Heterogeneity of primary outcome measures used in clinical trials of treatments for intermediate, posterior, and panuveitis

Alastair K. Denniston, Gary N. Holland, Andrej Kidess, Robert B. Nussenblatt, Annabelle A. Okada, James (Jim) Rosenbaum, Andrew D. Dick

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number97
JournalOrphanet Journal of Rare Diseases
Volume10
Issue number1
DOIs
StatePublished - Aug 19 2015

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Panuveitis
Outcome Assessment (Health Care)
Clinical Trials
Uveitis
Therapeutics
Registries
Consensus
Macular Edema
Health Services Needs and Demand

Keywords

  • Clinical trials
  • Composite endpoints
  • Endpoints
  • Outcome measures
  • Uveitis

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Heterogeneity of primary outcome measures used in clinical trials of treatments for intermediate, posterior, and panuveitis. / Denniston, Alastair K.; Holland, Gary N.; Kidess, Andrej; Nussenblatt, Robert B.; Okada, Annabelle A.; Rosenbaum, James (Jim); Dick, Andrew D.

In: Orphanet Journal of Rare Diseases, Vol. 10, No. 1, 97, 19.08.2015.

Research output: Contribution to journalArticle

Denniston, Alastair K. ; Holland, Gary N. ; Kidess, Andrej ; Nussenblatt, Robert B. ; Okada, Annabelle A. ; Rosenbaum, James (Jim) ; Dick, Andrew D. / Heterogeneity of primary outcome measures used in clinical trials of treatments for intermediate, posterior, and panuveitis. In: Orphanet Journal of Rare Diseases. 2015 ; Vol. 10, No. 1.
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abstract = "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.",
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