1. Reconsidering patient and public involvement (PPI) in clinical trials: When participants become involved
Claire Vale, Annabelle South, Bec Hanley, Will Cragg, Ben Cromarty, Richard Stephens, Kate Sturgeon and Mitzy Gafos
MRC Clinical Trials Unit at UCL
9th May 2017

2. Background
INVOLVE
Public involvement in research: Research being carried out ‘with’ or ‘by’ members of the public rather than ‘to’, ‘about’ or ‘for’ them.
The ‘public’ includes: Patients / potential patients, carers, people who use health / social care service, people from organisations that represent service users
“For most studies it is not appropriate for people involved in the research to also be participants in the research…”
Possible exception of participatory / action research
I’m not going to tell you all what PPI is – I am assuming that as you are here you have a pretty good idea! Just wanted to draw attention to number 3 – from Involve – which states that …
We would like to challenge that – and hope to convince you of our thinking and position in the next 10 minutes or so!

3. Background
Patient and public involvement (PPI) in clinical research has been increasing
More researchers are ‘walking the walk’ (Boote et al, Health Expect. 2015)
MRC CTU (Vale et al, Trials 2012):
Reasonable evidence of increased PPI in clinical research in more recent times –
Review by Boote et all, walking the walk
Our own experience is that PPI in our studies had been increasing – over time the study opened up – recently updated shows that since 2010, all except one of our new clinical trials have PPI

4. Involvement at MRCCTU at UCL
MRC Clinical Trials Unit at UCL has a policy that states that all trials being run from our Unit should have PPI
Backed up with improved support for researchers and patient contributors, e.g.
Guidance documents
Induction packs
Training
Workshops
We’d like to thing that in part that is due to efforts of our PPI Group at the unit –
By raising the profile among colleagues and by thinking of ways to try to support both staff and PPI contributors in variety of ways…

5. How we involve people
Usually we would look to identify PPI contributors in variety of ways
Via clinical colleagues
From involvement in previous / related trials
Through networks e.g. charities, support groups
Like many of you I am sure, when we start to plan PPI activities for our trials we would typically start to try to identify potential PPI contributors and have a number of preferred or tried and tested routes
Which is all well and good except for where our trials are looking at harder to reach or seldom heard populations, e.g.

6. Trials in hard to reach groups
How can you achieve meaningful PP for trials in hard to reach groups? e.g.
People with rare conditions
People ‘at risk’ of a condition
Can you involve trial participants?
So we started to think of ways to achieve meaningful PPI when it is difficult to identify contributors from the potential trial population where they may be healthy people at risk of developing a condition or when the condition is too rare to have much in the way of established networks that we can contact and work with
This caused us to question whether you could practically and feasibly involve trial participants as PPI contributors…

7. What we did at MRC CTU
Held 2 discussion meetings focussing on participant involvement
Drew on experiences from 2 trials:
MDP 301
Randomised trial evaluating a vaginal microbicide gel to prevent new HIV infection in women in Southern Africa
PROUD
Randomised pilot trial evaluating PrEP in men who have sex with men in England
This question was triggered a bit because we had 2 trials that the Unit led that had involved participants…
The PPI group – which includes staff who worked on these 2 trials – met to reflect on lessons form these trials and further consider participant involvement
MDP was…
And PROUD was…
So on the face of it, being HIV prevention studies were where the similarities begin and end for these 2 studies. But from a PPI perspective…

8. MDP301 and PROUD Very different populations / settings
Difficult to reach potential PPI contributors
Not necessarily accessing health services presently
No established networks
Stigma associated with use of prevention
Societal / cultural norms (male dominated)
Both trials were testing novel therapies
Unavailable locally outside the trials
No one has experience of the treatments already
Although the populations and settings were wildly different , both were potentially hard to reach in terms of potential PPI contributors because the people we were trying to work with were…
And another similarity is that both of these studies were trialling novel therapies – that were currently unavailable locally and had not been previously used in other trials meaning that nobody really could provide a user’s perspective on these treatments apart form the participants in these 2 trials themselves.

9. Why involve participants?
Already identified / agreed to participate
Trial participants uniquely placed
Had unique insights into
Using the treatments
Trial processes and procedures
Trial teams worked to set up mechanisms to involve participants:
Participant involvement meetings
mailing lists
So in both cases the trial teams involved participants because they were…
They had already consented to be in the trial,
Because of issues around confidentiality of participants in trials , within the Unit we don’t hold names and contact details of any participants locally, and so there were hurdles to overcome in order to do this, but the trial teams were able to set up mechanisms to involve participants that complied with ethical and legal requirements and importantly were acceptable to the participants themselves. They were able to set up and run participant involvement meetings – face to face as well as be telephone and video conferences and also through discussion lists etc

10. What participants did: MDP 301
Participants raised concerns e.g.
Cleanliness of specula being used at clinic
Levels of transport allowances
Delays in test results
Resulted in
Introduction of disposable specula
Increase in reimbursement rates
Streamlining of laboratory reporting processes
And though these different mechanisms, participants were able to influence the conduct of the trials, so for example in MDP 301….

11. What participants did: PROUD
During trial recruitment:
Fed back on initial slow recruitment
Advised on ways to increase awareness of PROUD / improve communication with participants
Reassured researchers (e.g. about trial design)
Gave advice on how PrEP could best be rolled out in a future trial (or beyond)
Once results were obtained:
Input into presentation of findings
Championed results / became strong advocates
Whilst in PROUD….

12. When to involve participants
Key: PPI contributors
Identify research question
Design the clinical trial
Carry out the trial
Analyse / interpret results
Publish the results
Share the findings
Participants
So if we think about PPI more generally, we have looked at examples and models of PPI activities across the entire research cycle. Its widely accepted that PPI can and should take place in all of these stages
For participant involvement the cycle is slightly different…
Obviously in advance of recruitment starting in a trial, there are no participants,
And while we think that participant could be involved throughout the rest of the trials, there may be certain activities that it may be difficult or impossible to involve participants – so for example the obvious one that comes to mind would be participants in a DSMC where there is potential risk to the trial of the participant(s) being unblinded

13. Some challenges Managing participant confidentiality
e.g. needing to hold contact details
Ethics committee approval
Explaining participant involvement
Particularly to researchers and PPI contributors - no problems on the part of the participants!
Distinguishing participant involvement and qualitative research and / or engagement
Paying participants
For their PPI contributions, not for participating
I don’t want to gloss over the challenges but they perhaps weren’t that bad.
I’ve already touched on difficulties around participant personal details being confidential - in addition there were inevitably some additional hurdles in ethics applications for involving participants – PPI doesn’t in itself require ethical approval
Asides these practical challenges for trial teams there were some problems with explaining what participant involvement was –
Or related to that, making a distinction between PPI and qualitative research
One final issue – not really a challenge but something to be aware of was the issue od paying PPI contributors – including participants but making clear this payment was for PPI activities and not for participation

14. Benefits of involving participants
Enables PPI when usual mechanisms don’t exist / are less obvious
Unique insight
Over and above other patient contributors
In particular where other networks don’t already exist or where voices are seldom heard
Improve experience of current / future participants
Things that only participants notice or know about
Strong advocates
Participants can provide a powerful message e.g. to health professionals and policy-makers
So the challenges our researchers faced weren’t insurmountable but there were benefits perceived..
I’ve just summarised the key ones here -

15. Lessons learned for all trials
Involving participants can be done
As well as NOT instead of PPI
Additional gains / benefits to trials
Some added complexities /challenges
Some clear areas where participants are not able to be involved
Developing a new study - no participants
DSMC – risk of unblinding
Others?
And so we think that there is no reason why participants can’t be involved as contributors to PPI activity,
Just to be clear, we’re not advocating this instead of PPI – but alongside
We think and hope we’ve highlighted some of the additional gains we found in our trials. Obviously our experiences are limited to prevention settings, but we can’t / haven’t really come up with any good reasons why these aren’t transferable to intervention trials
But we do need to consider why participant involvement may not be feasible or desirable

16. Rethinking recommendations?
INVOLVE states that for most studies:
“..it is not appropriate for people involved in the research to also be participants in the research as that can compromise both the researcher and the person involved, with the possible exceptions of participatory or action research studies…”
Is it time to re-evaluate?
Just want to leave you with the statement I showed at the start which is the INVOVLE recommendation about who to involve wrt participants.
We wonder if that statement could or should now be reassessed?

17. PPI contributors and participants in PROUD and MDP301
Acknowledgements
MRCCTU at UCL PPI Group Members:
Annabelle South, Mitzy Gafos, Will Cragg, Kate Sturgeon, Bec Hanley, Ben Cromarty, Richard Stephens
PPI contributors and participants in PROUD and MDP301