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)

WITH THE SUPPORT OF…

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

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

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

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”!!!

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

Delphi Results

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

Tot 164: 44 Surgeons; 93 Parents; 27 Patients

Tot 100: 36 Surgeons; 46 Parents; 18 Patients

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

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

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

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

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

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%

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.

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

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