Documents from the SMILE trial

University of Bristol has created a website with the documents from the SMILE trial.

http://www.bristol.ac.uk/ccah/resea...bility/chronic-fatigue/smile/smile-documents/

Note that does not include the data, of course.

 

Can't read the link (works but no brain power) but thats silly but not unexpected,
They probably think we are being open and giving you everything, that we deem you worthy of seeing and we will argue meets relevant laws.

 

What has been provided doesn't really clarify much the way the feasibility study became the full study, it was supposedly assessing the feasibility of, along with a change in primary outcome.

Doesn't it look like the only funding they got was for the feasibility study?

 

I notice that they have not included information about the two amendments just the letters saying they were accepted.

The two lines

refer to the same document which appears to be a convenient mistake.

So as far as I can tell by scanning through the documents they have not said what the amendments they applied for were. I notice that one amendment was approved by a two person sub committee. The second went to the full committee so I assume that is upgrading the study from a feasibility study to a full trial.

 

From this letter

http://www.bristol.ac.uk/media-libr...hics - REC Review of SMILE Project Letter.pdf

I thought that he was promoting the fact the trial was being done by the NHS.

 

I only saw the amendment approval from the two person panel. Did I miss one going to the full committee? Can you remember which that was?

These ones all seemed to mention just two people (one of whom seems to be a GP specialising in homeopathy):

Ethics - Amendment 2.0 (PDF, 42kB)

• Ethics - Amendment 2.1 (PDF, 197kB)

• Ethics - Amendment 2.2 (PDF, 185kB)

• Ethics - Amendment 2.3 (PDF, 185kB)

 

So the point of the SMILE study was...?

 

This was just for the feasibility study, which was only to assess the feasibility of doing a trial of LP... it morphed into a full study in ways that don't seem entirely clear.

 

Amendment 2.0 seems to have been reviewed by the R&D committee which I assume is the full thing?

It includes

So it looks like the ethics committee did approve the conversion to a full study. But I still think that seems dodgy. In that I would question whether they gave it their full attention in the way they would a new study. I remember at the time the first papers (from the feasibility study) came out it looked like they were optimizing the primary outcomes to get good results. I wonder if such issues were considered by the ethics committee. The inclusion of the earlier data after such outcome switching also seems dodgy.

What we haven't seen with the release of the documents is the case that Bristol University presented to the ethics committee.

 

Yeah... you're definitely right about them having approval for the amendment to change to a full trial, I'm just not sure if the way they did this meant that they got reduced oversight, or how involved the full committee was.

There is this letter (13th Sept): http://www.bristol.ac.uk/media-library/sites/ccah/documents/Ethics - Amendment 2 - 20 August 2012 1.pdf

That one also refers to 'amendment 2', saying it was approved by a two member sub-committee, and came just before the letter saying that the amendment was approved by the "R & D committee" on the 17th:
http://www.bristol.ac.uk/media-library/sites/ccah/documents/Ethics - Amendment 2 - 20 August 2012 - Reply.pdf

It would be good to speak to someone who is used to how these processes work, and might know if amendments do get the same level of oversight as initial applications, or if they just get looked at by a sub-committee and then rubber-stamped? The letter from the 17th seems fairly cursory compared to the others.

Maybe, given the other problems with SMILE, this is a bit of a minor technicality? Given the other problems with the way the feasibility study was used to change outcomes, and then data from it was used in the main trial, it may still be important though.

Am I being a fool, or are 2.1, 2.2 and 2.3 all the same?

 

I don't think I am write and I think they are trying to mislead. The letter I quoted suggesting they had ethical approval for the change:
http://www.bristol.ac.uk/media-libr...cs - Amendment 2 - 20 August 2012 - Reply.pdf
Is from the hospitals R&D committee not the ethics committee. Although its placement on the Bristol university website is misleading. Then as you say the next 3 letters concerning amendment 2 look identical and seem to come from the ethics committee. They appear to approve a new protocol because it is listed in the document list along with "Notice of substantial amendment". I assume this is the one that is missing and replaced by an earlier document. Then the letter of approval for amendment 2 does as you say suggest that it was approved by just 2 people on a subcommittee.

The cynic in me believes that the information is deliberately not there and in a misleading order with duplicates. Which makes me think there is more to find out.

@JohnTheJack have you made any sense of the documents or do you have additional ones.

 

My head can start swimming with this stuff. I'd been confused by what the R&D committee was. Time to start printing things out and going through with a highlighter!

 

There are websites setting out the process but they are confusing,

From https://www.myresearchproject.org.uk/help/hlpamendments.aspx#1

The boundaries don't seem clear around converting a feasibility study to a full study.

This link also seems relevant
https://www.myresearchproject.org.uk/help/hlpamendmentsresearch.aspx

It would be interesting to know what category amendment they considered it,

 

[QUOTE="
@JohnTheJack have you made any sense of the documents or do you have additional ones.[/QUOTE]

I haven't looked through them properly. I don't have any additional documents.

 

Changing the entire purpose of a study from assessing the feasibility of conducting a trial to assessing the efficacy of an intervention in a full trial, would have to count as a substantial amendment. I'm not sure that would mean there should be more oversight than the two person sub-committee (with one homeopath) we saw though. It could be that SMILE got the approval required without needing much scrutiny.

 

I have today received the result of the review undertaken by Bristol about the SMILE trial data.. They still claim an exemption. I'll refer it to the ICO. It usually takes about 4 months to get a decision.

 

Does Ben Goldenacre still run this ?
http://compare-trials.org/methods
Maybe too much of a hot potato to bring in PACE, SMILE etc?

 

I think so. Could raise SMILE, but I doubt you will get anywhere with them.

 

We've tried many times to involve Goldacre but for some reason the former student of Simon Wessely refuses to look at it. He's too busy, apparently. Though not too busy to tweet about harassment of researchers by ME militants.

 

Especially as the full trial it morphed into was the very trial being assessed for feasibility in the first place. Not just outcome switching when much of the outcomes were already clearly signposted, but as you say, switching the fundamental objectives of the trial as well. It started out as a feasibility study, for assessing the viability and worth of subsequently doing a fully independent trial. Instead it was spliced/grafted into further work that rendered it nonsensical overall.