1. ‘Cohort multiple RCT’ design workshop Clare Relton & Jon Nicholl School of Health and Related Research (ScHARR) Faculty of Medicine University of Sheffield c.relton@sheffield.ac.uk j.nicholl@sheffield.ac.uk

2. Purpose of workshop Share knowledge, experiences and ideas

3. Programme 10.35 Introduction to the cmRCT design 11.00 Current research using the design 12.25 Panel Q&A 12.40 LUNCH 13.40 How to analyse cmRCTs 13.50 Talking Circles I & II (35 mins each) 15.00 Tea/coffee 15.20Plenary feedback/ Panel discussion 16.30End

4. Housekeeping Exits Loos Name No mobiles Workshop information Talking circle topics

5. Backstory

7. Introduction to cmRCT design Problems with standard designs cmRCT design defined Differences with other designs Benefits Most suited to.....

8. Pragmatic trials ‘pragmatic’ first applied to clinical trials by Schwartz & Lellouch (1967) who made the distinction between: explanatory trials (which aim to further knowledge as to how and why) pragmatic/practical trials (which aim to inform healthcare decisions within routine practice).

9. Problems with standard designs poor recruitment rates – implications for cost, validity, reliability, comparability of the results informed consent barrier to recruitment (Ross, 1999) unrepresentative recruited population patient & clinician treatment experiences altered lack of long term outcomes poor external validity....

10. Components of cmRCT *1 Cohort * 2 Random selection * 3 Informed consent – patient centred

11. * 1: Cohort Recruit observational cohort of patients Regular outcome measurement for whole cohort

12. * 2: Random selection Capacity for multiple RCTs over time For each RCT eligible patients identified from which some randomly selected to be offered the intervention Outcomes of randomly selected patients compared to not randomly selected.

13. * 3: Informed consent Patient information and consent replicate real world routine healthcare i.e. patients are not told about treatment that they might not receive

14. Copyright ©2010 BMJ Publishing Group Ltd. Relton, Torgerson, O’Cathain & Nicholl. BMJ 2010;340:c1066 ‘Cohort multiple RCT’ design

15. 09/05/2015 Based on (Zelen) randomised consent design Reviews: Schellings 2006, Adamson 2006

16. Differences: cmRCT & other designs *1: Cohort *2: Randomisation *3: Informed Consent – patient centred

17. *1. Cohort Characterised/ phenotyped population’ Contacted again Use their data comparatively Access to routine health records Facility for multiple trials

18. *2. Randomisation Something that is ‘done’ to everyone? Random allocation of all Or Random selection of some

19. *3. Informed Consent

20. Memory research Many people suffer from poor memory and there are few treatments available However, US research has found that as well as helping lower blood pressure (Buitrago-Lopez 2011), chocolate (epicatechin) can boost memory in mice particularly when combined with exercise. University of Sheffield researchers are now planning a study to measure the effectiveness of chocolate on memory. We (researchers) are looking for people to participate in this research. If you decide to participate you will be asked to provide information about your general health and physical activity (using an online form) and asked to perform a short online memory test once a week for 6 weeks. We are not sure if chocolate is more effective than no chocolate. Participants will be randomly selected to receive either chocolate or no chocolate

21. *3. Informed Consent Patient centred Replicates procedures in routine healthcare Patients not told about treatments that they are not then offered Patients not told that their treatment will be chosen ‘at random’

22. 09/05/2015 (II) …and there is research ongoing… (III) … and we want to observe you…. (IV) …and we are not sure which treatment is best…. (V) …and we are going to play a game of chance’… (I) There is a treatment and the benefits are… the risks are … Type and timing of information (standard RCT design)

23. 09/05/2015 (II) …there is research ongoing… (III) … and we want to observe you…. (IV) …and we are not sure which treatment is best…. (V revised) …and you have been selected at random to try it.... (I) There is a treatment and the benefits are… the risks are … Type and timing of information: ‘patient centred’ as used in ’cmRCT’ design

24. Benefits of ‘cohort multiple RCT’ approach Recruitment – improved quantity and more representative sample multiple RCT facility long term outcomes as standard ongoing information as to the natural history of the condition and treatment as usual increased comparability between each trial conducted within the cohort increased efficiency, particularly for expensive or high risk interventions (unequal randomisation)

25. Opportunities Open trials with ‘treatment as usual’ as comparator Easily measured & collected outcomes Clinical conditions where many trials will be conducted Chronic conditions Highly desired treatments or expensive treatments

26. Least suited to.. Closed trial designs with masking or placebo arms Research questions with hard to measure and hard to collect outcomes Acute or short term conditions

27. Examples Ongoing Funded

29. Talking circles Your topics Facilitator Report back: Issues discussed Conclusions reached Actions required

30. Thank you Speakers Brett Thombs Kate Thomas CLAHRC – SY Sue & Emily