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Me, ten minutes after the end of this post.  EXTREME!

 

It is summer vacation for me in Eastern Oregon at Sunriver. Unbelievable geology, fantastic hikes, great biking, wonderful golf, delicious beer and good food. The thesaurus fails me for superlatives. It is hard to get too riled up about all things SCAM to produce a blog entry when I could be doing one or all of the above. I really don’t want to do this. Sadly, David keeps threatening me with the video he has of me touting the benefits of Integrative Medicine with its holistic approach to health care, and I just can’t have that published on the ‘net. So some brief speculation to fill the time between golf and a pint of IPA overlooking the Sisters.

Ethics, and the purpose of SBM

Steve started this blog in 2008 in part because he realized that evidence-based medicine was inadequate for the task of evaluating pseudo-medicines. He coined the term ‘science-based medicine’ with the realization that for fantastical therapies like acupuncture or homeopathy, all the potential biases and flaws in the evidence from clinical studies could result in pseudo-medicines appearing effective when at heart they are all Oakland California.

I do not suppose there could be science-based ethics. One person’s ethical certainty is another’s belly laugh. I remember a grand rounds on human cloning years ago and they had, among others, a priest discussing the ethics of human cloning, and I thought at the time there would be few speakers with less legitimacy. And really, I can see no harm in cloning an army of zombie super soldiers, especially if they were under my control.

Still, one of the issues I remain amazed at is how many clinical trials testing pseudo-medicines are approved by institutional review boards (IRB).

The changing practice of medicine

Let us ignore for the sake of this essay the issue that there is little point in testing pseudo-medical therapies from a medical practice perspective. In real medicine we do studies to guide therapies, eventually adding or abandoning interventions as the data accumulates as to their benefit or lack thereof. I have been in medicine for 30 years and the old saw that half of what you learn in medical school will be proven wrong is off by a log. So much of what I used to do has either been abandoned or superseded as new clinical trials and diagnostics have become available.

This is the opposite of pseudo-medicine. No therapy is ever abandoned as a result of the accumulation of negative clinical studies. Pseudo-medicines do change, but usually the unholy merging of two different pseudo-medicines to give a third, say, laser acupuncture or chiropractic nose balloons. But there is little reason from a practical point of view in doing pseudo-medical research as practice will never, ever, never change as a result of research. They are reality-proof endeavors. The end result of 30 years of negative or inconclusive pseudo-medical research is the growth of Integrative Medicine divisions in all the major universities.

The ethics of SCAM research

Let’s talk instead about the ethics of research. Clinical trials have to be approved by an IRB, and usually these IRBs are often at the institution where the research is being performed. Perhaps it is not for the best that your friends and colleagues are the ones to determine if a given SCAM clinical trial is actually appropriate. I would be willing to bet the average person sitting on an IRB has as much understanding and background about pseudo-medicines that I did 10 years ago: almost nothing.

The purpose of an IRB:

…is to assure, both in advance and by periodic review, that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in the research. To accomplish this purpose, IRBs use a group process to review research protocols and related materials (e.g., informed consent documents and investigator brochures) to ensure protection of the rights and welfare of human subjects of research.

And it is important that they:

Safeguard the rights, safety, and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects, such as pregnant women, children, prisoners, the elderly, or persons with diminished comprehension.

The IRB should, I suspect, follow the NIH ethical guidelines. Although guidelines are not commandments, they do form a conceptual framework to guide the evaluation of a clinical trial:

Social and clinical value

Every research study is designed to answer a specific question. Answering certain questions will have significant value for society or for present or future patients with a particular illness. An answer to the research question should be important or valuable enough to justify asking people to accept some risk or inconvenience for others. In other words, answers to the research question should contribute to scientific understanding of health or improve our ways of preventing, treating, or caring for people with a given disease. Only if society will gain useful knowledge — which requires sharing results, both negative and positive — can exposing human subjects to the risk and burden of research be justified.

Scientific validity

A study should be designed in a way that will get an understandable answer to the valuable research question. This includes considering whether the question researchers are asking is answerable, whether the research methods are valid and feasible, and whether the study is designed with a clear scientific objective and using accepted principles, methods, and reliable practices…Invalid research is unethical because it is a waste of resources and exposes people to risk for no purpose.

Favorable risk-benefit ratio

Uncertainty about the degree of risks and benefits associated with a drug, device, or procedure being tested is inherent in clinical research — otherwise there would be little point to doing the research. And by definition, there is more uncertainty about risks and benefits in early-phase research than in later research. Depending on the particulars of a study, research risks might be trivial or serious, might cause transient discomfort or long-term changes. Risks can be physical (death, disability, infection), psychological (depression, anxiety), economic (job loss), or social (for example, discrimination or stigma from participating in a certain trial). Has everything been done to minimize the risks and inconvenience to research subjects, to maximize the potential benefits, and to determine that the potential benefits to individuals and society are proportionate to, or outweigh, the risks? Research volunteers often receive some health services and benefits in the course of participating, yet the purpose of clinical research is not to provide health services.

Independent review

To minimize potential conflicts of interest and make sure a study is ethically acceptable before it even starts, an independent review panel with no vested interest in the particular study should review the proposal and ask important questions, including: Are those conducting the trial sufficiently free of bias? Is the study doing all it can to protect research volunteers? Has the trial been ethically designed and is the risk–benefit ratio favorable? In the United States, independent evaluation of research projects is done through granting agencies, local institutional review boards (IRBs), and data and safety monitoring boards. These groups also monitor a study while it is ongoing.

Informed consent

For research to be ethical, most agree that individuals should make their own decision about whether they want to participate or continue participating in research. This is done through a process of informed consent in which individuals (1) are accurately informed of the purpose, methods, risks, benefits, and alternatives to the research, (2) understand this information and how it relates to their own clinical situation or interests, and (3) make a voluntary decision about whether to participate.

There are exceptions to the need for informed consent from the individual — for example, in the case of a child, of an adult with severe Alzheimer’s, of an adult unconscious by head trauma, or of someone with limited mental capacity. Ensuring that the individual’s research participation is consistent with his or her values and interests usually entails empowering a proxy decision maker to decide about participation, usually based on what research decision the subject would have made, if doing so were possible.

To my mind almost all studies of pseudo-medicines like acupuncture, homeopathy, chiropractic, reiki etc. all fail first with scientific validity. Research with these modalities are the poster child for being “invalid research [that] is unethical because it is a waste of resources and exposes people to risk for no purpose.”

The ethics of dividing by zero

And clinical trials for pseudo-medicine fail to “gain useful knowledge” as well as a risk/benefit that has no meaning. Can’t divide by zero after all.

What amazes me is the perfect storm of pseudo-medicine testing in vulnerable populations, where the IRBs have failed in all ethical aspects of clinical trials.

Homeopathy is water. I cannot imagine how it could be ethical to test water for any process in children. I can’t understand how an IRB that understood homeopathy could approve a study in at risk populations.

But there are no end of homeopathy studies in children:

A total of 326 articles were identified, 91 of which were retrieved for detailed evaluation. Sixteen trials that assessed 9 different conditions were included in the study. With the exception of attention-deficit/hyperactivity disorder and acute childhood diarrhea (each tested in 3 trials), no condition was assessed in more than 2 double-blind randomized clinical trials. The evidence for attention-deficit/hyperactivity disorder and acute childhood diarrhea is mixed, showing both positive and negative results for their respective main outcome measures. For adenoid vegetation, asthma, and upper respiratory tract infection each, 2 trials are available that suggest no difference compared with placebo. For 4 conditions, only single trials are available.

And there shouldn’t be even one.

The University of Toronto (yes, that University of Toronto) wants to test homeopathy in ADHD children even though a prior pilot study was:

…unblinded, devoid of randomization, had no control group and relied on a subjective outcome, making any data derived from it essentially meaningless.

A good basis for experimenting on children. Ignoring the question of why such a study would be done in the first place, how does such a study even meet bare ethical requirements for performing a study? Maybe Canadians have a different set of ethical standards.

SCAM ethics around the world

Not that researchers around the world are any better. There are a half-dozen studies evaluating acupuncture for tonsillectomy pain in children, and studies in children for acute appendicitis. And there are trials of acupuncture in dementia patients and coma patients. And theraputic touch for the demented. And no end of chiropractic in children, from asthma to bedwetting, with all its downsides.

To my way of thinking, the most egregious abuse of at-risk populations were the trials of homeopathy for diarrhea in Nepal, Honduras, and Nicaragua. Truly vulnerable and impoverished populations who desperately need real medications have the magic that is homeopathy inflicted on them with the approval of IRBs. The gaster is flabbered.

The NCCIH evidently has an ethics counselor. As best I can determine, she has no publications on either PubMed or the NCCIH site. And I can find no discussion on the ethics of pseudo-medicinal research on the NCCIH website. Why am I not surprised?

Children, the demented and the comatose. So much for protecting at risk populations.

The paving stones to Hell, and IRBs

How do these studies get past IRBs in this century? I suspect I know the answer. I would bet that like so much SCAM treatment, the believers make a compelling argument while those on the IRB take them at their word, knowing little about the interventions and trusting to the good intentions of the researchers. And as I have recently discovered:

The opposite of good is not evil. The opposite of good is good intentions.

– Kurt Tucholsky

The PubMeds find discussions both ways: those who have no issues with the ethics of SCAM and those who find the use problematic at best. These references concern the use of pseudo-medicines, but if there are discussions concerning the ethics of CAM research, I can’t find them.

I do not see how to hold IRBs accountable for approving studies on magic. Maybe they should read their mission statement and apply it. It remains one of the conundrums of modern medicine. There are no astrologers publishing in astronomy journals or alchemists in the chemistry journals, but the study of magic continues apace in medicine with no signs of slowing down, ethical or not.

But time for a bike ride then a hike in the Sisters.

 

 

Posted by Mark Crislip

Mark Crislip, MD has been a practicing Infectious Disease specialist in Portland, Oregon, since 1990. He is a founder and  the President of the Society for Science-Based Medicine where he blogs under the name sbmsdictator. He has been voted a US News and World Report best US doctor, best ID doctor in Portland Magazine multiple times, has multiple teaching awards and, most importantly,  the ‘Attending Most Likely To Tell It Like It Is’ by the medical residents at his hospital. His growing multi-media empire can be found at edgydoc.com.