In my last post, I started wading into the question of what kinds of ethical questions arise from clinical trials on “alternative” medical treatments, especially clinical trials supported by the National Center on Complementary and Alternative Medicine (NCCAM). The ethical questions include whether alternative treatments expose human subjects to direct harm, or to indirect harm (by precluding a more effective treatment), not to mention whether the money spent to research alternative modalities would be better spent on other lines of research. I think it’s worthwhile to dip into the NCCAM website to look at some of the clinical trials this federal agency has supported.
From the NCCAM website’s discussion of clinical trials being conducted on complementary and alternative medicine (CAM):
Yes, clinical trials on CAM are taking place throughout the United States and the world.
While many CAM treatments have already been in use for a long time (sometimes for centuries), there is not the kind of scientific knowledge available about them that has been gained from studies of conventional medicine. Many people are already using CAM, and without this scientific knowledge, they may be at risk-for example, for serious effects from taking the wrong dose, using the treatment in the wrong way, or using it with another treatment with which it interacts.
Researchers, including many supported by NCCAM, are studying CAM treatments in well-designed clinical trials to find answers to such questions as:
- Does it work?
- If so, how does it work?
- For which diseases and conditions does it work?
- What dose is safe?
- What dose is effective for a specific disease or condition?
- What are the side effects?
- How should it be given?
- Are there situations in which it might be harmful?
- Can it be used safely with other forms of treatment?
- Is it better than, or an adequate alternative to, other treatments that are available?
NCCAM is funding studies on a variety of CAM treatments. A few examples include acupuncture; herbs, such as Ginkgo biloba and saw palmetto; dietary supplements, such as glucosamine and chondroitin; and massage. Examples of diseases and conditions for which these CAM therapies are being studied include arthritis, neurological disorders, cardiovascular disease, and cancer. Some of these studies involve partnerships with other institutes at the National Institutes of Health (NIH). Institutions outside the Federal Government are conducting studies as well.
The questions enumerated above sound like reasonable ones to ask about substances or treatments people are using. To the extent that they can be answered in clinical trials that pass ethical muster, answering them ought to be a good thing.
The ClinicalTrials.gov website lists the clinical trials sponsored by NCCAM. A commenter on the last post indicates that not all the studies funded by NCCAM appear in this listing, though. Still, these listings give a flavor of the kinds of projects sponsored by NCCAM.
Among the 235 NCCAM-sponsored studies listed when I searched the site were:
Although evidence of its effectiveness is limited, cranberry juice is widely used to prevent urinary tract infections (UTIs). However, recent studies have shown that cranberry juice may affect the way the body absorbs and metabolizes antibiotics used to treat UTIs. This study will determine whether concurrent cranberry juice administration lowers the urinary concentrations of two commonly used antibiotics, amoxicillin and cefaclor.
This study will involve children being treated for UTIs and adults without UTIs. All of the children will continue their prescribed amoxicillin/cefaclor treatment. After 7 to 10 days of antibiotic treatment, the children will be assigned to receive either cranberry juice for 2 days or no additional treatment. Urine samples will be collected from all child participants before and after the administration of cranberry juice to examine the excretion of the antibiotics.
Adult participants will receive two different doses of amoxicillin, with or without cranberry juice. Blood and urine samples will be collected to evaluate the effect of cranberry juice on the absorption and elimination of amoxicillin.
(Study completed; no publications provided.)
To determine the effect of hawthorn extract 450 mg bid vs. placebo, in addition to standard medical therapy in ambulatory patients with NYHA class II to IV chronic heart failure on submaximal exercise as measured by the 6-minute walk test
(Study completed; publication: Zick SM, Blume A, Aaronson KD. The prevalence and pattern of complementary and alternative supplement use in individuals with chronic heart failure. J Card Fail. 2005 Oct;11(8):586-9.)
Little is known about acupuncture’s efficacy for Irritable Bowel Syndrome (IBS). This trial uses a manualized acupuncture treatment format that closely follows clinical practice and allows flexibility in designing individualized treatments. In addition, a second parallel qualitative study will follow a subgroup of patients throughout the trial to explore the relationships between patients’ interpretations and understandings (what anthropologists call “meaning”) of irritable bowel and their response to treatment. Cortisol levels (an important stress hormone) will also be assessed.
This will be a 3-arm trial: Active acupuncture, placebo acupuncture, and wait list.
(Study completed; no publications provided by NCCAM, but one automatically indexed to this study: Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE, Kirsch I, Schyner RN, Nam BH, Nguyen LT, Park M, Rivers AL, McManus C, Kokkotou E, Drossman DA, Goldman P, Lembo AJ. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ. 2008 May 3;336(7651):999-1003. Epub 2008 Apr 3.)
In recent years, western health practitioners have become increasingly aware of the potential health benefits of yoga. This study will comprise two substudies that will evaluate the effects of yoga in two distinct populations.
Participants in the first study will be people who are at risk for developing diabetes; participants in the second study will be people with both HIV and depression. All participants will practice yoga 3 to 6 days per week for 3 months. Blood collection will be done and weight and blood pressure measurements will be taken in study 1 participants; questionnaires will be used to measure depression and stress in study 2 participants. All study participants will be assessed at entry and at 3 and 6 months.
(Study completed; no publications provided.)
Shingles, also known as herpes zoster (HZ), is more common in older persons due to the weakening of the immune system with advancing age. Psychosocial stresses in the older adult also correlate with the decline in immunity. In addition, preliminary data indicate that the presence of depressive symptoms in older adults is associated with a decline in the response to varicella zoster virus (VZV) vaccination. Taken together, the untoward effects of age and depressive symptoms on VZV immunity raise the question as to whether a behavioral intervention might augment VZV specific immunity in the older adult.
Preliminary data has shown that administration of a relaxation-response based intervention, Tai Chi Chih (TCC), results in improvements in health functioning and VZV immunity in older adults as compared to a control group. TCC is a slow moving meditation comprised of twenty separate standardized movements for use in elderly populations. By standardization of training and practice schedules, TCC offers an important advantage over prior relaxation response based therapies. This controlled trial has 3 goals:
1. determine whether the practice of TCC for 16 weeks influences unstimulated- and vaccine-stimulated VZV specific immunity in adults 60 years of age and older;
2. demonstrate that TCC can produce significant changes in psychological adaptation, health behaviors, and health functioning and well-being;
3. assess whether changes in psychological adaptation, health behaviors, and health functioning correlate with changes in VZV immunity following TCC in older adults.
(Study completed; four publications: Miller GE, Cohen S. Psychological interventions and the immune system: a meta-analytic review and critique. Health Psychol. 2001 Jan;20(1):47-63., Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84., Irwin M, Pike J, Oxman M. Shingles Immunity and Health Functioning in the Elderly: Tai Chi Chih as a Behavioral Treatment. Evid Based Complement Alternat Med. 2004 Dec;1(3):223-232. Epub 2004 Dec 1., Irwin MR, Pike JL, Cole JC, Oxman MN. Effects of a behavioral intervention, Tai Chi Chih, on varicella-zoster virus specific immunity and health functioning in older adults. Psychosom Med. 2003 Sep-Oct;65(5):824-30.)
The primary objective of this project is to develop and evaluate two different alternative or complementary medical modalities that have been used in children with cerebral palsy by practitioners in an attempt to decelerate the complications from the neurologic insult and resultant muscle imbalance.
The specific aims are: 1) The development and incorporation of two alternative modalities (osteopathic manipulation and acupuncture) into available services in southern Arizona for individuals with cerebral palsy. 2) The evaluation of the uptake of and compliance with the two modalities in the clinical services for cerebral palsy. 3) Conduct pilot studies of each of the two modalities to determine their efficacy in decreasing the degree of muscle tension in children with spastic cerebral palsy.
(Study completed; no publications provided.)
The goal of this study is to improve the overall physical health and quality of life of patients attached to mechanical hearts or assist devices while awaiting heart transplantation. Qigong, an ancient Chinese exercise that involves active participation of the individual in the form of meditation, breathing exercises and simple physical movements, will be used as an adjunct to the therapies, including a structured exercise program, currently provided to these patients at the University of Arizona Health Sciences Center. Based on the results of studies that have demonstrated physiological and psychosocial benefits of structured exercise programs and the practice of qigong, the following hypotheses are proposed: 1) a structured exercise program that combines aerobic and resistance training will improve the cardiovascular health of patients on mechanical hearts and assist devices; these conditioning effects will be amplified by the practice of Qigong; 2) a structured exercise program that combines aerobic and resistance training will improve the quality of life of patients on mechanical hearts and assist devices; these conditioning effects will be amplified by the practice of Qigong; 3) improved quality of life and physical conditioning effected by the structured exercise program and Qigong will enhance quality of life and physical conditioning after cardiac transplantation. To test these hypotheses, the following specific aims will be accomplished: 1) obtain pilot data to evaluate alterations in specific measures of cardiovascular function and health in patients attached to mechanical heart or assist devices who have participated in a structured aerobic/resistance exercise program, with and without Qigong; 2) obtain pilot data to evaluate alterations in specific quality of life measures in patients attached to mechanical heart or assist devices who have participated in a structured aerobic/resistance exercise program, with and without Qigong; 3) as part of the clinical follow-up of these patients following heart transplantation, obtain pilot data to evaluate specific parameters of cardiovascular health and quality of life of individuals who were attached to mechanical heart or assist devices prior to receiving the transplant.
Information gained from this research will serve as a basis from which the application of exercise training and Qigong can be applied to the treatment of other chronic disease states in which the physical conditioning and/or quality of life of individuals is compromised.
(Study completed; no publications provided.)
The use of complementary and alternative therapies by parents of young children remains common despite the lack of clinical trials demonstrating either the efficacy or safety of these treatments. Two of the more common complementary therapies used in young children with a history of recurrent otitis media are preparations of the herb Echinacea purpurea and cranial osteopathic manipulative treatment. This study represents one of the first double-blinded, placebo controlled trials of each approach in a population of young children who presented with three or more recent episodes of acute otitis media.
Significant numbers of people with HIV/AIDS seek spiritual or “psychic” treatment. Distant healing could potentially be of benefit to large numbers of HIV/AIDS patients, as it is widely available and requires no travel or other activity on the part of the patient. However, the treatment can be costly and has not yet been proven effective in a controlled clinical trial. This study will evaluate the efficacy of distant healing in patients with HIV/AIDS.
Participants in this study will be randomly assigned to either the distant healing group or a control group. All participants will have hour-long study visits at entry and Months 6 and 12. At study visits, participants will complete a demographic questionnaire, self-report health and symptom inventory, quality of life assessment, and profile of mood states. Blood will be drawn at each study visit.
(Study completed; no publications provided.)
Acute otitis media (inflammation of the middle ear) occurs in 60% of infants during the first year of life and in 85% by age 3. Approximately 17% of children suffer recurrent otitis media during the first year of life. Following acute otitis media, middle ear fluid effusions can persist for weeks to months. Approximately 40% of children with middle ear effusions have mild to moderate hearing loss for the duration of the effusion, and several studies have found evidence for impaired speech and language development among children with prolonged middle ear effusion. Since antibiotic use has become widespread, concern has emerged regarding antibiotic resistant S. pneumoniae strains and other bacteria. Children with recurrent otitis media commonly receive prophylactic antibiotic therapy or surgical insertion of tubes to prevent accumulation of middle ear effusion. The prevalence of pediatric use of complementary alternative medical (CAM) approaches for prevention of otitis media has not been widely quantified. This study will evaluate the use of osteopathic manipulation and echinacea therapy to prevent ear infection in children with recurrent otitis media.
(Study completed; no publications provided by NCCAM, but one automatically indexed to this study: Wahl RA, Aldous MB, Worden KA, Grant KL. Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial. BMC Complement Altern Med. 2008 Oct 2;8:56. )
That information about these studies is publicly available strikes me as a good thing – transparency about how public moneys are spent and all. That significant NCCAM-funded research trials, like the Trial to Assess Chelation Therapy (TACT), don’t appear in this listing strikes me as a not very good thing.
A bunch of these studies seem not to have resulted in publications. Why they didn’t result in publications is unclear from the information presented here. Maybe the results were inconclusive. Maybe manuscripts were written and submitted to journals but were rejected (or are in a long-lag submission-to-publication process involving multiple exchanges between authors, reviewers, and editors). In some fields, publishing results that amount to, “It didn’t work!” is quite hard. However, I would hope that the results of clinical trials – conducted on actual humans, who undertook risks so that the data could be generated – would be published in some form. For one thing, this would make it easier to eliminate unnecessary duplication of research efforts. For another, when we’re talking about interventions that people are actually using of their own accord, even in the absence of good scientific evidence that it works, publicizing the finding that they don’t work adds information to the public conversation that may change behavior. No, it’s not a sure thing that a negative finding in a clinical trial will make every patient abandon his or her cranberry juice or yoga in favor of conventional medical treatment. Respecting patient autonomy means respecting it even when its exercise involves what we might consider dumb choices. However, the chances of making good choices ought to be higher in the presence of good information.
Some of these studies seem to be more focused on what alternatives patients are already pursuing, rather than on the effectiveness of these alternatives per se. I’m guessing opinions will vary as to whether the funds for such studies amount to money well spent. If the alternatives patients are pursuing interact with the medical treatments they are “officially” receiving, then good data on the prevalence of these alternative treatments could help practitioners of conventional medicine treat their patients more effectively. Such data might also lead to better insights about why patients seek out alternative treatments in the first place.
To my eye, some of these trials have studied pretty improbable treatments (like distant healing). However, if these treatments are the kind of things actual patients are seeking out and using, I have to believe that they don’t seem improbable to everyone. This raises an ethical conundrum. If people who think treatment X is plausible are faced with results from a carefully designed and conducted clinical trial, will they revise their view of whether X is a plausible treatment? Would such a revision be a big enough benefit to justify conducting what seems at the outset to be a pretty implausible clinical trial? And, in the absence of such concrete scientific findings, what options do you have to convince the X-seeker about the implausibility of X as a treatment?