Janet Wisely gets on OBE after years of approving ethics of SMILE, PACE, etc at NREAP. [Minutes of their discussions included]

[Esther12]

It's that time of year again... when they worst people in Britain are celebrated by being given the chance to grovel on their knees in exchange for a special badge. One of this years remarkable people is Janet Wisely.

I was planning to go through all the minutes of all the National Research and Ethics Advisory Panel Meetings, but I've only ended up doing a little more than a years worth. I want to come back to this, it was pretty interesting Also, it seems like @maxwhd from twitter has already done something similar here, focussing more on PACE excerpts: http://www.twitlonger.com/show/n_1so4td9

The full list of minutes are here: https://www.hra.nhs.uk/about-us/committees-and-services/nreap/nreap-meetings/

I focussed on the time when SMILE came up a lot.

10 November 2010:

7. Submissions from the ME Association and others to NRES concerning the ‘SMILE’ study
Received for discussion:
The ME Association and the Young ME Sufferers Trust joint statement NRES response letter Notes written by Hugh Davies in early response IRAS application for the „SMILE‟ study
The ME Association has raised concerns over a study of ME in young people that was recently approved by a REC. The panel were asked for comments/advice on the broader ethical issues and the actions proposed by NRES:

“…we feel that a fair way forward is to seek the responses of the researchers, sponsor and the ME charities involved in the development of the study before asking the REC to review its favourable opinion. We also note that in this project, subjects will not be deprived of what is current care in this clinic. Research participants will receive this intervention in addition to their standard treatment.
We will also be seeking the views of our National Research Ethics Panel.”

The panel were supportive of the proposed NRES action put forward to deal with the concerns raised by the ME Association and others. It agreed that the main REC should be asked to review its favourable opinion in the light of new information (as per current NRES SOPs). The panel were in broad agreement with the preliminary notes written by Hugh Davies in response to complaints made about the SMILE study. However, the panel felt that in reviewing its decision the REC involved should limit itself to considering only the relevant new information regarding the study itself and not to consider allegations which were outside of its remit or competence to comment upon.

The panel stated that it was important to conduct impartial research into ME and that, where appropriate, it was equally important to ensure the benefits of research are extended to children in line with existing guidelines. It was noted that in the SMILE study participants were not being deprived of current care and the research question was the effectiveness of the additional tool which the study was designed to evaluate.

Agreed: The panel agreed and endorsed the proposed NRES action

https://www.hra.nhs.uk/documents/343/2010-11-10_NREAP_Minutes.pdf

08 December 2010:

4. Matters Arising
4.1 The ‘SMILE’ Study

JW informed the panel that the main REC had now reviewed its favourable opinion in the light of new information (as per current NRES SOPs).
The main REC had voted unanimously to confirm the favourable opinion of the application with the following additional conditions:
1. PIS for Teenagers and PIS for Parents: Please add the fact that the Lightening Practitioner is
not clinically (medically) qualified (trained).
2. PIS for Teenagers and PIS for Parents: Please include the following text in the „Are there any disadvantages to taking part‟ section:
“Teenagers with CFS/ME can get worse with any intervention offered. There is no data in teenagers, see tables 1 and 2 for data in adults.”
3. PIS for Teenagers and PIS for Parents: Add the figures for GET, CBT and the LP from the Parliamentary Inquiry into NHS Service provision for ME/CFS include Data taken from Action for ME (AfME) and Association of Young people with ME (AYME) joint report “M.E. 2008: What progress” and reference it.
4. PIS for Teenagers and PIS for Parents: Add the figures for GET, CBT and the LP from the 2008 MEA survey and reference this.

The main REC also suggested (not as an additional condition) that in future Dr Crawley should consider using Lightening Practitioners who were additionally clinically qualified.

https://www.hra.nhs.uk/documents/344/NREAP_Minutes_2010-12-08_FINAL.pdf

12 January 2011

4.2 The ‘SMILE’ study
Received for information only:
NREAP Minutes 12 January 2011 Page 2 of 5
Letter from Joan Kirkbride

https://www.hra.nhs.uk/documents/345/NREAP_Minutes_2011-01-12_FINAL.pdf

2. Declarations of Interest:
6. The SMILE Study
Janet Wisely (NRES Director) and Hugh Davies (NRES Ethics Advisor) left the room during the discussion of this item.

...

6. The SMILE Study: Charles Warlow
Received for discussion:
Report for the National Research Advisors Panel - Charles Warlow

JW and HD left the room whilst the panel discussed this item.

Following the verbal report from CW the panel agreed that:

Whilst the panel did not feel that any "material issues" had been raised to categorically require a second review by the main REC it was felt that NRES had acted appropriately and reasonably in asking the main REC to review its favourable opinion in the light of the „new information‟ (in line with NRES SOPs). Whilst the panel were not in a position, nor had the remit, to comment upon the initial and subsequent review provided by the main REC they considered the REC‟s opinions to be entirely appropriate. If any further studies involving the lightning process are to be reviewed by an NRES REC then the panel felt it would be appropriate for the main REC involved to be appraised of the history of the ethical review of the SMILE study.

The panel supported the NRES operational view that the correspondence received after the REC meeting, in response to the REC decision not to suspend the ethical opinion, does not raise new issues that require a further review by the REC at this time.

https://www.hra.nhs.uk/documents/346/NREAP_MINUTES_2011-02-09_FINAL.pdf

Minutes for 9th March meeting seem to be missing. What happened here?! Next they were contacting 'Understanding Animal Research'!

April 13 2011:

4.4 The SMILE Study
AG had contacted „Understanding Animal Research‟ who were happy to explore areas of common
ground in handling correspondence with regard to conducting research in contentious areas.

https://www.hra.nhs.uk/.../NREAP_MINUTES_2011-04-13_-_revised_2012-01-11.pdf

08 June 2011

4.2. PACE Trial – Text of joint letter calling for more information, 24 May 2011
Received for information only:
PACE Trial – Text of joint letter from the ME Association together with the Young ME Sufferers Trust and the West Midlands ME Groups Consortium to Professor Peter D White (investigator, PACE Trial) calling for more information, 24 May 2011 (http://www.meassociation.org.uk/?p=6171)

https://www.hra.nhs.uk/documents/350/NREAP_MINUTES_2011-06-08_FINAL.pdf

13 July 2011

4. Matters Arising

4.1. CFS/ME Research
Richard Tiner drew the panel's attention to a recent article in the BMJ entitled “Living with CFS/ME” 1
by Ollie Cornes which he felt would be of interest. CC would circulate the article to the panel by email.
It was also pointed out that the MRC has highlighted Chronic Fatigue Syndrome/Myalgic
Encephalomyelitis (CFS/ME) as a high priority and will be making available up to £1.5M for new
research into the mechanisms of CFS/ME. The MRC has also set up a new group, the CFS/ME
Expert Group (chaired by Professor Stephen Holgate, chair of the MRC Population and Systems
Medicine Board), to consider how new high-quality research into CFS/ME and partnerships between
researchers already working on CFS/ME and those in associated areas might be encouraged.2

4.2. Disruption of Research
Janet Wisely explained that she had met with Barbara Davies (Communications Director,
Understanding Animal Research) to discuss possible ways forward with regards ensuring that
medical research may be carried out without fear of harassment. This issue would be discussed
further at a future meeting of the panel.

https://www.hra.nhs.uk/documents/351/NREAP_MINUTES_2011-07-13_FINAL.pdf

 

[Esther12]

I probably decided to do this after looking up Trish Groves on social media. She seems to have played a role in presenting misleading info to COPE, as David Tuller as explained:

http://www.virology.ws/2018/01/02/trial-by-error-the-school-absence-study-revisited/
http://www.virology.ws/2018/01/03/trial-by-error-cope-to-bmj-open-more-details-please/

She's pleased about the level of transaparancy Wisely has achieved in medical research:

 

[Jonathan Edwards]

'Trish Groves (MBBS, MRCPsych) trained in medicine and psychiatry before going to The BMJ in 1989. She is now director of academic outreach and advocacy for BMJ, editor in chief of the online only journal BMJ Open, and honorary deputy editor of The BMJ.'

What a Lilliputian world we live in. It's a bit like celebrities congratulating each other on a Christmas panel game. The only difference is that it is so much more sinister.

Sometimes I do wish I tweeted, but I like the delusion that there is still a nice little old world one can live in without twitter where people behave properly (complete delusion I know).

 

[Revel]

I like the delusion that there is still a nice little old world one can live in without twitter where people behave properly

Hey, don't overcrowd me!

 

[Adrian]

Whilst the panel did not feel that any "material issues" had been raised to categorically require a second review by the main REC it was felt that NRES had acted appropriately and reasonably in asking the main REC to review its favourable opinion in the light of the „new information‟ (in line with NRES SOPs). Whilst the panel were not in a position, nor had the remit, to comment upon the initial and subsequent review provided by the main REC they considered the REC‟s opinions to be entirely appropriate. If any further studies involving the lightning process are to be reviewed by an NRES REC then the panel felt it would be appropriate for the main REC involved to be appraised of the history of the ethical review of the SMILE study.

I wonder if concerns that a future review process may be more rigorous and bring up the issues again means that Crawley went through the backdoor to approve the full trial via a protocol change on the existing ethical permission.

 

[Esther12]

I wonder if concerns that a future review process may be more rigorous and bring up the issues again means that Crawley went through the backdoor to approve the full trial via a protocol change on the existing ethical permission.

That's an interesting point. I hadn't thought of that.

Alternatively, they seemed to shift to the view that concern about SMILE was anti-science harassment, so maybe they'd have been keen to 'stand up for science'?

 

[Esther12]

Some older minutes relating to PACE. Also, this thread hasn't been replied to since the HRA letter on PACE, so could be of more interest now? These minutes are hosted by the HRA, but may have been from a precursor?

After going through the minutes of this committee I've just realised that I posted a summary maxwhd had written of the same documents in the first post of the thread. I wish I'd spotted that an hour ago.

12May2010 https://s3.eu-west-2.amazonaws.com/www.hra.nhs.uk/media/documents/2010-05-12_NREAP_Minutes_Final.pdf

11.Any other business Withdrawal of Data Following Participation in a Study.JW asked the panel for their views on how long after consent to take part in a study can a participant ask to have their data withdrawn.Whilst the panel were not qualified to make any statements regarding the legal aspects of requests to withdraw data already collected in a research study they recognised that there was a tension between respecting an individual's wish to withdraw their data and the public interest in the validity of research and the integrity of research data. Whilst respect for autonomy demands that an individual has a right to withdraw their active participation in a study at any time, their right to withdraw data derived from their participation is clearly more complex and any specific advice will depend upon the details of the individual case.However, in general the panel noted that it wasaccepted practice to include in information sheets and consentforms the statement that that whilst participants were free to withdrawtheir active participationat any time any data collectedduring the study would still be included in any analysis. Itis not clear whether "participation" could or should be deemed to extend to the later analysis of non-identifiable data collected from an individual, but the panel felt that, in general, the public interest in the integrity of data produced by research trials would normally outweigh the perceived harm that might result from the retention and analysis of an individual's non-identifiable data against their will. NREAP Agenda12 May 2010Page 6of 7In addition, the panel felt that consideration would need to be given to whether the removal ofindividual's data would result in insufficient data remaining to produce any meaningful results thereby threatening the integrity of the trialThe issue of "ownership" of the data was also discussed by the panel. A parallel was suggested by AG with discussions regarding property rights in tissue and cell lines derived from tissue. It has been argued that where the "remover" manipulates and “improves”the tissue he thereby acquires property rights over the tissue1.AG suggested that the processing and analysis of an individual's personal data may be deemed to transfer intellectual property rights over that data to the “processor” thereby removing the right of the individual to request the removal of the data (now owned by the researcher). However, SWo pointed out that these arguments with regards to property rights in tissue and cell lines were somewhat controversial and may have limited applicability to any case involving data.Followingthe meeting the NREAP secretariat found the following guidance related to this issuethat broadly supportthe NREAP position outlined above:The FDA(U.S. Food and Drug Administration) has released guidance(Guidance for Sponsors, Clinical Investigators, and IRBs: Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials-September 20082) on the use of data following withdrawal:“III. DISCUSSIONIn summary, data collected on study subjects up to the time of withdrawal must remain in the trial database in order for the study to be scientifically valid. Ifa subject withdraws from a study, removal of already collected data would undermine the scientific, and therefore the ethical, integrity of the research. Such removal of data could also put enrolled subjects, future subjects, and eventual users of marketed products at an unreasonable risk. Finally, removal of data would fundamentally compromise FDA‟s ability to perform its mission, to protect public health and safety by ensuring the safety and effectiveness of regulated products.”“IV. FDA POLICYIf a subject withdraws from the interventional portion of a study and does not consent to continued follow-up of associated clinical outcome information, the investigator must not access for purposes related to the study the subject‟s medical record or other confidential records requiring the subject‟s consent. However, an investigator may review study data related to the subject collected prior to the subject‟s withdrawal from the study, and may consult public records, such as those establishing survival status.”In addition the Wellcome Trust has published guidance (Research involving people living in low and middle income countries: Position statement and guidance notes for applicants3) which highlightsissues for applicants to consider when designing and submitting a research proposal tothe Wellcome Trust for funding:“Withdrawal from participation in researchThe right to withdraw from ongoing participation in a research study is a fundamental right of any participant.Researchers need to give careful consideration to the implications of individuals withdrawing their participation from research. The feasibility and implications of withdrawing from research, and the extent to which that applies to the withdrawal of data and samples from a study, need to be clearly covered as part of the consent process. 1Doodeward v Spence (1908) 6 CLR 4062http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126489.pdf3http://www.wellcome.ac.uk/About-us/Policy/Policy-and-position-statements/WTD015295.htmNREAP Agenda12 May 2010Page 7of 7The Wellcome Trust would consider it appropriate to retain data and samples within a study if they are anonymised, there is no link back to the participant, the risk to the individual of retaining the data is minimal and the withdrawal of the data threatens the integrity of the study.

This response to being told that a participant can have their data removed from PACE is so typical of a certain sort of academic - throw a hissy fit and talk rubbish about how disastrous it is for you to not get everything you want:

09June2010 https://s3.eu-west-2.amazonaws.com/www.hra.nhs.uk/media/documents/2010-06-09_NREAP_Minutes_Final.pdf

4.1Withdrawal of Data Following Participation in a Study.Janet Wiselyexplained that following thePanel‟s discussion of this item at the last meeting the Information Commissioner hasinsisted that the study participant‟s data be removed from any analysisin the study that prompted the initial discussionof this issue.It was noted bythe Panelthat this is likely to mean that the study will now not be published. The Panelnoted thatthe decision taken by the Information Commissionermight have beenconstrained by the existingdate protection law, but strongly indicated that the consequence was that a study might be wrecked and that the autonomy of other participants in the study harmed NREAP Minutes 09June 2010Page 2of7Simon Woods (SWo) suggested that NRES might consider providing a template for researchers as it has done in other instances such as the MCA so that researchers have an example of appropriate wording to use when raising the issue of data retention at the time of consent to a study.The Panelfelt that it would be beneficial to seek the views of other interested parties, e.g. the MRC, to mount a coordinated response to this decision. It wasagreed that Andrew George(AG)should contactProfessor Janet Darbyshire(Head of the MRC Clinical Trials Unit and Joint Directorof NIHR CRN CC) about the Panel's concerns regarding the removal of valuable data from research studies.Action: AG

14July2010: https://s3.eu-west-2.amazonaws.com/www.hra.nhs.uk/media/documents/2010-07-14_NREAP_Minutes_FINAL.pdf

4.3Withdrawal of Data Following Participation in a Study.Received for Information: email from Andrew George toProfessor Janet Darbyshire (Head of the MRC Clinical Trials Unit and Joint Director of NIHR CRN CC) about the Panel's concerns regarding the removal of data from research studies.JW informed the panel that advice had been reported which referenced the requirements of the EU Clinical Trials Directive to retain integrity of trials data. There were interpretations to be made but current advice was that integrity of trialdata needed to be considered alongside interpretation of data protection issues.The panel discussed whether NRES or the NREAs should issue advice on the issue of the retention of data following the withdrawal of a participant. The panel agreed that the panel should review the current IRAS form and guidance and this issue should be discussed at a future meeting.Action: CC

11August2010: https://s3.eu-west-2.amazonaws.com/www.hra.nhs.uk/media/documents/2010-08-11_NREAP_Minutes_FINAL.pdf

4.2Withdrawal of Data Following Participation in a Study.AG informed the panel that he had received furtherconfirmation from Professor Janet Darbyshire (Head of the MRC Clinical Trials Unit and Joint Director of NIHR CRN CC)that they had received a response from the Information Commissioner‟s Office which they have interpreted as meaning that they do not need to withdraw the individual‟s study data from the PACE trial.

And now we're up to the 10th November meeting in the first post of this thread.