1. Dan Perry, MD (Presented by Jennifer Laine, MD)
Definition of a Core Outcomes Set for Clinical Trials in Perthes’ Disease
Dan Perry, MD
(Presented by Jennifer Laine, MD)

2. WITH THE SUPPORT OF…

3. Orthopaedics & Trauma Surgery University of Oxford
PhD Student
LJMU
Associate Professor
Orthopaedics & Trauma Surgery
University of Oxford
Hello everyone,
My name is Donato Leo and I am a 2nd year PhD student at the School of Sport and Exercise Sciences.
My current research aims to define a core outcomes set for clinical trials in perthes’ disease.
In my project I am collaborating with the University of Leeds, the Cardiff University and the Alder Hey children’s hospital.
Professor of Sport Sciences
LJMU

4. CORE OUTCOMES SET Difficult to compare results among studies.
Lack of a common set of outcomes: everyone reports different things!
The Outcomes of Perthes’ Disease
As many of you know, Dan Perry and his team from Oxford are working hard to establish the core outcomes of multiple conditions, as part of the COMET initiative.
To obtain large national grants in the UK, and now, in Canada, the NIH-equivalents in these countries are requiring that core outcomes be established.
These are outcomes that are meaningful to all of the key stakeholders in a condition. For Perthes, this would be parents, patients and surgeons.
By calling something a core outcome, you are basically saying that this outcome should be measured/studied in every bit Perthes pediatric outcome study.
This does not mean that other measures can’t be studied. Also, this is focusing on pediatric outcomes, not adult outcomes, such as arthritis, interference with work, etc.
Core Outcome Measures in Effectiveness Trials
Comet Initiative, 2018

5. Delphi survey (2 rounds) Parent and Child Qualitative Engagement
METHODS
Step 1
Literature Review
Step 4
Consensus Meeting
Step 3
Delphi survey (2 rounds)
Step 2
Parent and Child Qualitative Engagement
Step 5
COS report
Step 2
Interviews with ~13 families with a Perthes child regarding important outcomes
Leo et al., 2018

6. RESULTS 112 papers identified;
Outcomes classified in Clinical Outcomes (i.e. ROM; Pain) and Radiological Outcomes (i.e. femoral head shape; Stulberg Classification);
Basis for the Delphi Survey.
43 different outcome domains to describe “successful treatment”!!!

7. Delphi survey (2 rounds) Parent and Child Qualitative Engagement
METHODS
Step 1
Literature Review
Step 4
Consensus Meeting
Step 3
Delphi survey (2 rounds)
Step 2
Parent and Child Qualitative Engagement
Step 5
COS report
Step 2
Interviews with ~13 families with a Perthes child regarding important outcomes
Leo et al., 2018

8. Delphi Results

9. UK, USA, Australia, Canada
Including 22 IPSG-involved surgeons

10. Tot 164:
44 Surgeons;
93 Parents;
27 Patients

11. Tot 100:
36 Surgeons;
46 Parents;
18 Patients

12. Outcomes Evaluated 4 Domains: Radiographic Findings Clinical Signs
Impact on Life
Effects of Treatment
Surgeons-only for the first two domains
Asked to score each outcome measure (33 in the first round) from 1-9 with respect to importance
33 outcomes (round 1) + additional 5 outcomes (round 2) divided in 4 categories:
X-ray findings (Surgeons only): 10 outcomes (round 1) + 1 additional outcome (round 2);
Clinical Signs (Surgeons only): 5 outcomes (round 1) + 1 additional outcome (round 2);
Impact on Life: 13 outcomes (round 1) + 3 additional outcomes (round 2);
Effects of Treatments: 5 outcomes

13. If the 2 conditions do not apply, there is NO Consensus (NO)
GRADE GUIDELINES1
Consensus In (IN): Majority of the group (>70%) scoring outcomes extremely relevant (7-9), with only a minority (<15%) scoring outcome not relevant (1-3);
Consensus Out (OUT): Majority of the group (>70%) scoring outcomes not relevant (1-3), with only a minority (<15%) scoring outcome extremely relevant (7-9);
If the 2 conditions do not apply, there is NO Consensus (NO)
1Schünemann H. & Brozek J. GRADE handbook for grading quality of evidence and strength of recommendation, version 3.2. Edited by: Oxman. The GRADE Working Group, 2009

14. Round 1 Results: X-ray Findings Clinical Signs Impact on Life
Effects of Treatments
Acetabular coverage IN
Gait analysis NO
Activity of daily living
Complications of treatment
Acetabular shape
Muscle strength
Climb stairs
Deformity
Articulo-trochanteric distance
Hip Mobility
Family finance
Length of hospital stay
Broken Shenton’s Line
Trendelenburg sign
Impact on sport participation
Requirement for further surgery
Cartilaginous Radii
Uneven legs length
Limping
Skin Problem
Evidence of arthritic changes
Pain
Femoral head shape
Pick up objects from the floor
Neck shaft angle
Quality of life
Overgrowth of great trochanter
School attendance
Stage of the disease
Sit comfortably
Sleep quality
Use of walking aids
Walking distance
10 were ruled in
Conference call to discuss  5 added
There were a number that had no consensus, but no outcome measure was ruled out

15. Round 1 Results: Consensus IN: 10 outcomes Consensus OUT: NONE
No Consensus: 23 outcomes
New Suggested Outcomes: 5

16. Round 2 Results: X-ray Findings Clinical Signs Impact on Life
Effects of Treatments
Acetabular coverage IN
Gait analysis NO
Activity of daily living
Complications of treatment
Acetabular shape
Muscle strength
Climb stairs
deformity
Articulo-trochanteric distance
Hip Mobility
Family finance
Length of hospital stay
Broken Shenton’s Line
Trendelenburg sign
Family life
Requirement for further surgery
Cartilaginous Radii
Uneven legs length
Impact on sport participation
Skin Problems
Evidence of arthritic changes
Limping
Femoral head shape
Pain
Neck shaft angle
Pick up objects from the floor
Overgrowth of great trochanter
Psychological impact
Stage of the disease
Quality of life
Time of re-ossification
School attendance
Hip congruency
Sit comfortably
Sleep quality
Use of walking aids
Walking distance
Weight gain
Round 2
Allowed to see the answers from the first round

17. Round 2 Results: Consensus IN: 16 outcomes Consensus OUT: NONE
No Consensus: 22 outcomes
Participants’ dropped percentage from previous round:
Surgeons: - 18%
Parents: - 49%
Patients: - 33%
Total Participants: - 39%

18. NEXT STEP Consensus Meeting
We are going to discuss the outcomes obtained in the Delphi Survey in a final Consensus Meeting among experts in Perthes’ disease to define the final core outcomes set.

19. CONCLUSION
We aim to define a core outcomes set to be implemented in future clinical research, to define the minimum outcomes studies must collect to facilitate study comparisons and meta-analyses

20. Round 2 Results: X-ray Findings Clinical Signs Impact on Life
Effects of Treatments
Acetabular coverage IN
Gait analysis NO
Activity of daily living
Complications of treatment
Acetabular shape
Muscle strength
Climb stairs
deformity
Articulo-trochanteric distance
Hip Mobility
Family finance
Length of hospital stay
Broken Shenton’s Line
Trendelenburg sign
Family life
Requirement for further surgery
Cartilaginous Radii
Uneven legs length
Impact on sport participation
Skin Problems
Evidence of arthritic changes
Limping
Femoral head shape
Pain
Neck shaft angle
Pick up objects from the floor
Overgrowth of great trochanter
Psychological impact
Stage of the disease
Quality of life
Time of re-ossification
School attendance
Hip congruency
Sit comfortably
Sleep quality
Use of walking aids
Walking distance
Weight gain
Might combine some
Others, not as relevant for pediatric outcome
Some need further clarification: “deformity?”
This does not address HOW to measure these outcomes, just that they should be measured
Looking for input…and blessing. These may become important to us as we move ahead