But then by the time the protocol was published in 2007, actigraphy as an outcome measure was dropped.
It's very frustrating that, presuming this is the case, they could change this so radically from the multi-million pound grant that was approved.
This was an application at one stage, I'm not sure it was the final one:
THE PACE TRIAL IDENTIFIER.pdf
1drv.ms
As I recall, it was obtained using a freedom of information act request. One person editorialises is about it here:
LISTSERV - CO-CURE Archives - LISTSERV.NODAK.EDU
Thank you so much for digging these out,
@Tom Kindlon! So helpful. I've had a look.
It's unclear when the Pace Trial Identifier was written, but it's after October 2001 as they write
The outline proposal of this study (G010039) was approved for a full proposal in October 2001.
and well before April 2004, which when Jane Bryant's editorial is dated.
@Tom Kindlon, you mentioned that funding was announced in 2003, so some time between late 2001 and early 2003.
In the PACE Trial Identifier, the secondary measures are listed as follows [formatted with each measure on a separate line for ease of reading]:
Secondary measures:
Efficacy:
1. The self-rated Clinical Global Impression (CGI) change score (range 1-7) provides a self-rated global measure of change, and has been used in previous trials.30
2. Daytime physical movement (an objective measure of activity) will be measured over 48 hours with an Actiwatch attached to the ankle.
3. The Hospital Anxiety and Depression scale will measure change in anxiety and depression.31
4. The 36 item short-form health survey (SF-36) measures not only physical but also social and role functioning.24
5. The EuroQOL (EQ-5D) visual analogue scale provides a simple global measure of quality of life.32
6. The Client Service Receipt Inventory (CSRI), adapted for use in CFS,33 will measure hours of employment/study, wages
and benefits received, allowing another more objective measure of function.
7. An operationalised Likert scale (from much better to much worse) of the nine CDC symptoms of CFS.1
The secondary outcome measures in the published trial per the main paper were:
- CGI
- Work and Social Adjustment Scale
- 6 Minute Walk Test
- Jenkins Sleep Scale
- HADS
- CFS symptom count
- Poor concentration or memory
- Postexertional malaise
So there are numerous changes from what is stated in the PACE Trial Identifier. I would have thought it would be competely normal for many things to change between a funding application and the protocol, with changes after that needing to be well-justified. Since the protocol was published mid-trial, this case is a little different.
Actigraphy for 48 hours does indeed feature in the Identifier but the 6MWT does not, and the latter was ultimately used.
Let's say for argument's sake that that document is the final version and it was indeed submitted to the MRC. Would the MRC's decision have been different if actigraphy had not been listed as an outcome measure? Or if the 6MWT had been there instead of it? Those are genuine questions, not rhetorical. Was actigraphy a dealmaker?
The Trial Management Group Minutes start in June 2002. Unless I missed it, actigraphy doesn't get a mention until meeting #7 in May 2004, when the minutes note [underlining added]:
Objective Measures of outcome. We had much discussion aboutvarious potential objective measures of outcome, including a six-minute walking test where the patient is timed using a stopwatch and the distance walked is recorded. The possibilities of using actigraphy and the step test for fitness were also discussed. We agreed that we would pilot the use of actigraphy, the step test and the six minute walking test in the first three centres. We had some discussion about whether an objective measure was to be a primary outcome. We had some discussion about the power of the trial to detect clinically significant differences between groups using the six-minute walking test.
The next mention is in meeting #10 [underlining added]:
Primary outcome(s)
Discussion took place regarding the primary and secondary outcomes – number of outcomes and efficacy. It was decided that it was acceptable to have several primary outcomes for the trial, and that fatigue and disability could be considered separately and in combination. Cost utility could be considered as a fourth primary outcome. Actigraphy was not considered suitable as a primary outcome, but should remain as a predictor only.
Then in meeting #11, we hear why:
Actigraphy is to be given at baseline only, as a predictor. This is on the basis of research by the Dutch Nijmegen group who found it useful as a predictor (the more passive, the poorer outcome), but not useful for outcome.
And in meeting #12, we get the clanger:
The issue of using actigraphy as an outcome measure was raised. It was noted that the Dutch study by Bleijenberg and colleagues reported that actigraphy was not a good outcome measure since the majority of patients are reasonably active and there is no change in this in spite of improvement in fatigue. However, pervasively passive people at baseline may do worse on CBT and perhaps better on GET.
A final decision on using this as an outcome has been postponed until we see how much of a measurement load actigraphy is, and it was agreed that this may be changed later next year if desired.
So whatever was written in the Identifier, according to the Trial Management Group minutes, actigraphy was not a planned outcome measure at any point from 2002. If the MRC required or requested an objective measure of physical activity, and this was supplied with no intention to use it, then that would be deceitful, but I have not seen anything that would suggest that.
I think the thing for advocates to focus on is not that actigraphy appeared in the PACE Trial Identifier as a secondary outcome measure, but their stated reason for not using it as an outcome measure, and the fact that CBT participants did not improve on the objective measure that was used - the 6MWT - any more than those doing SMC or APT, and GET participants' improvement on the 6MWT was statistically significant, but small and unlikely to be clinically significant.
Tagging
@V.R.T. @Robert 1973 @Sean @rvallee to make sure you all see this update after Tom's helpful input.
