In response to the PACE trial principal investigators

This clinic did not cover questions in regard to funding, research or complaints against the NHS. Such questions need to be addressed to the local GPC (General Practitioner Council). However as there was so much interest on these subjects we have left many of them under this heading for viewing but they are intentionally not answered by the panel.

Moderator: talkhealth

Locked
3 posts
Jon Denberry
Posts: 3
Joined: Mon Aug 19, 2013 5:29 pm
Quote

by Jon Denberry on Mon Aug 19, 2013 6:10 pm

In response to the PACE trial principal investigators

The PACE trial principal investigators have posted some ambiguous information, and for the sake of balance, fairness and clarity, I would like this response and clarification to be allowed to stay on the forum...


"About six out of ten patients made a clinically useful improvement in both fatigue and functioning after CBT or GET."

This assertion is written ambiguously and, as such, is misleading. The statement suggests that ~60% of patients improved as a result of treatment with CBT or GET.

In fact, only an additional 14% and 16% of patients made a clinically useful improvement in both fatigue and functioning, when CBT and GET were added to SMC.

The ~60% figure includes the proportion of patients who improved in the SMC 'control' group of the trial who may have improved naturally over time without any treatment, or who may have improved as a result of the SMC treatment. So the ~60% figure does not indicate the number of patients who improved as a result of treatment with CBT or GET, but indicates improvements for SMC+CBT and SMC+GET, where SMC was the control.

Note that these figures apply only to improvements in subjective outcomes, and not in actual disability or other objectively measured outcomes.


"CBT and GET were also more effective in improving: general ability to do things..."

This was not the case for objectively measured physical disability (six minute walk test), for which there was no average improvement when CBT was added to SMC, and possibly no clinically significant average improvement when GET was added to SMC.

This statement also doesn't apply to employment and working hours, for which there were no improvements after CBT and GET were added to SMC.

It should be noted that, by all objective measures used to assess treatment in the PACE trial, CBT failed to make any improvements.
GET also failed to make any improvements in all objective outcomes, except that there was a small (and clinically insignificant) difference in six minute walking distance test, when GET was added to SMC.
On average, patients were still left with severe disability after treatment with CBT and GET.


"We went on to use a combination of self-reported measures (being within the population normal range for both fatigue and physical functioning, plus no longer meeting trial entry criteria, plus a self-rating of feeling “much” or “very much” better) to measure the numbers of patients who had recovered from their current ill-health, and found that both CBT and GET were about three times more likely to lead to recovery than the other two treatments."

With regards to 'recovery', the authors fail to point out the following:
1. It was possible for participants to have deteriorated after treatment with CBT/GET (in terms of 'physical function') and yet be reported as 'recovered'.
2. Participants could have had worse disability ('physical function') than when they entered the trial and yet still be reported as 'recovered'.
3. A participant could have severe physical disability ('physical function') and yet be reported as 'recovered'.
4. A participant could have physical impairment that was 'substantial' enough to qualify for a CFS diagnosis via the CFS empirical criteria (Reeves 2005), and yet be reported as 'recovered'.

So a PACE trial participant could have severe disability and be reported as being 'recovered', simultaneously.
This is an interesting scientific concept, but clearly it is not fair to discuss 'recovery' with a lay audience, when it means no such thing in lay terms.
Patients should not be told that they have a chance of 'recovery' after treatment with CBT or GET, when there is no evidence to support this claim.


For a published explanation of the above discussion regarding 'recovery', please see the following:
Letter to the Editor: ‘Recovery from chronic fatigue syndrome after treatments given in the PACE trial’: an appropriate threshold for a recovery?
Psychological Medicine, 43, pp 1788-1789.
doi:10.1017/S003329171300127X.
http://journals.cambridge.org/action/di ... 171300127X
Last edited by Jon Denberry on Tue Aug 20, 2013 2:27 am, edited 5 times in total.

biophile.pr
Posts: 6
Joined: Fri Aug 16, 2013 9:20 am
Quote

by biophile.pr on Tue Aug 20, 2013 4:36 am

Re: In response to the PACE trial principal investigators

Re: "no longer meeting trial entry criteria".

It is important to point out that this means failing to meet any single criterion for trial entry criteria, not that participants did not meet any of these criteria at all. Examples include:

• A participant could have scored 65 points in physical function at baseline, then score 70 points at 52 weeks, then be classed as "no longer meeting trial entry criteria".

• A participant could have been fatigued 55% of the time at baseline, then 45% of the time at 52 weeks, then be classed as "no longer meeting trial entry criteria".

• A participant could have a non-fatigue symptom, such as pain or PEM or POTS, become more important than "fatigue" during the trial, then be classed as "no longer meeting trial entry criteria".

No longer meeting Oxford criteria was a judgement made by non-blinded assessors. However, non-blinded assessors of subjective binary outcomes can generate substantially biased effect estimates in randomised clinical trials ( http://www.bmj.com/content/344/bmj.e1119 ).

Locked
3 posts