A variable placebo response has been previously described in the multiple sclerosis (MS) literature and in sham surgical trials involving other patient populations. Conditioning and expectancy models are proposed to explain the biological mechanisms of a placebo response. Possibly, when neuroimmune mechanisms are involved in the disease process, placebo and treatment responses interact. The measurement of a placebo response related to endovascular procedures in MS may be scientifically and ethically challenging. Based on the factors associated with larger placebo responses, it is estimated that a significant placebo response may be associated with these procedures. The factors and mechanisms associated with marked placebo responses should be considered in the design of future studies related to the investigation of endovascular procedures for MS.
The placebo effect reduces the disease element by 15-45% in many studies. This study discusses the placebo effect in relation to CCSVI. Based on talking to some CCSVIers it may be difficult too truly blind studies as one can feel the balloon inflate, and so it makes it more likely that a placebo effect will occur. We shall see when the trial data comes in.
Other posts of interest:
Multiple Sclerosis Research: What is the placebo effect? 10 Oct 2011; A placebo is a sham or simulated medical intervention. Sometimes patients given a placebo treatment will have a perceived or actual improvement in a medical condition, this phenomenon is called the placebo effect.
Multiple Sclerosis Research: Survey results: placebo effect 03 Nov 2011; “I am surprised by this result; this means that the respondents of this survey accept that the placebo effect can explain the perceived benefits of unlicensed therapies.” “This is exactly the reason why we (clinical scientists) need …
Multiple Sclerosis Research: New survey: the placebo effect 13 Oct 2011; Re: “Prof G, what would be your answer to this question:Do you think the placebo effect accounts for all the self-reported benefits of open-label or non-blinded therapies?” I would say possibly; the point I am trying to make is …
Re: "Based on talking to some CCSVIers it may be difficult too truly blind studies as one can feel the balloon inflate"
A few years back, Dr. Rubin (a vascular surgeon in Canada and a member of CHIR) did a presentation on CCSVI. He mentioned that you can't feel anything inside your veins since there are no nerves there. Is this correct?
Re: "He mentioned that you can't feel anything inside your veins since there are no nerves there. Is this correct?"
This is incorrect; all blood vessels are innervated with nerves and some of these are pain fibres. In fact one of the animal models for headache involves stimulating the lining of the venous sinuses with electrical shocks to cause pain.
How would you react to this piece?
http://www.psychologytoday.com/blog/prefrontal-nudity/201201/in-defense-placebos
Thanks for the clarification, Prof G. I may have misunderstood what Dr. Rubin was stating in his presentation. Anyway, in "Bad Science",Ben Goldacre wrote about a sham surgery that involved using a fancy laser catheter to do "angioplasties" (I guess they inserted the catheter but didn't turn on the laser), with results that were as positive as those who had the real angioplasties done. Can't the same methodology be employed with CCSVI trials? Would it be unethical to put all trial participants completely under and give some of them the sham surgery while another group gets the full procedure? Also, isn't the trend now to determine if an experimental treatment is better than the best treatment currently available, rather than if it performs better than a placebo? Of course, the issue here is what symptoms angioplasty is supposedly an effective treatment for. From what I’ve read, the symptoms supposedly alleviated vary from person to person.
As for the Psychology Today" article, it's unethical for doctors to lie to their patients about their treatments since it violates the principle of non-malfeasance (aka "First, do no harm"). And angioplasty doesn’t have the same safety profile as a sugar pill. There are complications with the surgery, hence the need to determine if there's any benefit to subject MSers to the risks.
Re: "In "Bad Science",Ben Goldacre wrote about a sham surgery that involved using a fancy laser catheter to do "angioplasties" (I guess they inserted the catheter but didn't turn on the laser), with results that were as positive as those who had the real angioplasties done. Can't the same methodology be employed with CCSVI trials?"
Yes; they could blow up the balloon in an irrelevant part of the vein, i.e. an area that has no stenosis or narrowing vs. an area of stenosis/narrowing. The wholw point is to randomise subjects to get rid of any potential confounders and only focus on what is relevant.
"Would it be unethical to put all trial participants completely under and give some of them the sham surgery while another group gets the full procedure?"
No, provided you get informed consent, i.e. subjects knew what they were signing up to. Provided we have equipoise, i.e. we don't know whether or not opening the stenoses would help this is not unethical.
The problem I have is more fundamental than this. The problem at the moment is detecting these stenoses. From the latest studies they appear to be rarer than previously reported and non-specific, i.e. found in control subjects. Therefore they may be unrelated to MS.
Re: "Also, isn't the trend now to determine if an experimental treatment is better than the best treatment currently available, rather than if it performs better than a placebo?"
This only applies if we have a licensed treatment. In relation to CCSVI we don't, hence the recent FDA statement.
"As for the Psychology Today" article, it's unethical for doctors to lie to their patients about their treatments since it violates the principle of non-malfeasance (aka "First, do no harm")."
I would not propose lying to the patients. I would propose doing the study under informed consent.
"And angioplasty doesn’t have the same safety profile as a sugar pill. There are complications with the surgery, hence the need to determine if there's any benefit to subject MSers to the risks."
Yep, angioplasty is not a safe procedure. We know what the risks are already from other studies. Participants of a study will be told about this risks and they would have to sign-up them whether or not they had sham or real angioplasty.
The Psychology Today article does not say doctors should lie to patients.
It is suggesting that patients could lie to themselves and take advantage of the placebo effect to feel better
"This is incorrect;"
"stimulating the lining of the venous sinuses "
If you ever had venography you would feel the difference between having a roadmap catheter insinde a vein and inside a venous sinus. In the first case you feel absolutely nothing, but in the second there is an extremely uneasy feeling. The reason, as you know, is that venous sinuses are not exactly veins, but more like engraved venous paths inside the skull. They retain their diameter irrespective of the blood volume inside them, unlike veins.
It's a whole different case when a balloon is inflated inside a vein. You certainly FEEL that but in more ways than you can imagine. There is a pressure feeling, sometimes pain, and sometimes a sense of hypertension, since an inflated balloon inside a jugular vein completely blocks the outgoing blood flow. Just imagine having the contralateral jugular vein also blocked by a valvular stenosis…
Re: "There is a pressure feeling, sometimes pain, and sometimes a sense of hypertension, since an inflated balloon inside a jugular vein completely blocks the outgoing blood flow."
This proves the point that veins are innervated by nerve endings; to perceive pain you need pain fibres. The point about venous sinuses is that the lining of the sinuses is the same as veins and hence are also innervated with pain detectors.