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PACE Trial and PACE Trial Protocol

Discussion in 'Latest ME/CFS Research' started by Dolphin, May 12, 2010.

  1. oceanblue

    oceanblue Senior Member

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    I don't think that point about overlapping arms is right: according to your ref (and others I've seen) arms can overlap by half a length and still be statistically significant at 95%.

    As I was trying to say in the earlier post, since SMC has a higher baseline than GET/CBT you can't directly compare the 52-week end points.

    IC SMC data: 52.1-39.1=+13.1
    Full cohort: 50.8-39.3=+11.6 (nb lower increase for SMC full cohort)

    Having done a quite a bit of work to get this data, I wish the results had been more 'interesting', but this is the way they turned out.:(

    Intersting that the effect with fatigue appears to be quite a bit stronger than for physical functioning, which is seen in the full cohort too.
    Not sure how much difference adjusting makes in practice. The difference between CBT/GET and SMC I calculated from the graph data almost exactly matched the adjusted difference figure in table 3.
  2. Dolphin

    Dolphin Senior Member

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    Have you seen any that overlap by a full arm and are not statistically significant. That paper is only talking about half an arm. It seems very likely to me trying to think about in terms of probability density functions with different frequencies at each point, that it would be significant in the case of 2F and 2G (if it was simply left at the final value i.e. ignoring any adjustments for the moment).

    If one takes the example of two distributions with confidence intervals (CIs) of the same magnitude where the touch each others means: one already has half the area one needs as 50% of the time for the lower one, it will be above the end of the other arm (which will occur with a probability of 0.025 by definition i.e. 0.0125. One only needs it that more than 0.025 of the time, the lower one is higher than the upper one, and the confidence interval for the difference overlaps (at p=0.05).

    For what it's worth, looking at Table 3, the unadjusted changes are +19.2, +20.0 and +11.6 for CBT, GET and SMC. This give unadjusted change differences of +7.6 (CBT vs SMC) and +8.4 (GET vs SMC); the adjusted change differences actually were: +7.1 (CBT vs SMC) and +9.4 (GET vs SMC).

    Not sure why you are disappointed. That 1.3/1.5 could make the difference and it may no longer no statistically significant.

    The confidence intervals for the differences will be bigger than those in Table 3 because of smaller sample sizes as I understand it.

    I missed what you were saying there; however adjustment for baseline values doesn't always mean that one simply subtracts - sometimes it can be more or less e.g. if values tend to plateau, those on 38 and 39 could end up with similar final values and one wouldn't adjust or the adjustment might be less. Basically, many times researchers don't look at change. Anyway, not a major point. The overlap is my major point.
  3. Sean

    Sean Senior Member

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    Now there is a warning bell. Anything that relies on that simplistic checklist assessment is going to be suspect.
  4. oceanblue

    oceanblue Senior Member

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    Specialist Medical Care - includes quite a bit of pacing advice?

    Below is the description of Specialist Medical Care taken from the Patient Information Leaflet given to patients before they decide to enter the trial - as detailed in the full protocol.

    It looks to me like there is a significant element of Pacing in SMC that goes beyond simply saying 'don't do to much or rest too little'. Nb the SMC-only group had an average of 5 SMC sessions vs 3 for the other groups, so there was scope for quite a lot of advice. Specialist doctors included Simon Wessely too, who wouldn't just be there to write a prescription.

    While the similarity between SMC and Pacing might have reduced any relative improvement with APT, I presonally think APT was doomed to failure by it's bizarre 'within 70% of perceived energy' limits so I'm not sure we can conclude anything from the trial re pacing.

    Here's how the Lancet paper described SMC:
  5. oceanblue

    oceanblue Senior Member

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    Recovery rates according to the original protocol - estimates

    Since the results for recovery according to the original protocol (SF36 of 85 or more, bimodal chalder of 3 or less) will probably never be released I've had a stab at estimating them from the data we do have.

    I've explained the logic below, but here are the results, with the PACE figures for 'within the normal range' in brackets

    CBT: 12% 'recovered' (vs 30% 'within normal range')
    GET: 12% (28%)
    SMC: 5% (16%)

    The authors might have commented:
    OK, they didn't say this, but they have said the therapies are moderately effective.

    And now for the rationale. There's no substiture for having the correct calculations done on the real data but I don't think this will be a million miles out.
  6. Dolphin

    Dolphin Senior Member

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    oceanblue, interesting you're looking at it.
    For SF-36, you used 80. It should be 85 (or 82.5???). Thinking about it, for CFQ, they had a figure like 18.8 and said the threshold was the next lowest number (18) so 85 may seem reasonable in such circumstances i.e. the next possible number.
    Maybe you could calculate the figures again. I'm not sure on that. Maybe you could calculate it both ways (82.5 and 85).

    Also, here's the full "recovery" definition:
    If you wanted to bring in CGI info, you could consider using Kathy Fulcher's PhD http://hdl.handle.net/2134/6777 which has raw data on SF-36, CGI, etc. for 66 or 33 exercise and 33 flexibility then exercise (although there is a bit of missing info). For the first 33, one needs CGI2full as the others are just rated 1/2 (improver/non improver). So for example number 6 got to 95 but only had a CGI of 2. One even has Chalder Fatigue Scale scores (called Wessely and Wesp and Wesm for physical fatigue and mental fatigue scores although unfortunately this is the 14 question version. But 18*(14/11)=22.91 so you could use the threshold of 23 (say). I'm not necessarily looking for a lot of work - just the breakdown of the CGI scores of those scoring >=85 on SF-36 and <=23 on "Wessely fatigue".
    ETA: number #6 has a Wessely fatigue score of 20 (out of 42) i.e. with a SF-36 PF score of 95 and a Wessely fatigue score of 20 (out of 42) (almost certainly <=18 out of 33), this person didn't have a CGI score of 1 and so wouldn't be counted in "recovery".
  7. oceanblue

    oceanblue Senior Member

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    Good point, thanks. Recalc on 85 gives estimated recovery rates as defined by original protocol of:
    CBT & GET: 9%
    SMC: 4%


    that's probably a better estimate.
    Basically I assumed if you hit both sf36 and cfq thresholds you would almost certainly score yourself 'very much better' and very likely no longer hit any CFS criteria but, yes, the figures above might need a little shaving off them. however, the margin of error of my approach is quite wide already so I'm not sure I want to finesse this much more; it might not add much to accuracy, esp as I've already used 85 instead of 82.5 on sf36.

    Anyway, I think that looks better now; feel free to add you own assumptions to this and I can supply my spreadsheet if that helps.
  8. Dolphin

    Dolphin Senior Member

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    Thanks for that.
    Figures of under 10% (or 5% more than SMC) could be quite easily dismissed as not very impressive at all esp. when it's just an Oxford cohort to start with, relatively short illness duration on average (they could tell us the characteristics of these people), lots of people opted not to take part, didn't have any co-morbidities that would exclude them from taking part, these figures don't necessarily represent full recovery (many of the people may still not be working so we don't know how they might cope trying to work), etc.

    Yes, feel free to send on Excel file, thanks.
  9. WillowJ

    WillowJ Senior Member

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    @all:
    I thought the APT group was told pacing would create the most likely conditions for "natural recovery"?

    How much difference is there between the CBT and GET ("this will cure you"?) and the APT "this is not a cure but will create the best conditions for a possible natural recovery" themes?
  10. Esther12

    Esther12 Senior Member

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  11. urbantravels

    urbantravels disjecta membra

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    I was the one who raised the issue of expectations management and the nocebo effect vs. placebo effect, especially when outcomes are being measured by subjective self reports.

    It's very clear that in PACE, there was not even an attempt at objectivity in how the different treatments were presented to the patients. The CBT and GET arms were told that they could get better and that the therapy would help them do so; the APT people were told that there was nothing that could be done to cure their disease, but that by living within their limits they "might" create the conditions for "natural recovery" to occur. (We all know how good it feels waiting around for that to happen...), versus being told repeatedly that the therapy being given is going to improve you, and that you can improve your health via your own efforts. There was no comparable "Is this a cure? Be honest, the answer is no" statement in the CBT and GET manuals, as there was in the APT manual.

    I really don't understand why this alone doesn't get the whole study discredited on ethical grounds.
  12. Angela Kennedy

    Angela Kennedy *****

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    Yes- you're right I think, Urban. Malcolm Hooper of course relates to the situation in 'Magical Medicine'. It is quite shocking.
  13. Dolphin

    Dolphin Senior Member

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    They published one letter this week:
    http://www.imt.ie/opinion/2011/03/caveat-needed-on-safe-and-effective-declaration.html

    Don't forget - they published 5 over a number of weeks last year so plenty of time to write in.
  14. Dolphin

    Dolphin Senior Member

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    Just came across the following.
    The point I'm highlighting is the only relevant one: the population that was used for the norms for the Chalder Fatigue Questionnaire was people who attended their GP in the last year. If these figures were correct, then a large chunk of the population were missed. I think oceanblue mentioned 80% of the population go to their GP every year earlier in the thread (??). Anyone else ever come across a figure (esp. for the UK).

    http://www.gponline.com/News/article/1043685/Demeaning-phrases-stop-men-checking-health/
  15. Dolphin

    Dolphin Senior Member

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    They published 2 more today i.e. 3 this week:
    http://www.imt.ie/opinion/2011/04/p...for-the-‘biggest-rift’-among-me-patients.html

    http://www.imt.ie/opinion/2011/04/the-pace-study-is-out-of-step-with-mecfs.html
  16. urbantravels

    urbantravels disjecta membra

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    What on earth is "man flu"? Some slang term that hasn't made it to the US yet, apparently.
  17. Dolphin

    Dolphin Senior Member

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    It's a term that the media have used occasionally and the public now use sometimes - it involves claiming men if they have a sniffle say they have influenza/make a big deal out of their minor symptoms.
  18. urbantravels

    urbantravels disjecta membra

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    I'm so confused now!! I thought it was women that were hypochondriacs, exaggerating minor symptoms, making a big fuss and pestering doctors unnecessarily. Now it's men too?

    Clearly the problem is more widespread than we thought - it's sick people that are unreliable, irrational exaggerators who need to shut up and not complain so much about being "sick" or talk so much about their "symptoms." Got you.
  19. WillowJ

    WillowJ Senior Member

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    yes, because doctors can find out everything they need to know via a cursory visual examination and standard screening tests. they do not want or need patients to "self-report" the "status" of being "sick" or experiencing "symptoms"
  20. Dolphin

    Dolphin Senior Member

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    Except when they are doing UK5m (US$8m) trials of CBT and GET in which case what patients self-report on particular questionnaires is perfectly fine.

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