PACE Trial and PACE Trial Protocol

[WillowJ]

http://handbook.cochrane.org/chapter_10/10_2_2_5_outcome_reporting_bias.htm

In many studies, a range of outcome measures is recorded but not all are reported (Pocock 1987, Tannock 1996). The choice of outcomes that are reported can be influenced by the results, potentially making published results misleading....

 

[WillowJ]

Hi, our (New Zealand) government is putting together a report on ME/CFS and it looks like they are going to say that CBT and GET are the best treatments. Probably influenced by the NICE Guidelines and the PACE Trial. We would like to present them with some contrary findings before the report is finalised. I thought this might be a good thread to find people who could let us know of any contrary findings.

Thanks in anticipation.

Don

this may be rather late, but they may find the following helpful:

Dr. Peter Rowe and Dr. Chris Snell talk about the PACE trial at an FDA meeting:

ETA: I hadn't watched that yet. Their full talks without any commentary can be found here in Panel 3:
http://www.tvworldwide.com/events/fda/130425/#

Tom Kindlon's harms paper (has a section on the PACE trial; this is a peer-reviewed publication):
http://iacfsme.org/BULLETINFALL2011/Fall2011KindlonHarmsPaperABSTRACT/tabid/501/Default.aspx
interview with Tom: http://phoenixrising.me/archives/15567

video on changed targets in the PACE trial:

enitre series: https://www.youtube.com/user/MEAnalysis/videos?flow=grid&sort=da&view=0
website with more detailed info: http://evaluatingpace.phoenixrising.me/homepageanim.html

Nunez paper showing that when symptoms other than fatigue are checked, one might find declines:
http://www.ncbi.nlm.nih.gov/pubmed/21234629

 

[alex3619]

Information on a FOI request regarding PACE:

Original FOI request:
https://www.whatdotheyknow.com/request/request_for_deterioration_rates
Final decision:
http://www.informationtribunal.gov.uk/DBFiles/Decision/i1020/20130522 Decision EA20120229.pdf

 

[taniaaust1]

Hi, our (New Zealand) government is putting together a report on ME/CFS and it looks like they are going to say that CBT and GET are the best treatments. Probably influenced by the NICE Guidelines and the PACE Trial. We would like to present them with some contrary findings before the report is finalised. I thought this might be a good thread to find people who could let us know of any contrary findings.

Thanks in anticipation.

Don

Make sure they know about the International ME Consensus criteria.. there's a link to it on the front page (on the right in you scroll down) on the SA ME/CFS society website. That probably has stuff in that about GET and CBT and cautions etc and could be used.

 

[taniaaust1]

Information on a FOI request regarding PACE:

Original FOI request:
https://www.whatdotheyknow.com/request/request_for_deterioration_rates
Final decision:
http://www.informationtribunal.gov.uk/DBFiles/Decision/i1020/20130522 Decision EA20120229.pdf

That really sucks. At least thou they will have to publish that data as it will look very bad on them if they dont within the next couple of years and they must realise that now (fortunately their freedom of the card they played will not keep holding out.

The card they tried to play about how it would affect "academic freedom "by being forced to publish didnt work for them (if it had, they would of thought they could forever get away with never publishing the info). They see now they HAVE to publish info in a reasonable time.

Thank you Robert Courtney for taking that to court.

 

[Valentijn]

That really sucks. At least thou they will have to publish that data as it will look very bad on them if they dont within the next couple of years and they must realise that, they card they played will not keep holding out.

Exactly ... from what I understand, all of their other excuses have been dismissed, and the "we're gonna publish, honest guv" is all that's left. And it won't hold up forever

 

[taniaaust1]

Exactly ... from what I understand, all of their other excuses have been dismissed, and the "we're gonna publish, honest guv" is all that's left. And it won't hold up forever

I wonder how they are going to spin the whole thing, it must be difficult to keep making bad results look good, I hope its giving them stress.

I wonder if they will put out a completely different thing in their favour (a new study or a new spin on a different old one) at the same time they put out the spun poor results, to try to get attention away from them.

 

[Simon]

Information on a FOI request regarding PACE:
Original FOI request:
https://www.whatdotheyknow.com/request/request_for_deterioration_rates

Final decision:
http://www.informationtribunal.gov.uk/DBFiles/Decision/i1020/20130522 Decision EA20120229.pdf

This request went all the way to the tribunal and even though the Tribuanl ruled in favour of Queen Mary University London withholding the information, it was only on the basis that publication of that information in a journal was imminent:

We remind ourselves that we are evaluating the consequences of disclosure now rather than at a date in the near future.

Hats of to Robert Courtney who made the initial request and perservered with it too:

I would like the “deterioration rates” for each of the therapy groups (CBT, GET, APT, SME) for both the primary measures (Chalder fatigue and SF-36 Physical Function).

His point was that the initial 2011 Lancet PACE Trial paper gave the improvement rates, but that to properly assess the effectiveness of the trial it was important to know how many patients deteriorated by the same measure.

And the ruling also contained and important precedent in favour of disclosure, by explicitly rejecting the argument of the 'academic freedom' to choose what, where and when to publish as suits the interests of the academics:

22. To the extent that the University’s argument includes an assertion that disclosure under FOIA would impinge upon academic freedom and that those collecting the data should have academic freedom to choose what to publish, where and when for reasons of academic prestige regardless of the public interest; where the research has been conducted with the use of public funds, we reject this. We consider academic freedom to relate to the freedom to pursue research wherever the evidence takes a researcher and the freedom to disseminate, publish and teach no matter how unpopular and controversial the conclusions. That academic freedom must be viewed in the context of the public interest is clear from the structure of s22 FOIA which is subject to the public interest test.

Hopefully we will see the those deterioration results published shortly.

edit: the best news is that situations like this should not arise in future. The MRC has said that trials funded by them from 2012 onwards are expected to release ALL trial results within 12 months of trial completion. PACE will have taken around 2 years to release these deterioration results.

 

[Sean]

Thank you, Robert Courtney.

 

[Valentijn]

I wonder how they are going to spin the whole thing, it must be difficult to keep making bad results look good, I hope its giving them stress.

I wonder if they will put out a completely different thing in their favour (a new study or a new spin on a different old one) at the same time they put out the spun poor results, to try to get attention away from them.

When the Nijmegen BPS group had bad actometer results but good questionnaire results in a set of three studies they 1) didn't mention actometers in the initial papers 2) published the actometer data a couple years later for all three studies in one paper and 3) spun the results to say that actual physical functioning isn't relevant to CFS patients because it's not associated with reporting less fatigue.

I think we'll see something similar from the PACE group regarding deterioration rates. Hopefully it'll get more attention than the ludicrous Nijmegen spin got though.

 

[biophile]

When the Nijmegen BPS group had bad actometer results but good questionnaire results in a set of three studies they 1) didn't mention actometers in the initial papers 2) published the actometer data a couple years later for all three studies in one paper and 3) spun the results to say that actual physical functioning isn't relevant to CFS patients because it's not associated with reporting less fatigue.

4) They speculated that hidden increases in activity actually occurred halfway through the trial after the baseline actometer measurements but were converted into increased social activities before the followup actometer measurements.

 

[Sean]

'speculated'

being the key word here.

 

[Esther12]

Thanks for that. Looks like Rob Courtney did a good job, and it was just that they are now planning to release the data that led to the appeal being denied.

lol at the way the actometer results were spun.

Personally, I'm not expecting CBT and GET to have particularly bad deterioration rates from PACE. The sessions were all being recorded and assessed as part of the trail, so I think that the therapists would be less likely than normal to cause problems. Also, APT looked pretty rubbish to me, with the 70% rule and the various forms and diaries that needed to be done quite possibly making people feel worse too. It would not surprise me if APT did worse than CBT/GET... although the fact that the data has been slow to be released does make me suspect that CBT/GET could come out less well.

But then, all three of those treatments involved much more therapist time than SMC alone, and this would be likely to bias towards more positive questionnaire results.

It is hard with PACE as i) these researchers have shown that they cannot be trusted and are happy to spin data in order to sell their treatments and expertise, ii) it is genuinely difficult to measure the impact of behavioural interventions on symptoms.

 

[biophile]

Good work Robert Courtney! If you happen to visit Phoenix Rising and read this thread, I just want you to know that I think you still practically succeeded anyway, because I doubt PACE would have published this data on their own so at least we get to see it. I doubt the AllTrials movement would have bought their excuses either, and as Simon suggested earlier, the result sets important precedents and the stonewalling we have gotten used to is becoming less accepted.

All the PACE-related FOI requests I am aware of (eg https://www.whatdotheyknow.com and Co-Cure) are similar to this, about accessing unpublished data which should have been published already or was promised to be published in the past. A few may be expecting too much, but where are all the FOIs which supposedly amount to vexatious harassment and choking up White's time (according to news coverage on PACE)? Is this FOI request what White personally regards as vexatious harassment and one example of what he claims to be wasting 1/4 of his time on?

Well, I guess FOI requests would be "vexatious" i.e. annoying if one does not like the implications of the data being released or does not like losing control over the context it is interpreted in. As one of Tom Kindlon's posts on Co-Cure exemplifies, even simple questions about the recovery paper are being turned into official FOI requests. But it would appear that people such as Paul Smallcombe et al are doing all the work responding, not Peter White et al.

 

[Valentijn]

Personally, I'm not expecting CBT and GET to have particularly bad deterioration rates from PACE.

Good point. From what I recall the CBT and GET treatments were actually both pretty similar, and had a strong pacing element in them - being told to back off if symptoms intensify, rather than sticking to a scheduled increase in activity?

 

[biophile]

I'm not expecting CBT and GET to have particularly bad deterioration rates from PACE.

Good point. From what I recall the CBT and GET treatments were actually both pretty similar, and had a strong pacing element in them - being told to back off if symptoms intensify, rather than sticking to a scheduled increase in activity?

Agreed. I doubt the deterioration rates will be shocking. The CBT and GET groups did have a pacing element, but were encouraged to tolerate more temporary symptom exacerbations than APT. Everyone also received SMC and material which contained several key elements of pacing. The vast majority of people in the trial failed to improve or "recover" due to CBT and GET, so will need to fall back on simple autonomous pacing to prevent relapses.

 

[Dolphin]

"One final observation. QM nearly got itself into trouble in this case because of its curious publication strategy. It is odd to publish research about the merits of a given set of treatments, without having finalised one’s analytical work on the therapy-specific demerits. From a medical ethics perspective, I wonder to what extent the clinicians and patients appreciated that to some extent the 2011 Lancet publication was work-in-progress – because that is the implication of QM’s arguments on this appeal."

final paragraph from

http://ukhumanrightsblog.com/2013/0...-from-a-randomised-controlled-trial-on-mecfs/

JUNE 12, 2013 BY DAVID HART QC

Freedom of information and unpublished data from a randomised controlled trial on ME/CFS

I set up a thread on this at: http://forums.phoenixrising.me/inde...-unpublished-data-from-a-rct-pace-trial.23716

 

[Dolphin]

Peter White letter in the BMJ.

Of course, there have been lots of other freedom of information requests which would not break confidentiality e.g. the data for the original primary outcome measures, deterioration rates, recovery rates (as in original protocol), etc. and he has released virtually nothing following such requests.

Also, no researchers may request the data in which case important data might not be released.
Or researchers who do request the data may only do minimal analyses that still don't reveal interesting information within the data.

LETTER
Sharing data from clinical trials
Is sharing data from clinical trials always a good idea?
BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f3379 (Published 28 May 2013)
Cite this as: BMJ 2013;346:f3379

Peter D White, professor of psychological medicine1


p.d.white@qmul.ac.uk

Not many clinicians or scientists would argue with the campaign by “AllTrials” to register and report the full methods and results of clinical trials.1 But is it sensible to go so far as to “encourage authors of all BMJ papers to share their datasets publicly,” so that all may see?2

We routinely reassure participants in clinical trials that their data will be held securely and confidentially. Research ethics committees rightly insist on locked filing cabinets and ensuring that only the researchers have access to digital data. Is this reassurance consistent with public release of patients’ confidential data without their consent? Although only “anonymised” data are proposed for public release, are data truly anonymous when details of age, sex, and perhaps locality are linked to past and current medical details?

And what will potential trial participants of the future think of the reassurance of confidentiality when they know that their “anonymised” data will be publicly available for anyone to access? Will this encourage more patients to take part in trials or will it have the opposite effect?

I prefer the Medical Research Council’s current policy on access to research data. The council considers release only to bona fide researchers, who work for bona fide research organisations, and who sign up to the same standards of respecting the confidentiality of the data as did the original researchers.3

Notes
Cite this as: BMJ 2013;346:f3379

Footnotes
Competing interests: PDW has received several Freedom of Information requests from members of the public for all the data from a recent trial of non-pharmacological treatments of chronic fatigue syndrome.

References
↵Groves T, Godlee F. The European Medicines Agency’s plans for sharing data from clinical trials. BMJ2013;346:f2961. (8 May.)FREE Full Text
↵AllTrials. All trials registered. All results reported. www.alltrials.net.

↵Medical Research Council. Data sharing requirements for population and patient studies. www.mrc.ac.uk/Ourresearch/Ethicsresearchguidance/Datasharing/policy/PHSpolicy/requirements/index.htm.

 

[Esther12]

Not many clinicians or scientists would argue with the campaign by “AllTrials” to register and report the full methods and results of clinical trials.

Only the most repulsive of quacks would try to wriggle out of releasing data in the manner they laid out in their registered protocol Peter.

https://www.whatdotheyknow.com/request/pace_trial_recovery_rates_and_po

 

[Sasha]

Although only “anonymised” data are proposed for public release, are data truly anonymous when details of age, sex, and perhaps locality are linked to past and current medical details?

No they're not, which is why government statistics departments who request datasets from other departments specify which variables they need for their analysis. Any that they don't need, or can't adequately justify needing, are stripped out. Such data requests are considered on a case-by-case basis by someone whose job it is to analyse at what level of aggregation of variables confidentiality might be breached.

God forbid that somebody applies some common sense, let alone expertise, to this problem. Just take locality out, for a start. Who wants that?

This disgusts me.