****** !!!!!!!! ****************!!!!!!!!!!!!!!!! Junior version of PACE funded PI Dr Crawley

[user9876]

Fidelity of GET and activity management: we will monitor protocol adherence and evaluate whether the two interventions are distinct and being delivered in a consistent manner across centres. Two clinicians, from centres other than that in which the session was delivered, will listen to a random sample (∼10%) of the audio-recorded sessions in a blinded fashion and rate them on a five-point Likert scale as being GET or activity management or a mixture of the two using the mandatory, prohibited and flexible elements for each intervention. We will estimate intervention fidelity as the percentage of sessions in each intervention arm which were correctly identified by the clinicians assessing recordings.

They clearly think there is a lot of flexibility in their protocols and overlap. But their measurement as to what is being tested here doesn't seem well defined in terms of an actual question and how to weight different aspects. Also no definition of how differences between the two clinicians are managed or whether they are looking at separate or the same sessions.

They also don't seem to be checking whether the therapists within a center are consistent (but I'm just picking bits at random so it could be elsewhere).

 

[user9876]

Both parents will be asked to complete three inventories online at baseline, 6 and 12-month follow-up, including socioeconomic status (baseline only);

So are single parent families not allowed to participate?

 

[Jenny TipsforME]

What can we do?

1) It is possible to do a petition through #MEAction or any other platform. While it might seem like there are a lot of petitions out there about ME, the University of Bristol likely hasn't seen them. ...

2) Check this out: http://www.bristol.ac.uk/research/integrity/...

research-governance@bristol.ac.uk...

(I believe. Please do feel free to double-check.)

3) Why, look, they have a Twitter about engaging with the public: University of Bristol Engage.
I might use this ONLY once we've started the petition, and use Twitter to link to the patient survey that shows harms, AND the petition. It would be really amazing to tweet them each time we reach milestone signatures: 500, 1000, etc.

-J

@JaimeS are you 'going' to the ME Action Network meeting later today? I have raised this issue with LA Cooper (now MEActNetUK) on twitter. This is likely the best way to communicate as an organised patient voice and not appear to be individuals harassing a researcher. Obviously other UK charities joining forces would be even better.

I wonder what the experts on the IoM SEID report have to say? It goes against their conclusions after reading all the (inadequate) literature.

Knowing that claims of harassment are a likely comeback (even if not a fair one), we should try to plan so that this claim itself looks ridiculous. There's plenty of reasonable evidence and well qualified people to say that GET on children is irresponsible and unethical.

I think you're right about timing, eg hold off contacting the UoB engagement twitter account until we have something of weight to report and then comment from an official account. Thinking through the order of actions may be key. We don't just want to let it be known that we are angry in this instance, we want to do something that will actually stop children being subjected to this.

You might be right about petitions. The UoB may be surprised at the number of people upset about this. Even if they know something of the controversy it has probably been spun as a minority concern. ME action petition would be better than official parliamentary one as non UK folk can sign? In publicity we'd need to do something so people know that they haven't already signed this one. I have no idea which I've signed (obviously I agreed with them).

Is this in a public bit of PR that their lawyers could trawl through if relevant? It may be prudent to be more discreet? I was shocked to read that lawyers went through our comments to do with freedom of information requests. Feels like a violation but in reality we're publishing our thoughts here for anyone to see.

 

[Jenny TipsforME]

https://twitter.com/i/web/status/751367677978013696

What is perhaps interesting for this is this tweet:

https://twitter.com/i/web/status/751024991957811201

It suggests that the protocol was written by someone quite junior who has just got a PhD studentship

https://twitter.com/i/web/status/751027287236218881

I guess they would claim that it was supervised and reviewed

These tweets and the timing are interesting.I know nothing about blee6387 (she may have a lot of prior experience yet to be accredited) but this protocol seems like a big responsibility for someone who has just got PhD funding. Has she been asked to cobble something together from existing published protocols? It may make some sense of why it doesn't feel like a full protocol (we wouldn't be able to follow it and do the same experiment). This isn't a criticism of her personally, it's often the most junior members of a research team who do all the major work and supervision varies. I partly mention this so we remember that we are criticising the work of a student, not a weathered researcher. The controversy around her paper is likely to be a shock to her and she is likely to believe that the research will help the children. Remembering that there are people on the other side of this may help us avoid the type of comments which get interpreted as harassment.

Of course overall I am more concerned about the wellbeing of already very sick children who need us to advocate for their interests. Also reviewers should be more rigorous before things are published.

I pick up that professorships often coincide with a well funded project coming into the University. If this is the case it will be a very big deal to EC. Also the university would have to be extremely convinced to turn down such a pot of money. To overturn this isn't a small task. A good plan is essential.

 

[Sasha]

Is this in a public bit of PR that their lawyers could trawl through if relevant? It may be prudent to be more discreet? I was shocked to read that lawyers went through our comments to do with freedom of information requests. Feels like a violation but in reality we're publishing our thoughts here for anyone to see.

Whether it's a public part of the site or not, you should assume that everyone can read everything you say. There's nothing to stop anyone registering as a member and reading all parts of the site. Material from Phoenix Rising has been quoted by QMUL to try to avoid releasing the PACE data and it's easily possible that PACE researchers or people who work for them are registered here as members.

If you're uncomfortable about what you've said being public on the internet, you can edit your posts to remove it and move the discussion to somewhere private, such as a PM (private conversation) with interested parties.

Just tagging @JaimeS too.

 

[Jenny TipsforME]

@user9876 @Keela Too @JaimeS @Sasha

I'll ask about this at the ME Action meeting later (5pm BST on Blue Jean). If it's taken on as an action then we can probably stop talking about details on here. Seems a little foolish to give prior warning about what we plan to do (although the plans won't include harassment or anything illegal, just peaceful protest).

 

[user9876]

Reading the protocol what it is basically saying is a way of doing a trial for GET on children where the GET intervention is, as far as I can tell, based on the PACE GET manuals and the NICE guidelines.

The first level of criticism should be concerned with them testing a treatment on children that was shown to be ineffective on adults (See the PACE long term follow up paper). In addition to that serious issues have been raised about the positive results coming out of the PACE trial (letter from 40 academics). With the PACE trial practicing outcome switching and spending over 200k on suppressing recovery results then a trial of the methods should not be carried out on children until the effectiveness of PACE on adults can be carefully examined according to both the trial outcome and objective measures.

Secondly there is considerable evidence of deterioration from patient reports with in patient surveys and this should be communicated to parents and children. I think there was a report of deterioration from PACE within the latest MEA report.

I think we should argue that in getting consent they should be telling both children and parents that these techniques showed no advantage over pacing and standard medical care in the largest trial and that in practice several patients have reported significant deterioration and relapse.

I would say that authorities should be held to account for any harm coming to children and the failure to give adequate consent if they do not warn patients of the lack of benefits and potential dangers. However, in the current medical system within the UK I cannot see this happening. But perhaps there is the question about whether those in authority would feel happy defending this after a headline in a paper. I suspect not a british one but I can see the US press taking up the issue. So perhaps the question is would the Vice Chancellor of Bristol University feel happy defending this trial without adequate consent to the press.

The protocol itself is concerned with how the measurements are made and I think is flawed. Although it goes further than PACE in using accelorometers and trying to measure compliance. The compliance aspects I think create further danger of bullying children into doing more than they should and in something that wasn't tested with adults.

 

[user9876]

The plan for use of accelorometers seems a little bit strange to me. They say there will be three measurements:

measure physical activity for 7 days within 1 month of randomisation and at 3 and 6-month follow-up

What is of interest is the first measure within 1 month of randomisation. In figure 1 they talk about it as a baseline but as far as I can see in the protocol they don't say that this happens prior to treatment starting. I'm not even convinced that this is implied but it could be.

 

[A.B.]

The plan for use of accelorometers seems a little bit strange to me. They say there will be three measurements:



What is of interest is the first measure within 1 month of randomisation. In figure 1 they talk about it as a baseline but as far as I can see in the protocol they don't say that this happens prior to treatment starting. I'm not even convinced that this is implied but it could be.

This could be a trick to create an improvement where there is none. Their idea of establishing a baseline often goes together with the idea of first reducing activity levels.

 

[user9876]

It is worth pointing out that this trial started recruting in september 2015
http://www.isrctn.com/ISRCTN2396280...15&page=1&pageSize=10&searchType=basic-search

Recruitment start date
01/09/2015

Recruitment end date
31/08/2016

Yet the protocol was only submitted in Jan 2016 and revised in May. So the reviewers couldn't affect the running of the trial (PACE played the same trick and the editors warned that changes should be looked for).

In fact there are is only a month and a bit of time left for recruitment.

 

[AndyPR]

Just throwing this in to the mix in case it's useful.

I looked at the results of the ME Association's "Managing my M.E." illness management requirements survey, specifically those who responded to the question on how GET affected their symptoms. A total of 906 people gave answers (of 4,217 who took part in the full survey), so we already have a larger sample size than took part in the PACE trial (640 I think it was?). However only 88% of people who responded to the whole survey had had their ME/CFS diagnosis confirmed, applying this to the total of those who had received GET we still get a total of 797 people. Link to survey

Using this figure then of 797 and applying it to the percentages given get us;

• Symptoms greatly improved, 3.4% = 27 people
  
• Symptoms improved, 18.7% = 149 people
  
• No change, 21.4% = 170 people
• Slightly worse, 23.4% = 186 people
• Much worse, 33.1% = 263 people
• and 2 people get lost due to rounding all figures down

So what these people are proposing is to use a 'therapy' that, using these figures, in adults, had only a 22.1% chance of any improvement and 56.5% chance of causing a deterioration of symptoms.

Now, according to http://me-pedia.org/wiki/PACE_trial#Findings, the results showing improvement actually match pretty well with what is officially claimed for recovery from the PACE trial (22%), so there would seem to be no reason to doubt the deterioration rates given in the survey.

So this seems to be showing that there is a better than 1 in 2 chance that any child who takes part in this trial will get worse and only slightly more than 1 in every 5 will see an improvement - all of this on the basis that these figures for adults can be used with children, and who knows if that is true or not?

I think my point here is to highlight the fact that the PACE trial is often used as solid evidence due to the number of people involved, yet we have a larger number involved with the ME Association's survey and, thinking on that, perhaps a similar survey could be set up using the #MEAction network, surely then we'd stand a chance of getting more responses (the ME Association's survey was run in 2010 so I'd anticipate there are even more sufferers online nowadays).

 

[Jenny TipsforME]

BTW ethics approval listed is NHS and from the sites the research (fieldwork) will take place. It doesn't mention approval from Bristol http://www.bristol.ac.uk/ccah/resea...ability/chronic-fatigue/magenta-trial/ethics/ probably treated as a given?

 

[Jenny TipsforME]

It is worth pointing out that this trial started recruting in september 2015
http://www.isrctn.com/ISRCTN23962803?q=&filters=conditionCategory:Nervous System Diseases,recruitmentCountry:United Kingdom&sort=&offset=8&totalResults=315&page=1&pageSize=10&searchType=basic-search



Yet the protocol was only submitted in Jan 2016 and revised in May. So the reviewers couldn't affect the running of the trial (PACE played the same trick and the editors warned that changes should be looked for).

In fact there are is only a month and a bit of time left for recruitment.

Oh that is very confusing. So is the trial already underway or will they start the trial at the end of the recruitment period, all of the participants together?! In other words, are we too late?

 

[Jenny TipsforME]

Oh that is very confusing. So is the trial already underway or will they start the trial at the end of the recruitment period, all of the participants together?! In other words, are we too late?

No the trial is nearly finished!
Recruitment Start Date
01 Sep 2015

Recruitment End Date
31 Aug 2016

Trial Start Date
01 Sep 2015

Trial End Date
31 Aug 2016

Not sure how I missed this last year! So the protocol reports what they have done not what they intend to do?!

BUT is this just a small feasibility study for a bigger follow on?

 

[user9876]

No the trial is nearly finished!
Recruitment Start Date
01 Sep 2015

Recruitment End Date
31 Aug 2016

Trial Start Date
01 Sep 2015

Trial End Date
31 Aug 2016

Not sure how I missed this last year! So the protocol reports what they have done not what they intend to do?!

BUT is this just a small feasibility study for a bigger follow on?

I'm not sure they are good at filling out their forms as the trial has a 6 month follow up and so won't be finished for at least 6 months after the last recruitment.

@Keith Geraghty do you have any insights into the timings of the trial and the publication of the protocol. It would seem to make the reviews irrelevant.

 

[Dolphin]

3) Page 34, Line 24 – revised manuscript. Target heart rate of between 60 – 80% . The NICE guidelines state 50 – 70% of max HR. I used 60-80% as an example in my previous review. If the authors wish to follow NICE guidelines, I suggest they amend the HR zone to 50-70%. I also, again, strongly recommend that the authors include RPE (rate of perceived exertion) alongside HR to monitor intensity, as RPE is also recommended in the NICE guidelines.

Thank you very much for highlighting this. We have revised the heart rate training zones from 60-80% to 50-70%. We have reworded the protocol from “Participants will be advised to stay within the target heart rate zones of 60-80% of their maximum heart rate1 3” to “Participants will be advised to stay within the target heart rate zones of 50-70% of their maximum heart rate1 3”

The reviewer posted their comments on May 3. Not sure when Crawley et al replied but it was certainly on or after that.

This is all very odd for a trial which started on September 1, 2015 and plans to finish recruiting on August 31. This would mean that participants would be given different advice depending on when they started!

 

[Dolphin]

There was a brief discussion (16 posts) on the MAGENTA trial protocol in this (now closed) thread:
http://forums.phoenixrising.me/inde...-of-conducting-a-trial-investigating-t.44920/

 

[Dolphin]

Mandatory, flexible and prohibited elements of both trial arms (Graded Exercise Therapy and Activity Management)

Flexible:

[..]

Advice on length of time at school (full days, half days, one lesson a day)

http://bmjopen.bmj.com/content/6/7/e011255/DC1/embed/inline-supplementary-material-1.pdf

Looks like not going to school (some people could benefit from home tuition) is not an option.

 

[Dolphin]

Note:

Accelerometers are not being used as part of the clinical intervention; neither participants nor clinicians see the data. The data from the accelerometer is being used purely as an outcomes measure.

 

[Dolphin]

Interesting to see how this exercise therapist from Australia thinks the UK exercise protocols are not suitable for CFS.

P 8, Lines 4 and 29-30: A progression of 10-20% per week in physical activity is regarded as standard for healthy adults. Other CFS research suggests that progression for CFS patients should be a lot less or at least self-paced with periods of no progression if symptomatic. Can the authors explain why the 10-20% progression was chosen and support this with references from CFS literature?

Thank you. We have clarified that this is following UK guidance. A progression of up to 20% is the guidance provided by the National Institute of Clinical Excellence1 and is standard practice in the UK. This is also consistent with the PACE trial, the largest trial done to date. We have now included a reference to NICE guidelines and the PACE trial, the protocol now reads: “The intervention will encourage children and adolescents to find a baseline level of exercise which will be increased slowly (by 10-20% a week, as per NICE guidance1 and the PACE trial2)”.

Our published systematic review on behavioural treatment approaches did not find evidence that a lower progression rate was preferable 3.

I remember seeing somewhere that Peter White said that the exercise regime of CFS patients (5 times a week for 30 minutes, gradually then increasing the intensity) was based on the standard NHS advice for healthy people, which didn't seem very specific way to treat people with CFS.

----
Another similar comment from the reviewer:

The other issue is that of monitoring exercise intensity, HR may be somewhat inaccurate; for CFS patients other research shows that rate of perceived exertion (RPE) used in conjunction with HR, is more useful for detecting fatigue and exercise limits