Defining consensus opinion to develop randomised controlled trials in rare diseases using Bayesian design: An example of a proposed trial of adalimumab versus pamidronate for children with CNO/CRMO

被引：23

作者：

Ramanan, A. V. ^{[1
,2
]}

Hampson, L. V. ^{[3
]}

Lythgoe, H. ^{[4
,5
]}

Jones, A. P. ^{[6
]}

Hardwick, B. ^{[6
]}

Hind, H. ^{[6
]}

Jacobs, B. ^{[7
]}

Vasileiou, D. ^{[8
]}

Wadsworth, I. ^{[8
]}

Ambrose, N. ^{[9
]}

Davidson, J. ^{[10
]}

Ferguson, P. J. ^{[11
]}

Herlin, T. ^{[12
]}

Kavirayani, A. ^{[13
]}

Killeen, O. G. ^{[14
]}

Compeyrot-Lacassagne, S. ^{[15
]}

Laxer, R. M. ^{[16
]}

Roderick, M. ^{[1
,2
]}

Swart, J. F. ^{[17
]}

Hedrich, C. M. ^{[4
]}

Beresford, M. W. ^{[4
,5
]}

机构：

[1] Bristol Royal Hosp Children, Paediat Rheumatol, Bristol, Avon, England

[2] Univ Bristol, Bristol Med Sch, Bristol, Avon, England

[3] Novartis Pharma AG, Stat Methodol & Consulting, Basel, Switzerland

[4] Univ Liverpool, Dept Womens & Childrens Hlth, Inst Translat Med, Liverpool, Merseyside, England

[5] Alder Hey Childrens NHS Fdn Trust, Dept Paediat Rheumatol, Liverpool, Merseyside, England

[6] Univ Liverpool, Clin Trials Res Ctr, Dept Biostat, Liverpool, Merseyside, England

[7] Royal Natl Orthopaed Hosp, Paediat, London, England

[8] Univ Lancaster, Dept Math & Stat, Fylde Coll, Lancaster, England

[9] Univ Coll Hosp, Rheumatol, London, England

[10] Royal Hosp Children, Paediat Rheumatol, Glasgow, Lanark, Scotland

[11] Univ Iowa, Stead Family Dept Pediat, Carver Coll Med, Iowa City, IA USA

[12] Aarhus Univ, Dept Paediat, Aarhus, Denmark

[13] Oxford Univ Hosp NHS Fdn Trust, Paediat Rheumatol, Oxford, England

[14] Our Ladys Children Hosp, Natl Ctr Paediat Rheumatol, Dublin, Ireland

[15] Great Ormond St Hosp Children NHS Fdn Trust, Rheumatol, London, England

[16] Univ Toronto, Dept Paediat, Hosp Sick Children, Toronto, ON, Canada

[17] Univ Med Ctr Utrecht, Paediat Rheumatol, Utrecht, Netherlands

来源：

PLOS ONE | 2019年 / 14卷 / 06期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

RECURRENT MULTIFOCAL OSTEOMYELITIS; CHRONIC NONBACTERIAL OSTEOMYELITIS; THERAPY;

D O I：

10.1371/journal.pone.0215739

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Introduction Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder primarily affecting children and adolescents. It can lead to chronic pain, bony deformities and fractures. The pathophysiology of CNO is incompletely understood. Scientific evidence suggests dysregulated expression of pro-and anti-inflammatory cytokines to be centrally involved. Currently, treatment is largely based on retrospective observational studies and expert opinion. Treatment usually includes nonsteroidal anti-inflammatory drugs and/or glucocorticoids, followed by a range of drugs in unresponsive cases. While randomised clinical trials are lacking, retrospective and prospective non-controlled studies suggest effectiveness of TNF inhibitors and bisphosphonates. The objective of the Bayesian consensus meeting was to quantify prior expert opinion. Methods Twelve international CNO experts were randomly chosen to be invited to a Bayesian prior elicitation meeting. Results Results showed that a typical new patient treated with pamidronate would have an 84% chance of improvement in their pain score relative to baseline at 26 weeks and an 83% chance on adalimumab. Experts thought there was a 50% chance that a new typical patient would record a pain score of 28 mm (pamidronate) to 30mm (adalimumab) or better at 26 weeks. There was a modest trend in prior opinion to indicate an advantage of pamidronate vs adalimumab, with a 68% prior chance that pamidronate is superior to adalimumab by some margin. However, it is clear that there is considerable uncertainty about the precise relative merits of the two treatments. Conclusions The rarity of CNO leads to challenges in conducting randomised controlled trials with sufficient power to provide a definitive outcome. We address this using a Bayesian design, and here describe the process and outcome of the elicitation exercise to establish expert prior opinion. This opinion will be tested in the planned prospective CNO study. The process for establishing expert consensus opinion in CNO will be helpful for developing studies in other rare paediatric diseases.

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页数：16