Evidence Based Medicine; Opportunity or Turmoil for Acupuncture?

 These days Evidence Based Medicine (EBM) is quite the fad. Everyone in the medical field is talking about EBM and they want to take part in it. As acupuncturists, we are not the exception; we want to prove acupuncture treatments are effective enough to be part of the conventional treatment module. Complementary and alternative medicine(CAM) research in the 21st century will rely upon an evidence-based model of systematic evaluation of research evidence.  We believe this growing global trend is finally providing the stage for acupuncture to meet the needs demanded by  modern medicine. To communicate with the scientists, medical doctors and policy makers we need to speak their language and we have been making an effort to do so. With recent advances in neuroscience, several scientific research studies have been conducted to explain the mechanism of acupuncture, but none has fully satisfied the scientific community (Vincent& Richardson 1986); we are not at the "threshold of a precise scientific explanation" (Peng & Greenfiled 1990) and thus far we can only make a decent hypothesis about the mechanism of acupuncture.  FMRI has connected acupuncture to  brain function and endocrine control. This showed the possibility that acupuncture makes the body secrete neuromodulators, which explains how pain can be systemically subsided. Clement-Jones observed the increase of beta-endorphins in CSF among subjects who received acupuncture. We got excited when Matsumoto explained the effect of acupuncture on the autonomic nervous system control in experiments with rabbits. We were also proud to help find clues about treating hard-to-cure diseases like cancer, but has this been enough evidence to place  acupuncture in the "evidence-based" realm?  




Elucidation of 'Evidence' in the context of EBM


Let us first define what is evidence in EBM. If it looks like evidence, if it sounds like science, is it enough to be considered "evidence?" In his book "Clinical Epidemiology: A Basic Science for Clinical Medicine" Dr. David L. Sackett states Evidence-Based Science is a "conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients."  Gray Ellrodt on the other hand, defines it as "an approach to practice and teaching that integrates pathophysiological rationale, caregiver experience, and pat preferences with valid and clinical research evidence." The Journal of Academic Medicine states that evidence based Medicine "Defines the value of medical interventions in terms of empirical evidence from clinical trial." One thing we should focus on is the word "clinical" in the context of "clinical research evidence" and "clinical trial." All evidence that is considered in EBM is a result of clinical studies.  There exist a acceptive standard of hierarchy of evidence in EBM. The US Preventive Services Task Force categorizes evidence as following:

    • Level I: Evidence obtained from at least one properly designed randomized controlled trial. 
    • Level II-1: Evidence obtained from well-designed controlled trials without randomization. 
    • Level II-2: Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group. 
    • Level II-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence. 
    • Level III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees. 

One can conclude that all the evidence categorized here is clinical evidence- even case studies which are classified at the lowest evidence, are a clinical resource, not a laboratory resource.


All glitters are not gold: Clinical evidence as golden standard


Through the clinical evidence we can avoid the possibility of false positive conclusions that often occur in human observational studies or non-experimental studies. Clinical implications should be decided based on the clinical data. As an epidemiologist, Dr.Sackett insisted clinical evidence as a scientific rationale. Epidemiology itself is not biology or laboratory work but is statistical work with clinical evidence.  He used "clinical epidemiology" as a tool to guide diagnosis and prognosis. EBM followers urge that for proper consideration of practical application, evidence should be empirical and clinical, and not include any scientific inference which is not proven in a clinical setting. Before EBM, we accepted something as true, if it was explainable in a scientific way. We can see this in the example of  using steroids and antiviral agents for Bell's palsy: Both had a scientific rationale for explaining their usage and the combination appeared very logical;  Steroids were used to reduce inflammation with the idea that it may improve facial function by reducing damage to the nerve. And an anti-viral agent was added to relieve viral infection. At the time, there was controversy among practitioners regarding the use of these agents, which was  eventually settled through clinical trials. One well-composed clinical review determined that "Current evidence suggests that Prednisolone is effective for this common condition, but there was no statistically significant difference observed with Valacyclovir." The anti-viral agent provided minimal added benefit to the steroid.  The usage of both drugs was explainable in a scientific way, but one was suggested and one was rejected through clinical evidence. There are many other examples which make sense in scientific theory but are not proven in a clinical way. Vitamin C is known to subside the secretion of the prostaglandins that contribute to fever and inflammation. Vitamin C works on some pathway or mechanism inhibiting prostaglandins like anti-inflammatory medicine, but no clinician will prescribe vitamin C for a high temperature.   We also have many new drugs now for the treatment of obesity. The mechanism of action of these drugs is explainable with scientific theories, which are proven through laboratory experiments, and in vivo studies: carbohydrate re-absorption inhibitors within the small intestine, serotonin agonist for appetite control, sympathetic nerve stimulators like caffeine, ephedrine, and others. Very few of them however, have proven to be effective enough to control obesity in long-term randomized clinical trials. These are a few examples showing that non-clinical evidence, although scientific in nature, is not enough to be evidence for clinical implications.


EBM on the apogee of modernism, and the beginning of post-modernism.


EBM is basically a bottom-up approach.  It is an inductive process, like collecting the threads of clinical facts and weaving them together to knit a fabric. Modern science has developed from a more top-down approach. "Rational analysis" as the basis of scientific method has become transformed into "rationalism." R. Descartes(1596-1650) described the human body as a delicate watch, and from this we began to think the human body and all its actions could be reduced to small elements like parts of watch; the human body became nothing more than the whole sum of small materials. This became the basic concept of natural sciences of the modern era and the cornerstone of all scientific academies.  Even in sociology the scientific method was applied to study human behavior and the mind. S. Freud(1856-1939) worked arduously to scientifically explain his psycho-analysis. The medical field also yielded to this tendency.  In 20th century America the "Flexner Report" made a big change in the medical field. At the core of Flexner's view was that this kind of thinking was integral to the natural sciences. The Flexner Report reformed medical research and education to be based on laboratory experiments and natural science which could be termed “scientism,” and it was at this point when most natural therapies like herbs, homeopathy, and energy therapies disappeared from the system. 

Now in the 21st century modernism is facing turmoil. In 1994, then-President of the Czech Republic and renowned playwright Václav Havel gave a hopeful description of the postmodern world as one based on science, and yet paradoxically “where everything is possible and almost nothing is certain.” The first reflection of the postmodern era started from physics. Modern physics has strongly suggested a surprisingly uncomplicated, non-mysterious, "ultimate reality." A postmodern view from quantum physics insists that we can only define the possibility.  We started to doubt the absolute and ultimate truth of natural science. Postmodern science challenges the modern ideal of the neutral scientist who applies formal rules of deduction to develop theories that objectively explain empirical data. Postmodernism is challenging the modern paradigm and is also affecting the medical field. Dr. Chiappelli(2005) referred to post-modernism as a contemporary view of Scientism which encompasses mind and body. We began to need a new proper standard, one not based on modernism. EBM appeared in history in this context and it is getting more and more followers. EBM most definitely emerged on the apogee of modern medicine, and ironically at the opening of the post-modern era. There is a time-gap between the emerge of philosophical thought and its implementation to applied science. Rationalism in medicine was completed in the age of Flexner report(1990), and pragmatism is fully reflected in medical field in EBM. It is modern medicine's turning point beyond rationalism. Yang becomes Yin at its pinnacle. When Yang accesses too much, it resembles yin. EBM has two very pragmatic points. First, even though one theory fits the common sense of science, if it is not clinically proven, it couldn't be practiced. On the contrary any kind of medical practice, even if it looks like black magic, can be implicated for practice only if it is proven effective and safe in clinical studies.

Though we don't know why they work, research has shown that they do 


EBM presents itself to be a great opportunity for all traditional medical interventions to prove themselves. Once neglected, now all fields are competing for efficacy and safety in one big coliseum called EBM.  How is research in acupuncture these days? So far research in acupuncture has been tipped towards basic science research. Clinical researchers in the 1960s and 1970s began to decline, replaced by PhD full-time bench researchers. Research about biological mechanisms of actions could be devoted to the advancement of science in the fields for basic research. We have been working on this desperately through laboratory research to make a scientific rationale.  Most articles published in Korea have been only literature or basic science studies. One researcher at the Korean Health Industry Development Institute addressed this at the symposium for the National congress: "We only spent money for basic science research for development of oriental medicine, we should shift the center of research from laboratory research based at the academy to clinical research based in hospital."  We don't need to clarify the mechanism to imply it’s efficacy in practice. We don't have to make it scientific or explain it in a scientific way. (The term, science, here refers basic science which represents the laboratory. The epidemiology which is used by EMB is also a part of science). These efforts are like playing Chinese checkers with western chess pieces. It is two separate games under a similar name, science. Let me use another analogy. Taekwondo is part of the Korean military training. We do not examine scientifically the mechanisms of Taekwondo, or how it works. Instead we examine whether Taekwondo is effective and useful. Medicine is not the same as natural sciences such as biology, chemistry or physics; it is applied science. A science that can treat disease should be practiced, not just explained.  In applied-science, application- implication- is the top priority.  To determine the proper implications of treatment, we need a standard rule to decide if a treatment is safe and effective. EBM can be that standard rule. Having said that, we require more clinical evidence, even if it doesn’t explain mechanisms from the perspective of the basic sciences. Research about infertility performed at Cornell University is a good example. They didn’t try to explain how acupuncture works for infertility, but rather its effectiveness and positive outcomes. I am looking forward to saying the following about acupuncture treatments very soon: "Though we don't know why they work, research has shown that they do."



Future of Acupuncture Research: A Balanced Approach


Among the research performed between 1966 to 1994, clinical trials are very few (fig 2).  Now is the time to change our direction. According to Normile, Asian governments hope that high-volume screening and rigorous clinical trials will unlock the secrets of ancient herbal remedies. Korean researchers had been focusing on basic research done in the university laboratory, but now they are moving to clinical research done in the hospital. In the United States, NCCAM spent $50.98 million for clinical trials in 2009, the budget for extramural basic or non-clinical research was $35.9 at that same time. The whole research field is changing after the appearance of  EBM.  EBM has changed a lot of things, and it now seems to be the time for researchers to investigate acupuncture in a new way. The next decades will witness an increasing number of evidence-based research directed at establishing the best available evidence in CAM.  

It is true that we need a scientific guideline for acupuncture research and EBM can be a good guide, but we should avoid extremism which only support clinical studies or basic science. All the interventions of CAM do not have to go through tough clinical trials, as it has been successfully used for thousands years before concerns about the mechanisms of action. Some academic researchers are uncomfortable with practicing not knowing bio-mechanism, but clinicians are pragmatic. Medical doctors willingly used aspirin long before learning how it worked.. On the other hand, EBM followers are uncomfortable with practicing without proof by clinical trials. They insist proving everything through clinical studies even though it already fits common sense. They are on the extremity of pragmatism. There is a huge amount of research to be done in the acupuncture field. Besides clinical studies, acupuncture research can benefit from improved research methodology, basic science research such as biological mechanisms, and even history and philosophy. All this research should be balanced for each purpose in a big picture. We need balance in research as we need balance in the human body; theoretical and practical, yin and yang.


References


1 Chiappelli F, Prolo P, Cajulis OS. Evidence-based research in complementary and alternative medicine I: history. Evid Based Complement Altern Med 2006;2:453–8. 
2 Filshie J, White, A. Medical Acupuncture, A Western Scientific Approach.  Churchill Livingstone 1998 p 14
3 Clement-Jones V, McLoughlin L, Tomlin S, Besser GM, Rees LH, Wen H. Increased beta-entorphin but not metenkephalin levels in human cerebrospinal fluid after acupuncture for recurrent pain. Lancet 1980; 2:946-949
4 Matsumoto T, Hayes MF. Acupuncture, electric phenomenon of the skin and post-vagotomy gastrointestinal atony. American Journal of Surgery 1973 125;176-180
5 Sackett DL, Rosenberg W, Gray JA, et al. Evidence based medicine: what is it and what it isn't. BMJ. 1996: 312:71-2.
6 Ellrodt G. Evidence-based disease management, JAMA 1997;20: 278
7 Tonelli MR. The Philosophical limits of evidence based medicine. Academic Med 1998;73 (12): 1234-40
8 Sackett DL, Rosenberg W, Gray JA, et al. Evidence based medicine: what is it and what it isn't. BMJ. (1996): 312:71-2.
9 Worster, A, Keim SM, Sahsi R. Do Either Corticosteroids or Antiviral Agents Reduce the Risk of Long-Term Facial Paresis in Patients with New-onset Bell's Palsy? J Emerg Med. 2009 Oct 19.
10 Elatter TMA, Lin HS. Effect of vitamin C and vitamin E on prostaglandin synthesis by fibroblasts and squamous carcinoma cells. Prostaglandins Leukot Essent Fatty Acids. 1992;47(4):253-7
11 Molly Cooke, David M. Irby, William Sullivan, Kenneth M. Ludmerer, American Medical Education 100 Years after the Flexner Report  NEJM 2006;355:1339-1344
12 Hwang SI, Reform of the Medical Education in the Early 20th Century America and the Flexner Report of 1910. Korean journal of medical history 1994;6: vol2, 1.
13 Vaclav Havel. "The Need for Transcendence in the Postmodern World," speech in Independence Hall,Philadelphia, July 4, 1994.
14 Toulmin, Stephen. The Return to Cosmology: Postmodern Science and the Theology of Nature. Berkeley: University of California Press 1982;283:21
15 Petersdorf, RG. Is the establishment defensible? New England Journal of Medicine 1983;309:1053-7
16 Symposium for National strategic industry development. Kookmin daily newspaper, 7.16.2008.
17 Chang R, Chung PH, Rosenwaks Z. Role of acupuncture in the treatment of female infertility.  Fertility and sterility  2002;78:6
18 Micheal F.Rozen, Mehmet C. Oz. You the owner's manual. HarperCollins, 2005, 288
19 Normile D. The new face of traditional Chinese Medicine. Science 2003;299:188–90. 
20 Cooper EL. Complementary and alternative medicine, when rigorous can be science. Evid Based Complement Alternat Med 2004;1:1–4.
21 National institues of health, Office of Budget. http://officeofbudget.od.nih.gov/gbpriceindexes.html
22 Chiappelli, F. Commentary on Designations of Medicines by Nigel Wise- man. eCAM 2005;2:111–112. 
23 Elizabeth H. Logue. Geffen Faculty Highlight Concerns Linking CAIM and Conventional Researchers at UCLA Symposium Evid. Based Complement. Altern. Med., March 2010; 7: 29 - 32