Documents from the SMILE trial

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

The two lines
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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.
 
Adrian said:
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.
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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)
 
Esther12 said:
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)
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Amendment 2.0 seems to have been reviewed by the R&D committee which I assume is the full thing?

It includes
Changes to all patient information sheets
Interviews re: study process have now been stopped
Integrated study has now been stopped and removed from all study documentation
Setup of data monitoring committee
Opt out letter sent to all participants to ensure they are happy for their data to be used for the full study
Changes to protocol measures used in the study
Changes to protocol to reflect all amendments
Changes to Consent/assent forms
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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.
 
Adrian said:
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.
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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?
 
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Esther12 said:
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.
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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.
 
Esther12 said:
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!
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There are websites setting out the process but they are confusing,

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

A substantial amendment is defined as a change to the terms of the REC application, the protocol or any other document submitted with the application, which significantly affects one of the following:
  • The safety or physical or mental integrity of study participants
  • The conduct or management of the study
  • The scientific value of the study
  • The quality or safety of any investigational medicinal product used in the study
Addition of new research sites or changes to the local Principal Investigators listed in Part C of IRAS qualify as substantial amendments if the study requires site-specific assessment (SSA). Please refer to the correspondence from your Research Ethics Committee to check whether your study requires SSA, or seek advice from the REC office.
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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

After you have submitted your amendment you should wait to receive communication, which will usually be in the form of an email or letter. IMPORTANT: You should read all correspondence very carefully as it may require further action from you before the amendment can be implemented.

The communication will confirm:
  • Whether the submission is complete.
  • The amendment category A, B or C or new NHS/HSC site
  • The implementation date (if applicable).
  • Any actions you are expected to undertake (e.g. providing information to sites; planning implementation of amendment with sites).
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It would be interesting to know what category amendment they considered it,
 
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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.
 
Esther12 said:
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.
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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.
 
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