The Double Standard

[joshualevy]

I was reading the various responses to the Ampligen trials and the PACE trial, and something really jumped out at me:

The basic argument for the Ampligen study was this "there is anicdotal evidence that some people have been helped, so therefore it should be approved so those people who can be helped, will be". The basic aregument for the PACE study is this "there is anicdotal evidence that some people have been hurt, so therefore it should be shut down immeadiately and no more research like this done".

The double standard is very clear.

Someone without emotional attachments would either say "If anyone was helped by PACE we should make it widely available, just like the argument for Ampligen", or they should say "If anyone is hurt by Ampligen, we should stop it quickly, just like PACE". Those would at least be consistent standards.

As it is, it's pretty clear that people are NOT reacting to the results of the study, but the suggestion by Ampligen that ME/CFS is immune based and the suggestion by PACE that it's psychological.

A similar double standard is that PACE has published data showing cure rates (based on their definition of a cure) which everyone attacks immediately, but Ampligen has never published any cure data at all, and everyone loves that! Of course the situation is worse with Rituximab vs. PACE. Rituximab has zero objective measures of improvement, while PACE has one such measure. Everyone complains about PACE's one but no one says anything about Rituximab's weaker study.

Again: the key to support in this community is not strong science: support for "ABP" Anything But Psychiatry!

Joshua (not Jay!) Levy

 

[Little Bluestem]

The argument for Ampligen (and Rituximab) is that it should be available to those who want to try it. As I understand it, PACE is being forced on people whether they want it or not while at the same time denying them the testing and treatment that they do want. As I see it, the argument is about choice, not about what is the one best treatment for ME/CFS.

 

[Valentijn]

Another big difference is that CBT/GET are based around deceit. Patients are told how great it is, how well it works, and given some justification for using it that doesn't involve the false illness beliefs which BPSers believe really lies behind our illness.

I also disagree that most of us are necessarily opposed to CBT/GET research - its pre-eminence is what is more disturbing, especially since it has long come at the expense of a lack of funding for biomedical research. Also the poor manner in which it is conducted is highly worrying, such as the seeming deliberately exclusion of many patients with PEM and taking measures to minimize the seeming effect of PEM upon trial outcomes - while still claiming the results apply to ME patients.

Personally I'd love to see some quality CBT/GET research - with CCC criteria, actometers, good control groups, etc. It would be utterly doomed to fail

 

[Sparrow]

I think the real answer should be somewhere in the middle for both of them. "This seems to have helped a small group of people, so it can be made available to the people who want to try it, but they should also be made aware of the risks of doing so. The success rate and safety record is not yet high enough that any patient should be strongly encouraged to use this treatment against their will." Period. End of story. For all of the above.

The problem I see is that the double standard is working the other way around as well, and that's what there has been a backlash to.

"Elements of the research on Ampligen were possibly a little slanted. It appears to help a small number of people, and harms another group. Take it off the market! That is clearly insufficient to risk exposing patients to it, even if they want to try it."

"Elements of the research on CBT and GET were possibly a little slanted. It appears to help a small number of people, and harms another group. Everyone should be pushed into trying this treatment. Other treatment options should not be offered."

If GET was banned because of the effect it has on some patients, but every person was forced to do a trial of Ampligen, I would have a problem with that too. Either extreme is a poor one. Choice and acknowledgement of the risks are essential with any treatment option.

 

[maryb]

JL - to put it simply the PACE trial wasn't science.

 

[PhoenixDown]

Rituximab has zero objective measures of improvement, while PACE has one such measure.

Which was what exactly? The walking test?

 

[Guido den Broeder]

All experimental studies should have reliable objective measurements. The PACE walking test is not one of those.

 

[irwinsturtle]

I think you'll find its a lot more complex than your "double standard" notion Joshua.

 

[joshualevy]

All experimental studies should have reliable objective measurements. The PACE walking test is not one of those.

Of couse the walking test was objective. You just don't like the results.

But let me guess: the walking test done by PACE was not objective (evil PACE!) but the walking test done by Ampligen was perfectly objective (good Ampligen!). Come on: the double standard shines through.

I completely understand: the PACE study is very stong envidence that pyschological treatments help many people who have ME, CFS, or whatever you choose to call it. You hate it for that reason; but claiming that a walking test is suddently not objective, because it's part of the PACE study, is just silly! And claiming that it's objective when used for Ampligen but subjective when used for PACE, doublely so.

Joshua Levy

 

[joshualevy]

The problem I see is that the double standard is working the other way around as well, and that's what there has been a backlash to.

"Elements of the research on Ampligen were possibly a little slanted. It appears to help a small number of people, and harms another group. Take it off the market! That is clearly insufficient to risk exposing patients to it, even if they want to try it."

"Elements of the research on CBT and GET were possibly a little slanted. It appears to help a small number of people, and harms another group. Everyone should be pushed into trying this treatment. Other treatment options should not be offered."

If GET was banned because of the effect it has on some patients, but every person was forced to do a trial of Ampligen, I would have a problem with that too. Either extreme is a poor one. Choice and acknowledgement of the risks are essential with any treatment option.

But Sparrow, remember that in both quotes above, you are refering to stories, not data. You are refering to what people have said about the various studies, not the statistical results of everyone who participated. When you look at all the data, the results are clear:

1. For PACE, both the adverse effects and the severe adverse effects were about the same for all four groups. So the statement that CBT or GET hurt some people is specifically disproven by the data: all groups had the same level of problems. The idea that people in the GET group of PACE had more or worse side effects than those in the other groups, is a lie, nothing more. The original Lancet publication was very clear there.
2. For the Ampligen studies (taken together), there was not a staticially significant improvement in the people who took Ampligen. Now, the company pushing Ampligen did some other analysis, where they excluded certain people from the study, and excluded certain adverse side effects from contsideration, and they were able to get a tiny improvement with those changes, but that is just statisical manipulation.

Science is about looking at the data from research trials. All the data. Not listening to stories about people.

Joshua Levy

 

[biophile]

Are the same specific people commenting positively on Ampligen also commenting negatively on PACE, or is the "double-standard" a generalized one for the entire community? I do not doubt that some people may treat different studies differently, according to their interests and understanding, but I think irwansturtle is correct to write that it is a little more complicated than brute double-standards.

I am not a fan of Ampligen, but I do not know much about it. IIRC the last set of results were not impressive at all for subjective measures but there was an improvement in objective exercise capacity? I do not believe it should be rolled out as a routine treatment, but I think it should still be available to those who do want it; some people appear to respond well to it, and I would not want to deprive them of that if they can afford it and understand the risks.

I have a similar position to CBT and GET, although I am more weary of GET: I do not believe these should be rolled out as a routine treatment, but a slim minority appear to respond to them so I would not want to deprive them of that. That said, we do not know much about the nature of this response, and not enough is known to predict the responders. I cannot support a blanket approach if there are remaining concerns or uncertainties about generalizability and safety.

People are often accused of a No True Scotsman fallacy if they claim that CBT/GET responders do not have the same illness as themselves who do not respond to CBT/GET. However, when considering the heterogeneous wastebasket nature of a somewhat arbitrary CFS diagnosis, I think it is a quite reasonable to wonder whether those responding to CBT/GET do in fact have the same biological composition and illness characteristics of those who do not respond, just as it would be reasonable to wonder the same about those CFS patients who respond to Rituximab or Ampligen compared to those who do not respond to those drugs.

If joshualevy wants to talk about double-standards, let us address the fact that unlike the trials on Rituximab and Ampligen, the PACE Trial was not blinded and was not placebo controlled, which puts it on a lower grade of evidence. Why not just compare PACE to open label drug studies or even open label alternative medicine? Furthermore, the PACE results are being promoted as conclusive evidence which convincingly ends the debate once and for all, so of course it has come under scrutiny after decades of controversy.

joshualevy chided Guido den Broeder for claiming that the walking test was not a "reliable objective measurement". The walking test gave an objective outcome (distance walked in meters), but it can be influenced by psychological factors, particularly when the trial was not blinded nor placebo controlled. I guess that was the reason Guido den Broeder thinks it is unreliable? Another reason would be that it does not measure activity levels, only distance walked in a single test, without taking post-exertional symptomatology into account. The differences between groups were not clinically significant anyway, CBT and GET does not have a clinically useful benefit for walking distance over 6 minutes.

CBT and GET aim to increase activity levels and proponents claim these therapies do just that. Unfortunately, PACE conveniently dropped the use of actometers as an outcome measure, so we do not know whether that occurred, yet it is often alluded to that it either did occur or does not really matter if it did not occur. The study on Rituximab had no objective measures of improvement, but it was double blinded, and it was just a pilot study, one which may hold clues into the cause and/or pathophysiology of CFS. If Rituximab proponents claimed for 20 years that Rituximab worked in CFS largely because of a specific biological mechanism or had a specific effect on said mechanism, would it not be important to include an objective measure for this in a "definitive" trial costing 5 million pounds? Just imagine the uproar if a large "definitive" Rituximab trial dropped an important objective biological measure as an outcome.

 

[biophile]

Of course the walking test was objective. You just don't like the results.

I missed the part where Guido den Broeder said he did not like the results. The results of the walking test demonstrated no advantage whatsoever for CBT, and a statistically significant but not clinically significant advantage for GET. Nothing much to "like" about that, but it does show the disability patients generally experience, and what skeptics of CBT/GET have suspected all along (that these therapies generally make little if any difference to disability). I will guess you believe he does not like the results because they go against his alleged hatred for CBT and GET? Ironically, he may also not like the results because they are essentially dismal and disappointing (and yet unsurprising for skeptics of CBT/GET).

But let me guess: the walking test done by PACE was not objective (evil PACE!) but the walking test done by Ampligen was perfectly objective (good Ampligen!). Come on: the double standard shines through.

The two studies did not use the same walking test, the one used for Ampligen was a more demanding test for cardiopulmonary exercise tolerance. Apples and oranges?

PACE: "I am going to assess your walking. Please walk as far as you can. I will let you know when 3 and 5 minutes have passed. You should walk continuously if possible, but can slow down or stop if you need to. Please aim to walk as far as you can in 6 minutes. I am not going to give you any encouragement or talk to you during the test as I will be preoccupied counting, although I will say when 3 and 5 minutes have passed."

Ampligen: "Participants were asked to walk until they could walk no more on a treadmill which tilted up and got harder to walk on the longer they walked. [...] At the end of 40 weeks, the patients on Ampligen were able to stay on the treadmill about 108 seconds longer while the patients not on Ampligen were able to stay on the treadmill about 27 seconds longer. This translated to an 16.6% increase in exercise tolerance – far surpassing their goal of at least 6.5%. In fact, according to the study, the 16.6% increase makes Ampligen the best exercise intolerance reducer yet tested by the FDA. (The next best result was posted by Tracleer for pulmonary hypertension (10.6%) and then Remodulin (8.0%).)"

I completely understand: the PACE study is very strong evidence that psychological treatments help many people who have ME, CFS, or whatever you choose to call it. You hate it for that reason; but claiming that a walking test is suddenly not objective, because it's part of the PACE study, is just silly! And claiming that it's objective when used for Ampligen but subjective when used for PACE, doubly so.

PACE was strong evidence that a slim minority of a carefully selected Oxford criteria cohort will benefit modestly or at least mediocrely from CBT and GET on some subjective measures but not others. There was no placebo control and there were different levels of encouragement and optimism between groups. Using the same definition applied to self-reported fatigue and physical function, the "objective" 6MWD demonstrated no clinically significant advantage for any therapy group (although some individuals probably did benefit from GET).

Guido den Broeder never indicated that the walking test used in the PACE Trial was "suddenly not objective" because he hated PACE. He said (note underlined emphasis): "All experimental studies should have reliable objective measurements. The PACE walking test is not one of those." I explained in a previous post why some people may not find the 6 minute walking test to be a reliable objective measurement. Can you vouch for the reliability as well as the objectivity of the 6MWT as it was used in the PACE Trial? What are your thoughts on the failure for any therapy to demonstrate a clinically significant advantage, does this mean that on average CBT and GET have no objective benefit of much use?

But Sparrow, remember that in both quotes above, you are referring to stories, not data. You are refering to what people have said about the various studies, not the statistical results of everyone who participated. When you look at all the data, the results are clear:

For PACE, both the adverse effects and the severe adverse effects were about the same for all four groups. So the statement that CBT or GET hurt some people is specifically disproven by the data: all groups had the same level of problems. The idea that people in the GET group of PACE had more or worse side effects than those in the other groups, is a lie, nothing more. The original Lancet publication was very clear there.

There were several different grades of non-serious adverse events (mild/moderate/severe) but these were lumped together in the original Lancet publication, which was not made clear. It was possible to have a "severe" non-serious adverse event which was relatively incapacitating for up to 4 weeks, but this was not distinguished from milder events. No data has been published for how many of these non-serious adverse events were reactions to treatment/therapy. There were significantly more serious adverse events in the GET group, but once the "independent scrutinizers" were unblinded to allocation and found out these were for GET, it was arbitrarily decided it was not related and "suddenly" the difference disappeared. SAEs were also graded mild/moderate/severe but this distinction was not made in the publications either.

Keep in mind that the safety of the confines of a carefully monitored trial on a carefully selected cohort may differ from the real world clinical practice. The controversy about CBT/GET began many years before data on adverse effects were even published. Such data is very recent. The mediocre PACE results apply to those with the same characteristics of those accepted into the trial. No one can guarantee that all or most CFS patients complaining about the harm of CBT/GET, online or in surveys, have the same characteristics and would not have been excluded from the trial. 80% of candidates thought to have CFS were excluded from the trial. Although the most common reason was not having CFS according to the assessors, the Oxford criteria and medical assessments/exclusions employed in the PACE Trial are not entirely compatible with the Canadian criteria, for example.

For the Ampligen studies (taken together), there was not a statistically significant improvement in the people who took Ampligen. Now, the company pushing Ampligen did some other analysis, where they excluded certain people from the study, and excluded certain adverse side effects from consideration, and they were able to get a tiny improvement with those changes, but that is just statistical manipulation. Science is about looking at the data from research trials. All the data. Not listening to stories about people.

I do not know enough about the Ampligen studies to comment on the statistical analyses. You wrote that the company pushing Ampligen "excluded certain adverse side effects from consideration". Similarly, PACE has not published data on how many of the thousands of reported "non-serious adverse events" (which can be relatively incapacitating for up to 4 weeks at a time) were severe and/or reactions to the treatment or therapy. When given, the "data" does not automatically trump all the "stories" if the data does not reliably apply to the people offering those stories.

 

[biophile]

Is this the first Ampligen study? http://www.ncbi.nlm.nih.gov/pubmed/8148460

Is this the second Ampligen study? http://www.ncbi.nlm.nih.gov/pubmed/22431963

 

[irwinsturtle]

Accusing other people of emotional responses is not an successful counter argument, Joshua.

 

[Guido den Broeder]

To clear things up, I am very happy with the PACE trial, because it provides definite proof that (a) CBT/GET is not helpful and (b) the advocates of CBT/GET will go to any length to misrepresent their results.

 

[FancyMyBlood]

But Sparrow, remember that in both quotes above, you are refering to stories, not data. You are refering to what people have said about the various studies, not the statistical results of everyone who participated. When you look at all the data, the results are clear:

1. For PACE, both the adverse effects and the severe adverse effects were about the same for all four groups. So the statement that CBT or GET hurt some people is specifically disproven by the data: all groups had the same level of problems. The idea that people in the GET group of PACE had more or worse side effects than those in the other groups, is a lie, nothing more. The original Lancet publication was very clear there.
2. For the Ampligen studies (taken together), there was not a staticially significant improvement in the people who took Ampligen. Now, the company pushing Ampligen did some other analysis, where they excluded certain people from the study, and excluded certain adverse side effects from contsideration, and they were able to get a tiny improvement with those changes, but that is just statisical manipulation.

Science is about looking at the data from research trials. All the data. Not listening to stories about people.


Joshua Levy

Let me first say that I agree with your statement about many patients/forum members using double standards. It's not only unscientific, but also unnecessary to ''prove'' ME/CFS is not a psychological illness. Everyone agrees (even the psychiatrists and psychologists) ME/CFS is likely a heterogenous disorder, so it's no suprise some patients improve by CBT/GET. This is why subsetting is so important. Even the psycholobby agrees with this, but instead of admitting there might be a subset that has a genuine organic disorder, they want to find out why most people don't respond to CBT/GET. This is a dead end IMHO, and even when you consider CBT/GET helps some patients, the response rate and effectiveness of these treatments are pretty low in the majority of patients.

However most arguments you're using are incorrect and/or incomplete:

''the PACE study is very stong envidence that pyschological treatments help many people who have ME, CFS, or whatever you choose to call it.''


I wouldn't call a 22% ''recovery rate'' (which is nowhere near actual recovery, I suggest you read the MEA respons to the recovery paper) very effective and or helpful to many patients with ME/CFS.

''For PACE, both the adverse effects and the severe adverse effects were about the same for all four groups. So the statement that CBT or GET hurt some people is specifically disproven by the data: all groups had the same level of problems. The idea that people in the GET group of PACE had more or worse side effects than those in the other groups, is a lie, nothing more. The original Lancet publication was very clear there.''

While there is no doubt these were the conclusions of the PACE trial, it was inherently biased. Patients with ME/CFS, who were too sick [to attend the clinic] and/or housebound or were biased against psychological treatment were inherently excluded.
I don't know what percentage of patients fall into this group, but it's probably an important caveat to the PACE trial.
It's beyond me why people deny the safety results of GET in the PACE trial though.

"For the Ampligen studies (taken together), there was not a staticially significant improvement in the people who took Ampligen. Now, the company pushing Ampligen did some other analysis, where they excluded certain people from the study, and excluded certain adverse side effects from contsideration, and they were able to get a tiny improvement with those changes, but that is just statisical manipulation.''

I've not read too much into this, but I also think Ampligen's efficacy data is greatlyexaggerated by Hemispherix. However, I also believe the FDA advisory committee said it's very likely Ampligen is effective in a subset of patients. So, I'm not sure if the efficacy data is merely statistical manipulation.