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Rituximab for Chronic Fatigue Syndrome: Jumping the Gun

Now that the XMRV myth has been put to rest,  patients with Chronic Fatigue Syndrome (CFS) are no longer jumping the gun to demand anti-retroviral treatments. But they are jumping the gun in new ways, based on very preliminary data coming out of Norway.

A correspondent in Norway wrote to tell me patients from Norway with myalgic encephalitis/chronic fatigue syndrome (ME/CFS) are travelling to the US to have Dr. Andreas Kogelnik in San Francisco treat them with IV infusions of rituximab, apparently to no avail. A course of treatment costs over $6000, not to speak of travel and other expenses.

What is Rituximab?

It’s a chimeric monoclonal antibody against the protein CD20, and it destroys B cells. It is used to treat diseases with excessive, overactive, or dysfunctional B cells such as some lymphomas, leukemias, transplant rejection, and some autoimmune disorders, notably rheumatoid arthritis. It is expensive (several thousands of dollars per infusion), must be given IV, and can cause serious adverse effects including infusion reactions, reactivation of infections, and cardiac arrest.

Using it for CFS is not based on any clear scientific rationale, but only on a few observations of patient improvement and on speculation about a possible cause of CFS that might explain the observations. It has certainly not been established that CFS symptoms can be attributed to B cell abnormalities.

A Patient’s Story

A blogger in Canada has chronicled her experience at great length. She has been travelling to San Francisco for treatments, and she believes she is enrolled in a pilot study. A quote from her blog:

The treatments I would receive are not considered a clinical trial, but a pilot study because clinical trials are tightly regulated and operated. It needs a lot of work from investigators to establish guidelines and procedures, obtain approval from ethic boards, etc.

When questioned, she elaborated:

a pilot study is not a registered clinical trial. It’s a one person trial. It gives the opportunity for the physician and researcher to gain experience with the drug and to refine the protocol associated with its administration. The goal for this is to move forward with a very formal and well controlled clinical trial.

She is hopelessly confused about what constitutes a pilot study. I can’t tell whether she was misinformed or simply misunderstood what she was told, but it raises questions about informed consent. She had worked as a chemo nurse and had been involved in phase 1 studies of new drugs so she should know better.

She says Kogelnik told her he was in touch with the Norwegian researchers (see below) every two weeks; she got the impression that he was collaborating closely with them on pilot studies. But my Norwegian correspondent contacted those researchers and they told her that while they are in touch with Kogelnik now and then, they only have general discussions about ME and immunology. He has told them he is doing some kind of study; but they have never seen the protocol, don’t know how many patients are enrolled, and are concerned that he hasn’t officially registered his study.

The blogger has made multiple trips from Canada to San Francisco. The Genentech Foundation apparently pays for the drug under a patient assistance program if the patient can document 2 refusals by insurance, but the trips and special lab tests cost her around $6000 for the year. She vividly describes the difficulties of traveling with her symptoms, arranging for wheelchairs and oxygen, etc. She says travel makes her sicker.

She has come to hate the term CFS because of its associations. She prefers to call it ME. Now she says Kogelnik has changed her diagnosis to CVID (Common Variable Immune Dysfunction), but it seems to me neither her symptoms nor his treatment match very well with that diagnosis. Perhaps she means chronic fatigue immune dysfunction syndrome (CFIDS), which is essentially a synonym for CFS. She suggests that he is using a different diagnosis because it is more acceptable to insurance companies and regulators and helps to justify what he is doing.

Her B-cells were effectively eradicated by the drug, but she got worse instead of better. She says:

I have known to expect worsening of my symptoms. Dr K warned me about it….Dr K think that it takes about 3 months to start feeling durable effects of Ritux and they seem to taper the dose down as they go.

Here’s her protocol.

Rituximab induction: Day 1 and Day 15. Dose #3 at Week 8 (I got mine at Week 9). Dose #4 at Week 24. Dose #5 at Week 44 and Dose #6 at Week 60. Pretreatment for each infusion with Tylenol, IV Benadryl, and Phenergan (to reduce the risk or severity of infusion reactions).

Despite her initial enthusiasm, the drug has not helped her. In fact she has developed various new symptoms and abnormal liver function tests, but she refuses to attribute any of these to the treatment.

I am getting resigned that I may not respond from Rituximab- but then I guess if it happens, that’s totally fine too. I hope that this process can be of help to research, notably finding out who responds and why, and who doesn’t and why.

This is particularly sad, since she was not treated as part of a controlled study that might have actually accomplished those goals. She was merely a guinea pig in an irresponsible uncontrolled experiment.

What Is the Evidence?

An initial observation. Fluge and Mella observed that a patient with CFS had an unexpected, marked recovery of CFS symptoms lasting for 5 months during and after cytotoxic chemotherapy for Hodgkin’s disease. They reasoned that the improvement was probably related to her treatment with methotrexate, a drug known to induce immunomodulation in part through B-cell depletion.

A small case series. So they decided to try depleting B-cells with rituximab in the original patient plus two others. This was published as a case series in 2009.  The treatment was 2 IV infusions given 2 weeks apart, with a maximum dose of 1000mg. 2 of the 3 patients were also given oral methotrexate for recurrent symptoms.

All three patients, with 7–10 years of CFS disease duration, had substantial relief of all symptoms related to CFS after rituximab intervention. Patients 1 and 2 had a marked symptom improvement after approximately 6 to 12–16 weeks, followed by slowly increasing symptoms (yet still a benefit 6 months after treatment). Patient 3 had slight symptom improvement from 6 to 26 weeks after treatment, thereafter a major recovery of all symptoms lasting until 40 weeks after treatment, followed by a gradual worsening the following month.

One randomized controlled trial. Their next step was to do a randomized, double-blind, placebo-controlled comparison of rituximab to IV saline. 2 infusions were given 2 weeks apart to 30 patients.  All patients were pre-treated with cetirizine, paracetamol and dexamethasone to minimize the risk of reactions.

They are calling it a positive study; but for their primary end-point (effect on self-reported CFS symptoms three months after intervention) the results were actually negative. They continued to observe the patients for secondary endpoints, and other secondary endpoints were added to the protocol mid-stream. They found a significant difference between the groups at 6-10 months after treatment.

They characterized this as:

significant, though generally transient clinical responses, with CFS symptom improvement in two thirds of the included patients.

Of the patients on rituximab, 10 had a major or moderate response lasting from 8–44 weeks; the other third failed to respond. Two patients in the placebo group had a major or moderate response.

The study design could have been better. There were some significant differences between the patient characteristics in the two groups, and it doesn’t appear that they questioned patients to see if they could guess which group they were in (i.e., whether blinding was adequate).

More studies in progress. They announced:

Based on new pilot patient experiences [what does this mean? Are they, too, confusing pilot studies with anecdotal evidence?] we have now started two new open-label phase-II studies investigating Rituximab treatment with two infusions two weeks apart (as in the present study) followed by maintenance Rituximab infusions at 3, 6, 10 and 15 months, to further explore this treatment principle in CFS (ClinicalTrials.gov, NCT01156909 and NCT01156922).

Strangely, both of these studies are open-label, with no control group and no blinding. What were they thinking?

What Is Kogelnik Doing?

Kogelnik founded the Open Medicine Institute to facilitate electronic information sharing in a community-based process. It is crowd-sourcing private funds. It has great plans for research, but as yet no studies have been registered at ClinicalTrials.gov. As far as I have been able to determine, he is offering individual patients treatment outside of any legitimate study. I don’t know how he is representing this to his patients, but at least one medically trained patient believed she was participating in a pilot study Kogelnik was doing in collaboration with researchers in Norway. I have no way of knowing whether the misunderstanding was on her part or his.

Some of this reminds me of Burzynski’s deceptive tactics, but Kugelnik is no Burzynski. I’m willing to believe he is sincerely trying to help patients who have no other options. But I think he’s on the wrong track. The way to really help these patients is to insist on providing the drug only in the context of well-designed clinical studies to establish once and for all whether rituximab treatment is effective. Jumping the gun is not scientifically or ethically justified.

Don’t expect anyone to try to stop him. Rituximab is an FDA-approved drug for other indications, and it is not illegal to prescribe the drug off-label. Offering experimental treatments to patients is not illegal. Medical boards have disciplinary power: the infamous Dr. Mark Geier, chemical castrator of autistic children, lost his license for “almost total disregard of basic medical and ethical standards,” but that kind of medical board action is the exception to the rule. Similar malfeasance (Dr. William Rea, for example) has typically been ignored or punished only with a mild slap on the wrist. Even Burzynski has not lost his license. In the absence of regulatory action, the only remedy would be a lawsuit if a patient died or was seriously harmed by the treatments.

Conclusion

So basically, the evidence consists of one case report (involving a different drug!), a case series of 3, and one preliminary controlled study with 30 patients showing a 2/3 response that was delayed and transient. Preliminary studies serve to justify further studies but they are not sufficient to justify forging ahead with offering the treatments in clinical practice. All too often, attempts to replicate preliminary studies fail, and initially promising results are discredited by larger, better studies. XMRV was a prime example of that.

The protocol in the studies was 2 IV infusions 2 weeks apart. The protocol that Kogelnik is using (treatments 2 weeks apart, then at 8, 24, 44 and 60 weeks) doesn’t correspond to the published study or even to the Norwegian studies in progress.

In my opinion, what he is doing is not based on acceptable evidence and is not ethical. He is indulging in irresponsible, uncontrolled experimentation. He is knocking out a vital part of his patients’ immune systems (B cells produce antibodies to fight off infections) with little understanding of what he is accomplishing, of whether it addresses some basic underlying causal mechanism of CFS, or of what the possible long-term consequences might be. By jumping the gun he is putting patients at risk; exposing them to considerable cost, discomfort, and inconvenience; and by running around the track prematurely by himself, he is missing out on the real race to understand and treat patients diagnosed with CFS/ME/CFIDS.

 

 

Posted in: Clinical Trials, Medical Ethics, Pharmaceuticals

Leave a Comment (179) ↓

179 thoughts on “Rituximab for Chronic Fatigue Syndrome: Jumping the Gun

  1. TonyMach says:

    I read Kogelnik’s name once every while, but I don’t really know much about him – so I can’t asses him very well. And I don’t know enough (yet) about Fluge and Mella to say whether they and their research can be trusted. So I will refrain from commenting one way or the other about them.

    (Unlike XMRV, with Mikovits, Lombardi and Ruscetti, who are as far as I know frauds.)

    But when I read this, I had to say something.

    “In my opinion, what he is doing is not based on acceptable evidence and is not ethical. He is indulging in irresponsible, uncontrolled experimentation.”

    The sad fact is that not only will do doctors do experimentation when faced with an disease of unknown etiology, unknown pathology and unknown treatment options, but *people* with ME/CFS *will* try irresponsible and uncontrolled experiments themselves and seek any “help” they can get. From vitamins in high doses, to herbs that have unknown side effects and dangers, “detox”&”chelation” regimes that massively harm, to long term antibiotics that do harm as well.

    (Not to mention “expert” clinics who will gladly take $$$ for a two day check-up, but leave patients empty handed – these people will after such an experience gladly go to quacks who offer anything that looks like a solution.)

    And while I agree that Rituximab might be problematic (for the reasons you stated), I think it is more responsible to give desperate patients access to this drug now, instead of accepting that they will experiment with worse things – and that, they will.

    And if your aim is to reach (and warn) patients who would consider going to Rituximab: I think you will fail.

    The question that needs to be asked: Does Kogelnik work with specialists who have knowledge and experience with the drug? If no, this is a major red flag and something that can be communicated to people with ME/CFS. If he does, I don’t think you have a case.

  2. TonyMach says:

    And just to clarify: with “expert” clinics I mean the big names, not some “Open Medicine Institute”.

  3. Kati_Rituximabtourist says:

    Mrs Hall, I am the blogger and RN you are mentioning on this blog opinion.

    With all due respect, i don’t think that you understand anything, nor that you ever met a patient with ME. I invite you to live in our shoes for a while and see for yourself.

    Rituximab by itself is very safe, not only it is used for cancer, it is also used for other rheumatologic applications, like lupus and RA. Then the questions comes to, why me, a patient who got sick with EBV, never recovered, barely able to walk 50 meters and do my groceries, would be left behind and does not deserve a trial of Rituxan, considering they would give it to patient with joint destructions?

    It always revolves around the fact that patient swith ME are never worthy of research. Govern,ents don’t think we are worthy of research and clinical trial grants, and researchers do not want to get in the field of ME, staying inthe safe areas of HIV and Cancercwhere they are sure to secure grants.

    Patients have been neglected for over a quarter century. i know somewho got ill intheir teens, are now in theor thirties and are too sick to live ontheir own, and have never finished their schooling, held a job or marry and have children.

    I am very very comfortable with Rituxan flowing in my veins, because it gives me hope. I have been monitored properly and furthermore, despite all of my B-cells gone, my CBC cannot be more normal, which means my body can handle at least some infections, but I am also watching for the possibility of infection becauseof my getting rid of the B-ells.

    If it was to be done all over again, I would take that chance, because there are no other options that are acceptable at the moment for me, and I know other patients would do it too if given a chance, because the life we are living is a living death.

    Patients face the stigma of this dam disease dayin and day out and we all want out of this nightmare. i applaud the work of Dr Kogelnik for organizing a stateofthe art biobank/research and hopefully official clinicaltrial when fundingcomes, and yes us patients will have to fund that too.

    So please, don’t bash my blog, and don’t bash the work of Dr Kogelnik, and perhaps spend time in our shoes, or lend a hand through research and collaborativework.

    KatiRituximabtourist.

  4. TonyMach says:

    Just one more thing: I took a look at the Open Medicine Institute and the “OMI-MERIT Initiative Signators”. While some names are not or not well known to me, the names I know are manly solid researchers: Especially Lucinda Bateman, Nancy Klimas, Kathleen and Alan Light, Chris Snell and Staci Stevens know what they are doing. Well, Ila Singh and Jose Montoya might be overselling their research, but none of them is a quack, and none is a fraud AFAIK. And none of the household quacks and idiots of ME/CFS research (that I know of, at least) are included in the list.

    So take that for what its worth, but I think the Open Medicine Institute is most definitely *not* a “den of quacks”. (Kogelnik and some of the other OMI-MERIT names may or may not be sub-par, however.)

  5. The Dave says:

    “Rituximab by itself is very safe,”

    wrong: http://www.drugs.com/sfx/rituximab-side-effects.html

    “It always revolves around the fact that patient swith ME are never worthy of research. Govern,ents don’t think we are worthy of research and clinical trial grants, and researchers do not want to get in the field of ME, staying inthe safe areas of HIV and Cancercwhere they are sure to secure grants.”

    wrong:
    Open trials for key word “Chronic Fatigue”: http://clinicaltrials.gov/ct2/results?term=chronic+fatigue&recr=Open
    Open trials for keyword “Myalgic Encephalitis”: http://clinicaltrials.gov/ct2/results?term=myalgic+encephalitis&recr=Open

    And that’s filtering out the trials that have been completed or being run and no longer recruiting

    “Patients face the stigma of this dam disease dayin and day out and we all want out of this nightmare. i applaud the work of Dr Kogelnik for organizing a stateofthe art biobank/research and hopefully official clinicaltrial when fundingcomes, and yes us patients will have to fund that too.”

    If his research is so state-of-the-art, why can’t he register a clinical trial like all the others? Also, (Forgive my naivete, I don’t have first hand knowledge of research/clinical trial funding, etc) is it normal for the cohort of a clinical trial to provide the funding for that trial? That doesn’t seem right. Shouldn’t the cohort be compensated BY the trial for their participation?

  6. geo says:

    I don’t remember other posts on SBM focusing quite so much and so critically on one patient.

    At this point, I do not think that it would be appropriate for anyone to be making money out of treatments for CFS outside of registered trials with genuinely informed consent, but it does seem that there is little funding for research and a lot of patients desperate to try something which will allow them to regain their health.

    I think that this lack of funding is behind ‘what they were thinking’ with Mella and Fluge’s uncontrolled study. From what I understand, they are working to get funding for a blinded multi-centre RCT, but the cost of doing this research properly is very high.

  7. WilliamLawrenceUtridge says:

    It always revolves around the fact that patient swith ME are never worthy of research. Govern,ents don’t think we are worthy of research and clinical trial grants, and researchers do not want to get in the field of ME, staying inthe safe areas of HIV and Cancercwhere they are sure to secure grants.

    May I suggest a different explanation. CFS is a diagnosis of exclusion, only when a doctor has ruled out all determinable causes of fatigue they can think of is a patient given the diagnosis. In some cases the doctor has doubtless missed some subtle or difficult to determine cause. The result is that the pool of CFS patients is very heterogeneous, which makes it hard to conduct any research. I am sure years from now, they will find out that some subsets of CFS patients actually had a previously diagnosed physiological condition, and henceforth they will be removed from the pool. I am also sure that in some patients, the fatigue is purely psychogenic. Determining which is which is extremely difficult. In the mean time, like the XMRV fiasco, doctors, researchers and desperate patients are jumping the gun and jumping to conclusions regarding etiology and treatments. The unfortunate fact is, there are simply no good, evidence-based treatments that are effective for all CFS patients, and the graded exercise therapy and cognitive behavioural therapy options currently offered are objectionable to many patients, I’m sure with good reason.

    Do not mistake “we do not have an explanation or a cure” for “we don’t care” or (in this case) “let me take your money”. You are receiving and paying for this treatment on the basis of hope. While this is understandable, because doubtless you are desperate, it is not the same thing as proof. Pointing out the flaws in Kogelnik’s “research” and treatment is necessary to determine whether it holds genuine potential as a treatment, or is merely an expensive way to benefit from the placebo effect.

  8. nybgrus says:

    @TheDave:

    is it normal for the cohort of a clinical trial to provide the funding for that trial?

    No. That is not normal and at best highly dubiously ethical and almost always unethical. At its most simplistic, a clinical trial must try and prove that the potential benefit to the individual will outweigh the potential risks to get IRB approval. There are numerous variations and provisos for allowing research in cases where this cannot be met but there are reasonable expectations that the generalizable knowledge will be of great use to future patients. Since this latter criteria is harder to meet it requires more scrutiny. But in any event, there is always the assumption of harm with the knowledge that it may be greater than feasibly anticipated a priori. As such, the added burden of cost to the participant would be very easily considered to tip the balance of harm in the wrong direction and is easy pickin’s for an IRB to say no.

    That said, mitigating factors such as limited funding can be use to justify small burdens of expense and time (like not reimbursing for transportation costs to trial sites) but this must be a carefully explicit part of the patient consent. In an ideal world, any and all costs possibly associated with a trial would be covered by the trial itself. This is a small part of why Burzynski is so incredibly unethical.

  9. PernilleN says:

    @Nybgrus: “That said, mitigating factors such as limited funding can be use to justify small burdens of expense and time (like not reimbursing for transportation costs to trial sites) but this must be a carefully explicit part of the patient consent.”

    Kati, after a lot of trouble, got refund for the medicine from The Genentech Foundation, but the Norwegian patients (and, I suppose, the other overseas patients) are paying 8000$ per treatment, plus travel expenses. And travelling from Norway to US isn’t exactly cheap. Several of these poor souls have taken up private loans to finance this. One of them has spent something like 45,000$ till now, and is no better. She’s just even more exhausted after four trips to US. I don’t think this is ok.

    Kogelnik is absolutely no Burzynski, but I can’t understand how he can stomach running a “study” that costs the patients half a fortune. And I can absolutely not understand why he doesn’t register his research. For one thing, he’ll have trouble getting his research published when he hasn’t got approval from the ethical board. Ethical rules aren’t just red tape, they are there to protect patients. If he’s a serious scientist, he should know, and he shouldn’t neglect them.

    @Kati, Rituximab is not “very safe”. It can have very serious side effects, especially long term, and nobody knows the long term side effects (after years, that is). And you don’t give it to just anyone with rheumatological conditions. And when you do, you follow them very closely and monitor their immune function.
    RA and lupus are very serious diseases, lupus can even be lethal, so there’s sometimes good reason to give immunosuppressive drugs. But Rituximab isn’t the first choice, even though it’s well documented for some rheumatological diseases. You first try other drugs that aren’t that risky and have been on the market longer.

    If Rituximab turns out to really work for certain groups of ME/CFS patients, they will naturally “deserve” them. But it’s still early days, we simply don’t know enough yet, though the Norwegian results are promising.

    What these patients really deserve is that all research, and treatment they are offered, is scientifically and ethically sound, and that noone, whether doctor or quack, experiments with them.

    Excuse my sometimes clumsy English,

    Pernille Nylehn
    Norway

  10. irenef says:

    I suppose I’m one of those “poor souls” except I live in San Francisco. Open Medicine charges me less than $300 per infusion. The real money goes for the rituximab itself, which is a separate expense. No one is getting rich here, except Evil Big Pharma.

    And yes, I *do* deserve scientifically and ethically sound treatment, thank you very much. Got some? Think I should refuse the only option around–oh, I forgot about the fermented antler velvet, the Venezuelan equine encephalitis vaccine, and the placental extract referred to in the clinical trials–because it’s not on the strait and narrow path of EBM? (BTW, the Norwegian trials did not get funded.)

    There are some people here riding *very* high horses. Presumably through the halls of academe, and nowhere near me.

    Yours in pathos, ignorance, and victimization,

    Irene Fuerst

  11. elburto says:

    Pernille has it pretty much spot on.

    Slow/minimal research is annoying, upsetting and frustrating. However, jumping at any hint of a possible treatment is a waste of time and money. Pouring money into DMARDs, ARVs, chemotherapeutic agents etc. is dangerous and counterproductive.

    Science takes time. I understand the frustration and pain, but spending money I don’t have on “treatments” that aren’t, isn’t an option.

    My two main diagnoses are massively neglected. Both are potentially fatal (one is always fatal without treatment) , both have caused me permanent disability (spinal cord damage, blindness, hearing impairment, constant pain, etc), and neither are researched anywhere near the level that CFS/ME is.

    With the first disease, it’s too rare to attract any attention. There’s only one foundation studying it (US-based), and doctors are largely ignorant of the disease and how to manage it (One drug is available. If that doesn’t work neurosurgery is needed)

    The second disease is pretty common, but only in the elderly. Anyone else who develops it is usually left to get horribly ill before receiving a diagnosis. Ironically they’re often diagnosed with CFS or fibromyalgia when doctors neglect to perform the single simple diagnostic text.

    Treatment is simple, but the favoured regimen was designed for pensioners, in a “one size fits all” fashion. Sadly, it hasn’t really been revised in the decades since its inception, and. rarely works sufficiently in anyone under sixty. Those who can pay for private treatment, or import the treatment and self-treat, can live relatively normal lives.

    Again, in the UK, there is one advocacy group trying to change how the condition is treated. They’ve had to raise money to pay for research into treatment and management.

    Neither disease is “sexy” or controversial enough to warrant media interest, scientific and research interest, or public interest. Mentioning either gets blank stares, or shrugs. So I understand the feelings of total powerlessness and desperation. However, attacking researchers who are trying to shed light on either issue is not an option, even if the hypothesis is unpalatable. A study investigating a very contentious, upsetting theory in one of my conditions ended up disproving a “fact” of what triggered the onset of symptoms. It changed the course of research and patient management after decades of set practice.

    Ultimately, all research is good research if it contributes to the knowledge base about a given condition. The damage is already done in my case, but I know future patients won’t have to suffer in the same way. I’ll happily engage in anything I’m able to, although now I’m limited to surveys only until I can leave the house. I’ll do that to help future ‘Mes’, so that they can stay productive and remain symptom-free.

    However, charging patients thousands to take dangerous treatments, with the added “bonus” of costly and exhausting international travel, with the endpoint being neutral or even harmful, is not research. It’s unethical, Burzynski-lite experimentation. Where’s the documentation? The accountability? What if someone dies or is maimed, who picks up the tab?

    This isn’t the way to go about things. All it does is empower the quacks and charlatans

    Lessons need to be learned from the disgraceful XMRV debacle..

  12. David Gorski says:

    For one thing, he’ll have trouble getting his research published when he hasn’t got approval from the ethical board. Ethical rules aren’t just red tape, they are there to protect patients. If he’s a serious scientist, he should know, and he shouldn’t neglect them.

    Indeed. He won’t be able to publish in a reputable journal if he doesn’t register his trial with ClinicalTrials.gov and if it doesn’t have ethical approval from an accepted IRB. I’m not aware of any reputable peer-reviewed journals that don’t require these two things before it will publish clinical trials. Again, it’s to protect patients by making it harder for investigators to disseminate their results if they’re not funded by the federal government or working for an academic university that receives federal funding and can thus get around the Common Rule. So, even if he were doing research worth publishing, the best he could do would be to self-publish the way quacks do or to publish in a bottom-feeding journal that doesn’t subscribe to standards that reputable biomedical journals subscribe to.

    My conclusion? Kogelnik is a “brave maverick doctor” who has so deluded himself into thinking that he’s doing so much good, that he’s discovered something so astoundingly awesome, that it leads him to believe that the regular rules don’t apply to him and that he can prove he’s right without going through normal clinical trial channels.

  13. Quill says:

    My conclusion? Kogelnik is a “brave maverick doctor” who has so deluded himself into thinking that he’s doing so much good, that he’s discovered something so astoundingly awesome, that it leads him to believe that the regular rules don’t apply to him and that he can prove he’s right without going through normal clinical trial channels.

    This fits in with the Open Medicine Institute’s overall vibe, if you will. OMI is flush with venture capitalist cash, incorporated as a public benefits corporation, and does not need the money of any one patient.

    A read through their website notes that it is chock-full-o’ catch phrases of the 21st century digital marketing kind, but basically it’s the same 19th century and onward venture capitalist scheme: toss a lot of money at obscure problems, expect novel solutions (that are patentable) and sit back for that 50x return which should occur in a year or so.

    Dor Kogelnik is probably very enthusiastic about whatever it is he has found and is likely being encouraged in his “maverick” thinking by the board, advisors and management of OMI. It would be better for the public at large if less lucrative for OMI if the good doctor sat back and played by the rules that will make his discoveries applicable to the world.

  14. Quill says:

    ^(Excuse my not policing the blasted auto-correct: that should be Dr. Kogelnik, not “dor.”)

  15. irenef says:

    I once admired the skeptical community, being something of a science junkie. But you are losing me by equating my doctor to that mephitic scoundrel Burzynski. I thought y’all were above ad hominem attacks and so on. Sorry, Gorski, I used to think you were my kind of guy.

    No one is being lured by expensive false promises. AFAIK Open Medicine is not trolling for patients. I realize that rituximab isn’t aspirin (although, come to think of it, aspirin has its dangers) and that I may not get any benefit. If I were in a clinical trial I might not get any benefit, either, and I don’t see how off-label use of a drug is denying other patients something. This is the kind of logic behind the Defense of Marriage Act: let’s stop people we don’t like from doing something we get to do.

    To reiterate: I pay less than $300 per infusion to Open Medicine. The large amounts of cash being cited go directly into the money-grubbing pockets of Evil Big Pharma.

    I’ve had five infusions so far. I can’t say I’m much better. I can’t say I’m much worse, either. I have no regrets.

    I’m pretty much housebound, can’t do much, in constant pain, all that fun stuff. So what I supposed to do? Listen to my betters and suffer in compliant silence? What have you done for me lately?

  16. irenef says:

    @Quill:

    I think OMI’s web site sucks, too, but no one asked my opinion. I know nothing about VC funding. Do tell. You seem to know something the rest of us don’t.

  17. WilliamLawrenceUtridge says:

    I suppose I’m one of those “poor souls” except I live in San Francisco. Open Medicine charges me less than $300 per infusion. The real money goes for the rituximab itself, which is a separate expense. No one is getting rich here, except Evil Big Pharma.

    You are paying $300 for the privilege of being involved in an scientifically useless clinical trial of one, for a treatment that has minimal prior probability, uncertain benefits and definite, recognized risks.

    And yes, I *do* deserve scientifically and ethically sound treatment, thank you very much. Got some?

    No, but the fact that there are few treatment options for CFS does not mean this option works. The fact that patients are undertaking uncontrolled, scientifically questionable, low-n trials presents several problems. First is the cost, money which could be better used in other ways (irrespective of if it’s an individual’s funds or government research dollars). Second is the way the trials will muddy the scientific process. Third is the way these uncontrolled observations and anecdotes will be circulated on the internet. Fourth is the hope it provides. While real hope is a good thing, false hope is not. If rituximab has no effect on CFS, individuals who undertake treatment and circulate their allegedly positive results on the internet are responsible for encouraging already vulnerable patients to experience more risks with placebo-only benefits.

    GED and CBT have research support, but many patients find them objectionable because of the stigma and implications attached. This is a shame on many levels and for a variety of reasons.

    Think I should refuse the only option around–oh, I forgot about the fermented antler velvet, the Venezuelan equine encephalitis vaccine, and the placental extract referred to in the clinical trials–because it’s not on the strait and narrow path of EBM? (BTW, the Norwegian trials did not get funded.)

    It’s less that, than it is the consequences of your action. If rituximab is genuinely effective, your actions will almost certainly delay its acceptance. If rituximab is ineffective, your blog is encouraging desperate patients to undertake expensive and risky treatment. It is truly unfortunate that the etiology of CFS is not understood, even more unfortunate that the treatment options are less than ideal. That doesn’t mean rituximab is an effective treatment and it doesn’t mean these scientifically useless and expensive trials are risk-free or ethically unproblematic.

    There are some people here riding *very* high horses. Presumably through the halls of academe, and nowhere near me.

    You appear to be misinterpreting valid scientific concerns over an extremely problematic treatment with condescension. Science attempts to arrive at correct solutions through rigorous criticism that divorces facts from emotions. It is unfortunate that CFS has no confirmed cause or easy treatment. It is unfortunate that CFS patients feel stigmatized. That doesn’t mean these criticisms are scientifically invalid, nor does it mean rituximab is effective.

    Yours in pathos, ignorance, and victimization,

    I could do without the sarcastic martyrdom.

  18. Harriet Hall says:

    “you are losing me by equating my doctor to that mephitic scoundrel Burzynski.”

    I can’t see where anyone has equated Kogelnik to Burzynski. I specifically said he is no Burzynski, and other commenters have echoed that.

    Elburto did say “charging patients thousands to take dangerous treatments, with the added “bonus” of costly and exhausting international travel, with the endpoint being neutral or even harmful, is not research. It’s unethical, Burzynski-lite experimentation.”

    That’s undeniably true. Kogelnik is doing some things that can be compared to some of the things Burzynski does, but that doesn’t “equate” him just as walking on two legs does not equate humans to chickens.

  19. Quill says:

    irenef remarked:

    I know nothing about VC funding. Do tell. You seem to know something the rest of us don’t.

    No special knowledge on my part.

    http://en.wikipedia.org/wiki/Venture_capital

  20. irenef says:

    @WilliamLawrenceUtridge:

    What blog? I don’t have a blog. I’m not encouraging anyone to do anything. Up until now only a few people have even known that I have received rituximab.

    I was never under the impression I was in any kind of clinical trial. I am receiving an off-label treatment. My blood samples are being saved and I have given permission for them to be shared.

    And I think my sarcasm pales in comparison to equating Drs. Kogelnik and Burzynski.

  21. WilliamLawrenceUtridge says:

    I once admired the skeptical community, being something of a science junkie. But you are losing me by equating my doctor to that mephitic scoundrel Burzynski. I thought y’all were above ad hominem attacks and so on. Sorry, Gorski, I used to think you were my kind of guy.

    Assuming your doctor is honestly motivated by laudable concern for his patients and not the apparent profit motive imputed upon Burzynski, that does not discount the fact that he is conducting scientifically flawed trials that will not really help the CFS patient community. Perhaps you should talk to him about the importance of a proper clinical trial – if rituximab is genuinely effective, he is restricting its use to only those who can afford it, and a trip to his clinic. If it’s not, he’s exposing you and other patients to risks for no benefits.

    No one is being lured by expensive false promises.

    Um…it kinda is. Perhaps not “false” promises, but certainly “unproven”.

    AFAIK Open Medicine is not trolling for patients. I realize that rituximab isn’t aspirin (although, come to think of it, aspirin has its dangers)

    Aspirin has recognized, proven benefits that are extremely well validated. The same can not be said for rituximab. If someone tried using aspirin to treat CFS, charging $600 per treatment for the privilege, you would see similar criticisms.

    If I were in a clinical trial I might not get any benefit, either, and I don’t see how off-label use of a drug is denying other patients something.

    It denies the opportunity to test the hypothesis in a meaningful way, thus the ability to deliver the treatment to large numbers of patient if effective, or protect patients from unnecessary risks if not effective.

    This is the kind of logic behind the Defense of Marriage Act: let’s stop people we don’t like from doing something we get to do.

    The Defense of Marriage Act is a social and political issue, where the scientific process has little involvement and the health consequences are tangential at best. Off-label use of rituximab is a medical and thus scientific issue. The logic is, providing people with false hope and exposing them to risks with no proven benefits, is inherently bad. A properly-controlled clinical trial would address this – risks are real but are offset by the ability to determine if there are benefits.

    To reiterate: I pay less than $300 per infusion to Open Medicine. The large amounts of cash being cited go directly into the money-grubbing pockets of Evil Big Pharma.

    There is an opportunity cost for this use of money, editors and commentors here are indifferent to who gets the money, the objection is that resources are being used for benefits that may be illusory.

    I’ve had five infusions so far. I can’t say I’m much better. I can’t say I’m much worse, either. I have no regrets.

    If you had been part of a clinical trial, you could have helped determine whether this is a viable treatment or not.

  22. irenef says:

    @Quill:

    So Open Medicine is accused, on someone’s sayso, of bleeding patients’ wallets with false promises, but when I point out that I pay them what’s basically chump change, you claim they are flush with VC funds and don’t really need my money. So am I being used for some nefarious purpose? My cells are going to be patented, no doubt. What evidence do you have?

  23. Harriet Hall says:

    @irenef,

    It’s reassuring to know you were not under the misapprehension that you were enrolled in a clinical trial, as blogger Kati apparently was.

    Question: would you rather do what you have done or would you rather you had been given the option of enrolling in a randomized trial with a 50/50 chance that you would be assigned to a placebo control group but with the understanding that the knowledge gained would help determine once and for all if the drug was really effective?

  24. Quill says:

    irenef, you are combing, conflating and mixing up comments and including me in a group I am not a part of. I shouldn’t step in this, but:

    “So Open Medicine is accused, on someone’s sayso, of bleeding patients’ wallets with false promises,…”

    Hyperbole at best and I don’t see them accused of this on this blog.

    “…but when I point out that I pay them what’s basically chump change…”

    If three hundred dollars is “chump change” to you then bravo for your affluence.

    “…you claim they are flush with VC funds and don’t really need my money…”

    They do not. It is a matter of public record for OMI that they are quite well funded.

    “…So am I being used for some nefarious purpose?…”

    I have no idea but I suspect not, as do the medical commentators here. They are pointing out that your doctor is likely overly enthusiastic and isn’t following protocols in the field of medical research. He is passionate but unless he follows the rules he will not persuade.

    “My cells are going to be patented, no doubt.”

    Eh? I’ve no idea what you mean by that. Any patentable process or drug would be the goal of OMI, not attempting to patent a person’s individual cells, which as far as I know isn’t legal.

    “…What evidence do you have?”

    Evidence that you aren’t reading closely here and as stated in the start of this reply are confusing a lot of issues.

  25. irenef says:

    @WilliamLawrenceUtridge

    I am not part of a trial. I have never told anyone I was part of a trial. No one told me I was going to be in a trial. I tried to get into one but didn’t meet the qualifications. Open Medicine has not claimed–to me, anyway–to be enrolling patients for a clinical trial.

    My doctor is not conducting a clinical trial. He is offering an off-label treatment that presents risks to a seriously disabled group of patients.

    There is no clinical trial.

  26. irenef says:

    @Quill:

    Please point me to the public records that detail OMI’s funding. I would like that information..

    And I do believe that human cell lines are patentable, just like rose bushes, and that this has gone to the supreme court. The human being involved does not need to be compensated. I do not have references offhand but I can get the details if it interests you.

    @ Harriet Hall:

    I’d go for the RCT. That’s a no-brainer.

  27. WilliamLawrenceUtridge says:

    I am not part of a trial. I have never told anyone I was part of a trial. No one told me I was going to be in a trial. I tried to get into one but didn’t meet the qualifications. Open Medicine has not claimed–to me, anyway–to be enrolling patients for a clinical trial.
    My doctor is not conducting a clinical trial. He is offering an off-label treatment that presents risks to a seriously disabled group of patients.
    There is no clinical trial.

    Yes. That is the problem.

  28. irenef says:

    I suppose we’re all agreed, then: There is no clinical trial.

    How dull the day has become. Someone, please, argue with me. This is the most fun I’ve had in months. Really.

    @Quill:

    Moore v. Regents of the University of California. Went before the California Supreme Court in 1990. From Wikipedia:

    “Moore v. Regents of the University of California (51 Cal. 3d 120; 271 Cal. Rptr. 146; 793 P.2d 479) was a landmark Supreme Court of California decision filed on July 9, 1990 which dealt with the issue of property rights in one’s own body parts. John Moore underwent treatment for hairy cell leukemia at the UCLA Medical Center under the supervision of Dr. David W. Golde. Moore’s cancer was later developed into a cell line that was commercialized. The California Supreme Court ruled that Moore had no right to any share of the profits realized from the commercialization of anything developed from his discarded body parts.”

    There’s more, of course. Quite controversial.

  29. elburto says:

    This is the kind of logic behind the Defense of Marriage Act: let’s stop people we don’t like from doing something we get to do.

    How about “No”?

    I’m a woman with a wife. That does not endanger lives, waste time, give anyone false hope, mislead people, or cost
    anyone money.

    However, being denied the right to wed causes serious harm to same-sex couples. The US considerably privileges heterosexual couples WRT property ownership, healthcare, hospital visitation, having/adopting/fostering children, financial matters, and so on.

    By all means, throw your money away on a non-treatment that’s potentially dangerous and apparently not helping you, go for it! I only wish I could come by that amount of money and then part with it so easily as mere “chump change”

    But don’t compare legitimate scientific criticism of research-that-isn’t with the systematic abuse and denial of basic human rights of an entire class of people, because it doesn’t help your case.

    Oh, and the whole “Evil Big Pharma” thing? Sort of disproves your whole “I was a super skeptic till you said mean things about CFSers using rituximab” schtick.

    No doubt this topic will end up at 150+ comments of word salad and conspiracy theories, as CFS articles are prone to do.

    Ah well, it’s a vibrant start to the SBM New Year, if nothing else. I can use my pharma-shill minion money (Draconi$ LizarDollar$) to spring for some popcorn.

  30. Quill says:

    “But don’t compare legitimate scientific criticism of research-that-isn’t with the systematic abuse and denial of basic human rights of an entire class of people, because it doesn’t help your case.”

    elburto, I was getting ’round to mentioning that, so thank you kindly for beating me to it. :-)

    “No doubt this topic will end up at 150+ comments of word salad and conspiracy theories, as CFS articles are prone to do.”

    One can hope. ;-) But seriously, you get enough pharma-shill money for popcorn? I’m impressed! I only got enough for a postage stamp.

    And irenef, since you’ve just demonstrated you can do online research, kindly go to it for the answers to the questions asked to me unless you want me to send you my rate sheet for such work. ($300 ain’t “chump change” for me although I’ll be the first to admit to being a chump.)

  31. WilliamLawrenceUtridge says:

    How dull the day has become. Someone, please, argue with me. This is the most fun I’ve had in months. Really.

    I don’t want to tire you out.

  32. cort says:

    This kind of holier than tho, you’re not living up to medical gold standards so stop what you’re doing approach is common and is incredibly naive. We met up with the same attitude at the FDA hearing for Ampligen when the some members of the panel blithely said well, Hemispherx just do another trial, ignoring that there is no money to do a big trial.

    The blogger simply wants evidence that B-cells issues contribute to ME/CFS. Is the blogger aware that the NOrwegian research council recently turned down funding for another Rituximab trial? Or that the NIH currently provides all of $6 million dollars a year for CFS funding. Where does the blogger expect the evidence to come from. Would the blogger suggest that sick patients simply wait another 10 years or so in the off chance that funding will improve? (Its gone down substantially in the last 10 years)

    Dr. Kogelnik and other doctors are doing what they can for very sick patients who don’t have recourse to clinical trials for drugs for chronic fatigue syndrome because, for the most part, there aren’t any…because there isn’t interest and there certainly isn’t any money. They are doing the best they can with what they haveand people with ME/CFS are lucky they are around.

    I find this statement incredibly ironic “he is missing out on the real race to understand and treat patients diagnosed with CFS/ME/CFIDS.” Please tell me where the real race is because when I look through the research and the funding…I don’t really see much a race going on.

  33. Janet says:

    Thank you Dr. Hall, for bringing this questionabletreatment to our attention. My 23 yr old granddaughter has recently been diagnosed with RA (and has psoriasis since aged 9) and my 38 yr old son also has RA. They are both just beginning treatment and understand that not everything works for all patients. Should they have difficulty and this stuff comes to the attention of any of us, I am glad I’ll be ready to sort things out–being the family matriarch (or busybody–depends on who you ask). At least this problem came from the other side of the family–there’s enough on my side already.

    @Irene

    I think the people here all mean well when they reply to you, and I think they are factually correct. Having said that, I don’t think being correct is enough and that they are not responding with enough compassion to your condition or point-of-view. You seem basically well-informed, so I hope you will look through what can seem insensitive from some commenters and make good (rational) decisions going forward.

  34. irenef says:

    @elburto:

    My logic: As my choice of medical treatment doesn’t affect anyone else, a gay couple’s marriage does not affect anyone else. I was/patients like me were being criticized for a rather personal choice that was interpreted as being bad for other patients, as gay marriage is asserted to be a threat to society/Western Civilization/whatever.

    “Chump change” with respect to what 1) quacks like Burzynski charge, 2) what most medical procedures lasting several hours cost, and 3) the amounts being bandied about by people who didn’t know what they were talking about, who assumed that because the treatment is expensive Open Medicine was pocketing unconscionable profits.

    Evil Big Pharma=sarcasm. That’s why I used the caps. My husband has pharma clients. I don’t especially like them, but are putting a bit of food on the table.

    I don’t think I’ve supplied any word salad, conspiracy theories, or death threats. I could tell the boyos to come on over–I know the rocks they live under–but I’d prefer to keep things entre nous.

  35. irenef says:

    @Quill:

    So you make an assertion about Open Medicine’s funding but then refuse to document it, because I called $258 chump change and know something about intellectual property rights?

    Touchy, aren’t we.

  36. Quill says:

    My logic: As my choice of medical treatment doesn’t affect anyone else, a gay couple’s marriage does not affect anyone else.

    Then your logic is flawed as neither statement is true. Your choices do affect others, and such choices can be measured. For instance, how much of other people’s time (here and elsewhere) was taken up with your decision to go for such treatment? What else would you have spent that reoccurring $300 on? How many others know of what you do and have decisions altered or influenced by it? And gay marriage does affect many people, from changing public discourse to time and effort spent in legislatures, litigation, and lives able to be bound in legal union. It even affect heterosexual marriages in many ways, such as when such couples start to think about what makes a marriage especially in terms of commitment.*

    We are all interconnected on this little rock in space and much more alike than different.

    The thing here is that these choices can and should be made with the best available evidence, conscientiously and hopefully with an eye to benefitting other people. In the first case, by choosing to take part in what is apparently an unethical practice, you may be influencing others to do the same. That being said, I can’t fault you and only wish you the very best, mindful of what Janet has posted, and knowing I would be sorely tempted to do the same thing. I sincerely hope you not only get relief from your suffering but also complete remission. I just hope you do it in a way that won’t lead you or others to false hopes based on questionable practices.

    *(Just in case my words seem too salad, I view gay marriage as an overwhelmingly positive thing and a basic human right.)

  37. Quill says:

    @irenef: you assumptions about that which you know not are not very precious.

  38. Sialis says:

    If rituximab is genuinely effective, your actions will almost certainly delay its acceptance.

    WLU, would you please explain to me how this would be the case? How would the actions of one physician doing their own in-house trials delay the acceptance or proper testing and trials of that drug by others elsewhere?

    @WLU, in any case, I have to say you seem to have the risks associated with this whole patient/doctor test-this, try-that thing down cold. I’m rather impressed.

    I spent about an hour yesterday begging my doctor to just try something for some pain relief. I can’t tolerate most medications and have already tried the usuals. This article couldn’t have been more timely since we were discussing DMARDS. I’ll hold off without anything for a while longer, and so I walked away without a prescription. It’s rough not having any effective treatment, especially for disabling symptoms. I completely understand where irenef and Kati are coming from, but I hope they set a cut-off point, otherwise it’s too easy to be misled into trying one unproven treatment after another, chasing rainbows, expensive ones at that.

    Thank you Dr. Hall, for bringing this questionable treatment to our attention. My 23 yr old granddaughter has recently been diagnosed with RA…

    @Janet, I’m of the impression that Dr. Hall meant this treatment as being questionable for use with CFS patients. It is accepted treatment for those with RA.

  39. Harriet Hall says:

    @Janet and Sialis,

    Yes, as I mentioned, Rituximab is an FDA approved treatment for RA and several other conditions. Nothing I wrote can be construed as a reason to be suspicious of its use for RA.

  40. Harriet Hall says:

    I have no problem whatsoever with patients trying experimental treatments when they are out of other options and are informed of the risks. I fully empathize with patients who are desperate for relief.

    It may seem cruel to ask for controlled studies before treatment, but it is kindest in the long run. When multiple anecdotes of improvement circulate, it becomes just that much harder to accept later results of well-controlled trials. Stories trump science in our psychology. Jumping the gun muddies the waters. If patients had no access to these treatments outside of clinical trials, the pressure of public opinion might lead to funding.

  41. irenef says:

    @William Lawrence Utridge:

    Quitter…watch Monty Python much?

    Except for a nasty headache and an unpleasant jetlagged/wired/underslept feeling with a touch of tremulous hypoglycemia–possibly because I forgot last night’s meds–I am doing okay today.

    @Janet:

    Thanks for your kind words. I hope the kids do okay.

    The only reason I’m here is that I think the regular posters are essentially honest if perhaps overconfident, but not really nasty. The big danger in skepticism is being overly skeptical–thinking you know more than you really do. I would hesitate before making the kinds of assumptions some of these people make.

    @Quill:

    Re: people’s time. I don’t know. I discussed the decision with my husband. He bills very high, but for me … special. I have paid Open Medicine for their time. The commenters here? I don’t know. I don’t think they are looking for compensation. I’m a slow writer. I can’t extrapolate very well from me to them.

    The recurring $300–let’s call it $1500 for the sake of argument. It would have gone to paying off bills.

    Very few people know me or know of my treatment. I am not a blogger, I don’t get too involved with online forums.

    I’m not going to get into gay marriage anymore. I used it metaphorically and you are choosing to use it literally.

    You say you would be tempted to do the same? I think many people would. You can’t be risk averse and do this. Or, to put it another way, life has to really suck.

    Confession: I have been feeling better, off and on, since I had my last infusion a month ago. I just am not comfortable making any kind of statement to the world at large, because I am not sure it it will last. And the improvement is modest right now. Really, laughably modest.

  42. nybgrus says:

    I had no intention of jumping into this fray but I feel I must.

    Forgive me if I make some mistakes due to lack of information. I did re-read Dr. Hall’s post just to make sure I got the point of what she was trying to say.

    Firstly, in the case of Irenef, I tend to agree with her. She is absolutely within her rights to seek any treatment she wishes for any condition, and Dr. Kogelnik is perfectly within his rights to prescribe and provide her any treatment so long as it is under fully informed consent. From what Irenef is saying, she seems to be clear that this is a purely off-label and experimental use of a drug not at all in conjunction with any clinical trial. At base, neither party seems to be violating any rules, laws, or ethical standards.

    I do not think the same can be said about Kati. Regardless of Dr. Kogelnik’s intent, it at least seems as if she is under the impression that this is some sort of study. The understanding of the treatment is fundamentally different between the two persons. Since it is the physician’s onus to ensure the patient has proper understanding in order to fulfill the requirements of informed consent, it is his responsibility to rectify this misunderstanding. Whether this is an actionable level of misinformation is not something I can determine.

    All that said, it seems as if Dr. Kogelnik is potentially misleading Kati at least, if not Irenef. Part of this could be the very fact that Open Medicine is stated as being a research consortium of sorts and this could lend the false impression or it could be an intentional impression for false means. Regardless, is the the onus of Dr. Kogelnik to ensure that the research mission of OM is not misconstrued in his off label treatments of patients. If he is running a non-registered and not fully informed clinical trial of any kind, this is a serious violation, even if he has no intention of publishing his findings. And it seems, from what Dr. Hall has presented, that some degree of this appears to be the case. This may not apply at all to Irenef, but as long as it applies to at least one person it is of serious concern.

    As for why doing such “research” would likely delay the acceptance of ritux for CFS if it were a legit treatment – it is simple: it would become a black sheep and much harder to study by legitimate groups because of perceptions of guilt by association. It wouldn’t necessarily be fair but it would reflect reality. The lone maverick doc thing just doesn’t help in the long run.

    In the case of Irenef, I can see no such rationale. And this is coming from a “staunch card carrying skeptic firmly against CAM.” In the case of fully informed consent Irenef has every right to utilize her resources – regardless of who thinks they may or may not be “chump change” – for whatever means she wishes. Such is a free society. Sure, we could argue that resources are much better spent elsewhere and I think we would be scientifically correct. But unlike some commenters here think of me, I am not in the game of forcing everyone to my standard of scientific evaluation. If she wanted to try fermented antler velvet also her choice. Both avenues would be a waste of resources, but they are hers to waste.

    Now from the scientific standpoint there is no rationale for administering ritux for CFS. There can’t be since we don’t have good clinical data to support it and we (obviously) don’t know the pathophysiology of CFS in order to employ Bradfrod-Hill criteria for scientific plausibility. So on this level I would simply advise Irenef that if she wouldn’t be willing to waste her money and time on fermented antler velvet she shouldn’t be willing to waste it on ritux treatments. If she understands this but still wants to anyways, I would implore her to be vigilant of her progress and set an a priori cut off point where she is comfortable saying it doesn’t work for her.

    From a medical ethics standpoint however, I don’t think Dr. Kogelnik has a leg to stand on. Off-label use doesn’t mean “make up whatever you want.” There should be scientific rationale for the off-label use and the amount of evidence available simply cannot meet muster for that. If it did, the standard would be so low as to be meaningless. But that is an issue to take up with his employer (if any) and the state medical board.

    On the allegations of pseudo-trial running, that is a much larger issue and should be the focus of this discussion – not bashing Irenef for making an informed decision that we disagree with. Regardless of whether we are right about our scientific opinion on the matter. I didn’t want to enter the discussion because I don’t have the time, energy, or desire to do the legwork on taking a serious stance as to whether Dr. Hall’s allegations regarding the pseudo-trial running are accurate. I also trust her integrity and ability and believe that if she thinks this is the case, she has good reason to. But I am not about to jump in and add my own voice without having done my own work on it.

    But when I see the commenters here bashing someone who is clearly rational and informed, albeit making a decidedly poor decision from a scientific standpoint, it saddens me a bit and I felt the need to speak up. You guys aren’t clinicians so I suppose it isn’t fair for me to hold you up to the same standard, but at least a standard of decency should apply. Of course, it is a free.. um.. internet… so you may of course do as you please. But I believe it is counterproductive.

    I’ll close by saying to Irenef – despite the unnecessary bashing, they are right in principle at least. There really is no scientific rationale to justify taking the ritux for your condition. I also absolutely believe your condition is real, but that we simply do not know the etiology of it. There are distinct dangers with taking ritux (and aspirin too – I wouldn’t recommend taking that either). And there is also the danger of confirmation bias if your condition improves – we simply would have no idea what caused the improvement. I absolutely appreciate your consternation and the debilitation your condition causes. I would simply implore you to save your money, resources, and energy since in cases where we genuinely don’t know – like this one – all the evidence shows us doing nothing is usually better than doing something. If you still wish to pursue the treatment knowing full well the complete lack of scientific rationale for it, so be it. I would merely ask that you be kind enough not to make it a point to tout the ritux as a cure for CFS if your condition improves because nobody could possibly know that to be the case.

  43. irenef says:

    @Quill:

    “you assumptions about that which you know not are not very precious.”

    Sorry? I don’t get that.

  44. nybgrus says:

    Seems Dr. Hall and I posted at the same time.

    I agree with her concerns about anecdote – if a number of these off label trials lead to a few people having improvements and attributing it (rightly or wrongly, we simply cannot know) to the ritux, then a legitimate trial showing no effect would be much harder to convince people with. Hence my beseech at the end of my post.

    That said, Dr. Kogelnik should be held accountable by his peers for what I can only see as irrational and irresponsible off-label use, regardless of the level of informed consent of his patients.

  45. irenef says:

    @nybgrus

    Here, here. Thank you.

    The rituximab treatment was based on serendipitous results from Norway. I think Dr. Hall mentioned that.

    There is a rationale for the treatment having to do with dysfunctional signaling between natural killer and B cells. I don’t think it’s necessary to go into it now, but let’s just say there’s more to it than the healing qualities of fermented antler velvet.

    I have several years of frozen blood samples sitting in a university lab, so if I do improve there’s at least the potential for someone to see what they can find in before and after samples.

    I have no intention of touting ritux as a cure. I am no kind of evangelist.

    A responsible journalist–I know I’m not talking to a newsroom, but there are points of comparison, as this is a public forum that wishes to assume a mantle of scientific impartiality–would never publish accusations of irresponsible behavior without contacting the person or corporate entity being accused. No one here has bothered to do this, which brings into question the impartiality of at least the practitioners of science-based medicine and dilutes any claims to authoritative knowledge.

  46. nybgrus says:

    @irenef:

    The serendipitous results are not sufficient scientific rationale.

    I do not know enough about dysfunctional signaling between NK and B cells, especially in the context of CFS to comment, though to my knowledge such a pathophysiological link has not been documented.

    As far as I know, while the rationale for ritux is undoubtedly more than that of fermented antler velvet, it is still not enough to warrant its use and for all practical and clinical applications the two can be considered equivalent. For research purposes, that is a different story.

    You seem educated enough on the topic and if you have sources I would be interested to read them (regard the NK/B cell/CFS interaction). If anyone else does I welcome that as well.

    The years of frozen blood samples could prove to be a useful hypothesis generator in the future. Hopefully that pans out.

    As I said, I have not reviewed the primary source data of Dr. Hall to further expound on it myself, but I trust her integrity enough to say that she is likely correct in her assertions of research impropriety and that she hedged her discussion of the matter adequately. For the purpose of calling to light potential research ethics violations and cautioning that the use of ritux for CFS is entirely premature and off-label use is unfounded, I do believe she has enough data to say that. If the veracity of her data is in question that is another story entirely, though as I said I certainly trust her ability and integrity on the matter. I am also absolutely certain that if more information comes to light that explains the data differently she would be the first the admit so and retract her comments. But as it stands, it seems research ethics violations may well be in play and regardless, ritux for CFS as off-label use is scientifically unfounded (with the unlikely exception of strong prior probability based on references I don’t know to exist on the pathophysiology of CFS).

  47. irenef says:

    @nybgrus:

    Right now I’m not healthy enough to leave the house. The only resource I have is PubMed, so all I could provide would be what’s there. I’m not really sure I’m up to a literature search, either, so I’m not willing to make a commitment to that. I also don’t know how up to date their indexing is.

    I also don’t know why I, as a patient, should be expected to know the pathophysiology of my diagnosis.

    No one here knows much about the pathophysiology of CFS. Even coming from a self-confessed position of ignorance you still feel qualified to criticize someone else’s therapeutic choices.

    I am willing to play the role of guinea pig and have told my doctors as much.

    If y’all wanted to help instead of kibbitz, you’d write a grant proposal, get funded, and do some actual work. It’s actually an interesting disorder. An unequivocal, practical diagnostic test would be a good start.

  48. irenef says:

    @nybgrus:

    Look at what Nancy Klimas has done.

    Here’s a start:

    Brain Behav Immun. 2010 Oct;24(7):1209-17. doi: 10.1016/j.bbi.2010.04.012. Epub 2010 May 4.
    A formal analysis of cytokine networks in chronic fatigue syndrome.
    Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Fletcher MA.

  49. elburto says:

    Irene – Where did nybgrus imply that you should know?

    Nybgrus – nobody was “bashing Irene”

    Dr Hall had written about some seriously shady “research”, and that was being discussed. Then, straight out of the gate, Irene posts:

    And yes, I *do* deserve scientifically and ethically sound treatment, thank you very much. Got some?

    Nobody said she (whoever she is) or anyone else didn’t deserve treatment.

    Yours in pathos, ignorance and victimisation

    Huh? Until that point people had been discussing the doctor who was apparently misleading patients. Nobody said “People with CFS are pathetic ignorant victims”

    That initial comment is followed by more concern over this “pilot study” and the necessity of registering trials.

    Irene comes back with allegations of ad hom attacks against her doctor, criticism of Dr Gorski, and comparing Dr Hall’s criticism of Kogelnik to laws denying gay couples of their human rights. Signed off with more passive-aggressiveness;

    I’m pretty much housebound, can’t do much, in constant pain, all that fun stuff. So what I supposed to do? Listen to my betters and suffer in compliant silence? What have you done for me lately?

    It’s like she’s either picking out keywords and commenting on them, regardless of their context, or having a conversation that we can only see one side of. Who said that CFS patients should be denied treatment, should never complain, that they were inferior?

    Back to Irene – like I said, I understand your frustration, but research takes time. Some people will never live to see a miracle cure for their illness. However, railing at any skepticism or criticism is counterproductive.

    I mean, after the car-crash that was XMRV (which is still being touted as gospel truth by some) are you surprised that people are urging caution?

    Anger and frustration are natural. I’ve spent almost an exact year in this bed. I was moved off it once to facilitate a mattress flip. I stayed in my sling the entire time, then was lowered back down. I’ve seen nobody but my wife, my doctor and my district nurse team in that year.

    I’ve been too ill to attend hospital appointments, I’ve had to miss funerals (including a parent), my best friend’s wedding, new babies, birthdays, Christmas, etc. Add the unrelenting pain that gave morphine such a huge kick up the ar$e that I might as well have been taking Skittles, and it’s been a hell of a year.

    One year in exactly the same spot, without leaving the room. I’ve got frustration, confusion, disappointment, and every other negative emotion, in spades. Like I said earlier, my two main disabling health problems have no exciting new research, no studies.

    Condition #1 is officially a rare disease, with only one US foundation dedicated to research.

    Condition #2 has only one advocacy group in the UK that cannot convince the establishment that one size does not fit all patients. They are entirely member (ie. patient) funded. A recent EU-wide symposium revealed that woo and sCAM are trying to gain ground, and causing demonstrable harm to condition #2 patients.

    So I’m alarmed, and concerned that nobody will ever gain ground in furthering knowledge of these problems, as they’re not ‘sexy’ or exciting enough to matter to researchers, let alone gather funding.

    However, jumping on board such dangerous “treatments” as MMS, or wasting time and money on nonsense such as homeopathy, acupuncture, Rife etc. is just pointless. That’s especially true given that the time and money could be spent productively on assisting those who are trying to set up case studies of varying treatment regimens.

    So my choices are nonexistent. But I’m hopeful that things will improve in the future for others, that genetic research could yield a cure, that. transplants might work, that using stem cells may be an option. That the mechanism behind #1 is found, studied, and reversed.

    Until then, I just have to bide my time, and that doesn’t involve having a google alert for #1 or #2, or shouting down criticism or scrutiny, or spending my online time on the solitary websites for #1 and #2, reinforcing my negativity, and jumping at shadows of false hope.

    I’d quickly lose the last traces of my sanity if I lived like that, as I’ve seen in others. I’m also not going to demand that commenters on SBM either propose their own hypotheses and compete for grants, or shut up altogether. I thought you Americans loved your free speech?

    I have to take every day as it comes. I have to be grateful that I have a bed to lie in, and a wife to love and care for me, and a smartphone. There are too many 35 year olds who simply aren’t that lucky. That’s why I get annoyed at people who profit from misery, and exploit the vulnerable and desperate, because life’s bad enough as it is, without deliberate harm being added to bad luck.

  50. nybgrus says:

    @irenef:

    I apologize if you perceived my writing as an expectation that you should know the pathophys of your condition. Based on your specific comment about NK/B cell interaction it sounded like you did not that you should. I was merely asking that if you did, could you share some references you had handy. I do not expect you to do a lit review.

    No one here knows much about the pathophysiology of CFS.

    My contention is that it is not just those here who don’t know about the pathophys of CFS… nobody does. It was a topic we discussed in medical school and that was the extent of the discussion – that it is a diagnosis of exclusion.

    Therefore, the statement of ignorance justifies my stance that there cannot be rationale for off-label use of a drug. Without a decent amount of clinical data or at least an understanding of the actual pathophys of the disease, how can one make a rational decision about therapy?

    In other words, it is not my ignorance making claims, I am claiming the ignorance of medical science. If there is evidence to the contrary I am quite open to it.

    The last bit is also unfair. We each have our lives, jobs, studies, and expertises. I do sepsis and comparative effectiveness research – I can’t just suddenly change gears and do CFS research. But what I can do is comment on the scientific aspects of treatments of diseases and caution people against using treatments with no way to know the likelihood of success. History has shown us that in cases where we don’t have an understanding of something, doing anything is usually worse than doing nothing. That is all I am advocating. I can fully understand the frustration and desire to do something. As such I cannot fault you or anyone else for doing that something, regardless of whether I think it is scientifically justified or not. But what I can do is state the case of science, so that others who may – upon further information – change their thoughts on pursuing a course of action. If you recognize that there is no grander utility beyond maybe helping yourself (and nobody else, due to the nature of the therapeutic regimen you are doing) whilse acknowledging that it is at best a long shot and at least as likely to harm as help (and much more likely to harm) and you still wish to pursue this treatment, that is absolutely your right and I respect it.

    But it is still my right to discuss the lack of scientific rationale and to critique a colleague of mine as acting unethically simply based on that fact alone.

  51. nybgrus says:

    @elburto:

    First off, I am genuinely curious as to condition 1 and 2. I’ll take you at face value that you have these conditions regardless of whether you name them or not, but I am genuinely curious.

    Also, people did begin to bash Irene. Whether it was expected, reasonable, or justified is a separate question. I personally feel as a (aspiring) clinician that I should hold myself to a higher standard and take the short end of the stick in such situations in refraining from the bash. I also clearly stated that others here aren’t and I can’t hold them to my standard, but that I felt in this situation it was counterproductive. This is not a creationist or Joe Mercola we are dealing with.

    For that reason both here and in practice I accept a higher amount of “abuse” from patients since I acknowledge that in their shoes I would be very hard pressed not to act differently. It is not an excuse for the behavior, but an acknowledgement of empathy. I am certainly not perfect at this, and anyone here can track down my failures of the past, and I will certainly fail in the future. But whenever I can, I try and live up to the ideals I strive for in this regard.

    I’m reminded of my mother (an RN) commenting about a particular hospitalist and saying she could never understand why he let patients abuse him so (verbally yelling at him and calling him a shitty doctor). He said that it was his burden to accept their abuse in order to work past it and achieve his goal of improving their health and their life. At the time this did not resonate with me as it does now. But learning more and actually caring for patients myself has made that lesson stick. I’m not a burger flipper who can tell off a patron who yells at me for neglecting to remove the pickles from her hamburger. I’m literally dealing with the single most important and valuable thing someone has – their life and their health. If I demand a uniform and rigorous standard from my colleagues, I’d be quite hypocritical to not to so myself… anonymously on the internet or not.

  52. pmoran says:

    elburto, man, — wow! No words can do justice to that.

    (Not meaning to respect the disability of our CFS visitors any less, or their right to pursue treatments at their own expense and risk, and, to a considerable degree, according to their own judgment.)

  53. WilliamLawrenceUtridge says:

    No one here knows much about the pathophysiology of CFS.

    Nobody anywhere knows much about the pathophysiology of CFS. It is entirely possible the condition is neurological or even purely psychological. I know patients object to the possibility, I know they find it insulting, but the reality is CFS is a diagnosis of exclusion. It is not known if there is “one” CFS, multiple potentially separable subtypes, or multiple completely different types that get lumped together. Nobody knows, and the insults, harassment and condemnation both experienced by and made by CFS patients doesn’t help.

    Even coming from a self-confessed position of ignorance you still feel qualified to criticize someone else’s therapeutic choices.

    Yes, for very good reasons listed repeatedly above. If nothing else, the fact that publicly discussing your treatment has tremendous potential to delay research is a reason to take down your blog and remain silent about it on message boards.

    An unequivocal, practical diagnostic test would be a good start.

    Absolute agreement there. However, chances are it would merely result in shrinking the pool of CFS patients as those who can get diagnosed are no longer given the diagnosis of CFS and called something else instead. The central symptom of CFS is fatigue, which is nonspecific and extraordinarily common. An unfortunate reality.

  54. geo says:

    I can certainly see the problems related to patients trying a treatment like Rituximab at this point, even with informed consent. But given the way in which CFS patients have been routinely treated by many medical staff, it seems very strange to focus upon the use of Rituximab as an example of poor medical practice.

    Many patients have been treated as if their symptoms were a result of depression, or a fear of exercise, or just deconditioning, without informed consent and based upon even weaker evidence than that which currently supports the use of Rituximab as a treatment for CFS.

    If we were to compare the problems with the Rituximab study to the problems found with the PACE trial, the largest and most expensive investigation of biopsychosocial interventions for CFS, run by the psychiatrists who developed these interventions:

    Rituximab trail showed no significant result at what had been determined to be the primary end point in it’s protocol. PACE still has not released what had been determined to be it’s primary outcome measures, and completely abandoned most of the outcome measures laid out in it’s protocol, while refusing Freedom of Information requests for this data, eg: http://www.whatdotheyknow.com/request/pace_trial_recovery_rates_and_po

    In the blinded Rituximab trial patients were not questioned about whether they thought they recieving active or placebo treatment. PACE was entirely and necessarily unblinded. Evidence from subjective questionnaire scores did not correlate well with data from more objective outcome measures, like the walking test or number of patients on disability benefits, but it was jsut subjective questionnaire score used to promote efficacy.

    We have not identified a testable mechanism to explain the value of Rituximab as a treatment. In the editorial which accompanied PACE it was explained that while the models seem to be wrong, the (minor) improvements in subjective questionnaire scores are enough to justify these approaches. The models which underpinned CBT and GET as treatments for CFS have been tested, and found lacking.

    There is a danger that patients with CFS could try Rituximab before there is good evidence of efficacy, despite the researchers involved saying that we should wait for more evidence and RCTs. The researchers from PACE have been saying that all patients with CFS should try their treatments, and that the only reason some patients do not want to devote more resources to them is anti-psychiatry or a fear of the stigma of mental health.

    It seems that the promotion of psychosocial treatments for CFS is less ethical and more widespread. It would be wonderful if the high standards of care promoted above were a normal part of how CFS is treated, but at the moment it is not, and it seems strange to focus upon the use of Rituximab as an area of concern.

  55. nybgrus says:

    it seems very strange to focus upon the use of Rituximab as an example of poor medical practice.

    Dr. Hall certainly wasn’t. That was part of the focus. The other part was the implications of the information found regarding the research and ethics of OM.

    Also, it makes perfect sense to point out that ritux is not reasonable to use for CFS outside a properly conducted study. In fact if I were sitting on the IRB to approve such a trial I would be extremely reticent because ritux is serious drug with serious side effects and from what I know currently there is not enough scientific data to justify the potential harm to study subjects to meet ethical standards. No matter how you slice it the discussion is reasonable.

    And this isn’t the only discussion of CFS that has been had here at this site.

    Many patients have been treated as if their symptoms were a result of depression, or a fear of exercise, or just deconditioning, without informed consent and based upon even weaker evidence than that which currently supports the use of Rituximab as a treatment for CFS.

    That is a misunderstanding. CFS is, by definition, a diagnosis of exclusion. That means that in order to diagnose it we must rule out all those other conditions you listed. Often this means trying the treatment for each one. If it doesn’t work we rule out the Dx. It is absolutely not correct to called that “without informed consent” since the patient is informed that the provisional (i.e. most likely) Dx is [X] but it could be other things and treated for that knowing they would move down the differential diagnosis until CFS is reached at the bottom. It is the only way to scientifically do it.

    It seems that the promotion of psychosocial treatments for CFS is less ethical and more widespread.

    Considering that it is likely at least a subset of what gets callsed CFS is psychosocial in nature and everything we know would indicate that psychosocial outlook would influence the symptoms of CFS regardless of the underlying cause, it hardly seems unethical to treat it psychosocially. Unfortunately the stigma of such treatments remains, and indeed the medical field would do better to actively reduce that stigma, but the fact remains it is not only ethical but probably the best treatment we actually do have, especially considering there is no better one elucidated.

  56. nii says:

    Many patients are wary of graded exercise therapy (GET) and cognitive behaviour therapy (CBT) involving the scheduling of increased activity or exercise, due to the adverse events that have been associated with the therapies. See, for example:
    Kindlon T. Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Bulletin of the IACFS/ME. 2011;19(2):59-111

  57. irenef says:

    @WilliamLawrenceUtridge:

    “…the insults, harassment and condemnation both experienced by and made by CFS patients doesn’t help.”

    Except for a single post by another patient, I think I am the only CFS patient here. I have not consciously insulted, harrassed, or condemned anyone. I have not labeled anyone or implied that anyone is unethical, irresponsible, pathetic, passive-aggressive, or a host of highly inflammatory terms that have appeared in this discussion.

    “If nothing else, the fact that publicly discussing your treatment has tremendous potential to delay research is a reason to take down your blog and remain silent about it on message boards.”

    I don’t have a blog. My discussions here are far greater than anywhere else. I don’t see how anything I’ve said has the remotest influence on research. Attempting to silence someone because you disagree with their personal medical decisions is moving to a place I’d rather not go.

    ” The central symptom of CFS is fatigue, which is nonspecific and extraordinarily common.”

    No, fatigue is not the central symptom of CFS, and the use of “chronic fatigue syndrome” as the name of the condition is misleading for that reason. The term is way too broad and non-specific and leads to confusion.

  58. geo says:

    @ nybgrus

    I do not see what it is that you think I have misunderstood.

    I was describing models of CFS which have been used to justify the treatment of patients, not alternative diagnoses. Also, the cognitive aspects of some of the psychosocial approaches taken to CFS (which should be seen as only experimental) make it difficult for informed consent to be given. If a ‘treatment’ involves encouraging a patient to believe that their illness is “real but reversible by his or her own efforts”, then genuinely informed consent requires that a patient first be informed how likely it is that these cognitions are true, which would rather undermine the treatment. Perhaps this is why those researchers promoting and making money out of these interventions are so keen to avoid releasing data from publicly funded trials in the manner laid out in their published protocol: http://www.whatdotheyknow.com/request/pace_trial_recovery_rates_and_po

    “everything we know would indicate that psychosocial outlook would influence the symptoms of CFS regardless of the underlying cause, it hardly seems unethical to treat it psychosocially.”

    What does this really mean? All human behaviour and experience is heavily affected by psychosocial factors. The difficulties still faced by African-Americans will be affected by psychosocial factors – but medicalising the cognitions and behaviours of all African-Americans because of this would still be recognised as poor practice, and the unreasonable views of African-Americans such an approach would require and promote would be recognised as a cost ‘treatment’. Considering that medicalising and treating the cognitions and behaviour of all CFS patients seems to lead to only small improvements in subjective questionnaire scores in unblinded trials run by advocates, the unmeasured social costs to patients of such an approach is quite likely to outweigh any real benefits – social costs cannot be dismissed as mere ‘stigma’ by those wanting money for the psychosocial benefits that they bring to patients. If we are to hold those making money from the psychosocial treatment of CFS to the same standards those using Rituximab for CFS are being held to, then many of them seem much more deserving of criticism.

  59. Harriet Hall says:

    “many of them seem much more deserving of criticism.”

    If we tried to measure who deserves the most criticism and only write about those, we wouldn’t get much done.

  60. PernilleN says:

    Som update about the Norwegian research: Fluge and Mella’s application to the Norwegian research board for 9 million NOK (about 2 million dollars) funding for their RCT was turned down (… along with 400 other good applicants, so this is hardly discrimination against ME-patients). But the Norwegian Secretary of health has given then 4 million NOK, and there’s an ongoing crowdfunding project, so they will probably be able to start their RCT.

    @Irene: Kogelnik has said several times, e.g. to a Norwegian newspaper, that he has a project. He sometimes calls it a pilot study, sometimes a case-by-case study. He has also said, or implied, that he is collaborating with Fluge and Mella about it. According to you there’s no project but off-label treatment. It’s all rather confusing.

    Perhaps someone could ask Kogelnik to comment? Harriet Hall, I suppose you’ve tried asking him?

    About IreneF, I think many of you are confusing her with Kati, whose blog Hall quotes in her article. Irene has tried to say several times she doesn’t have a blog, but several people here keep criticising her for what she allegedly writes in her blog.

    What about believing what se says, and checking your facts?

    Regards
    Pernille Nylehn
    Norway

  61. WilliamLawrenceUtridge says:

    Except for a single post by another patient, I think I am the only CFS patient here. I have not consciously insulted, harrassed, or condemned anyone. I have not labeled anyone or implied that anyone is unethical, irresponsible, pathetic, passive-aggressive, or a host of highly inflammatory terms that have appeared in this discussion.

    I’ve interacted with CFS patients here and on wikipedia. In both cases I have been called stupid, insensitive and biased. I am pretty sure I know why the CFS patients react the way they do – their suffering is trivialized – but that doesn’t mean their claims are valid or mine are invalid.

    I don’t have a blog. My discussions here are far greater than anywhere else.

    Then clearly my comments do not apply to you, and you are welcome to consider them as abstract observations aimed at no particular individual.

    I don’t see how anything I’ve said has the remotest influence on research. Attempting to silence someone because you disagree with their personal medical decisions is moving to a place I’d rather not go.

    I would never try to silence someone because of their personal medical decisions. However, I will object to shoddy science, poor reasoning and decisions that have real-life consequences. I’m not arguing or advocating for blogs being shut down by some sort of ham-fisted state action. I’m merely pointing out that if someone tries rtuximab and ends up dead, comatose or permanently injured, some of the blame goes towards those who publicize their unscientific trials and create false hope for desperate patients.

    No, fatigue is not the central symptom of CFS, and the use of “chronic fatigue syndrome” as the name of the condition is misleading for that reason. The term is way too broad and non-specific and leads to confusion.

    From PubMed Health: “Chronic fatigue syndrome refers to severe, continued tiredness that is not relieved by rest and is not directly caused by other medical conditions.”
    From the CDC: “Chronic fatigue syndrome, or CFS, is a debilitating and complex disorder characterized by profound fatigue that is not improved by bed rest and that may be worsened by physical or mental activity.”
    From the 2011 ICC: “Marked, rapid physical and/or cognitive fatigability”
    From cfids.org: “CFS is characterized by incapacitating fatigue (experienced as profound exhaustion and extremely poor stamina)”
    From MEFMAaction: “The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level and is usually made worse by exercise”

    There are other parts to the definitions, but clearly fatigue is at least one core symptom. I doubt that if someone had all the symptoms except fatigue you would be diagnosed with CFS, ME or CFIDS. I’m delighted to see the ICC’s 2011 publication has identified “profound dysregulation of the central nervous system and immune system, dysfunction of cellular energy metabolism and ion transport and cardiovascular abnormalities” and hope it represents real and meaningful results, not just pandering. I was particularly intrigued to see a 2009 citation that appeared to indicate objective measures of mitochondria dysfunction in 71 patients. Then I noticed they recommended dietary supplements and detoxification and lost interest. Then I clicked on the lead author’s website and despaired. If nothing else, were her arguments factually correct it would indicate that a subset of CFS patients were not actually CFS patients, they had nutritional deficiencies – once again indicating that CFS is a wastebasket diagnosis including people with conditions that are undiagnosed, not people with a hitherto-unrecognized condition.

  62. Harriet Hall says:

    I wanted to ask Kogelnik to explain what he is doing, but I was unable to find a email address. I would appreciate it if one of his patients would ask him to comment here.

  63. WilliamLawrenceUtridge says:

    Unsurprisingly, it looks like Dr. Myhill has yet to find a form of quackery or logical fallacy she doesn’t like:

    http://drmyhill.co.uk/wiki/Detoxification

    That website deserves a heapin’ helpin’ of insolence. Respectful, of course.

  64. PernilleN says:

    And IreneF, when I said “poor souls”, I was talking about the Norwegian patients who travel to USA and pay 8000 dollars per treatment at OMI. I think some of them has managed to get funding, but most of them don’t. One of them has spent 200,000 NOK so far, which equals about 40,000 dollars. That’s rather a lot of money, don’t you think? And most patients with ME aren’t well off, but living on welfare money from the state, or supported by relatives.

    There are also several British patients coming to OMI for treatment, I suppose they pay the same price, plus travel expenses.

  65. KAL says:

    I think there are some good points being made here once you sift out the misinformation.

    * I think venture philanthropy has been confused with venture capitalism.
    * XMRV was science working the way it is supposed to work and scientists whose work is not replicated are not automatically frauds they are mistaken. Happens all the time in science – just ask John Ioannidis.
    * Big Pharma is a regulated business that should probably be more closely regulated. If you don’t like “evil” artificial interventions then don’t take them. It’s pretty simple really. At least in the United States, no one can force a treatment you don’t want on you.
    * There seems to be some confusion between what is appropriate for an individual vs how science is done. The decision between a physician and a patient to use a drug off-label, as pointed out, is not illegal or necessarily unethical. However, decisions about whether a drug is appropriate for entire populations must be based on clinical trials not individual (N=1) successes or failures. That requires significant sums of money regardless of how it is obtained and no matter what the treatment or the disease.

    * Regarding ME and CFS, there are multiple definitions (both clinical and research) that define very different populations. The broader and less specific the definition the more likely it is to draw in people who are not ill or patients who have other diseases. Currently definitions range from the least specific (White et al 1991) to the most specific (Carruthers et al 2011).

    For example, GET and CBT apparently do help a modest number of people (about 15% over standard care for GET), but the evidence base is very narrow and it is premature to extrapolate to patient groups who have not yet been specifically tested and are defined very differently from the original group tested. In the case of GET this would be patients with post exertional exhaustion lasting 24-hours or longer, unrelieved by rest and upon minimal exertion.

    The gold standard for making comparisons across groups of patients identified by varying case definitions would be studies with completely separate cohorts by definition, not one large sample with embedded subgroups.

    It is quite possible that ME and CFS are multiple discrete entities under an umbrella term. If so, the answer is may be subgrouping – not trying to make treatments one size fits all. Different forms of arthritis for example have very different causes and treatments as does hepatitis.

  66. mousethatroared says:

    @Geo – I don’t know if you’ve had a chance to read any of James Coyne’s posts on this blog – if not check them out. He is quite outspoken/skeptical of some claims of benefits from psychological interventions and how those claims are published. He does focus primarily on cancer, though, so it’s not a perfect fit. But I don’t think it’s too outlandish to wonder if reputable journals are publishing questionable studies about the benefits of some psychological interventions in cancer survival rates, that there may also be questionable studies published in popular psychological interventions and CFS.

    Personally I’d love to see an article on that topic – but I’m a big fan of skeptical psychologists like Scott Lilienfeld, Jean Mercer and Coyne. Not because I’m against psychology, but there is alot of bad psychology, bad therapists and bad advice out there. Things could be so much better with more skepticism applied.

  67. WilliamLawrenceUtridge says:

    For example, GET and CBT apparently do help a modest number of people (about 15% over standard care for GET), but the evidence base is very narrow and it is premature to extrapolate to patient groups who have not yet been specifically tested and are defined very differently from the original group tested. In the case of GET this would be patients with post exertional exhaustion lasting 24-hours or longer, unrelieved by rest and upon minimal exertion.

    I’m willing to bet shiny money that if you did a series of careful studies on those who respond to those two interventions, they would have significantly different characteristics from the overall average. It’s a wastebasket, hopefully it’ll turn into a recycling bin.

    Assuming everyone else’s recylcing program involves separating out paper, plastic, mental and compostables.

  68. geo says:

    @ H Hall:

    “If we tried to measure who deserves the most criticism and only write about those, we wouldn’t get much done.”

    That’s true.

    @ KAL:

    “For example, GET and CBT apparently do help a modest number of people (about 15% over standard care for GET), but the evidence base is very narrow and it is premature to extrapolate to patient groups who have not yet been specifically tested and are defined very differently from the original group tested.”

    It’s also important to note that those figures (assuming that they are from PACE, which it looks like they are) are for quite an undemanding criteria for clinically significance – much less stringent than the criteria which had been laid out in the trial’s protocol. Secondary data from the trial, like the failure to improve the amount of paid employment those in treatment groups were able to do, could indicate that the subjective questionnaire scores used as primary outcomes are not be entirely reliable. Evidence from earlier trials of CBT for CFS have shown that it leads to patients answering questionnaires more positively, but not being able to increase their objectively measured levels of activity. That has not stopped those providing these treatments from claiming that PACE showed a recovery rate of 30-40% for CBT and GET. If homeopaths had behaved similarly with an unblinded trial of their treatments, I do not think that many people would be impressed.

    @ mousethatroared:

    I agree. Unfortunately I think that people are less likely to spend time upon a critical analysis of the evidence surrounding psychological interventions for CFS because of the uncertainty and controversy that surrounds CFS itself. Discussions very often descend to uninteresting observations about the fact that it’s possible for emotional problems to cause physical symptoms, the danger of dualism, or that patients are so ungrateful for the psychosocial research being done on them because of their unreasonable views about mental health matters. Also, almost all of the work around psychosocial aspects of CFS is done by those with an interest in justifying psychosocial interventions. Data is very often presented in misleading ways, so it takes a lot of work to be able to consider: ‘Do we really know what we’re doing here? Are we doing more good than harm?’

    When there is so much uncertainty, and so little good quality research, it’s very easy for people to just assume that they can trust those who are making money as experts in this area.

  69. irenef says:

    This page has contact info. for Open Medicine Inst./Dr. Andreas Kogelnik:

    http://openmedicineinstitute.org/contact-us/

  70. Harriet Hall says:

    @irenef,

    I found that page but it only offers contact information for the Institute, not Dr. Kogelnik’s e-mail address. Since you are his patient, why don’t you contact him yourself and make him aware of my article and ask him to respond in the comments?

  71. irenef says:

    @Harriet Hall:

    You can reach Dr. Kogelnik using that e-mail address. I cc-ed him a link to your post yesterday. He’s aware of what’s going on.

    Here’s another link:
    http://openmedicineinstitute.org/research-initiatives/mecfs-merit/

    BTW, you and your colleagues have managed to silence Kati. I don’t think it was because of your superior and impartial reasoning, but through intimidation. Is that what you wanted? Do you feel like you struck a blow for rationality?

    There has been little discussion of your failure to contact *anyone associated with Dr. Kogelnik* before posting your criticisms. I don’t see much difference between your methods and AM radio “news”.

  72. Harriet Hall says:

    “There has been little discussion of your failure to contact *anyone associated with Dr. Kogelnik* before posting your criticisms.”

    In the world of science, we have no obligation or custom to contact researchers before we critique their research. Perhaps you think Dr. Gorski should have contacted Dr. Oz or Dr. Burzynski before he wrote criticisms of them; I don’t. Their record and their spoken and written words speak for themselves. Now that I know Dr. Kogelnik is aware of my article, I eagerly await his explanation of what Kati reported and of what Pernille tells us he has told reporters in Norway. If he was mis-quoted, he can set the record straight.

  73. WilliamLawrenceUtridge says:

    BTW, you and your colleagues have managed to silence Kati. I don’t think it was because of your superior and impartial reasoning, but through intimidation. Is that what you wanted? Do you feel like you struck a blow for rationality?

    This is a form of ad hominen, essentially saying you are free to ignore our substantive points because we are mean. However, the criticisms were presented calmly, with civility, and no name-calling. Perhaps you can call attention to the flaws in our “superior and impartial reasoning” rather than trying to shame us into silence for hurting someone’s feelings.

    Well-intentioned false hope is still false hope. Thinking happy thoughts does nothing to cure any disease. Shoddy science helps nobody over the long term, but it’s great at wasting scarce resources – both money and patients.

    Please feel free to respond to matters of substance instead of continuing with your current approach.

  74. David Gorski says:

    In the world of science, we have no obligation or custom to contact researchers before we critique their research.

    Complaining that a blogger didn’t contact the subject of her blog post is a common trope used by supporters of doctors who are doing dubious science to attack critics of such doctors. It’s a trope rooted in the thinking of journalists, not scientists. In journalism, in any controversy or scandal it’s obligatory to get a quote from the person at whom the criticism is being leveled. Kogelnik’s words and actions as described in the public record, including irenef’s blog, combined with Kogelnik’s website, are more than enough material for a scientific critique, either in a blog or in a scientific article.

    On the other hand, last year I did contact the Burzynski Clinic for comment about Marc Stephens’ harassment of skeptical bloggers who were criticizing Burzynski, but I did it more to see if I could get a response. I didn’t really expect one. Unfortunately, that means that Dr. Burzynski and his PR flack now have my university e-mail address, because I used that address to prove that I was an academic and not just some schmo off the street. :-)

  75. irenef says:

    @Harriet Hall:

    We are not in the world of peer review. This is not a scientific journal. It is a public forum about medicine.

    How can Dr. Kogelnik bear responsibililty for what his patient says in a blog? I don’t see how he could provide an explanation for what she “reports”, or what someone else claims he said to people–who may or may not be professional journalists–in a foreign country.

    No wonder science-based medicine is ignored by people who could benefit by a little critical thinking. You have convinced me that you are more invested in making points with each other than in discourse with the world at large.

  76. irenef says:

    @Gorski:

    This is at least the third time I’ve said this: I don’t have a blog. I never had a blog. I’m not going to have a blog. Move along.

    @WilliamLawrenceUtridge:

    No, I haven’t ignored your points, I’ve argued them. As far as Kati goes–the patient who had a blog–she didn’t go black because of any substantive points. You failed to convince her that she is pursuing false hope.

  77. Harriet Hall says:

    @irenef,

    Dr. Kogelnik is not responsible for what a patient says in a blog, but he is responsible for correcting the record if he discovers that he has been misquoted or misrepresented. He is also responsible for communicating accurate information to his patients and correcting any misunderstandings when he becomes aware of them.

  78. irenef says:

    @Harriet Hall, David Gorski, et al:

    I think you are preaching to the choir. You have failed to convince anyone beyond people who I think are regulars here of your arguments. You have failed to convince me of anything but your failure to communicate effectively with people with whom you disagree, which I believe is something you want to do.

    I am pre-disposed to agree with you. I have lurked, off and on, for a couple of years. I’m not completely ignorant. Yet you have alienated me, you have done the same to at least one other person, and some people here have expressed support for my position. What has this accomplished for you or anyone else?

  79. Sialis says:

    Many patients have been treated as if their symptoms were a result of depression, or a fear of exercise, or just deconditioning,

    That is a misunderstanding. CFS is, by definition, a diagnosis of exclusion. That means that in order to diagnose it we must rule out all those other conditions you listed. Often this means trying the treatment for each one. If it doesn’t work we rule out the Dx.

    Providers do tell patients that their symptoms are due to “fear of exercise”, or depression, as well as a host of other incredibly unethical and disproven pseudo-psychological diagnoses. It seems that most providers will readily prescribe an antidepressant or antipsychotic even to treat symptoms of muscle spasms, pain, tremors and dizziness just because they have no definitive test results that point to a confirmed disease. Too many doctors require a test result that says “The patient has Disease #5″. When a definitive test result is lacking, then the patient goes untreated, except for the offering of psychiatric medications, rather than attempt a careful trial treatment approach as described by nybgus. It seems to me that perhaps too many patients are incorrectly categorized as having CFS, or FMS simply because the physician doesn’t know what else to do.

    You have failed to convince anyone beyond people who I think are regulars here of your arguments. You have failed to convince me of anything but your failure to communicate effectively with people with whom you disagree, which I believe is something you want to do.

    I’m not completely ignorant. Yet you have alienated me, you have done the same to at least one other person, and some people here have expressed support for my position.

    I don’t see where anyone has called you names, or stated that you were ignorant. nybgrus made a few comments like the one shown below, but it is clearly about the concept in the statement, and not intended as a personal attack or insult. I think the misunderstanding here lies more with the fact that people here have different levels of communication and language skills – basic comments like the one below are being misunderstood.

    Therefore, the statement of ignorance justifies my stance that there cannot be rationale for off-label use of a drug.

    I find that nybgrus, WLU, Dr. Hall and others have been patient in explaining their points. I tend to give people the benefit of the doubt and consider that many may not have the communication skills and experience to engage in these types of discussions without misunderstanding some things. It has been a real learning tool for me to read and comment here. It takes practice, like most things, people need to learn how to disagree and express their viewpoints in the best possible manner. It can be difficult for patients to read how doctors talk about their condition.

    What has this accomplished for you or anyone else?

    It’s reinforced to me that it is counterproductive for one to turn defensive and make comments like this: “How dull the day has become. Someone, please, argue with me. This is the most fun I’ve had in months. Really.”. As far as nybgrus’ comments go, they should be written up in a textbook for physicians to study on how to communicate with patients. I’m at a loss as to how anyone could object to those statements, other than due to being ill and irritable and desperate for effective treatment, all of which I can completely empathize 100%.

    Other than confusion surrounding the owner of that blog, I see no other failure to communicate effectively. Effective communication doesn’t necessarily mean being successful at changing someone’s mind. That takes two, and both parties need to be open to it. Although, I think it is challenging for anyone new at reading information discussed in this manner to understand and relate.

    @Irene, I’m curious as to what you consider as being the central symptom of CFS if it is not fatigue. Would you share that with us please?

    @elburto, when you mention Rife, MMS, and homeopathy, it causes me to wonder if you have been diagnosed with Lyme disease.

  80. nybgrus says:

    Providers do tell patients that their symptoms are due to “fear of exercise”, or depression, as well as a host of other incredibly unethical and disproven pseudo-psychological diagnoses.

    Sure, there are lazy and/or bad practitioners. But that is not how we are trained nor what we should do.

    It seems that most providers will readily prescribe an antidepressant or antipsychotic even to treat symptoms of muscle spasms, pain, tremors and dizziness just because they have no definitive test results that point to a confirmed disease.

    Tough call to be so sweeping. There are many cases where it is evidence based and justified to administer such treatments, especially in attempting to make a diagnosis of exclusion, but even alone.

    t seems to me that perhaps too many patients are incorrectly categorized as having CFS, or FMS simply because the physician doesn’t know what else to do.

    This is true. And at my institution we have conferences and in-services regularly and many of them address these sorts of concerns directly.

    As far as nybgrus’ comments go, they should be written up in a textbook for physicians to study on how to communicate with patients.

    I’m genuinely flattered, thank you. I strive for excellence in communication, especially with my patients, and have a long way to go. But it is always nice to hear some positive encouragement, so thank you.

    I’m at a loss as to how anyone could object to those statements, other than due to being ill and irritable and desperate for effective treatment, all of which I can completely empathize 100%.

    Which is precisely why I don’t take such comments personally. I’ve been ill, injured, and post-op without narcotics (I’m allergic). It isn’t fun and it is very, very hard to keep ones words and thoughts in check no matter how hard you try. The additional motivation is that in any case, responding in kind does absolutely no good for anyone involved.

    Other than confusion surrounding the owner of that blog, I see no other failure to communicate effectively

    LOL. Yeah, that one was pretty glaring. But it happens. I re-read comments a lot, especially my own, to make sure I understand and also learn for the future. I once read that Ben Franklin was a terrible writer and so he set out to get better. He wrote and wrote and spent countless hours reading and re-reading his writing, critiquing it and learning from it. Ever since then I re-read my own comments at least once almost always (after I post them I mean, to learn from them after responses come in). Sometimes I am in a hurry or typing fast, but nobody is perfect.

  81. irenef says:

    @Sialis:

    When I first got sick, I had flu-like symptoms that would come and go. A neighbor thought I might have CFS, but I pointed out I felt sick, not tired. My symptoms have changed since then, and fatigue is a major problem, but it is one of many.

    Secondly, there’s no good definition of fatigue. I used to swim, and I’d be pretty beat after, say, 40 laps, but it wasn’t what I experience now.

    My symptoms now and in the past include:

    Muscle pain

    Sinus headache, congestion, occasional infections

    Sore throat

    Tachycardia

    Orthostatic hypotension

    Weakness

    Feverish sensations

    Light-headedness

    Hives

    Striated nails

    Depressions in my tongue

    Mouth sores

    Glazed, red eyes

    Circadian disruption

    Hypoglycemia

    Cognitive dysfunction/inability to concentrate/”brain fog”

    Memory problems

    Tremulousness/shakiness

    I probably have postural orthostatic tachycardia syndrome (POTS) and delayed sleep phase syndrome.

    My blood work shows antibodies to several infections that seem to be common among CFS patients: EBV, HHV-6, parvo B-19, Mycoplasma pneumoniae, and perhaps something else. I also have low NK cell function. I have wondered whether there’s a relationship between the higher-than-expected antibody production to this group of pathogens and the inactive NK cells. Not an infection but a consequence of an immunological dysfunction.

  82. irenef says:

    @sialis:

    I like to argue with people who are worth arguing with and who have something important to say. I don’t get to do it much. And I will concede a certain degree of snarkiness.

    I am not complaining about people calling me names. I don’t think I’ve misunderstood anyone. What I’m trying to express is more fundamental. What is the purpose of this blog? Are you, collectively, committed to changing people’s minds about choices in medical treatment? Do you think because you play by certain rules–that you seem to make up as you go along–you are winning the game?

    I love science. It’s one of the most fun things in the world. But I don’t think you’re doing a good job.

  83. PernilleN says:

    @IreneF, if you don’t mind my asking: You pay 300$ per treatment. But who’s paying for your medicine? It costs 6000$ per dose. Do you also get refund from Genentech foundation?

    Regards,
    Pernille Nylehn

  84. Quill says:

    “I like to argue with people who are worth arguing with and who have something important to say. I don’t get to do it much. And I will concede a certain degree of snarkiness.”

    If you knew your true worth, you could talk with anyone. If you knew the worth of others, you would know everyone has something important to say. If you ever allow yourself to discover what you -really- want to say, you will have limitless opportunities to say it. And if you had true self confidence, you would not need to hide and sneak behind elided lies, aka snark. Or so I’ve been told.

  85. irenef says:

    @PernilleN:

    I don’t want to discuss my financial arrangements any further.

  86. PernilleN says:

    @IreneF: Ok! :)

  87. mousethatroared says:

    @geo “Discussions very often descend to uninteresting observations about the fact that it’s possible for emotional problems to cause physical symptoms, the danger of dualism, or that patients are so ungrateful for the psychosocial research being done on them because of their unreasonable views about mental health matters. ”

    Yup, those discussions are not my favorite, either. :) And it’s hard to find a blog that focuses on real nuanced discussions on skepticism in clinical psychology, a shame.

  88. Sialis says:

    @sialis:

    I love science. It’s one of the most fun things in the world. But I don’t think you’re doing a good job.

    I’m not a scientist or a physician and I have done even better than a damn good job considering where I was at just a few years ago. In fact I have done such a damn good job that to most people the progress is unfathomable. In fact most people would not even believe me when speaking of the progress at first, but I’m building trust and support – and I’m doing that by not insulting and demeaning those who have the intelligence, training and experience to either possibly help me in the future by educating me a bit, or at least continue to offer emotional support and good will, and I intend to pass that along to others as best I can. I all too fully appreciate the dangers in the treatments, irrational off-label prescribing, bogus studies and treatment trials as described on this blog and others like it.

    As for why doing such “research” would likely delay the acceptance of (Fill in the blank for the drug and disease of your choice) if it were a legit treatment – it is simple: it would become a black sheep and much harder to study by legitimate groups because of perceptions of guilt by association. It wouldn’t necessarily be fair but it would reflect reality. The lone maverick doc thing just doesn’t help in the long run.

    This is so true, it seems rather apparent to me now that progress on any disease can be sabotaged by the very patients, and some of the physicians who are treating it.

  89. WilliamLawrenceUtridge says:

    No wonder science-based medicine is ignored by people who could benefit by a little critical thinking. You have convinced me that you are more invested in making points with each other than in discourse with the world at large.

    If cognitive psychology has taught us anything, you’re probably more interested in maintaining a pre-existing world view than you are challenging it through new evidence. The reason science took tens of thousands of years to develop is because it is strongly counter to this self-confirmation bias, and instead uses empirical results as its main measurement tool. That’s also the reason that it has completely transformed the world, including medicine, in a little over three hundred years (a little over a century if you consider medicine, most of the early scientific work in medicine involved disproving previously held beliefs, it took a long time to start developing novel, effective treatments).

    This is the reason why medicine uses experts (doctors) to channel treatments, because regular people are not up to the task. Even doctors, with years of training, still fall prey to cognitive biases on a regular basis. We are, after all, just monkeys with more wrinkles in their brains.

    @irenef: Are you still fatigued, persistently, and this is not relieved by rest? If so, it seems like you may still have the core symptom of CFS. If you are not fatigued, I wonder if you would be diagnosed with something other than CFS. Again, an imperfect wastebasket diagnosis.

    My blood work shows antibodies to several infections that seem to be common among CFS patients: EBV, HHV-6, parvo B-19, Mycoplasma pneumoniae, and perhaps something else. I also have low NK cell function. I have wondered whether there’s a relationship between the higher-than-expected antibody production to this group of pathogens and the inactive NK cells. Not an infection but a consequence of an immunological dysfunction.

    The real test is whether these markers are different from non-CFS controls. You always need a control group, otherwise all you can say is “X is Y”, which tells you nothing (unless you are attempting to establish a baseline).

    I am not complaining about people calling me names. I don’t think I’ve misunderstood anyone. What I’m trying to express is more fundamental. What is the purpose of this blog? Are you, collectively, committed to changing people’s minds about choices in medical treatment?

    Changing minds is extremely difficult to do, humans are self-justifying animals. Try reading Mistakes were Made (but not by me) by Carol Tavris and some other guy, it does a great job of this. Particularly when one is strongly invested in a position, it is very difficult to get them to change that position. It is an intractable problem common to nearly any non-empirical system of thought, be it CAM, CFS, off-label trials, politics and the like. Very rarely will any criticism reach or change the mind of the committed believer, I hope my comments will be read by fence-sitters who are more likely to change their minds because they haven’t committed to a position yet and are thus open to logic and evidence.

    I love science. It’s one of the most fun things in the world. But I don’t think you’re doing a good job.

    By endorsing a series of uncontrolled n=1 trials, you are not really supporting the idea that you understand science. How do you define it? And how do you reconcile your definition with thinking n=1 trials are a good thing?

    @Quill

    If you knew the worth of others, you would know everyone has something important to say.

    Heh, clearly I do not know the worth of others, because there are many people I know who have nothing important to say :)

  90. irenef says:

    @WilliamLawrenceUtridge:

    Yes, I have post-exertional malaise. Sorry for not listing it.

    “By endorsing a series of uncontrolled n=1 trials, you are not really supporting the idea that you understand science. How do you define it? And how do you reconcile your definition with thinking n=1 trials are a good thing?”

    I am doing no such thing. We’ve been through this before. There is no trial. I never said there was a trial. (I don’t have a blog, either.). I am receiving an off-label medication. I have explained some of my decision-making process and my rationale for doing what I am doing. I am not endorsing anything.

    Another patient, an RN, who had a blog, used terminology that may have been imprecise in the context of clinical trials. I don’t know much about nursing education, so I don’t know whether she could be expected to understand the niceties of scientific vocabulary. She was relating her personal experiences to the world at large, and trying to get funding and better treatment for CFS patients. Now this advocate has gone dark.

    Someone else is worried because a CFS patient in Norway is flying to California for treatment. This may reflect more on Norwegian attitudes than anything else, since the the physicians who first used ritux on CFS patients issued an apology about their country’s previous attitude and treatment of this group.

    “The real test is whether these markers are different from non-CFS controls. You always need a control group, otherwise all you can say is “X is Y”, which tells you nothing (unless you are attempting to establish a baseline).”

    Yes. Exactly so. My own personal musings. It is something that struck me as odd.

    Re: changing people’s minds. It’s hard work. Repeating something over and over doesn’t usually do it.

  91. pmoran says:

    Irenef: “I love science. It’s one of the most fun things in the world. But I don’t think you’re doing a good job.”

    WLU:By endorsing a series of uncontrolled n=1 trials, you are not really supporting the idea that you understand science. How do you define it? And how do you reconcile your definition with thinking n=1 trials are a good thing?

    I haven’t followed this in great detail, but is Irenef actually saying that, or merely defending herself against attacks (or possibly perceived attacks) on her personal decision to try out this treatment under the terms that were available to her at the time? She should not be under attack for that — she has told Harriet that she would gladly have entered herself into a placebo-controlled trial if that option was on offer.

    It is true that the consequent uncontrolled observations are likely to be highly misleading with this condition, but clinical research is hardly her responsibility.

    Is this not a clash of different perspectives, both of which are largely valid? There can be unfortunate consequences from that clash, for both sides, depending upon which viewpoint prevails, but some things cannot be helped while personal freedoms are respected.

    Irenef’s perspective is exactly that of the the typical CAM user. Unmet medical need + something that might help = considerable use of “unapproved” medical treatments . It happens whether we like it or not. “Science” as it relates to clinical research has scant relevance.

  92. David Gorski says:

    Unmet medical need + something that might help = considerable use of “unapproved” medical treatments .

    Your equation is incomplete, as it is missing at least two variables. Try this instead:

    “Unmet medical need/desire” + something of marginal or nonexistent plausibility promoted as helping + [brave maverick doctor or charlatan] – proper informed consent = considerable use of [unproven or disproven] treatments

    There, fixed that for ya. No need to thank me. :-)

  93. irenef says:

    @pmoran:

    While being compared to “the typical CAM user” is a little wince-inducing, you have got most of it in a nutshell.

  94. WilliamLawrenceUtridge says:

    I am doing no such thing. We’ve been through this before. There is no trial. I never said there was a trial. (I don’t have a blog, either.). I am receiving an off-label medication. I have explained some of my decision-making process and my rationale for doing what I am doing. I am not endorsing anything.

    By taking off-label medication, particularly for a condition with an unknown etiology or pathophysiology, you are in fact undertaking an n=1 trial, with subjective endpoints. You are taking rituximab, which has an uknown effect on CFS, and seeing if you feel better. It’s a very poorly designed n=1 trial since it lacks demonstrated prior probability (a failing of the unknown etiology of CFS) and no empirical or objective way of determining if it is successful or whether the effects are due to placebo. Essentially every patient taking medication is invovled in a similar trial since responses to medications can only be predicted at an aggregate level, not an individual level. But with an existing evidence base, at least there is reason to expect some success.

    “The real test is whether these markers are different from non-CFS controls. You always need a control group, otherwise all you can say is “X is Y”, which tells you nothing (unless you are attempting to establish a baseline).”

    Yes. Exactly so. My own personal musings. It is something that struck me as odd.

    It’s not merely odd, it’s bad science. The kind that answers no questions, can not answer any question, but can (and often is) used by practitioners or (more often) sales people to flog a product or treatment. Often quacks will undertake such trials to co-opt the social capital of science and paint a thin veneer evidence that justifies their practices and can be used in publications. I would wonder what happens to your blood work results, and how it is used. If you are comfortable in saying so, I would be curious to know why you had the bloodwork done, and what your doctor said about it.

    Re: changing people’s minds. It’s hard work. Repeating something over and over doesn’t usually do it.

    Yes, but sometimes if you keep hammering a point home, eventually the person will come to understand it. If nothing else, it can emphasize the importance of the point. Sometimes people will think about it after the fact and come to understand a point they did not understand before. I also recommend a lot of books, because skeptical thinking requires considerable knowledge and awareness of specific facts and reasoning – why to use a control group, why to use objective endpoints, how the human mind can fool itself, and so forth.

  95. irenef says:

    @David Gorski:

    Is it so necessary for you to be insulting? It’s not helping your case.

    If you know something about the pathophysiology of CFS that indicates that ritux is implausible or marginally plausible as a treatment, please share it.

    Also, if you have any substantive evidence that Dr. Kogelnik is “a brave maverick doctor” (your link implied a comparison with Andrew Wakefield) or a charlatan, please share that, too. The Open Medicine website’s use of buzzwords that you don’t like doesn’t count. It’s not directed at you.

    I don’t know why you think any of Dr. Kogelnik’s patient’s haven’t given informed consent.

  96. PernilleN says:

    @IreneF says:

    “Someone else is worried because a CFS patient in Norway is flying to California for treatment. This may reflect more on Norwegian attitudes than anything else”

    That’s me. But you left out a rather important point in my worries: These patients are paying 8000$ per treatment, plus travel and lodging. One of them has spent more than 40,000$ so far.

    That worries me. Perhaps it’s a Norwegian attitude to be worried – no, angry – when very sick patients are charged that kind of money for taking part in a so called study (yes, they are told they are) with a treatment that is in practice experimental. If that’s a typical Norwegian attitude, I can’t say I’m sorry about being Norwegian.

    As for the Norwegian doctors who discovered that Rituximab may be useful for some ME patients: They have said very clearly that the drug should not be used outside clinical studies. In other words: Kogelnik is doing exactly what these two very serious and dedicated doctors ask us not to. If you should pay heed to any Norwegian’s attitude, I think it should be to the only two people who have actually done proper research into Rituximab for CFS/ME. They are also oncologists, and have many years of experience with Rituximab (does Kogelnik have that kind of experience?).

    I must say Kogelnik has a lot of nerve going against their advice. I’m sure he means well and wants to help, but what he is doing is still wrong. And even though he has he the patients’ informed consent, he is still the doctor, and he is responsible for what he is doing. And he will be to blame if something goes wrong. Rituximab is a potent drug that can have very serious side effects. And we don’t know yet if CFS/ME patients will have different, or more serious, side effects than other patients. That’s one of the many things we need to find out from properly performed clinical trials.

    Regards
    Pernille Nylehn
    Norway

  97. Harriet Hall says:

    Irenef seems to understand what she is doing, and I did not “attack” her for her decision. I have no problem with patients trying experimental treatments with informed consent, and I understand the desperation. My problem is not with the patients but with doctors who encourage experimental treatments outside of clinical trials, especially when the rationale for the treatment is shaky, when the treatment is dangerous, and when the patients think they are in a clinical trial. I have tried to explain why I think that is short-sighted and only tends to delay proper research and the acceptance of its conclusions. Arguably, doctors who refuse to treat patients outside of clinical trials are acting in the ultimate best interest of all patients.

    At least one of Dr. Kogelnik’s patients believed she was participating in a pilot study, and in this interview http://www.youtube.com/watch?v=08Qul7E-xv8 Dr. Kogelnik says he is doing a “pilot” and empirically treating patients. No such study has been registered, and Irenef herself provides evidence that he is simply treating patients outside of any formal study. She is taking the drug with informed consent, but a legitimate pilot study would require IRB approval and a formal consent to the study protocol.

    And please note that no one can say that Ritux is implausible in terms of the pathophysiology of CFS, because we don’t understand that pathophysiology. But in my opinion, the quality and amount of evidence available so far for Ritux is not a plausible justification for treating patients.

  98. David Gorski says:

    If you know something about the pathophysiology of CFS that indicates that ritux is implausible or marginally plausible as a treatment, please share it.

    You have it backwards. The burden of evidence is on the person making the claim; i.e., Dr. Kogelnik. It is not on the scientist (and I am a surgeon-scientist with a lab and everything) questioning the claim. Consequently, the correct version of your statement is: If Dr. Kogelnik has compelling preclinical evidence supporting his hypothesis that rituximab is likely to be an effective therapy for CFS, then he should first share it with his scientific and medical colleagues by publishing it in the peer reviewed literature—and he should do it before conducting N of 1 trials (which is, as WLU just pointed out, exactly what he is doing) or using it off-label.

    I don’t know why you think any of Dr. Kogelnik’s patient’s haven’t given informed consent.

    It’s very simple. Unless Dr. Kogelnik has compelling preclinical evidence of the efficacy of rituximab against CFS, then as part of the informed consent process he would ethically be obligated to tell potential subjects that he has no evidence that this would work and that there is currently no known plausible biological mechanism through which it could work. Consequently, he would be ethically obligated to tell patients that the potential for harm is far higher than any potential for benefit, and even in that case his behavior would still be dubious at best.

    “Informed consent” doesn’t mean that it’s OK for a doctor to do anything to patients, as long as he asks consent and is very blunt and negative about the risks and benefits. I could tell a patient with a migraine that amputating his leg “might” help his migraine but has all the risks and downsides of an amputation, and even if the patient said yes it wouldn’t absolve me of having practiced bad medicine and behaved unethically. Now, using rituximab to treat CFS might not be as implausible as the example I just gave, but the same principle applies because we know so little about CFS that it is impossible even to estimate the plausibility. When we don’t know, the conservative and safe default is to assume it’s implausible until there is some good positive evidence to support its plausibility. Dr. Kogelnik appears not to have anything even close to that sort of evidence.

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