How seperate were the pilot SMILE trial and the non-pilot SMILE trial? How seperate are they meant to be?
Sorry if I'm asking stupid questions, but I don't know what's normal with this sort of thing.
Was there seperate ethics approval for i) the pilot/feasability study ii) the non-pilot trial?
Was funding gained for the pilot, and then new funding for the main trial?
I hope
@Dx Revision Watch will be able to fill me in on this stuff.
My memory was that there was only really announcements on funding and ethics approval for the pilot. Was I just distracted by PACE after that? eg: I remember this getting attention, but I don't remember new of further funding after that:
http://www.meassociation.org.uk/201...o-the-lightning-process-and-children-with-me/
The non-pilot SMILE paper says:
This trial was funded by the Linbury Trust (grant number LIN2038) and the Ashden Trust (grant numbers ASH1062, 1063, 1064). EMC was funded by an NIHR Clinician Scientist fellowship followed by an NIHR Senior Research Fellowship (SRF-2013-06-013) during the trial.
The only mention I could see of an approved grant from the Linbury trust website was in 2010 - presumably for the pilot:
University of Bristol - £44,000 (Over three years) Towards the scientific study of the "Lightening Process" at Bristol University.
http://www.ashdentrust.org.uk/files/Ashden Trust Annual report - 5 April 2010.pdf
This letter dated Nov 2009 does seem to fit with this being for a feasability study:
https://meagenda.files.wordpress.com/2010/07/funding-linbury-trust-04-11-09.pdf
It looks like this was then paid out over a number of years.
In the non-pilot paper they say:
Between September 2010 and April 2013, we recruited participants after clinical assessment by the Bath/Bristol paediatric CFS/ME service, a large regional and national NHS specialist service.
In the feasability/pilot study paper they say:
A total of 56 children were recruited from 156 eligible children (1 October 2010 to 16 June 2012).
And then:
Full trial first randomization: 19 September 2012.
In the non-pilot paper they say:
Sensitivity analyses of the primary outcome adjusted for variables for which there was baseline imbalance; excluded those recruited up to 31 January 2011 preceding the protocol amendment; and used multiple imputation of missing data (see online
supplementary appendix 1 for details).
What's going on? This seems rediculous to me, but I have no idea how this sort of thing is meant to work. It looks like this supposedly non-pilot trial includes data from loads of participants who were part of the pilot study that was used to justify changing the primary outcome away from school attendance at six-months (this outcome showing no signifcant difference between groups in the non-pilot paper, and not being reported in the paper on the pilot study) to more subjective self-report outcomes. That can't be okay can it? It looks a bit like, instead of trying to get funding for a proper follow-up to the pilot, they just botched it and chucked a few extra participants in at the end. Surely they wouldn't try to get away with something else while they're already getting so much attention over PACE?
The only other mention of a protocol change in the non-pilot paper was this:
We used multiple imputation to correct for potential bias due to missing data and conducted sensitivity analyses restricted to participants recruited after the protocol changed to collect primary outcome data by telephone, which improved follow-up rates suggesting that results were robust.
Does anyone with some knowledge of how pilot studies are meant to work want to comment on this?
@Jonathan Edwards ?