"Rituximab in CFS: More research needed" letter in PlosOne

[redo]

Another point it might be worth mentioning on that thread. Anyway, I should probably stop making such suggestions. I'm just trying to point out that people can comment directly if they want.

I hope they will find out why the reaction was like this, but i guess this is also a point against a placebo effect having caused the observed results. I don't think there's a 6 to 10 months delayed placebo effect.

I hope you'll weigh in there Eric.

Combined with the fact, already mentioned here, that symptoms during and after infusion was pretty much similar in both groups, and that "All patients were given oral cetirizine 10 mg, paracetamol 1 g, and dexamethasone 8 mg prior to infusion." really indicates patients had no idea. The fact that all patients where given such a cortisol dose would really indicate that the placebo patients could just as easily have felt "something" during the infusion. The Rituximab doesn't do anything until long after the infusion anyway (even in RA and other syndromes), unless there's an infusion related emergency (of which there wasn't in the study).

 

[Sing]

I'll tell you why I got so seriously p*ssed off at the first response in PLoS One. I've been reading scientific literature regularly for over ten years.

The first sentence immediately sets the tone :
"The finding of Fluge et al [1] that B lymphocyte depletion the anti-CD20 monoclonal antibody, Rituximab (RTX) has beneficial effects in patients with chronic fatigue syndrome is astonishing, particularly since they do not present any theoretical justification for using RTX beyond a very small case series."

Note the word "astonishing". This is not meant to mean "very surprising but interesting", which is what you might think if you hadn't studied a bit of discourse analysis ( I have ). The word "astonishing" here is to raise an immediate red flag to other researchers. It's intended to mean something along the lines of "something grossly abnormal which shouldn't have happened and is probably a mistake". It's code to other researchers : "this should not have happened and must be some kind of error". They could have used the word "surprising" which would have been both accurate and less of a flag-waver to readers. If they wanted to praise this study they would have called it "elegant" or one of the other 'praise' favourites which crop up in a concordance analysis. I was going to do one of my degree projects on research discourse but ended up doing something else. I could now bore you with examples of the excessively negative tone of most of their comments but I hope you can see it for yourself ( it's fine to raise methodological issues - it's the language being used ).

Actually this kind of stuff can become quite amusing. Scientists abhor emotional language. When things get heated they can go to substantial lengths not to show emotion but still give their opponent an intellectual slap, as it were. Handbags at dawn.

And I would say that a fairly hefty intellectual slap is being administered by Jonathan Edwards' response on the PLoS website ( as pointed out by Roy in post #11 ). Excellent stuff.

Frankly I think a bunch of Psychiatrists talking down ( oh yes they are ) to a couple of Oncologists is faintly ridiculous. Science, anyone ? There's a bunch more of the hardcore stuff in Oncology compared to Psychiatry. ( Not a fan of Psychiatry - studied Psychology for a year at university so not a complete layman. Too much guesswork, not enough data. Wait a minute, I knew there was a reason the Psychs stick to CFS like limpets...Too much guesswork, not enough data.....Hmmmm).

There are certainly some legitimate points contained in that first response but don't be fooled about where those people are coming from - it shows in their language. I would suggest that they try doing some proper science instead of meddling in a field where their negative contibutions have substantially outweighed their positive ones.

Oh, no ! I got my handbag out ! Perhaps I should just have told them to f**k off.

KFG, you are too funny! "Scientists abhor emotional language. When things get heated they can go to substantial lengths not to show emotion but still give their opponent an intellectual slap, as it were. Handbags at dawn."

I noticed that "astonishing" too immediately. It is a snobbish British type of put down..."And the Princesses Eugenie and Beatrice appeared in the most astonishing hats!"

I share your view of psychiatrists. They are constantly looking for someone else's business to mind, to take over, actually (another British snobbism). This makes them feel important and useful, which they are not.

Sing

 

[Dolphin]

I thought I'd point out, in case anyone posted anywhere, that none of these authors are psychiatrists.

I think this might be a deliberate thing: I wouldn't at all be surprised if Peter White was involved. For example, he co-wrote a letter with Alastair Miller (one of the authors) to the BMJ during the summer complaining about the Canadian criteria (sounded like the sort of letter Peter White wrote); he was the lead author of a letter to Science when XMRV first came out - and Andrew Lloyd and Dedra Buchwald were co-authors. He is also based in Barts and is doing research on CFS with Matthew Buckland; he and Van der Meer co-wrote:

Psychother Psychosom. 2007;76(3):171-6.
Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome?
Knoop H, Bleijenberg G, Gielissen MF, van der Meer JW, White PD.

and Brian Argus was one of the people who praised the PACE Trial in a press release when it came out (along with Alastair Miller) (see below).

Peter White is very inclined to write letters in recent years - not alone to medical journals, but also newspapers, sometimes even to the letters pages of patient organisations.

Anyway, who knows what happened. Van der Meer, Buchwald and Lloyd all wrote in letters when XMRV came out in Science trying to pour cold water on the theory. I don't know much about Buckland (White's colleague) but all the others are into CBT/GET (not sure the extent of this with Buchwald). Anyway, it is interesting to see the willingness of some to pour cold water on research that may lead to drug treatment.

--------
Alastair Miller and Brian Argus on the PACE Trial:

http://www.sciencemediacentre.org/pages/press_releases/11-02-17_cfsme_trial.htm

Dr Alastair Miller, Consultant Physician at Royal Liverpool University Hospital, Clinical lead for CFS services in Liverpool, Independent assessor of trial safety data for PACE trial and Principal Medical Advisor, Action for ME, said:

"Although NICE have previously recommended graded exercise and CBT as treatments for ME/CFS, this was on the basis of somewhat limited evidence in the form of fairly small clinical trials. This trial represents the highest grade of clinical evidence a large randomized clinical trial, carefully designed, rigorously conducted and scrupulously analysed and reported. It provides convincing evidence that GET and CBT are safe and effective and should be widely available for our patients with CFS/ME.

"It is clearly vital to continue our research into biological mechanisms for ME/CFS but recent 'false dawns' for example, over the role of retroviruses (XMRV) have shown how difficult this can be. In the current absence of a biomedical model for the causation and the absence of any pharmacological intervention, we have a pragmatic approach to therapy that works and we should use it."

Dr Brian John Angus, Clinical Tutor in Medicine and Honorary Consultant Physician, University of Oxford and Centre Leader for the PACE Trial in Oxford, said:

"This study is the largest ever done in CFS/ME and as such is critically important. The study should reassure patients that there is an evidence based treatment that can help them to get better and there is no need to worry about harm from the treatment. The other significant result is that looking at different ways of classifying the condition through different diagnostic criteria do not make any difference to the effect of treatments.

"We do not know what the underlying cause of CFS/ME is. There is ongoing research to find the cause, and I have been involved with this, but none of these studies has shown any consistent evidence of cause never mind any rationale for treatment. However in the meantime I see many patients in my clinic who need help with their fatigue. This was a pragmatic trial to help patients while there is no other treatment available.

"It was extremely rigorous. It was large and it was randomised. The study was carefully conducted in the manner of a drug intervention study to not only establish the superiority of one treatment over the other but also to carefully report any side effects or harm from those treatments. Since the treatments were therapies and not drugs stringent efforts were made to ensure the 'purity' of each treatment and to rapidly report any adverse effects. As a trial this involved a huge amount of checking and cross checking.

"This should mean that GET and CBT should be widely available throughout the country. Despite NICE recommendations I still see patients who are unable to access any treatment for their CFS/ME in their local GP area. Travelling is obviously difficult for patients with CFS/ME. The increase in the availability of CBT therapists for other conditions should be mirrored for CFS/ME.

"The trial was conducted to a high ethical standard. Patients were fully informed and randomised to the different treatments. It was rigorously performed. The study has definitively shown that there is no harm associated with GET."

 

[justinreilly]

thanks to everyone for posting good comments! I posted:

van der Meer still promoting the thoroughly discredited psychogenic theory of ME

justinreilly replied to JohnM on 30 Oct 2011 at 03:54 GMT

I agree with JohnM, Ms. Clout, Mr. Miller, Prof. Edwards and Mr. Kindlon, supra.

As JohnM notes, the authors including Prof. van der Meer claim to be 'astonished' that Rituximab could be effective against ME since he has long pushed the thoroughly discredited psychogenic/somatization theory of ME.

In the recently published Harrison's Internal Medicine [1], van der Meer paints ME as having proven psychological components and relatively unproven organic components.

For example, they claim that "a direct microbial causation is unproven and unlikely." And that CBT and GET are the only proven treatments while acyclovir and many others have been proven ineffective. And so on. All these statements are directly contra to the published science.

It seems here that here, as usual, he and his colleagues have their facts wrong, as noted by Prof. Edwards et al.


[1] Harrison's Principles of Internal Medicine: Volumes 1 and 2, 18th Edition; Fauci et al., McGraw-Hill Professional, (July 21, 2011), ISBN-10: 007174889X

 

[Dolphin]

Thanks KFG. No problem.

Some doctors can change into different "creatures" when talking about/dealing with CFS.

 

[Holmsey]

Between the lines

Glad Im not the only one reading the spaces and not the words, I was somewhat taken aback by the first few posts which appeared overly generous to the authors of this letter.
Myself, I was so angry after reading it late Friday last that I pretty much lost a nights sleep pouring over what it really meant.
As pointed out it pretty much sets out as a high brow trashing of the study just by calling it astonishing. But it goes way beyond that, it suggests that Mella and Fluge were taken in by a cohort who immediately realised which test group they were in and planned around that to deliberately deceive them. Stupid scientists, if only theyd brought on board some of those Psychologists who have our number.
But planned what? Well its obvious isnt it, because were all so conspiratorial and desperate to remove the psychological label at any cost we colluded to show that Rituximub can cure us, not in the slightest put off by the fact it can in extreme cases kill, were obviously all out to fool then into thinking its going to make us better? Obviously Mella and Fluge have no idea how committed we are to this cause when two of our number continue to selflessly feign wellness to this day just to keep them off the scent.
And almost as if to prove just how twisted we are we instructed the whole cohort to report feeling better not straight away but months later, at a point in time which would keep the mystery upon which weve built our illness well and truly alive, again back footing not only Mella and Fluge but even the authors of this letter who will no doubt be racking their brains right now trying to figure out just what were all up to this time.

Of course theres always the possibility everyone is just telling the truth, and that maybe one or two of those who felt better only months later almost reluctantly mentioned it for fear of being doubted again, while wishing it had happened earlier in the study when it would have made more sense.
But thats just me being fiendishly cleaver again, keep them guessing troops it wont be long before we have the psychiatrists needing psychiatry.

 

[urbantravels]

Some doctors can change into different "creatures" when talking about/dealing with CFS.

It's because we're not just sick people; we're scapegoats.

 

[SilverbladeTE]

It's because we're not just sick people; we're scapegoats.

It's because were the current...black, Jew, Moslem, Christian, rich, poor, untouchable or whatever scapegoat for weakminded, bigotted incompetant SOBs in the medical profession:
slap someone into the "untermensch" box, and thus, you are superior and can do ANY damn thing you like ot them because you are superior and they are weaklings, deserving of your sadism!
Blech :/

it's the ugly reality many simple won't accept. See contemptous way ME patients have been described, never mind TORTURED etc.

if this happened ot ANY other group the psychobabblers would be in JAIL, not merely out of a job, and that is a *fact*

Replace "ME/CFS" for any other group in their bigotted speech, and think about it...?

You have two choices: they are mentally disturbed or cold bloodedly, deliberately evil.

 

[paddygirl]

There is a post in Plos One from the Ass. Editor admonishing people for inappropriate comments and reminding them of the forum rules.

I can't for the life of me see anything wrong with them, except of course for the not so subtle Van der Meer put downs.

One thing that always strikes me about those who look to help us, and for once it's something that works in our favour. The abuse, subtle or not, heaped on anyone who steps up to seek genuine answers for us makes for fierce advocates.

Mella and Fluge for example, working in well respected relative anonymity. They find a thread of hope that must be followed, not to do so would almost be a crime. What happens? The knives are out and these researchers get a taste of what is flung at us.

Not too smart of the other lot, as it makes very committed friends for us.

 

[Dolphin]

BTW, Brian Argus' name is on the PACE Trial paper (Lancet).