Shadow Medicine: The Placebo in Conventional and Alternative Therapies

With medical costs growing exponentially from the 1970s on, there was mounting evidence that Americans were turning in increased numbers to unconventional therapies, spending billions each year on interventions ranging from dietary supplements to homeopathy, crystal healing, anthroposophy, therapeutic touch, high-energy perception, and meditation. Thus, it came as no surprise that political pressure would be levied on the NIH to find and justify the substitution of alternative therapies for orthodox medicine’s more costly treatments. In 1991, Senator Thomas R. Harkin (D–IA), chair of the appropriations subcommittee with oversight of the NIH and a strong advocate of bee pollen for allergies, captured this sentiment when he added a clause in the NIH 1992 appropriation creating a twenty-person advisory panel and charging it to recommend a research program that would “fully test the most promising unconventional medical practices.”¹ Elements within the NIH seethed with resentment that the testing of fringe therapies, some of which had already been barred by the FDA, would undermine the NIH’s credibility; others, less distraught, believed that if the panel members did their job, many of these unconventional practices could be disproved and buried once and for all.²

Within a year of the committee’s deliberations, the NIH created the Office for the Study of Unconventional Medical Practices, later the Office of Alternative Medicine (OAM), and sought a director. During the years that followed, the advisory panel was dominated by a group of so-called Harkinites that included former congressman Berkley Bedell, Frank Wiewel, Ralph Moss, Gar Hildenbrand, and Royden Brown—all outspoken advocates of unconventional medicine. Bedell, a longtime friend of Harkin, supported colostrum, derived from cow’s milk, as a cure for Lyme disease and 714-X, a derivative of camphor, for prostate cancer. Wiewel was a longtime enthusiast of immuno-augmentative therapy for cancer and operated a travel service called Patients Against Cancer for patients seeking unconventional therapies. Brown promoted high-desert bee pollen capsules for allergies; Hildenbrand was the executive director of the diet-oriented Gerson Institute for alternative cancer treatments; and Moss, a PhD in the classics, was an adviser on alternative cancer therapies and publisher of The Moss Reports, which provided extensive information on CAM modalities worldwide in the treatment of cancer.³

From the very beginning of the OAM, Harkin and his supporters used political clout to agitate, threaten, and bully NIH’s leadership. At issue was whether conventional research methods were appropriate in testing unconventional practices or, alternatively, whether there should be a reexamination and perhaps even a reconstruction of conventional medicine’s evidence-based pyramid. The latter position had been encouraged by several new CAM journals, including Cancer Chronicles (1989), Subtle Energies and Energy Medicine Journal (1990), and Alternative Therapies in Health and Medicine (1995), precipitating a flurry of competing opinions and causing one observer to remark that devising the appropriate plan to study CAM was like “orchestrating a roomful of cats…or setting the agenda for a convention of anarchists.”⁴

With each CAM therapy confident that its results, however managed, were “proof” enough of its claims, the NIH struggled under pressure from the Congress to find and implement an appropriate validation process. Because the RCT represented the gold standard of scientific validation within NIH, there was genuine apprehension among the institutes’ staff that practices such as mind–body interventions, bioelectromagnetic applications, yoga, acupuncture, homeopathy, and a host of nutritional supplements would be judged on standards different from conventional medicine.⁵ Evidence of this apprehension was the report prepared for NIH titled Alternative Medicine: Expanding Medical Horizons (1995), also known as the Chantilly Report, which one skeptic called “an uncritical catalog of virtually every dubious and unproven treatment method of the past 100 years.”⁶

With the appointment in October 1992 of Joseph Jacobs, a Yale-educated physician with a deep love for Native American healing, to head the OAM, all parties hoped that calm would ease the fevered opinions bantered on both sides. Recognizing that many of the CAM modalities had been around for hundreds, if not thousands, of years, Jacobs reasoned that simply because a particular treatment’s modus operandi was counter-intuitive to prevailing theories, its success should not be ruled out. This position, however disconcerting to conventional researchers, gave hope to CAM proponents that their particular modalities could gain approval as part of a new integrative medicine.⁷

Jacobs initially seemed to please the Harkinites as someone who, having Native American ancestry (son of a Cherokee father and a Mohawk mother), was willing to view CAM as compatible with conventional medicine. He began by looking for new approaches to clinical analysis, including the establishment of research centers within academe to test the validity of CAM therapies. He quickly realized after a congressional review undertaken by Harkin in 1993, however, that he was being held hostage by a not insignificant lobby whose advocates were using political muscle to force validation of their interest in bee pollen, shark cartilage, antineoplastons, Revici cancer treatment, and other dubious therapies.⁸ As one observer commented, the proponents of CAM were eager to have the “imprimatur” of the NIH on their particular therapies but were not interested in acquiring that status based on the rigor of the RCT. Jacobs, however, refused to capitulate. “As a taxpayer,” he explained, “I wouldn’t trust what comes out of my office under a system like that.” He insisted, therefore, that the prevailing methodology of the RCT remain the standard for evaluation and that all CAM therapies be evaluated in university-operated research centers.⁹ In keeping with this intent, he approved thirty proposals (out of 450 submissions) for funding and allocated $1.8 million to establish two research centers (at Bastyr University in Seattle and at the University of Minnesota Medical School) modeled on a recommendation from Harvard internist and professor David Eisenberg, a member of the OAM’s policy committee.¹⁰

Exemplary of naturopathy’s importance within CAM has been Bastyr’s recognition as a center for research on HIV and acquired immunodeficiency syndrome (AIDS) funded by the federal government. Founded by naturopathic physicians Les Griffith, William Mitchell Jr., and Joseph Pizzorno Jr., Bastyr University is a nonallopathic institution whose goal is to bring scientific legitimacy to natural medicine. Through the establishment of the Naturopathic Medical Research Alliance funded by the NIH, there has been a dramatic increase in peer-reviewed scientific literature assessing the efficacy of naturopathic therapies. In addition, cross-training in research now takes place in cooperation with the University of Washington School of Medicine and the Oregon Health Sciences University. Within the ranks of naturopathy are homeopaths, herbalists, and hygienists who are graduates of correspondence schools and practice without any formal training, certification, or licensing and so are often forced to operate under acupuncture and chiropractic licenses.¹¹ Much of naturopathic practice consists of principles and practices incompatible with EBM, including many unproven (i.e., homeopathy and reflexology) or disproven (i.e., rolfing and iridology) treatments. Hans Baer thus observes that “despite considerable rhetoric on the part of both the graduates of the four-year naturopathic schools and the partially professionalized naturopaths, it is virtually impossible in the absence of considerable ethnographic research to determine how their respective philosophies are implemented in their scopes of practice.”¹²

The combination of pressure from Harkin and the litany of complaints originating from OAM’s advisory panel accusing the director and his staffers of being too pro-establishment led to Jacobs’s resignation in September 1994 after only two years.¹³ His replacement was Wayne Jonas, a graduate of Bowman Gray School of Medicine in Winston-Salem, North Carolina, and former NIH deputy director. What appealed to CAM’s proponents was Jonas’s medical experience in Germany, where as a lieutenant colonel in the US Army and clinic director of the 130th General Hospital in Dexheim he had observed the widespread practice of homeopathy and had trained in bioenergy therapy, diet and nutritional therapy, mind–body methods, spiritual healing, acupuncture, and clinical pastoral education. Upon his return to the states, he had accepted a faculty position at the Uniformed Services University of the Health Sciences, where he codirected a seminar on alternative medicine and later chaired a conference on research methodology in alternative medicine. Jonas was also a student at the Esalen Institute in California, where he was introduced to Chinese, Tibetan, and Ayurvedic medicine as well as homeopathy, herbalism, rolfing, gestalt therapy, journaling, imagery, and bioenergetics.¹⁴

Convinced that CAM was a good thing and willing to entertain variants to the RCT, Jonas appeared to be an excellent choice to lead the OAM into a new era of consensus building. He included in his reorganization plans the establishment of research centers outside regular medical schools; the expansion of databases in the National Library of Medicine to capture a broader array of treatments and modalities; the sponsoring of assessment conferences; and an increase in sponsored research programs to test new CAM products. Considered by many as a “closet” homeopath, Jonas would eventually coauthor with Jennifer Jacobs, a member of his advisory committee, Healing with Homeopathy: The Complete Guide (1996) and Healing with Homeopathy: The Doctor’s Guide (1998).¹⁵ Under Jonas’s leadership and with the support of a Republican-dominated Congress, OAM benefited from yearly increases in funding. Harkin managed to double OAM’s budget from $3.5 million in 1994 to $6.0 million in 1995 and then to nearly $12 million in 1997, making it a focus of attention.¹⁶

The need to accommodate the diversity of CAM systems did not come easily to clinical researchers, basic scientists, and policymakers. Nevertheless, the demand for accommodation continued to grow. In his effort to find a satisfactory starting point, Jonas suggested three methods for determining relevance (qualitative methods, epidemiological and outcomes research, and health service research) and three for explanation and verification (laboratory research, RCTs, consensus conferences, systematic reviews, and meta-analyses). Depending on the purpose and goals for which the information was needed, he believed there was justification for a variable set of standards. To accelerate this process, Jonas organized the OAM into six service units (Public Affairs and Clearinghouse; Database and Evaluation; Research Development and Investigation; Extramural Affairs; Intramural Research Training; and International and Professional Liaison) and doubled the staff.¹⁷

According to Jonas, there were ten reasons to classify a proposed practice as CAM:

1. The explanatory model of the practice is not generally accepted, and so additional criteria are required for proof (e.g., homeopathy, prayer).

2. The origin of the practice is outside of the dominant system (e.g., acupuncture).

3. The amount of data or type of data is considered insufficient or otherwise inadequate (e.g., herbalism, megavitamin therapy).

4. The use of the practice is marginalized in that it is not available within conventional hospitals (e.g., relaxation techniques).

5. The teaching of the practice is marginalized in that it is not generally taught within medical, nursing, or graduate schools of the dominant institutions (e.g., nutritional therapy).

6. The amount of research funding, infrastructure, and capacity for investigating the practice is low (e.g., cancer, chiropractic).

7. The practice is not reimbursed by insurance companies and third-party payers.

8. The practice is not readily used for feasibility, acceptability, or other reasons (e.g., clinical ecology, complex lifestyle programs).

9. The practice is not regulated or licensed in most states (e.g., naturopathy).

10. An aspect of the therapy is marginalized under other names or subdivisions (e.g., antineoplastons, shark cartilage).¹⁸

The director’s goal was to bring together the worlds of science and spirituality, bridging a divide that had occurred during the Enlightenment and that effectively separated the rational, analytical, and objective from the intuitive, spiritual, and subjective. This division, which he and others viewed as artificial, had created a “face” on conventional medicine that turned toward the material and technical side of healing and away from the more human side of disease and suffering.¹⁹ However, bridging this divide proved difficult at best. Most CAM systems had remained unchanged over time, and their proponents had chosen to ignore hypothesis-driven testing and peer review for practices justified solely on the basis of their being holistic and anecdotal. Because most complementary systems ascribed to a unitary view of the body, which meant treating the body as a whole rather than as isolated organs, they preferred to disregard anatomy and physiology for subtle energies (chakras, auras, chi, etc.) that allegedly operated on the whole body.²⁰ For Jonas, this position was untenable. “To accept such views,” he reasoned, was “to falsely label conventional medicine as nonholistic and reject the hard-fought gains made in the use of basic biological knowledge, the randomized, controlled clinical trial, and evidence-based medicine for health care decision making.” Conventional medicine was the world’s leader in disease management, pathology, biotechnology, and drug development. To throw these developments over for practices that hid behind ratiocinations that denied the efficacy or applicability of RCTs endangered the whole of medicine.²¹

By October 1995, grants were allocated to establish eight more research centers in alternative medicine. OAM would eventually fund twenty-four research centers, most at biomedical institutions whose research methodology involved the double-blinded RCT. Each of these centers sponsored clinical trials and offered opportunities for training researchers in such topics as acupuncture, antioxidants, botanicals, phytotherapy, chiropractic, millimeter wave theory, mind–body medicine, meditation, osteopathic medicine, and traditional Chinese medicine (for a list of these centers, see the appendix).

Given the proliferation of alternative therapies in the US health-care system, some of which had already been integrated with conventional therapies, the members of the Quantitative Methods Working Group were divided on whether the RCT, amplified by the Cochrane Collaboration, should remain the gold standard. Not surprisingly, the advocates of CAM therapies urged a redesign of research methodologies, arguing that the distinctions between and among patients created situations inappropriate for comparison. There were distinctions not just between patients, but also in the same patient if evaluated at different stages in the history of an illness. Differences also existed between those complementary systems such as chiropractic that often use complex forms of intervention (i.e. spinal adjustment, ultrasound, heat and cold therapy, lifestyle coaching, and herbals), and others that rely on a single protocol with an expected sequence of outcomes.²³ Just two years earlier, in 1993, an entire book had been devoted to a scholarly analysis of alternative research methodologies for unconventional therapies.²⁴ That same year the New England Journal of Medicine published a study on the patterns of unconventional medicine that became one of the most influential publications on the subject.²⁵

Following considerable discussion, the working group agreed that even though all research projects did not lend themselves to the double-blind, placebo-controlled RCT, it was important to reaffirm the RCT’s place at the top of the evidence-based pyramid. All research projects required a clear statement of purpose in their study design, careful data collection through clinical trials, and meaningful data analysis. Nevertheless, the working group agreed that other designs capable of producing “valid and interpretable comparisons” should be admissible for addressing specific study questions. It recognized, however, several methodological challenges that had been raised by CAM supporters who argued against sole reliance on the RCT. These challenges included complex individualized interventions (i.e., CAM therapies treating AIDS might use a combination of dietary change, herbal medicine, counseling, and massage, making it hard to create comparisons); individualization of therapeutic effects (i.e., recognizing that the same protocol might elicit a different response in different individuals or in the same individual at a different time); focalized effects versus systemic perturbations (i.e., the delivery of a single intervention such as Bach’s water violet to bring serenity to the mind/body); systemic correspondences and correlations (i.e., the naturopathic assumption that pathological phenomena may be expressed on multiple levels of the system); long-term effects (i.e., believing that CAM therapies are intended primarily for prevention or the management of chronic problems); reconceptualization of the human body (viewing the individual as a unitary whole whose operation contravenes known physical laws); and multifactorial etiologies (i.e., chakras, disruptions in the bioenergy, impeded chi, and spiritual disturbances that offer alternative worldviews or paradigms).²⁶

Recognizing that most CAM modalities have had a history of practice without any systematic form of scientific testing using established rules of evidence, the working group sought to document the effects of specific unconventional therapies along with the methodological and analytic options available, including those social research methods outside of medicine. Soon after the group began its deliberations, it concluded that it was impossible to develop “practice guidelines” for CAM therapies.²⁷ Instead, it produced a “methodological manifesto” that listed seven principles intended to help frame approaches by clinical and basic science researches to CAM research (the material in italics is added summary):

1. Different study questions require different methodological and analytic approaches.

Every research project is contingent upon a clear statement of the purpose and objectives before the selection of the study design. Without such a statement, there is nothing to direct the collection of usable data. The question being asked determines the type of method or approach taken by the researcher.

It is possible to study the effects of a CAM therapy as a system rather than through its component parts, which could distort the treatment by deconstructing the overall intervention.²⁸

The issues challenging CAM research, explained the members of the working group, were not uncommon to research generally in that differences sometimes created difficult conceptual and measurement challenges. To offset these issues, acceptable options included large and small RCTs; nonrandomized trials with contemporaneous controls; nonrandomized trials with historical controls; cohort studies; case–control studies; cross-sectional studies; surveillance studies; consecutive case series; and single-case reports. In other words, established methodologies (i.e., experimental trials, observational epidemiology, and social survey research) and data procedures (i.e., analysis of variance, logistic regression, multivariate modeling techniques) were “quite satisfactory for addressing the majority of study questions related to alternative medicine—from research on therapeutic efficacy to basic science research on mechanisms of pathogenesis and recovery.”²⁹

Out of its deliberations, the working group concluded that if an unconventional therapy had an “identifiable, systematic, and consistent set of rules,” reliability could be ascertained even though its etiology was based on “unknown, mysterious, or novel mechanisms of action.” This meant that the unconventional nature of a given system would not, of itself, create an impediment to its validation through the use of appropriate research strategies.³⁰ Accordingly, there was no justification for an unconventional therapy to refuse testing based on the argument that the particular technical challenges posed by characteristics inherent to CAM made it impossible to assess. The working group also refused to countenance the argument that the rules of biomedical reductionism could not be applied to CAM because it represented “an alternative paradigm with its own standards.” With both propositions, the working group “emphatically disagreed,” arguing that new methodologies using nonlinear modeling (i.e., chaos theory, neural net theory, fuzzy sets theory) were potential substitutes.³¹

The working group cautioned against claims of special circumstances to delay or avoid evaluation. Unless or until unconventional therapies agreed to enter into research studies, they had only themselves to blame for any negative judgment leveled against them by conventional medicine. Besides, patients deserved to know if the therapies were “safe and effective.” Thus, although showing its willingness to compromise at the edges, the working group drew a line beyond which CAM therapies would lose their standing, however strong the political pressure to keep them in the public’s eye. Patients needed to feel safe when they sought treatment from unconventional systems. For that reason, CAM could not fail to accept closer scrutiny in the form of reasoned, well-executed research. Until this was done, cautioned Levin and his colleagues, CAM had to undergo the same degree of scientific scrutiny expected of conventional therapies.

The very fact that the Journal of the American Medical Association and the nine archive journals of the American Medical Association chose in 1998 to coordinate a thematic publication of CAM therapies served as a marker of CAM’s coming of age. That a majority of the nation’s medical schools now included discussion of CAM therapies in their curricula, that hospitals were operating integrated-medicine programs, and that managed care was brokering packages that included CAM practitioners suggested that mainstream medicine had to be more forthcoming in its accommodation. “We are in a culture with only a weak consensus on much of what passes for CAM,” wrote Fred Frohock, professor and chair of the Political Science Department at the University of Miami, “and maybe this culture is in a state of welcome transition to more reliable understandings of health and healing. Sometimes, it is possible to believe that we are on the verge of a new paradigm in medicine that will abandon the false polarities, and even distinctions, between mind and body.” Such an integrated model, however, required careful negotiation.³³

Notwithstanding the pressures coming from Senator Harkin and CAM proponents generally, conventional scientists remained unpersuaded by the arguments to change or replace the RCT. Evidence of this refusal was conveyed in a 1998 article in the Journal of the American Medical Association, whose editors were unequivocal in their assessment of what constituted acceptable research.

Equally important had been the joint editorial in the New England Journal of Medicine in 1998 by editors Marcia Angell and Jerome Kassirer, both of whom were longtime critics of the American health-care system and, in particular, of the pharmaceutical industry and who came down resoundingly against the category alternative medicine, which they viewed as little more than “junk science.” “There cannot be two kinds of medicine,” they insisted. “There is only medicine that has been adequately tested and medicine that has not, medicine that works and medicine that may or may not work.”³⁵ For them, there were not multiple levels of medical legitimacy, only one level: that which could be tested and shown to work. The postmodern crisis of medicine was in finance and delivery—not in the standard of scientific medicine. CAM medicine should be subjected to the same rigorous standards for safety and efficacy as biomedicine. “What we’ve learned, painfully and slowly over the last century, has been the necessity to test,” Angell explained elsewhere. “We’ve learned that the testimonial, the anecdote, even through very powerful, is not enough to say a particular drug works.”

We are applying a double standard, and there are lots of reasons why we’re doing that. The very term “alternative medicine” means there are two kinds of medicine, conventional and alternative. And we say conventional medicines needs to undergo rigorous scientific testing, but somehow we’re excusing alternative medicine from that same requirement. That was made quite explicit when Congress exempted the dietary supplement industry from the usual regulations on drugs that require the manufacturers to show that a drug is safe and effective before it can be marketed. Alternative medicine is now outside the FDA purview. So that’s what I mean by a free ride. Makers of dietary supplements can put anything they want in their bottles, as long as they label it a dietary supplement and don’t claim that it cures a particular disease. Nobody knows what’s in those bottles, and whether it works or not.³⁶

Supported by Representative John Porter (R–IL), who chaired the subcommittee that provided oversight of the NIH’s budget, as well as by Senator Arlen Specter (R–PA) and Senator Harkin, NCCAM became a reality despite the concerns voiced by scientists across the country. “Clearly the political push for expanding [OAM] into a center didn’t want to wait for any critical review,” complained Nobel Prize biologist Paul Berg of Stanford University.³⁹

Representative of this hardening of feelings, Harold Varmus, former director of the NIH and president of the Memorial Sloan-Kettering Cancer Center in New York, warned that “new facets” were being added to the NIH “without much thought to overall design.” Before the NIH became even more fragmented, he urged, supporters needed to give greater care to its structure. Prior to World War II, there existed only the National Institute of Health and the National Cancer Institute. In 1960, there were seven institutes. By 2001, the number had grown to twenty-four centers and institutes, along with the National Library of Medicine. At issue, explained Varmus, was the unnecessary duplication of responsibilities that would eventually affect the institutes’ respective budgets and grant-making authority. To make matters worse, other prospective institutes were waiting in the wings to be authorized. “Having more institutes also means less flexibility, less managerial capacity, less coordination, and more administrative burden,” he warned.⁴⁰

Stephen Straus, a virologist with strong research credentials, including twenty-three years at the National Institute of Allergy and Infectious Diseases, was appointed NCCAM’s first director and put his reputation on the line as he sought to assuage Harkin and his allies while insisting on continued scientific rigor for NCCAM’s funded research support. Given the breadth of alternative medicine’s treatments and practices, most of which had been unexamined for either safety or efficacy, Straus hoped to identify those therapies worthy of incorporation into conventional medicine and to inform the public of those that lacked credibility.⁴¹ To achieve both goals, he had to convince critics that the NCAAM was not simply “a counterculture enclave for pseudoscience.”⁴²

In 2000, NCCAM’s advisory board approved the investigation of so-called frontier therapies such as the use of magnets, energy healing, acupuncture, and homeopathy, which operated outside known biological mechanisms. Although acupuncture and homeopathy were relatively well known, therapies such as the Gonzalez Protocol were less known and poorly understood.⁴³ For critics from the scientific community, trials to examine these aberrant “sciences” constituted a waste of money and a disgrace to the scientific method. For Straus and his management team at NCCAM, whose intramural research programs had expanded each year due to CAM’s muscular lobbying, the pressure to test these fringe therapies remained an ongoing challenge.⁴⁴

An advocate of good science, Straus walked a careful path between the proponents of CAM and the scientific community hostile to CAM. His aim was to offer an opportunity to those frontier modalities whose modus operandi derived from forces outside scientific sensibility to seek legal status and protection that would legitimize their cures. To achieve this opportunity, he recommended validity through RCTs, preferably double-blind, to ensure a level playing field. Most alternative systems, however, considered the offer specious, if not irrelevant, arguing that Straus was seductively offering approval only by using reductionist medicine’s “house rules.” True to his word, Strauss supported large double-blind, placebo-controlled RCTs testing acupuncture for knee arthritis (University of Maryland); ginko biloba for dementia (University of Pittsburgh); glucosamine and chondroitin sulfate for knee arthritis (University of Utah); St. John’s wort for depression (Duke University); shark cartilage for lung cancer (M. D. Anderson Cancer Center); the Gonzalez Protocol for pancreatic cancer (Columbia-Presbyterian); and saw palmetto extract for benign prostatic hyperplasia (Veterans Affairs Medical Center, San Francisco).⁴⁵

At the National Cancer Institute, scientists drew up plans in 1998 for a $2.5 million clinical trial to test the effectiveness of the product Neovastat manufactured by Aeterna Zentaris, a pharmaceutical company located in Quebec. Unlike the more crude dietary supplements consisting of dried shark cartilage of dubious preparation and used for various cancers that were unresponsive to conventional therapies, Neovastat was derived from shark cartilage liquid extract. The product was tested on eight hundred lung cancer patients on the assumption that it stabilized tumor progression. The study, cosponsored by the newly created NCCAM, resulted from pressures stemming from both Congress and the CAM community to sponsor such a trial for shark cartilage, combining it with a placebo and with the standard regimen of chemotherapy or radiation or both. Other studies were carried out by the Mayo Clinic and the M. D. Anderson Cancer Clinic in Houston, testing both Neovastat and the product BeneFin against the placebo. The BeneFin experiment was halted early after enrolling only eighty patients in an initially planned six-hundred-cohort study of breast and colon cancers. The results, albeit limited, showed no evidence of an improved quality of life. An additional clinical trial was carried out on the orally administered Cartilade (powdered preparation of shark cartilage). To date, the cumulative evidence is either insufficient or inconclusive or both.⁴⁶

NCCAM also funded trials of chelation therapy for coronary artery disease at more than one hundred sites and at a cost of $30 million in spite of earlier controlled trials that had already found this therapy ineffective. The same was true of the Gonzalez Protocol for patients with stages II to IV pancreatic cancer.⁴⁷ In each of these trials, as well as those on St. John’s wort, echinacea, and saw palmetto, none of these treatments was found to be more effective than the placebo.⁴⁸ An NCCAM-sponsored clinical trial focusing on St. John’s wort and published in the Journal of the American Medical Association in 2002, found the herb to be “no better than placebo for the treatment of major depression.”⁴⁹ Despite a steady stream of criticism lodged by the herbal industry claiming that the tests had been flawed, Straus stood behind the clinical results.⁵⁰

For EBM critic Vincanne Adams, professor of anthropology at the University of California in San Francisco, Straus’s “house rules” had been predicated on the proposition that all alternative healing systems operated on the same “epistemological playing field.” This proposition, Adams noted, assumed a one-to-one correspondence between biomedical reductionist thinking and alternative medicine. “There is more at stake here than the question of whether we are talking about different names for the same diseases (or that the empirical foundation is the same even though the names we assign to them vary cross-culturally),” she complained. There were very real epistemological issues at stake. Disease categories did more than identify biological symptoms. They not only identified “unique approaches to bodily suffering, radically different models of anatomy, and logics of treatment protocols” but also defined “different empirical realities.”⁵¹

In the case of Tibetan medicine, for example, Adams felt that biomedical equivalents were conspicuously absent. Tibetan medicine classified diseases in terms of old and new cases and looked for patterns of imbalance in the body that related to the patient’s humoral constitution. Given this approach, patients with the same biomedically diagnosed disease would be seen in Tibetan terms as having different diseases with different etiological pathways requiring different treatments. Tibetan medicine included such diagnostic factors as spirit causation, karma (moral and immoral behavior) from past lives, and so-called inner winds that resulted from environmental and political influences, all of which were beyond the purview of biomedical reductionism. This approach undermined the logic of treating alternative medicine with RCTs and reduced the possibility of a “statistically successful outcome.” That a well-designed clinical trial with outcomes defined biologically, molecularly, cellularly, and biochemically would provide reliable empirical data on the comparative strengths and weaknesses of Tibetan medicine was an assumption that Adams considered untenable, particularly when both drugs and treatment changed over the course of a disease, preventing the use of studies designed to assess the efficacy of a single active ingredient. Moreover, because some Tibetan medicines were compounded of sixty or more different ingredients, outcome-based RCTs of them were difficult if not impossible to develop. Even more complicating was the claim that the active ingredients in a particular medicine were the result of a “spiritual” or “magical” empowerment brought about through karma, winds, chakras, auras, and so on.⁵²

Critics aside, NCCAM found collaborators in several federal agencies to promote conferences, workshops, and symposia on the importance of CAM research. These agencies included the Agency for Health Care Research and Quality, the FDA, the Centers for Disease Control and Prevention, the Health Research and Services Administration, the Substance Abuse and Mental Health Services Administration, the Department of Veterans Affairs, and the Department of Defense. While funding for NCCAM had increased from $50 million in 1999 to $68.7 in 2000 to an estimated $104.6 million in 2002, the total amount of funding through other agencies increased from $116.0 million in fiscal year 1999 to approximately $247.6 million in fiscal year 2002.⁵³ The NCCAM budget appropriation for 2005 was $123 million—an amount that actually understated the expenditures on CAM research, which totaled almost $305 million.⁵⁴

On March 7, 2000, President Bill Clinton signed Executive Order Number 13147, creating the twenty-person White House Commission on Complementary and Alternative Medicine Policy. The commission was directed to develop legislative and administrative recommendations that would “help public policy maximize potential benefits, to consumers and American health care, of complementary and alternative medicine (CAM) therapies—chiropractic, acupuncture, massage, herbs, and nutritional and mind–body therapies, as well as a host of other therapies.”⁵⁵ Appointments to the commission included conventional physicians, conventional health professionals who had integrated CAM into their practices, several interested health professionals, business executives, and patient advocates. To fulfill its charge, the commission held town-hall meetings in four cities, invited expert testimony during ten regular meetings held in Washington, and conducted site visits at institutions that were integrating CAM into their mainstream practice.

In “The Chairman’s Vision” in the commission’s final report, James Gordon, a Harvard-educated psychiatrist and founder of the Center for Mind–Body Medicine at Saybrook University in San Francisco, noted that most Americans had not turned their back on conventional medicine, knowing full well the benefits of modern scientific medicine. However, there was a general consensus regarding conventional medicine’s “limitations and side effects.” This consensus explained why so many individuals had turned to CAM therapies “without valid scientific information to guide them.” Because people were choosing a variety of approaches—reflecting both biomedical and CAM perspectives—it was in the interest of public safety to provide solid information with which the public could make sound health-care decisions.⁵⁶

Among the assumptions shared by the commissioners was the belief that in the absence of good information many Americans were making poor choices regarding CAM modalities; that science could help sort good CAM from the bad; that some CAM modalities would be proven safe and effective; and that ultimately there was only one type of medicine—namely, that which tested safe and efficacious. Given these assumptions, it was essential to understand the benefits and liabilities of CAM approaches because all systems of health and healing should be held to the same standards of good science.⁵⁷

The White House Commission’s final report, released in 2002, advocated a holistic orientation to future health care as a supplement to a strictly biomedical approach to health. “Health involves all aspects of life–mind, body, spirit and environment—and high quality health care must support care of the whole person,” stated its authors.⁵⁸ The term holistic medicine generally implies giving the individual patient an instrumental role—both conscious and unconscious—in building and maintaining his or her medical landscape, involving physical, social, and mental well-being through health promotion, treatment, healing, and disease prevention. In contrast to the positivistic framework of mainstream or regular medicine, holism looks beyond the formalized canon of reductionist science to the interrelationship of mind, body, and spirit as contributing factors in human wellness. It assumes, therefore, that each individual represents a complexity of interdependent functions that are affected by physical, mental, spiritual, and environmental factors, any one of which might negatively or positively influence the whole body as well as the individual part.⁵⁹

The commission listed ten principles intended to guide its recommendations:

Holistic medicine is by no means new to the Western world. From Native healing practices first glimpsed by Europe’s earliest explorers of the Americas to the healing practices of the botanics, Thomsonians, homeopaths, hydropaths, eclectics, physiomedicals, and mind-curists of the eighteenth and nineteenth centuries, it has been an integral part of any number of representative groups who have shown a greater interest in the connection between mind and body in the treatment of disease and illness than so-called medical orthodoxy. In other words, these groups have willingly accepted and integrated beliefs that have one or more physiological, environmental, psychological, or even spiritual components. This multidimensional approach, which is most evident in the postmodernist age, had roots well nourished by practitioners from antiquity into the modern age. As a consequence, the American landscape has been dotted with holistic practices dealing with health and health care that defy the more focused field of reductionist medicine.⁶¹

Premised, therefore, on the holistic belief that the mind, body, and spirit are integral elements in the healing process, the White House Commission recommended well-designed demonstration projects grounded in first-class scientific research to ensure the safety of products, appropriate levels of training of health-care practitioners, and dialogue between and among the different types of health-care providers. “The American people want their conventional healthcare practitioners to help them make wise decisions about whether to use complementary and alternative therapies—and which ones to use—and they want their CAM practitioners to be responsive and informed partners with their mainstream medical caregivers,” remarked Chairman Gordon. For this reason, he insisted that conventional health-care providers serve as “gatekeepers” by offering guidance to those seeking safe and effective CAM therapies.⁶²

Due to the lack of what it perceived as substantive domestic clinical trials of CAM interventions, the commission recommended that the nation’s future research agenda include not only comparisons of CAM therapies with conventional treatments, but the utilization of integrative and collaborative models as well. It also recommended a national coding system that would support standardized data collection. As a prerequisite to these recommendations, the commission urged the states to regulate and license those unconventional practitioners whose practices and products could be shown to be beneficial using standardized evaluative procedures. It also recognized the importance of CAM in the promotion of good health habits and attitudes in such areas as community and school-based programs addressing poor dietary habits, smoking, substance abuse, lack of exercise, depression, and other wellness issues affecting underserved and special populations. Finally, it urged the secretary of the Department of Health and Human Services to seek the cooperation of private, state, and federal agencies (e.g., Veterans Affairs, Defense, Indian Health Service) in partnering with CAM wellness and prevention programs to integrate safe and effective practices and products into the health-care system.⁶³

Given that the American public was relying on anecdotes, beliefs, testimonials, theories, and opinions to justify the safety and efficacious nature of CAM products and that most CAM research had been conducted beyond the research arm of academe, the commission urged comparability and replication in all future testing. It also understood the need for pharmaceutical and herbal manufacturers to agree on some level of standardized practice to ensure consistency in product purity and safety.⁶⁴ Although dietary supplements, for example, represented $17 billion in sales in 2000, reaching 158 million consumers, these products lacked the same level of testing and oversight demanded of prescription drugs. Understandably, the public should expect the same level of safety for these supplements that is guaranteed for prescription drugs. The commission therefore recommended that dietary supplement manufacturers register their products and suppliers with the FDA and maintain records of any adverse effects. To ensure a responsible level of safety, it urged Congress to “periodically evaluate the effectiveness, limitations, and enforcement of the Dietary Supplement Health and Education Act of 1994 and take appropriate action when needed.”⁶⁵

Because federal backing to assess the legitimacy of CAM modalities required an acceptable evidence-based methodology that would satisfy critics and proponents alike, the commission recommended that NCCAM collaborate with conventional medicine and its researchers to identify guidelines, research priorities, methodologies, and resources to examine those CAM therapies whose epistemological foundations lay outside the biomedical paradigm. It also encouraged alternate forms of evaluation, including basic research, nonrandomized studies, empirical observation, case studies, evaluations of practice-based data, and practice-based outcomes research. An understanding existed among the commission’s members that some of CAM modalities would be proven safe and effective, whereas others would fail in the process. Because research on unpatentable products was not likely to attract private research dollars, the commission’s report urged the government to offer incentives to stimulate private-sector investment.⁶⁶

The report insisted that both CAM and conventional medical researchers have rigorous training in the fundamentals of clinical, basic, and health services research. This training would include a proper grounding in “research process and methodology,” the “collection and recording of unbiased data,” “protocol or study design and execution,” and an “understanding of the expertise needed to form a research team.” The commission urged cooperation and even joint applications by CAM and biomedical researchers and their accredited institutions to realize these training elements. The results of this research, the commission urged, should be published in “recognized, rigorously peer-reviewed research journals” and collected in databases available through NCCAM, the Cochrane Collaboration, the Agency for Health Care Research and Quality, and both the PubMed and MedlinePlus databases in the National Library of Medicine.⁶⁷

Finally, the White House Commission urged that CAM be included in medical school curricula to ensure that it is taught in combination with reductionist medicine. With this inclusion, CAM students, practitioners, institutions, and organizations could benefit from loan and scholarship programs, gain greater appreciation for the fundamental elements of biomedical science, improve their competency as practitioners, and improve relationships with their biomedical counterparts. Moreover, CAM should partner with conventional medicine to provide service to medically underserved populations, facilitate better quality and accuracy of CAM information available to the public, and ensure consumer safety through improved training, licensing, and certification. With a better understanding of each other’s expertise and both group’s willingness to compromise, the commission hoped that CAM and conventional medicine would eventually build mutual respect, understanding, and an environment of improved health care for all.⁶⁸

Notwithstanding these objectives, the commission’s hopes were not always shared by the parties involved. Spokespersons for conventional medicine felt themselves dragged into an unholy relationship (i.e., a double standard) whose outcome had negatively impacted their share of the health-care market. Similarly, many CAM proponents remained fearful of being judged by the standards set by conventional research, causing them to be overly defensive to the point of denying comparable standards of quality and rigor.⁶⁹ Two of the commission’s members, Tieraona Low Dog and Joseph Fins, wrote a dissenting letter, recommending that funding for CAM therapies should be evaluated against all other proposals and disbursed on the basis of merit and not simply because they were CAM. “Asking for more research money to investigate an approach, practice or product simply because it is ‘CAM’ is an ideological, not evidence-based approach to science,” they complained.⁷⁰

According to Dónal O’Manthúna, professor of bioethics and chemistry at the Mount Carmel College of Nursing in Columbus, Ohio, the initial flaw in the commission’s report was its approval of a definition of CAM that was far too encompassing. The definition adopted included the following statement: “Complementary and alternative medicine, or CAM, can be defined as a group of medical, health care, and healing systems other than those included in mainstream health care in the United States. CAM includes the worldviews, theories, modalities, products, and practices associated with these systems and their use to treat illness and promote health and well-being.” This definition, O’Manthúna explained, included everything from religious and philosophical systems to physical manipulation and therefore led to serious issues of public policy. It made no distinction, he claimed, between those protocols that were complementary (some of which were evidence based and used by regular physicians); those that were scientifically unproven; those that were scientifically questionable (i.e., homeopathy); those that were so-called energy medicines; and, finally, those that were clearly fraud. Implied in these differences was the fact that the report ought to have adjusted its recommendations to the substantive differences between and among the categories. Moreover, he insisted that the inclusion of spirituality as a CAM therapy was patently wrong. Those practices that invoked spirituality (e.g., prayer, Reiki) should be treated conceptually different than protocols using acupuncture or St. John’s wort. Such inclusion violated the very evidence-based principles endorsed by the commission. More to the point, it transcended the assumptive premises of both conventional and unconventional medicine.⁷¹

Subsequent attempts to accommodate medical pluralism, or what Wayne Jonas, the second director of the OAM, once described as the “democratization” of medicine, has not been a peaceful process. Despite the popularity of CAM therapies across all levels of American society, clinicians have continued to find serious methodological issues in them. Having placed so much importance on the RCT, and having made it the gold standard for the testing and assimilation of new medicines and treatments, conventional researchers have found it difficult to substitute alternative analyses or what Kenneth Schaffner at George Washington University calls “methodological pluralism.”⁷²

Even with their fixation on the RCT, biomedical researchers seem open to exploring ways to address at least some of the issues. “Mind and body are…so closely connected in most healing practices,” explained Fred Frohock of Miami, “that there are good reasons to abandon the distinction altogether.” Examples abound of body-to-mind and mind-to-body responses to different stimuli. Unfortunately, the ability to “disentangle the placebo effect from the medicinal effect” continues to plague clinical researchers. Frohock suggested that “the binary self may be an inadequate model for the human person.”

The belief, not the clinical trials, may be the decisive variable in the efficacy of the product. The problem for determining efficacy is that a joining of mind and body makes it exceedingly difficult to identify the true antecedent variable bringing on the effect, whether beliefs or the substance taken. Put in terms of the deeper issue, mind and body may constitute a complex framework, perhaps a kind of layered unitary self, able to influence and undermine clinical trials with findings in the larger world of human experiences.⁷³

In his edited volume The Role of Complementary and Alternative Medicine: Accommodating Pluralism (2002), Daniel Callahan, senior research scholar and president emeritus of the Hastings Center, examined both the culture and practices of CAM and the challenges it has raised for mainstream medicine.⁷⁴ The essays in the book spoke of a new diversity in contemporary American culture that acts as a potential change agent to conventional medicine’s biomedical model, including the possibility of unintended consequences for the values and assumptions attached to biomedical research. The various authors stressed the need to respect the value preferences evident among different healing groups along with the need for clinical outcomes-based research that includes both CAM and conventional medicine. Callahan and his contributors encouraged the creation of a new paradigm dedicated to carrying on a more enlightened conversation about health and disease instead of following a path that distorts and devalues both orthodox and heterodox healing systems. Exemplary of this view, physician and anthropologist Marc Micozzi, author of Fundamentals of Complementary and Alternative Medicine (1996), executive director for the College of Physicians of Philadelphia, and former editor of the Journal of Alternative and Complementary Medicine, argued for greater tolerance and medical pluralism, with increasing focus directed to self-care and self-cure. Recognizing the power shift from physician to patient, he urged combining psychoneuroimmunology with concepts of vitalism, bioenergy, and holism, believing that these three elements offer a more comprehensive understanding of health and healing than strict biomedical reductionism. He suggested that quantum physics and biology/ecology are better evaluators of alternative therapies than the existing double-blind approach of the RCT. In looking at the varieties of alternative medicine, he seemed to favor naturopathy, which he called the “new eclectic medicine” in that it uses the best of everything regardless of source, theory, or methodology. To be sure, Micozzi stretched far beyond the opportunities and avenues of assessment offered by the Quantitative Methods Working Group in 1995.⁷⁵

A more paradigmatic change came from the Institute of Medicine (IOM), an independent, nonprofit organized in 1970 under the aegis of the National Academy of Sciences to provide unbiased advice to the public and to decision makers regarding issues of medical care, research, and education. The IOM’s sixteen-member committee to study CAM, which began meeting in 2003, published its report two years later.⁷⁶ The report, Complementary and Alternative Medicine in the United States, some three hundred pages in length, gave generous recognition to the fact that nearly a third of the US population was using CAM therapies routinely and often in a manner complementary or parallel with conventional therapies. It identified the major scientific, policy, and practice issues; reviewed the existing methods and approaches used in CAM research; made recommendations concerning the challenges of conducting CAM research; and stressed the need to translate CAM research findings into practice.⁷⁷

In his comments on the IOM report, David Eisenberg, director of the Osher Institute at Harvard and one of the sixteen committee members who shared in its authorship, stressed the need to ensure “that health-care professionals are providing evidence-based, comprehensive care that encourages a focus on healing, recognizes the importance of compassion and caring, emphasizes the centrality of relationship-based care, encourages patients to share in decision making about therapeutic options, and promotes choices in care that can include complementary and alternative medical therapies where appropriate.” This statement by itself represented a watershed change in thinking in that it demonstrated the degree to which evidence-based patient care had been affected by more holistic elements. To the committee’s credit, wrote Eisenberg, its members sought to create a “level playing field” on which all therapies could be judged. This meant that the same rules of evidence that weighed so heavily in conventional medical trials should apply as well to CAM treatments. Each and all, regardless of modality, should be put to the test of safety, efficacy, and cost effectiveness. What once applied only to conventional medicine now applied equally to CAM.⁷⁸

Eisenberg recognized that much remained unknown about CAM and the modus operandi behind its many therapies. Given this conundrum, the IOM committee encouraged research that would examine the complex social and cultural components of illness; the degree to which CAM users adhered to treatment protocols; the effects of CAM as a preventative; the manner in which the public accessed and processed CAM information; and an examination into the positive and negative interactions between CAM and conventional treatments.⁷⁹ Implied in this expanded viewpoint was a recommendation for considering a range of methodological approaches in addition to the RCT. These approaches included single-patient trials; testing bundles of therapies; qualitative research strategies; and the evaluation of nonspecific (placebo) effects. The committee also urged research into the use of multiple treatments, including the integration of CAM and conventional treatments, particularly because such combinations more accurately approached the actual use of CAM therapies by the adult population. Finally, the committee recommended the inclusion of CAM therapies in the curricula (at all levels) of the nation’s health profession schools—namely, medicine, pharmacy, nursing, and allied health.⁸⁰

In 2009, NCAAM began its second decade with the appointment of Josephine Briggs as its director. Educated at Harvard and trained at the Mount Sinai School of Medicine, Briggs pursued a career in research at Yale and later at the University of Michigan. From 1997 to 2006, she directed the Division of Kidney, Urologic, and Hematologic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases. In looking forward to NCCAM’s second decade, Briggs expressed her intention to reinforce the importance of EBM by giving increased emphasis to translational research, meaning an accelerated process for applying research outcomes to clinical and community practice. Noting that the boundaries between CAM and conventional medicine had narrowed in recent years, with numerous CAM interventions amalgamated into integrative medicine, and noting as well that approximately 40 percent of Americans were spending more than $33 billion for out-of-pocket CAM interventions, the time had come to ensure more accurate and timely evidence-based information on CAM for the public.⁸¹

NCCAM’s second decade is intended to advance the research priorities of its first decade with a leveraged focus on three long-range goals: (1) focusing on the science and practice of symptom management; (2) developing effective, practical, personalized strategies for promoting health and well-being; and (3) enabling better evidence-based decision making regarding CAM and its integration into health care and health promotion. Pointing to the reduced sale of St. John’s wort and echinacea following the publication of several NCCAM-supported clinical studies that identified issues of safety and efficacy, the agency took claim of its mission to promote a science-neutral approach to CAM practices and interventions.

Significant differences still remain. After NCCAM’s ten years of existence and more than $200 million spent testing the effectiveness of alternative therapies in more than 2,500 research projects, critic Wallace Sampson, editor of the Scientific Review of Alternative Medicine and emeritus clinical professor of medicine at Stanford University, remarked: “It is time for Congress to defund the National Center for Complementary and Alternative Medicine (NCCAM)…[because]…it has not proved effectiveness for any ‘alternative’ method. It has added evidence of ineffectiveness of some methods that we knew did not work before NCCAM was formed.”⁸² Gerald Weissman, editor of the Journal of the Federation of American Societies for Experimental Biology, added to the criticism: “If the trend persists, perhaps MIT or Cal Tech will march in step with the medical schools and offer prizes for integrative alchemy or alternative engineering.”⁸³ According to Donald Marcus of Baylor and Arthur Grollman of Stony Brook, the issue is not whether the NIH should support research into alternative therapies—their popularity has made it imperative from a public-policy point of view to properly evaluate their efficacy and safety. Rather, the issue is whether NCCAM is the appropriate agency to do the evaluations. For both Marcus and Grollman, NCCAM has fallen below the threshold standards of other NIH institutes in that it “funds proposals of dubious merit; its research agenda is shaped more by politics than by science; and it is structured by its charter in a manner that precludes and independent review of its performance.” Over and over again, funding was granted for clinical trials of therapies (i.e., echinacea, saw palmetto) already long identified as having no more effective outcomes than the placebo controls. Equally disturbing, NCCAM’s review groups included individuals with both limited scientific credentials and potential conflicts of interest due to their association with the botanical industry. Finally, according to these authors, oversight of the NCCAM’s extramural programs had “escaped critical evaluation because its charter required a preponderance of proponents of alternative medicine on its council.” For these reasons, they conclude that the evaluation of alternative therapies would be better performed by other NIH centers and institutes.⁸⁴

Issues and controversies continue to trouble the relationship between the supporters of CAM and the supporters of normative science. The Internet has numerous sites that track NCCAM’s newsletters for misinformation; check the accuracy of comments Briggs gives in lectures and to the press; comment on NCCAM’s hesitancy to address CAM objections to vaccinations; take frequent note of its indecisiveness toward homeopathy; and criticize its tendency to promote CAM in general as well as specific CAM modalities prior to evidence-based studies. “It seems to us that the NCCAM (at least so far) has never closed the door on any modality, no matter how implausible and no matter how much evidence for lack of efficacy there is,” complains Yale clinical neurologist Steven Novella. NCCAM’s public statements show “strict adherence to evidence-based medicine and science being neutral, but interspersed with this is an uncritical presentation of ancient superstition as if it were science, and endorsement of treatments that are not backed by science.” This pattern, Novella concludes bitterly, has only confirmed his worst fears—that NCCAM’s “very existence, and the generally positive and uncritical information it provides to the public, is used to promote and endorse unscientific medical modalities.”⁸⁵

For the moment, it would appear that biomedicine has tamed postmodernism’s enthusiasm for CAM by finding ways to integrate those therapies proven successful and containing the remainder through rigorous clinical trials. Rather than fight the forces of history with all its potential risks, conventional medicine chose a seductive and pragmatic approach, one that it has used time and again to co-opt the power of its adversaries: adopting those elements that can be incorporated into itself. Terri Winnick describes this strategy as “co-optation,”⁸⁶ meaning that those remedies and treatments shown to be safe and efficacious have been absorbed into conventional medical practice and those that remain on the outside face a judgmental condemnation relegating them to existence as unproven, unaccredited, and unlicensed. Thus, although conceding to pressure from Congress for the establishment of OAM and NCCAM, conventional medicine has been able to ensure that the program’s activities would be guided in a publicly responsible manner through the strict application of an evidence-based pyramid using the normative methods of science. The fact that so few outcomes have been judged successful suggests that most CAM modalities are faith-based practices, placebos, the detritus of psychosomatic medicine, entrepreneurial expediency, or, worse, outright quackery.