SBM: Kogelnik, Rituximab and CFS: Jumping the gun

[Valentijn]

You appear to be arguing for a legal process that only recognises actus rea and denies any role for mens rea (yes motive isn’t precisely mens rea but ‘motive’ is how the defence frequently approaches the issue of mens rea).

Mens rea is a completely separate concept - it's merely intent to do the action, not a motive. That is, the criminal deliberately punched the victim, rather than accidentally hitting them in the face while trying to put out a fire - there is no requirement that we know why the crime was committed, only (usually) that it was deliberate. Do you really want to argue legal technicalities with a lawyer, even a very sick one?

Not being able to show ‘why’ in science raises the bar for how much more relevant is the ‘how’.

I think "how" has already been somewhat established in the case of Rituximab - by depleting B-cells. And again, that is far more than drug companies are required to show. The FDA and other drug approval bodies have little interest in "why" OR "how", so long as the "what" is satisfactory.

On what basis is probability of safety in M.E/CFS to be derived from safety in Cancer ? Which cancer ?, which demographic ?

More broadly I would argue that the safety of Rituximab use in ME/CFS is derived from the safety of its use in human beings. Cancer patients do not have major differences in general physiological functions compared to ME patients, hence there is no reason to assume that ME patients will spontaneously combust when taking the same drugs that do not cause cancer patients to spontaneously combust.

And safety isn’t the only issue – risk/benefit judgements require some appreciation of the probability of potential outcomes. For example a mild improvement in 1 in a 100 patients, matched against possible permanent impairment would probably put most patients off a particular intervention. The Mella and Fluge study, just isn’t adequate to guide patients in terms of risk/benefit.

Preliminary studies on effectiveness indicate improvements are far more impressive than "mild" and in significant majority of patients. Benefit is thus far looking relatively high at least in the short term, while risk, as established in extensive studies with other diseases, is relatively minimal.

Yes ‘open label’ studies of Rituximab in different auto-immune disorders present some interesting data http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002645/ but participant numbers are low and levels of impairment are often profound.

And our levels of impairment aren't profound? I doubt there's a lot of ME/CFS patients at 80% functionality eager to try Rituximab at this point. From what I have read, and based on the studies thus far, the ME patients seeking treatment are severely impaired - unable to work and struggling to get out of the house or do basic household tasks.

And the risks are ? All that can be talked about are ‘known’ risks, and as none of the prescribing doctors have published a protocol it’s impossible to know what discussion of known risks is taking place. More concerning still are the levels of monitoring and co-operation with primary care providers, given how poor the PC support for M.E/CFS patients is, and at least in the case of Kogelnik patients are travelling significant distances monitoring during treatment seems likely to be problematic.

Known risks have been established in cancer studies, and the small trials done thus far haven't indicated additional risks. When a drug is prescribed, the FDA has a nice leaflet with it listing the side effects and their frequencies. So that gets to conveyed to the patient just like it does for every other drug. In the case of Rituximab, there's an increased chance of infection - something like 15% higher than the odds for controls.

I think it's improper of you to presume doctor misconduct in absence of any evidence, especially while naming a specific doctor. There is no indication that Dr Kogelnik or others are not keeping close tabs on their patients. I take a medication prescribed (so far) from a considerable distance, and my GP does not feel qualified to handle it, but it is very easy for me to email or Skype the prescribing doctor to discuss things. If side-effects do arise requiring emergency treatment, it is highly likely that the local hospital would be able to provide appropriate treatment for those side-effects.

 

[Research 1st]

IVI

Claims of dangerous 'safety' barries being breached by assumed rogue physicians for trying out licensed FDA approved drugs for CFS, are unfounded. Dr Nancy Klimas recently reminded us all (in a letter supporting Ampligen), drugs were given for MS before any established MS biomarker was in use.

Perhaps it irritates you that Americans don't have a British Big Brother BMA/GMC to stop them engaging in pioneering research that doesn't involve CBT and other psycho rehabilitation tools?

As much as it may pain some people in this world who desperately cling onto the faulty illness belief that 'CFS/ME' cannot possibly contain people who are suffering from untreated neuroinflammatory disease, drug trials will be funded, even if if they are to be funded by charitable donation and even if this takes years. There is nothing anyone can do to stop this happening. It is an inevitability. The more CFS ME patients are educated on the biomedical nature of this disease, the more they demand change.

This is precisely why you may find detractors of this change gaining ground appearing on the internet on CFS patients forums. People who are hell bent on allowing change to happen by spreading doubt and disinformation to try and keep patients minds contained within the status quo, often by using pleas to authority.

To evoke change, requires a strong will. Change with 'CFS' will happen sooner than some think. Too many people know, without the Internet this never would have happened. This is another reason why the author of the PACE trial (Psychiatrist Peter White) tells physicians in his presentations that belonging to a self help group worsens outcomes in 'CFS'.

What a strange situation this all is, that when the worlds first ever drug for CFS/ME is shown to have a significant effect on treating CFS symptoms (without any psychological intervention) that some slam a pioneering physician in the US brave enough to try and help CFS patients with their chronic immune disease.

However, CFS/ME contains a disease I should add that doesn't respond to psychotherapy at all (as demonstrated by the UK PACE trial), but impressively does respond to immunological drugs. (NB: None of the PACE trial participants had CFS, they had 'chronic fatigue', included the mentally ill, and excluded the neurologically ill). Hence the PACE trial failed. Imagine how worse the PACE trial would have fared if the patient cohort had contained severe grade CFS, housebound, with neurological evidence of CNS dysfunction using a TILT test!

The response rate in CFS patients in the Norwegian Rituximab paper was in line with other response rates noted in autoimmune illnesses, about 2/3 response rates. The response rate also far outweighed the placebo effect. The result, was thus spectacular as no biomarker was present at the time to 'select' patients as having a distinct immune illness. It will be in the future. And thus response rates will improve once researchers can select, immunologically, who ill be a responder.

It looks like within a few years, the 'CBT and exercise' therapies touted by psychiatrists will be exposed as medical fraud. Consequently, those selling 'CBT' to people with potentially fatal neuroimmune illnesses (such as ME) will be sued by patients for subsequent psychological damage because they were coerced or bullied to engage with these therapies, ironically.

I predict the first in line to sue for damages for inappropriate therapy promotion of CBT and exercise in CFS/ME will be Americans, and then me.

God bless America.

 

[orion]

Casting the argument in terms of 'patient's rights' is perverse, the right to purchase may exist but that doesn't obviate the duty of physicians to ensure patients are able to make informed choices and to take reasonable steps to ensure that treatment delivery is based on more than partial science and leaps of faith.

IVI

You're totally wrong. The "right to purchase" does not exist, at least not from a patient's perspective. In most parts of the developed world draconian laws have been put in place to prevent patients from obtaining most medications without a doctor's prescription. Far from being perverse, patient's rights are actually at the very heart of this issue.

That being said, the right to purchase is slowly becoming a de facto right thanks to the rise of internet based pharmacies. Once again the internet comes to our rescue. But we're not there yet. Many prescription drugs (probably the majority) are still not available via that route, and ordering drugs online from abroad obviously carries many additional risks.

I have never met Dr Kogelnik and I have no idea whether he is an ethical doctor or not. I also have no idea whether he is motivated by a genuine desire to help patients, or whether he just wants to make lots of money. And you know what, I don't really care. If he's a good doctor then that's obviously a big bonus. But it's by no means essential.

The reality is that most patients who want to try drugs off-label have no choice but to go though doctors like Dr Kogelnik, and for that reason alone I think he should be strongly supported regardless of his (alleged) motivation.

The only thing I find perverse is your apparent support for a system that forces seriously sick people to travel half way around the world to see a (probably very expensive) doctor they don't know, just to obtain the type of treatment they want.

 

[Living Dead]

By jumping the gun he is putting patients at risk; exposing them to considerable cost, discomfort, and inconvenience;

It's always confusing to me how some people assume that simply a risk of problems, discomfort and inconvenience is so much worse than being 100% sure one actually gets those things - no guessing involved.

 

[SOC]

It's always confusing to me how some people assume that simply a risk of problems, discomfort and inconvenience is so much worse than being 100% sure one actually gets those things - no guessing involved.

Agreed. I mean, seriously, "discomfort, and inconvenience"? I'd give my eyeteeth to only be dealing with discomfort and inconvenience. And considering it's only the risk of discomfort and inconvenience, it's a no-brainer as far as I'm concerned. As for cost, sitting around unable to work effectively costs me over $100, 000 a year, so by comparison the cost of a treatment that has even a 30% chance of returning to work is a reasonable bet.

Has somebody forgotten that many of us are severely disabled -- that inconvenience is the least of our worries?

 

[In Vitro Infidelium]

Mens rea is a completely separate concept - it's merely intent to do the action, not a motive. That is, the criminal deliberately punched the victim, rather than accidentally hitting them in the face while trying to put out a fire - there is no requirement that we know why the crime was committed, only (usually) that it was deliberate. Do you really want to argue legal technicalities with a lawyer, even a very sick one?

I'm trying to give it up as I feel I should be better person than the one who enjoys the exquisite schadenfreude of eliciting professional frustration as the mental clock of unbilled hours (or part thereof) runs inexorably onwards.

I think "how" has already been somewhat established in the case of Rituximab - by depleting B-cells. And again, that is far more than drug companies are required to show. The FDA and other drug approval bodies have little interest in "why" OR "how", so long as the "what" is satisfactory.

There is however a general approach in drug aproval processes that seeks to match 'how' with the actual disease process under consideration - that is what separates testing from definitive treatment, your argument seems to be based on cart before horse.

More broadly I would argue that the safety of Rituximab use in ME/CFS is derived from the safety of its use in human beings. Cancer patients do not have major differences in general physiological functions compared to ME patients, hence there is no reason to assume that ME patients will spontaneously combust when taking the same drugs that do not cause cancer patients to spontaneously combust.

This I don't understand at all - if there is not something that majorly distinguishes an M.E/CFS patient population from the global cancer patient population, then M.E/CFS can not be a distinct condition (or discrete set of conditions). We do not need to invoke the implausible to have a test of concern. Many cancers are present in people who are otherwise in robust health, which serves to allow tolerance of and recovery from, the very challenging interventionsof cancer treatment. But we also have to consider that not only are M.E/CFS patients not well placed to tolerate and recover from challenging interventions (are we seriously saying that GET is likely more challenging than Rituximab ?) but we must consider that M.E/CFS (at least in some cases) involves endemic vulnerabilites to any given treatment - Rituximab, GET or whatever. For a patient population that reports intolerance of a variety of substances, I can't see how this must not be a serious concern where benefit/disbenefit of a treatment is considered.

Preliminary studies on effectiveness indicate improvements are far more impressive than "mild" and in significant majority of patients. Benefit is thus far looking relatively high at least in the short term, while risk, as established in extensive studies with other diseases, is relatively minimal.

And our levels of impairment aren't profound? I doubt there's a lot of ME/CFS patients at 80% functionality eager to try Rituximab at this point. From what I have read, and based on the studies thus far, the ME patients seeking treatment are severely impaired - unable to work and struggling to get out of the house or do basic household tasks.

Known risks have been established in cancer studies, and the small trials done thus far haven't indicated additional risks. When a drug is prescribed, the FDA has a nice leaflet with it listing the side effects and their frequencies. So that gets to conveyed to the patient just like it does for every other drug. In the case of Rituximab, there's an increased chance of infection - something like 15% higher than the odds for controls.

I'm confused by these mix and match arguments. How are the most seriously ill able to travel significant distances to receive regular infusions ? And why are the most seriously ill M.E/CFS patients seen as being equivalent to a patient base in use in other ilnesses where the underlying aetiology may be profoundly different ? This seems to me to be connecting unrealted dots to draw a convenient picture.

I think it's improper of you to presume doctor misconduct in absence of any evidence, especially while naming a specific doctor. There is no indication that Dr Kogelnik or others are not keeping close tabs on their patients. I take a medication prescribed (so far) from a considerable distance, and my GP does not feel qualified to handle it, but it is very easy for me to email or Skype the prescribing doctor to discuss things. If side-effects do arise requiring emergency treatment, it is highly likely that the local hospital would be able to provide appropriate treatment for those side-effects.

I don't feel under any obligation to be proper - though I would feel uncomfortable making an initial claim of serious misconduct anyone against anyone with professional standing while hiding behind a pseudonym. The implication of unethical practice has already been made in this case - I don't see how it is improper to explore the issues related to that, the dangers of not doing so were amply demonstrated in the case of the VIPdx tests and the unfortunate role of WPI's licensing arrangement which cost M.E/CFS patients over $1 million on the back of intimations that research would be advanced.

IVI

 

[In Vitro Infidelium]

Donation made for the work of OMI-Merit. OMI's research program is bold, forward thinking and desperately needed. All patients from around the world will benefit.

For those who want Rituximab trials to happen, and more (biobank, other drug trials, pathophysiology of ME etc...) donate here: http://openmedicineinstitute.org/
Only through research can we move forward. OMI has all the ingredients to make it happen, but they need financial support.

Possibly not a problem, however the OMI structure and donation arrangements are bit puzzling:

The Open Medicine Institute main page has a donate tab, which clicks through to one of three pages: Give Money/Give Time, Current ME/CFS Campaign and Current Autism Campaign. Each of these pages lists the recipient of donations as the Open Medicine Foundation and a separate tab on the OMI site main page links to the OMF Mission statement and its board members. There is no 501c (IRS non profit) statement given and the OMF does not show up on the main US non profiting listing site (Guidestar: http://www.guidestar.org/ ) .

The California Secretary of State Business Search service http://kepler.sos.ca.gov/ provides details of three business entities that have Andreas M. Kogelnik listed as Agent of Process, all share the same address:

2500 Hospital Drive – Bldg 2 – Suite 210 , Mountain View, CA, 94040, USA. The businesses are:

Open Medicine Institute Incorporated and Open Medicine Clinic Incorporated, both of which have filed dates of 02/20/2009 and which have consecutive entity numbers, and the Open Medicine Foundation Incorporated which has a filed date of 04/06/2009. The California SOS register lists both OMC Inc. and OMI Inc. as ‘Active’ but puzzlingly OMF Inc. is listed as Suspended. The most common reason for Suspension is non filing of legally required annual/biennial statements. The suspended status does have implications: http://www.sos.ca.gov/business/be/faqs.htm#suspension and it is surprising that a suspended corporation should continue to accept donations. There may though be some technical reason why continued acceptance of donations is permitted.

IVI

 

[Roy S]

　
Valentijn said: <index.php?goto/post&id=329076>
Mens rea is a completely separate concept - it's merely intent to do the action, not a motive. That is, the criminal deliberately punched the victim, rather than accidentally hitting them in the face while trying to put out a fire - there is no requirement that we know why the crime was committed, only (usually) that it was deliberate. Do you really want to argue legal technicalities with a lawyer, even a very sick one?

I'm trying to give it up as I feel I should be better person than the one who enjoys the exquisite schadenfreude of eliciting professional frustration as the mental clock of unbilled hours (or part thereof) runs inexorably onwards.

Yeah, I'd encourage you to go in that direction. I've never seen "exquisite" combined with "schadenfreude".

schadenfreude [n. SHAW-den-froy-duh]
Taking malicious satisfaction in another person's troubles is schadenfreude. This noun comes in handy when someone feels glee or gloats over another person's suffering.


But it is Schadenfreude, a mischievous delight in the misfortunes of others, which remains the worst trait in human nature.
Arthur Schopenhauer

 

[In Vitro Infidelium]

　Yeah, I'd encourage you to go in that direction. I've never seen "exquisite" combined with "schadenfreude".

schadenfreude [n. SHAW-den-froy-duh]
Taking malicious satisfaction in another person's troubles is schadenfreude. This noun comes in handy when someone feels glee or gloats over another person's suffering.

But it is Schadenfreude, a mischievous delight in the misfortunes of others, which remains the worst trait in human nature. Arthur Schopenhauer

So no appreciation for ironic/sardonic perspectives then ? On a forum that is predicated on challenging appeals to authority (we're all experts here) any poster who appeals to their own 'special' authority, must expect a certain 'intolerance' by way of mild mockery of profession - here, an allussion to the mendacity of lawyers (of course it's unfair that's the point). And Schopenhauer ? Art therapy for all ! Still Nietzsche liked him so ........... hmmm I'll stop there I, think I may be about to fulfil Godwin's Law.

IVI

 

[perovyscus]

Per square inch, more false equivalency and strawman arguments in that article and forum comments than I've seen in any place.

Whether CFS patients have somatoform disorders or depression is irrelevant. Will those diseases even exist in a hundred years? Moreover, why rely on a MOA for the function of a drug independent of its efficacy, since all non-biological xenobiotics we have are brutally crude? Refined diseases with an unknown etiology are treated constantly.

Furthermore, that the biochemical markers of CFS are indistinguishable from healthy controls is a perspective lacking information (and not out of malice). Anymore so that somatoform disorders or hysteria can't be delineated based on data mining of biomarkers.

Try to avoid the arguments of "putting yourself in my shoes" and the Galileo Gambit, it tends to deflect off people who were statistically fortunate.