期刊论文详细信息
Orphanet Journal of Rare Diseases
Heterogeneity of primary outcome measures used in clinical trials of treatments for intermediate, posterior, and panuveitis
Andrew D. Dick6  James T. Rosenbaum3  Annabelle A. Okada2  Robert B. Nussenblatt5  Andrej Kidess1  Gary N. Holland4  Alastair K. Denniston7 
[1] Institute of Translational Medicine, Birmingham Health Partners, University of Birmingham, Birmingham, UK;Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan;Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, USA Legacy Devers Eye Institute, Portland, Oregon, USA;UCLA Stein Eye Institute and the Department of Ophthalmology, Ocular Inflammatory Disease Center, David Geffen School of Medicine at UCLA, 100 Stein Plaza, UCLA, Los Angeles 90095-7000, CA, USA;National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA;NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK;Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
关键词: Composite endpoints;    Endpoints;    Outcome measures;    Clinical trials;    Uveitis;   
Others  :  1224120
DOI  :  10.1186/s13023-015-0318-6
 received in 2015-03-18, accepted in 2015-08-06,  发布年份 2015
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【 摘 要 】

Background

Uveitis describes a heterogeneous group of conditions characterized by intraocular inflammation. Since most of the sight-threatening forms of uveitis are individually rare, there has been an increasing tendency for clinical trials to group distinct uveitis syndromes together despite clear variations in phenotype which may reflect real aetiological and pathogenetic differences. Furthermore this grouping of distinct syndromes, and the range of manifestations within each uveitis syndrome, leads to a wide range of possible outcome measures. In this study we wished to review the degree of consensus or otherwise in the choice of primary outcome measures for registered clinical trials related to uveitis.

Methods

Systematic review of data provided in clinical trial registries describing clinical trials dealing with medical treatment of intermediate, posterior, or panuveitis through 01 October 2013. We reviewed 15 on-line clinical trial registries approved by the International Committee of Medical Journal Editors. We identified all that met the following inclusion criteria: prospective, interventional design; target populations with intermediate, posterior or panuveitis; and one or more pre-specified outcome measures that were related to uveitis. Primary outcome measures were classified in terms of type (efficacy or safety or both; single, composite, or multiple); dimension (disease activity, disease damage, measured or patient-reported visual function); and domain (the specific study variable being measured).

Results

Of 195 registered uveitis studies, we identified 104 clinical trials that met inclusion criteria. There were 14 different domains used as primary outcome measures. Among clinical trials that utilized primary outcome measures of treatment efficacy (n = 94), 70 (74 %) used a measure of disease activity (vitreous haze in 40/70 [57 %]; macular oedema in 19/70 [27 %]) and 49 (70 %) used a measure of visual function (visual acuity in all cases). Multiple primary outcome measures were used in 23 (22 %) of 104 clinical trials. With regard to quality, in 12 (12 %) of 104 clinical trials, outcome measures were poorly defined. No clinical trial utilized a patient-reported study variable as primary outcome measure.

Conclusions

This systematic review highlights the heterogeneity of outcome measures used in recent clinical trials for intermediate, posterior, and panuveitis. Current designs prioritize clinician-observed measures of disease activity and measurement of visual function as outcome measures. This apparent lack of consensus regarding outcome measures for the study of uveitis is a concern, as it prevents comparison of studies and meta-analyses, and weakens the evidence available to stake-holders, from patients to clinicians to regulators, regarding the efficacy and value of a given treatment.

【 授权许可】

   
2015 Denniston et al.

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