alternative therapies, with homeopathy being one of the most frequent. Homeopathy is one of the most frequently used complementary therapies worldwide.

The challenge of complementary and alternative medicine

Complementary and alternative medicine can be defined as those medical systems, practices, interventions, and applications that currently are not part of the dominant or conventional medical system. There are more than 300 different topics under the term complementary and alternative medicine that can be divided into seven major categories on the basis of philosophy, approach to the patient, and orientation. Most patients seeking care from complementary and alternative medicine providers do so for the relief of signs and symptoms related to chronic illness while they are under the care of a physician. Clinical data derived from appropriately conducted clinical trials support the use and value of complementary and alternative medicine for selected indications. The challenge for both conventional medicine and complementary and alternative medicine is to fulfill the role of patient advocate by engaging in reciprocal open communication, facilitating the patients informed choice, avoiding harmful or useless practices, and implementing an integrated evidence-based care plan.

THE ROLE OF OUTCOMES RESEARCH IN EVALUATING COMPLEMENTARY AND ALTERNATIVE MEDICINE

The methodological superiority of the RCT stems from itscapacity to preclude several forms of bias: by randomizingpatients to treatments, groups are made statistically equivalentat baseline, at least in theory, such that observed differences atthe end of the trial can be attributed with more confidence to theintervention instead of group differences. By blinding patients,doctors, evaluators, and biometricians, bias stemming fromexpectations and knowledge is precluded, as well as the possibili-ty of fraud or subconscious preference on the part of raters, nurs-es, or statisticians. Therefore RCTs, if possible double blind,seem to be the most rigorous methodological standard availablefor evaluating complementary and alternative medicine(CAM).

Natural products and chronic hepatitis C virus.

Background: Chronic hepatitis C virus (HCV) infection is a significant public health problem, with a worldwide prevalence of approximately 170 million. The standard of care for chronic HCV, a combination of α‐interferon (IFN) and ribavirin, is only 50% effective, has serious side effects, and can be prohibitively expensive for low‐income countries with a high prevalence of HCV. Many patients use natural products, including those who are not eligible for IFN/ribavirin, cannot afford treatment, or fail to respond to IFN.

Homeopathy: Clarifying its relationship to hormesis

This paper presents the case that certain types of homeopathic medicine may represent a form of hormesis, that is, either pre- or post-conditioning hormesis. An example of a post-conditioning model by van Wijk and colleagues demonstrated successful enhancement of adaptive responses using below-toxic threshold doses (i.e. hormetic doses) of inducing agents when administered subsequent to a highly toxic chemical exposure, thus satisfying a basic experimental biomedical standard. Of note is that this model uses exposures within a measurable predicted hormetic range, unlike most forms of homeopathy. This experimental framework (along with a pre-conditioning model developed by Bellavite) provides a possible vehicle by which certain aspect(s) of homeopathy may be integrated into mainstream biomedical assessment and clinical practice.

Fever, Cancer Incidence and Spontaneous Remissions

Objective: Accumulating evidence exists for (1) an inverse correlation between the incidence of infectious diseases and cancer risk and (2) an inverse correlation between febrile infections and remissions of malignancies. This review is part of an effort of the Office of Alternative Medicine at the National Institutes of Health to examine this evidence. Methods: A review of the literature to a key word search was undertaken, using the following key words: fever, infectious diseases, neoplasm, cancer incidence and spontaneous remission. Results: The data reviewed in this article support earlier observations on the topic, i.e. that the occurrence of fever in childhood or adulthood may protect against the later onset of malignant disease and that spontaneous remissions are often preceded by feverish infections. Conclusion: Pyrogenic substances and the more recent use of whole-body hyperthermia to mimic the physiologic response to fever have successfully been administered in palliative and curative treatment protocols for metastatic cancer. Further research in this area is warranted.

Military Report More Complementary and Alternative Medicine Use than Civilians

OBJECTIVES The study objective was to estimate complementary and alternative medicine (CAM) use among active duty military and compare data with civilian use. DESIGN A global survey on CAM use in the 12 previous months was conducted. Final participants (16,146) were stratified by gender, service, region, and pay grade. Analysis included prevalence of CAM use, demographic and lifestyle characteristics. RESULTS Approximately 45% of respondents reported using at least one type of CAM therapy. Most commonly used therapies were as follows: prayer for ones own health (24.4%), massage therapy (14.1%), and relaxation techniques (10.8%). After exclusion of prayer for ones own health, adjusting to the 2000 U.S. census, overall CAM use in the military (44.5%) was higher than that in comparable civilian surveys (36.0% and 38.3%). CONCLUSIONS Military personnel reported using three CAM stress-reduction therapies at 2.5-7 times the rate of civilians. Among the military, high utilization of CAM practices that reduce stress may serve as markers for practitioners assessing an individuals health and well-being.

Can specific biological signals be digitized

At the request of the United States Defense Advanced Research Projects Agency, we attempted to replicate the data of Professor Jacques Benveniste that digital signals recorded on a computer disc produce specific biological effects. The hypothesis was that a digitized thrombin inhibitor signal would inhibit the fibrinogen‐thrombin coagulation pathway. Because of the controversies associated with previous research of Prof. Benveniste, we developed a system for the management of social controversy in science that incorporated an expert in social communication and conflict management. The social management approach was an adaptation of interactional communication theory, for management of areas that interfere with the conduct of good science. This process allowed us to successfully complete a coordinated effort by a multidisciplinary team, including Prof. Benveniste, a hematologist, engineer, skeptic, statistician, neuroscientist and conflict management expert. Our team found no replicable effects from digital signals.— Jonas, W. B., Ives, J. A., Rollwagen, F., Denman, D. W., Hintz K., Hammer, M., Crawford, C., Henry, K. Can specific biological signals be digitized? FASEB J. 20, 23–28 (2006)