1. Reducing bias in randomised controlled trials involving therapists:
To randomise or not to randomise - what are the questions?
Alex Wright-Hughes
Monday, May 8th, 2017

2. Objectives Reducing bias in randomised controlled trials involving therapists: To randomise or not to randomise - what are the questions?
Background
Rationale
Trial examples
SHIFT
OK-Diabetes
TIGA-CUB
Challenges
Conclusions

3. Partially Nested Design
Therapist variation
Clinical trials of behavioural and psychological interventions often involve therapists or other clinical specialists.
Adds further complexity to trial design:
Clustering effects
’multilevel’ randomised trials
Partially nested design
Therapist effects
Therapist allocation: Randomisation?
Partially Nested Design
Therapy 1
Therapy 2 T1 T2 T3 T4

4. Internal validity Allocation of therapists to patients
Involvement of more than one therapist per site can introduce selection bias - therapists can choose which patients they treat.
Therapist selection based on participant characteristics, e.g. the ‘best’ treat the ‘worst’ - confounds the effect of therapists and patient characteristics.
Limits the inferences a trial is able to make, particularly where the therapist effect is of interest.
Reduces the ability to attribute treatment effects to treatment alone, thus impacting a trial’s internal validity.
Walwyn R, Roberts C (2010) Therapist variation within randomised trials of psychotherapy: Implications for precision, internal and external validity. Statistical Methods in Medical Research

5. Random allocation of therapists to patients
To avoid this source of selection bias, allocation of therapists to patients can be concealed and random.
However, doing so can be problematic under constraints of therapist’s capacity, location, and a trials relative priorities.
Therapist
Intervention
Patient
Random
Non random

6. Example I: SHIFT
HTA-funded phase III definitive RCT set in 41 Child and Adolescent Mental Health Services (sites)
Teams of three Family Therapists each, 24 therapists overall, worked together to deliver therapy across services.
Allocation of lead therapist to patients:
Random: where teams worked across services
Aligned: where therapists more aligned within a particular service.
Random allocation
accounting for full
and part-time working
Manchester
All
15 Sites
Yorkshire
Leeds
3 Sites
Bradford
4 Sites
W & E Yorkshire
7 Sites
London
SLAM
OXLEAS
N London
City & Hackney
2 Sites
Randomly allocated lead therapists
Service aligned lead therapists

7. % participants seen by allocated lead therapist
Example I: SHIFT
Randomised therapists
76% compliance
Reasons where not possible due to:
case load (40%)
therapist leave/organisational issues (29%)
clinical reasons (11%)
therapist changeover (9%)
Aligned therapists
65% compliance
Reasons more likely due to case load
(61%) or organisational issues (27%)
Impact of different recruitment rates across sites
% participants seen by allocated lead therapist

8. Example II: TIGA-CUB
NIHR RfPB-funded feasibility RCT set in 6 sites involving 14 child psychotherapists
Variable numbers of therapists per service
Separate therapist allocation to child & primary carer participants
Trial therapy provided ‘within’ therapists usual clinical role
Greater constraints on therapist capacity (one case at a time)
Random allocation of therapists:
Possible for 9/16 (56%) patients
7/16 (44%) allocated based on single therapist availability.
Trust 1
Dudley
Site 1
6 therapists
Site 2
3 therapists
Trust 2
Bradford
Site 3 & 4
Trust 3
Sheffield
Site 5 & 6
2 therapists

9. Example III: OK-Diabetes
NIHR HTA-funded feasibility RCT recruited community-based participants with diabetes and a learning disability.
Diabetes nurse specialists were allocated to participants based on prior contact to ensure consistency in contact
Nurse randomisation occurred where there had been no prior contact.
Considerations
Vulnerability of patients limited randomisation
Timing of random allocation to nurse
Screening visit: Nurse X
SSM
TAU
Nurse X
Screening visit: No Nurse
SSM
TAU
Nurse 1
Nurse 2

10. Challenges
Challenges have included the practicality of randomly allocating therapists within a restricted service, therapist capacity following variable recruitment rates, and deviations from the allocated therapist.
Success of random allocation to therapists influenced by:
Therapist capacity and context
Number of therapists per service
Location: Randomisation may be possible in some but not all sites
Pre-existing therapist-patient relationships: Timing of allocation to therapists
Difficulties when limited capacity, especially if few therapists

11. Conclusions
Random allocation of therapists to patients improves internal validity: avoids selection bias and allows causal interpretation of therapist effects
The context in which therapists work, their capacity and the needs of the trial population all influence the feasibility and appropriateness of randomly allocating therapists.
Implications for analysis: under the intention-to-treat principle participants are analysed as allocated - how to analyse according to therapist?

12. The SHIFT, TIGA-CUB & OK-Diabetes teams
Acknowledgements
University of Leeds:
Rebecca Walwyn
Amanda Farrin
Liz Graham
Sadie Reed
The SHIFT, TIGA-CUB & OK-Diabetes teams

13. Questions?
Alex Wright-Hughes – Statistician
Dr Rebecca Walwyn – Statistician
Professor Amanda Farrin – Statistician
Dr Sadie Reed – Trial Manager

14. References
Walwyn R & Roberts C. Therapist variation within randomised trials of psychotherapy: Implications for precision, internal and external validity. Statistical Methods in Medical Research. 2010; 19(3).
Wright-Hughes A, et al. Self-Harm Intervention: Family Therapy (SHIFT), a study protocol for a randomised controlled trial of family therapy versus treatment as usual for young people seen after a second or subsequent episode of self-harm. Trials. 2015; 16 (1).
Edginton E, et al. TIGA-CUB: Trial on improving Inter-Generational Attachment for Children Undergoing Behaviour problems: study protocol for a randomised controlled feasibility trial of manualised psychoanalytic child psychotherapy versus treatment as usual for children aged 5-11 with treatment resistant conduct disorders and their primary carers. Trials (submitted).
Walwyn RE, et al. Supported self-management for adults with type 2 diabetes and a learning disability (OK-Diabetes): study protocol for a randomised controlled feasibility trial. Trials. 2015;16(1).