MS Journal: use of placebo unethical

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MS Journal: use of placebo unethical

Postby Cece » Tue May 08, 2012 10:29 am

Improvement needed in Multiple Sclerosis drug trials

Randomised controlled trials of multiple sclerosis drugs have consistently improved since the first positive result in 1993, but more transparent methodology is required as trials enter a “new era”, experts argue.

After analysing the methodology of 53 eligible RCTs that took place in the eighteen years up to 2010, the Italian trio note a steady rise in quality – mainly down to “many journals having statistical refereeing and clearer guidelines to authors.”

But with the clinical scenario in MS changing “rapidly” as trials become increasingly benign, certain questionable practices need closer scrutiny, the authors say.

“The advent of new therapies has made the use of placebo unethical, at least in trials lasting more than six months,” they write in Multiple Sclerosis Journal.

Despite general improvements there also remain problems with the use of significance tests for detecting baseline differences.

Occurring in about half of the trials analysed, the authors argue its use is null since randomisation guarantees that any baseline differences are due to chance.

A more significant practice would be to provide information on whether baseline factors are associated with outcome. This, however, is rare.

As well, there are enduring problems with subgroup analysis.

Interaction tests, used to assess the heterogeneity of treatment effect across different subgroups, are the “correct approach” but remain underused.

Smaller trials are often underpowered to use such tests effectively, say the authors, who argue for companies to work together and pool collective analyses – something they habitually avoid out of a reluctance to share information.

It is up to journals, so instrumental in boosting methodological quality to date, to encourage pooled analysis, they conclude.

Multiple Sclerosis Journal, 2012; doi:10.1177/1352458512444327

Source: Neurology Update (01/05/12)
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Re: MS Journal: use of placebo unethical

Postby 1eye » Tue May 08, 2012 1:18 pm

I have agreed with this a long time, even though I have been in a 2-year RCT (which, including wash-out for 6 months and a delay after the wash-out, was really 3 years). The drug didn't work, and the trial made people cry because they were having disease activity, and didn't know if they were on placebo or not. They wouldn't quit the trial because they thought there was no other hope. I was on placebo, and I suspected that from the first saline infusion. If I hadn't been "SP" before the trial, I certainly was when it was un-blinded. By then I was in a wheelchair. I was treated with cortisone for a relapse, during the trial. But still I could not be "Relapsing-Remitting". I think the subtypes are a matter of convenience, and not to patients.

Baselining should be much more prevalent in clinical treatment of a disease that is not understood, particularly when starting or changing drug therapy. When I was on Rebif, my GP tested my liver enzymes and found them high. I could not point to a baseline test to be sure the Rebif was causing it. I have not seen much testing, beyond what is necessary to get FDA approval to sell something new to "RR" patients. I have always thought that if the disease were being fundamentally "modified", my foot paralysis, and other symptoms, would still be affected by treatment, even during or after a change of subgroup. I think it is too easy to just blindly recite the mantra that these drugs won't help you anymore. You are faced with the same Catch-22 that you faced when you were called "RR". How much worse will I be if I don't take it? They can't tell you that, either, but they won't give it to you anymore, so it becomes moot.
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MS Journal Abstract: use of placebo unethical

Postby MarkW » Mon May 14, 2012 4:40 am

Here is the abstract and access to the whole paper for some. MarkW

http://msj.sagepub.com/content/early/20 ... ract?rss=1
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: MS Journal: use of placebo unethical

Postby Cece » Mon May 14, 2012 8:14 am

Unfortunately the argument against placebo is that it denies the patient the currently available drug treatments. In CCSVI trials, the patients are allowed to continue on their drug treatments, as venoplasty is being tested as adjunctive to the drugs and not instead of drugs. This could be confounding. It might be better to test ccsvi venoplasty on patients who are not on DMDs, if such patients were available. The researchers who are putting together trial designs of CCSVI do not have an easy task. (But an important one.)

Thanks for the link.
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Re: MS Journal: use of placebo unethical

Postby masci » Mon May 14, 2012 11:11 am

Cece, I completely agree with you. I already wrote that Brave Dreams should have an additional control group consisting of patients without medication.
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Re: MS Journal: use of placebo unethical

Postby 1eye » Tue May 15, 2012 12:44 pm

If you ran a trial where the exclusion criteria contained "RRMS"; i.e., a trial which included only the leftovers who have "converted" to SPMS, plus the "PPMS" people, I think you could absolutely prove efficacy, with placebo, in the absence of any DMDs. These people are denied by doctors and insurance companies access to DMDs. There should be no denial of a proven treatment for the people with no other option! That trial should be among the first. This treatment has a less reliable and less significant effect on that collection of people, according to the stats, but people who are suffering are not just stats.
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