1. ICTMC & SCT 2017 Conference, Liverpool
REGISTRY-BASED RANDOMISED CONTROLLED TRIALS – THE FUTURE FOR CLINICAL TRIALS?
David Beard GDPhys, MCSP, MA, MSc, DPhil, FRCS (hon)
Professor of Musculoskeletal Sciences
Co-Director Royal College Surgical Trials Unit (SITU, Oxford)
&
Extended Scope Practitioner (NHS Knee), Swansea

2. Disclosures Institutional Research Grants – Zimmer Biomet
Committees - Arthritis Research UK, Finnish Academy
Various Journal Review
Institutional support - ZB
PRO-MAPP Ltd – Non Exec Director – Oxford Uni Spin Out

3. Outline
General advantages of registry use for trials (focus on orthopaedic)
Challenges
Design
Response
Outcome measures
Validity of the data
Practicalities

4. General advantages Efficiency of effort Available infra-structure
Funding
Patient perspective (repetition)

5. Orthopaedic Registries – not just longitudinal data collection…..
1975

6. Purpose

7. Purpose
Survival ! (re-operation/revision)

8. Purpose

9. Orthopaedic Registry - Advantages
Mandated data collection – govt.
Response rate – usually v good
Ownership by many parties
Not onerous
Not cost prohibited
Level of standardisation
Third party evaluation - bias

10. Embedding RCT’s - Challenges
Design
Response rate
Outcome measures
Validity
Structure and pragmatics

11. IDEAL http://www.ideal-collaboration.net

12. IDEAL-D
Obvious need to evaluate using existing infra-structure or coherent methods

13. Design - comparison Same confounders Which Rx is best?
Device V Device : TKR1 v TKR2
(assumes standardised surgical technique) V V
Procedure V Procedure: P1 v P2

14. X Design - limitations V Surgery V No Rx : P1 v 0
Surgery V Conservative Rx:
P1 v C1 V
Surgery V Placebo Rx:
P1 v Plc

15. Design

16. Design – CSAW. Can Shoulder Arthroscopy Work?
Group AMSR: No Surg. Active Monitoring with Specialist Reassessment (natural Hx)
Group ASAD: bone removed, active surgical Rx
Group AO: Arthroscopy only (“placebo” ASAD)
No Rx
control V
Active Rx
Active Rx V
“placebo
ASAD”

17. Design (and response rate)
Non Acute
Population:
No data for non operative group
Response rate
Existing registry IT database
Patients with ACL rupture
A. ACL Reconstruction
(with post op rehab)
B. Non operative Rx
Rehabilitation
Questionnaires at
6/12 and 1 year - +
50%?
No ACLR
ACLR
Follow up at 18 months
KOOS 4
Follow up at 18 months

18. 98% down to 55% for same implant
Outcome
Most registries limited – SAFETY BASED failure by survival (re-operation)
Few with PROMs
Endpoint?
revision inadequate
poor function, pain
failing implants not revised
98% down to 55% for same implant

19. TOPKAT - Re-operations n=13
Complication
PKR
TKR
Major revision (single stage) 1 -
Minor revision (exchange of poly insert) 2
Manipulation under anaesthetic 6
Aspiration
Injection under anaesthetic
Sub Total (re-operations) 7

20. Primary Outcome - OKS 1.8 point diff 1.5 point diff p=0.03 p=0.09

21. Outcome measures – Marion Campbell/Rumana Newlands
Mapping exercise
England and Scotland
Various trials
outcome listing, ease of extraction, cost
Assessing clinical importance of missing outcomes
Core outcomes OK – secondary?

22. Outcomes
Inserting new trial specific outcomes without compromising registry data……
Hybrid outcome measures…

23. Validity Data collected with “registry” mindset?
Prospective OK – Retrospective??
Selection bias +++

24. Validity - research UTMOST – NIHR HTA Efficient Study Designs
Risk-benefit and costs of unicompartmental (compared to total) knee replacement for patients with multiple co-morbidities: a non-randomised study, and different novel approaches to minimise confounding.
Professor Daniel Prieto-Alhambra
Validate registry findings with RCT
Hawthorne type effects – RCT v cohort ?

25. Integrated process
Simple?
Registry Profile
10 yrs
Embedded RCT

26. Complexity of process and data input
L Davies

27. IT - Integrated Data Collection
Clinicians
Providers
Commissioners
Manufacturers
Patients
Unified platform, different applications
clinical pathway software
clinical PROMS
software
longitudinal surveillance software
dedicated trials software

28. Summary – Trials in Registries in Ortho
Several advantages ..and is possible
Not all trial designs – A V B only - no proof of efficacy
Response rate needs monitoring
Need to insert appropriate outcomes
Validity – potential…work in progress
Data collection system – work in progress

29. Thank You
Encaenia, Oxford
Three Cliffs, Gower