1. Brennan Kahan NIHR Doctoral Research Fellow
Using re-randomisation in clinical trials to increase patient recruitment
Brennan Kahan
NIHR Doctoral Research Fellow

2. Challenges in recruitment
45% of publically funded UK trials fail to recruit to target1
Implication:
Best method of patient care unknown
1. Sully BG, Julious SA, Nicholl J. A reinvestigation of recruitment to randomised, controlled, multicentre trials: a review of trials funded by two UK funding agencies. Trials. 2013;14:166.

3. The SWIM trial
RCT comparing ibuprofen vs. placebo for sickle cell patients presenting to A&E with a pain crisis
Poor recruitment -> trial terminated early

4. The SWIM trial Small patient group, large number of episodes
Parallel group designs miss out on >60% of episodes

5. Re-randomisation trials
Parallel group Re-randomisation

6. Estimated recruitment (sickle cell trial) Re-randomisation vs
Estimated recruitment (sickle cell trial) Re-randomisation vs. parallel group

7. Observed recruitment benefit in 11 re-randomisation trials
% increase in recruited episodes
Median: 31%
IQR: 25% - 47%
Range: 16% - 119%

8. Does re-randomisation work?
Does it:
Provide unbiased estimates of treatment effect
Correct type I error rate
Adequate power
Yes (if used appropriately)
Setting
Design
Analysis

9. Setting requirements
Some patients may require treatment on multiple occasions
The intervention(s) would be used for each new treatment episode

10. Design requirements
Patients are only re-enrolled and re-randomised when they have completed the follow-up period from their previous randomisation
Randomisations for the same patient are performed independently

11. Analysis issues
Research still ongoing to determine best analysis approach
Analyse episodes independently (i.e. ignore ‘patient’)
Counter-intuitive, but it works
More complicated analyses (GEEs, mixed-effects models) can introduce bias

12. Treatment effect estimates in re-randomisation vs
Treatment effect estimates in re-randomisation vs. parallel group trials (febrile neutropenia)

13. Settings where re-randomisation has been used
Episodes of febrile neutropenia
Asthma exacerbations
Sickle cell pain crises
Influenza vaccine
Smoking cessation
Complications from cirrhosis
Pregnancy
Release from prison

14. Summary
Re-randomisation is applicable to a wide variety of clinical areas
It can increase the recruitment rate
Can provide valid results

15. Acknowledgements and references
Collaborators
Sandra Eldridge
Richard Hooper
Rupert Pearse
Caroline Doré
Tim Morris
Andrew Forbes
Shaun Seaman
Erica Harris
Funding
Brennan Kahan is funded by a National Institute for Health Research Doctoral Research Fellowship
References
Kahan BC. Using re-randomization to increase the recruitment rate in clinical trials – an assessment of three clinical areas. Trials :595.
Kahan BC, Forbes AB, Doré CJ, Morris TP. A re-randomisation design for clinical trials. BMC Medical Research Methodology :96.