Scientific Studies Showing Serious Adverse Effects from GET?

[Woolie]

I can't speak for the UK but in the US, the pharmaceutical lobby has an unbelievable amount of political power with both parties. A drug can have significant adverse events but still make it through the FDA and remain on the market. If anyone doubts this, read Bitter Pills by Stephen Fried. The PACE trial is meaningless IMO b/c politics won out over science.

Undoubtedly true, @Gingergrrl, but at least there are some mechanisms for withdrawing a drug when adverse effects become excessive. With behavioural interventions, there are none.

 

[barbc56]

With behavioural interventions, there are none

You make a good point.

The only thing that comes to my mind that's even remotely close to regulating behavioral interventions would be the protocals for restraining patients in psychiatric facilities or in my case students with behavioral disabilities who are a harm to themselves or others. I think these are mandated by state, but to be honest I don't know if they are mandated by law or school code.

Barb

 

[Gingergrrl]

Undoubtedly true, @Gingergrrl, but at least there are some mechanisms for withdrawing a drug when adverse effects become excessive. With behavioural interventions, there are none.

There are mechanisms in theory but even when hundreds of thousands of people are injured by a drug and it is reported to the FDA Med Watch program, it is rare that anything happens. Some drugs get pulled off the market in other countries but continue to be given out like candy in the U.S. for financial and political reasons.

 

[joshualevy]

Much earlier in this thread, someone asked why I posted the original question. At the time, I thought that the study was trying to show that people who feared exercise had worse outcomes. Therefore, the question about if those fears were justified or not seemed like an important question. Many people were arguing the fears were based on solid evidence, and it seemed like an important question. (I was also curious if fearing exercise was just a marker for more serious symptoms, and what they were really seeing was more serious symptoms resulted in worse outcomes.)

But then I read the actual paper. You have to register, but it's free. And I realized that the data supported something different. What they found was that lowering the fear led to lowering other symptoms. It was the change in fear levels they were reporting, not the "starting fear" levels. That's quite different. For one thing, it means that the question of justified vs. unjustified fear doesn't matter. What they are saying is that it doesn't matter how or why you are fearful, but if you lower the fear, you are likely to lower the symptoms.

Now there is still a counter argument: causality. Maybe the lowering of symptoms causes the lowering of fear, and not the other way around. However, they measured everything at the beginning, middle, and end of the trial, so it looks like the data shows the lower fear happening first. That would imply the causality goes from fear to other symptoms (not the reverse) but I'm going to re-read that part of the paper. It's not simple to understand the first time through.

Finally, many people hated PACE because they felt it implied a psychological cause for ME/CFS. The basic idea was that since a psychological technique could be used as treatment (at least some of the time), that suggested that there was a psychological cause (at least some of the time). Therefore, it would make sense that people who don't believe in a psychological cause, wouldn't want to believe in a psychological treatment.

But that is obviously not the way drugs work, and I don't think it is necessarily the way psychology works, either. For example, lets say you have high blood pressure, and the doctors prescribes the drug Verapamil. Does that imply that you naturally have too little Verapamil? Of course not. The mechanism of the drug in treating the problem often has nothing to do with the mechanism of the cause of the problem. Maybe the same is true of Psychology in this case. Maybe the mechanism of the treatment has nothing to do with the mechanism of the cause.

Joshua

 

[Gingergrrl]

Joshua, I am not sure if I understand the exact point you are trying to make nor do I know all the details of the PACE trial. What I can tell you for certain is that I am extremely ill and I have absolutely zero fear of exercise. I was working out at a gym with a personal trainer 3x/wk up until the week that I became sick. I could run on a treadmill, I could lift weights, I could take my dog on a two hour walk, my energy was endless and I had no fear.

Even with mild ME/CFS and pre diagnosis by a specialist, on my honeymoon I went zip lining, kayaking, horse back riding, and played golf. I did not know why I was mildly sick at that time and did not know how far my illness would continue to progress. I never dreamed I would be this sick and still can't believe it now. I had a 16 year career in social work/psychology and am in no way anti-psychology in case you make this assumption.

I had a severely extreme case of mono from the EBV virus following a minor surgery in 2012. Three years later I have severe viral, immune, autonomic and cardiac symptoms from ME/CFS. At my first appt with an autonomic cardiologist, he felt I was so severe, he hospitalized me for five days for tests. I would do anything to be able just to walk and breathe at the same time without a wheelchair.

I can promise you that I have no "fear of exercise" (if this is indeed what you are premising) and it is my dream to be able to exercise again some day.

 

[WillowJ]

A lot of people objected to PACE because a very weak result which should have shown that CBT and GET really have no important effect were spun as a win for the PACE team. While the paper itself made moderate claims in response to very weak data, the team's news briefings led to it being reported with very strong positive effects in the newspapers.

 

[WillowJ]

Now there is still a counter argument: causality. Maybe the lowering of symptoms causes the lowering of fear, and not the other way around. However, they measured everything at the beginning, middle, and end of the trial, so it looks like the data shows the lower fear happening first.

PS, Some of the authors (not Chalder) specifically said in an interview, that the symptoms and "fear" changed at the same time.

This paper is being discussed on this thread:
http://forums.phoenixrising.me/index.php?threads/new-pace-paper-more-smc-spin.34924/unread

ETA: I saw the quote again and it might not have been authors of this paper; looked like colleagues from Belgium, IIRC.

 

[Sidereal]

But the study didn't find that lowering fear lowered other symptoms. It found that lower fear was associated with a few point change on some of the subjective rating scales and no change or trivial change on objective measures such as fitness test or walking distance. I don't doubt that psychotherapy can alter questionnaire taking behaviour in a subset of individuals. The issue is that these null results have been spun as having an actual, clinically significant effect on symptoms.

 

[barbc56]

@Sidereal

This makes a lot of sense, especially if you put it in context with the following study where patients reported improvement in ashma symptoms, whether they used abuteral or a sham inhaler. However, objective/physical measures showed that only the group getting abuteral showed phisiologic improvement.

Therefore the use of subjective measures is not Clinically relevant and shouldn't be the only assessment used to make a clinical decision when treating asthma?

http://www.ncbi.nlm.nih.gov/pubmed/21751905

@joshualevy

Is this related to what you are saying? I'm not sure if I made myself clear or if I even correctly interpreted what you said.

Barb

 

[Sidereal]

@Sidereal

This makes a lot of sense, especially if you put it in context with the following study where patients reported improvement in ashma symptoms, whether they used abuteral or a sham inhaler. However, objective/physical measures showed that only the group getting abuteral showed phisiologic improvement.

Therefore the use of subjective measures is not Clinically relevant and shouldn't be the only assessment used to make a clinical decision when treating asthma?

http://www.ncbi.nlm.nih.gov/pubmed/21751905

@joshualevy

Is this related to what you are saying? I'm not sure if I made myself clear or if I even correctly interpreted what you said.

Barb

Yes. I think it was @Woolie who recently posted links to meta-analyses showing that the placebo effect is marginal in studies using objective outcomes.

 

[MeSci]

Hi @MeSci, the paper you posted looks to be very carefully done, and being a review, is eligible for inclusion in things like wikipedia pages. But that would depend on the source. I don't suppose you know where it was published?

Not sure what you mean. The journal name appears to be Exercise immunology in chronic fatigue syndrome - no - that seems to be a category or section in the journal which is called Exercise Immunology Review. It comes up in PubMed searches. I just downloaded it from the thread I linked to, I think.

 

[Valentijn]

Someone said that PACE defined SAEs badly. I don't think that is an option. In the US, at least, it is a federal standard what an SAE is. I know PACE was UK, but all US studies use a similar definition, based on the federal one.

It happened. From the original PACE trial paper:

Serious deterioration in health was defined as any of the following outcomes: a short form-36 physical function score decrease of 20 or more between baseline and any two consecutive assessment interviews;16 scores of much or very much worse on the participant-rated clinical global impression change in overall health scale at two consecutive assessment interviews;25 withdrawal from treatment after 8 weeks because of a participant feeling worse; or a serious adverse reaction.

Patients had to start with a SF-36 PF of 65 or lower, so would have to be reduced to 45 or lower. I think we actually overlooked the bit where they specify that decreases have to be at assessment interviews, rather than therapy appointments. Therapy was monthly, which would have meant that the decline would have had to last between one and two months.

But since it was based on assessment interviews, the time-frame required for an SAE was quite a bit longer. Interviews were only at the start, 12 weeks (mid-therapy), 24 weeks (end of therapy) and at 52 weeks. So at a minimum, a PACE patient would have to be over 30% extra disabled for 6 months to qualify as having had an SAE.

And then unblinded "CFS specialists" not involved with the trial (but the authors' good friends) would determine if any SAE was an SAR:

Scrutinisers were then unmasked to treatment allocation to establish if any serious adverse events were serious adverse reactions.

That's when the elevated incidence of SAEs in the GET group magically transformed into SAR rates matching that of the control group.

The full text of the PACE trial is at http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60096-2/fulltext . Adverse events are talked about a fair bit in the text, and the numbers are in Table 4.

 

[Valentijn]

What they are saying is that it doesn't matter how or why you are fearful, but if you lower the fear, you are likely to lower the symptoms.

Maybe it would help if you paid attention to the symptoms being lowered. Objective physical disability? Nope - there was no improvement in any indicators of that. The only "symptom" which improved was self-reported fatigue and perceptions of disability. But it has been shown repeatedly that those subjective reports following CBT/GET contradict the reality demonstrated by use of actometers, employment outcomes, and reliance upon disability benefits.

Now there is still a counter argument: causality. Maybe the lowering of symptoms causes the lowering of fear, and not the other way around. However, they measured everything at the beginning, middle, and end of the trial, so it looks like the data shows the lower fear happening first. That would imply the causality goes from fear to other symptoms (not the reverse) but I'm going to re-read that part of the paper. It's not simple to understand the first time through.

It's not clear because they don't want it to be clear. There was correlation between the reporting of symptoms and the reporting of fear. If they'd been able to show causality of reduced fear resulting in reduced symptoms, they'd have that bit in flashing red CAPS with extra exclamation points Instead they're just implying things which are not supported by the data, the same tactic they've used for decades.

Finally, many people hated PACE because they felt it implied a psychological cause for ME/CFS. The basic idea was that since a psychological technique could be used as treatment (at least some of the time), that suggested that there was a psychological cause (at least some of the time). Therefore, it would make sense that people who don't believe in a psychological cause, wouldn't want to believe in a psychological treatment.

What a bunch of bizarre bullshit No one cares about psychological versus biological, except to the extent that psychological therapies have been proven to be worthless and even harmful in treating ME/CFS. Then there's the matter of all of the studies (including the original PACE paper) which have proven that CBT and GET do fuck-all for ME/CFS patients.

And then there's the hundreds of papers indicating various physiological and anatomical abnormalities which cannot even remotely be explained by psychological dysfunction or deconditioning. As an example, three independent groups have published objective evidence of PEM in ME/CFS patients, by comparing them to sedentary controls in maximal 2-day CPETs.

Even if PACE had respectable methodology (it doesn't) or any improvements in meaningful outcome measurements (nope), are we supposed to ignore our personal experiences, the experiences of pretty much every other ME/CFS patient we've talked to, and the extensive scientific publications which directly contradict fear-avoidance and other psychological theories? That would be insane.

For example, lets say you have high blood pressure, and the doctors prescribes the drug Verapamil. Does that imply that you naturally have too little Verapamil? Of course not. The mechanism of the drug in treating the problem often has nothing to do with the mechanism of the cause of the problem. Maybe the same is true of Psychology in this case.

Okay ... and how would you expect CBT and GET to cure twitching and spasming muscles? Or inability to use oxygen as efficiently as well-matched sedentary controls 24 hours after maximal exertion? How would they stop someone's blood pressure from plummeting and their heart rate from soaring when they sit up? How would CBT or GET stop my entire body from swelling when I eat certain foods which I'm not allergic to? How would they lower my ESR, or prevent blood from getting into every urine sample which has been analyzed since I got sick?

It's beyond ludicrous to think that psychological treatments could help with these things.

 

[Esther12]

What they found was that lowering the fear led to lowering other symptoms. ... What they are saying is that it doesn't matter how or why you are fearful, but if you lower the fear, you are likely to lower the symptoms.

They didn't measure patient's symptoms. They measured they way that patients filled in questionnaires about some symptoms in a nonblinded trial. Inducing changes here should not be assumed to reflect real changes in health, as it may simply reflect (for example) changes in beliefs about what sorts of questionnaire answers would reflect well upon themselves.

Now there is still a counter argument: causality. Maybe the lowering of symptoms causes the lowering of fear, and not the other way around. However, they measured everything at the beginning, middle, and end of the trial, so it looks like the data shows the lower fear happening first. That would imply the causality goes from fear to other symptoms (not the reverse) but I'm going to re-read that part of the paper. It's not simple to understand the first time through.

It seemed to me that they did not provide the data that would allow us to say whether the change in reported fear questionnaire scores came before or after the change in symptom questionnaire scores. Questionnaires scores for symptoms had already declined at 12 weeks, which is when they measured mediators. Have you seen something I have missed?

Finally, many people hated PACE because they felt it implied a psychological cause for ME/CFS. The basic idea was that since a psychological technique could be used as treatment (at least some of the time), that suggested that there was a psychological cause (at least some of the time). Therefore, it would make sense that people who don't believe in a psychological cause, wouldn't want to believe in a psychological treatment.

LOL. Sounds like the sort of spin and nonsense we get from Wessely, White and Chalder. I think that you may have been suckered. If results from PACE had been presented in the manner laid out in the trial's protocol, and with appropriate warnings about the difficulty interpreting results from a nonblinded trial, then I think that most patients would thought that the results were of some use, even if it was still regretful that so much money was spent on it.

 

[MeSci]

And then there's the hundreds of papers indicating various physiological and anatomical abnormalities which cannot even remotely be explained by psychological dysfunction or deconditioning.

There is a simple, non-invasive measurement that would be of interest - swelling of lymph nodes and glands in the neck. According to this admittedly non-scientific poll, over 70% of pwME have this, and it's frequently cited as a symptom/sign. I can't think of any way that 'fear' would cause this.

Researchers could measure swelling in the neck at various stages of treatment. If it's not reduced, would we expect other things to be? (That's an open question...I don't know.)

 

[Gijs]

Wessely, White and Chalder have delusional ideas, they need CBT therapy It is very sad to see these people getting more grazy every day.

 

[Valentijn]

There is a simple, non-invasive measurement that would be of interest - swelling of lymph nodes and glands in the neck. According to this admittedly non-scientific poll, over 70% of pwME have this, and it's frequently cited as a symptom/sign. I can't think of any way that 'fear' would cause this.

Researchers could measure swelling in the neck at various stages of treatment. If it's not reduced, would we expect other things to be? (That's an open question...I don't know.)

Ah yup, that's the one I forgot! Let's hear how CBT and GET can make my tonsils deflate

 

[ahimsa]

(edited to correct user name)

@joshualevy, have you seen any of these videos? They are great tools in helping to understand the issues with the PACE trials:

1. The Pace Race

2. 60 -- the new 75

3. Not So Bad

4. The Force of LOGic

Edit again: If you prefer reading text to watching videos then you can read more here:

http://evaluatingpace.phoenixrising.me/homepageanim.html

This is not recent information but it sounds like perhaps you have not heard about it.

 

[ahimsa]

Oops, I tagged the wrong user again..... @joshualevy , I meant to tag you in the the previous post, the one with 4 videos. I accidentally used the name you signed at the end of your post as a user name.

 

[Woolie]

Clicking on his "Messages", I see that joshualevy appears to have been posting for some years now on PACE/CBT/GET studies, which he consistently views as promising. He has also posted on studies of other treatments (including, Rituximab, Ampligen and antivirals), which he views as problematic. So I actually don't think he's new to this at all.

check out this thread: http://forums.phoenixrising.me/index.php?threads/the-double-standard.21895/

@joshualevy, I think your posts stimulate discussion, so keep posting them. This thread has helped me to learn more about the evidence regarding the dangers of GET in particular.

I actually agree with you that we here on PR need to take a more critical view of studies of biologically based treatments (Rituximab, etc.). Sometimes our hope triumphs over the evidence in these situations. But where I differ from you is that I also think we also need to take a critical view of CBT/GET/PACE.

I also think that many of the studies of biological treatments have been continued/discontinued based on the evidence they themselves provide, so the research has been self-correcting in that way. But not so for CBT/GET, which remains resilient despite a lack of strong supporting evidence (in my view). In that case, its the researchers' hope that triumphs over the evidence. I don't think behavioural research is self-correcting in the same way as biomedical research, and it has something to do with the very deep convictions of the researchers themselves.