Variation of clinical outcomes used in glaucoma randomised controlled trials: a systematic review

Methodological quality of the review: Low confidence

Author: Ismail R, Azuara-Blanco A, Ramsay CR

Geographical coverage: Not reported

Sector: Glaucoma

Sub-sector: Clinical outcomes

Equity focus: None specified

Review type: Other review

Quantitative synthesis method: Narrative synthesis

Qualitative synthesis method: Not applicable

Background: There is a need for robust and/or standard methods for the selection and reporting of proper outcomes to be used in glaucoma clinical trials. Outcomes should be relevant to patients, clinicians and policymakers to influence practice. Inconsistent selection, measurement and reporting of outcomes across clinical trials is a problem. A lack of standardisation may result in inefficient trials, difficult to conduct meta-analysis and selective outcome reporting bias.

Therefore, selection of appropriate outcomes in a trial is crucial to the comparison between different interventions. No attempt has been undertaken on the standardisation of the clinical outcome measures in glaucoma randomised controlled trials (RCTs).

Objectives: To identify different clinical outcomes reported in glaucoma randomised controlled trials.

Main findings: The authors identified 4323 potentially relevant abstracts, from which 315 publications were retrieved. After applying inclusion/exclusion criteria and checking eligibility, 233 RCTs were included. The location of studies was not clear from the review. A total of 967 clinical measures were reported. There were large variations in the definitions used to describe different outcomes and their measures. Intra-ocular pressure (IOP) was the most commonly reported outcome (used in 201 RCTs, 86%) with a total of 422 measures (44%). Safety outcomes were commonly reported in 145 RCTs (62%) whereas visual field outcomes were used in 38 RCTs (16%).

The authors concluded that there is a large variation in the reporting of clinical outcomes in glaucoma RCTs. This lack of standardisation may impair the ability to evaluate the evidence of glaucoma interventions.

Authors noted that future studies should take into account the selection of appropriate outcomes when designing clinical trials to compare different interventions.

Methodology: Review authors conducted a search using terms related to glaucoma and RCTs on Ovid MEDLINE (R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE (R) from January 2006 to the first week of March 2012. No specific search terms were used in this study (this is not clear from the methodology).

Authors excluded studies that did not evaluate patients with glaucoma, where the study design were not an RCT or was not written in English. All abstracts were screened by one author, then about 10% of them were reviewed by a senior researcher to test for agreement.

Included were all clinical outcomes and variations of reporting, information on population, duration of follow-up (months), sample size, type of intervention (medical, surgical, laser, others) and outcomes. Outcomes of either primary or secondary and methods used for documentation and measurement were also recorded, also by whom and when they were measured and analysed. Other types of outcomes such as patient-reported outcome measures (PROMs), pharmacokinetic evaluation and economic outcomes were excluded.

Authors conducted a narrative synthesis of included studies.

Applicability/external validity: Authors claim that the review has good external validity as the identified studies have included different glaucoma populations and different interventions. The applicability of outcomes of this study in different settings, especially low/middle-income countries, was not clearly discussed in this review. However, the outcomes of this study seem applicable to all settings as it seems that there is inconsistency in selecting and measuring glaucoma outcomes everywhere.

Geographic focus: This review focused on all countries. It is not clear from the review if they have found any results from low/middle-income settings or not.

Summary of quality assessment: Overall, low confidence was attributed in the conclusions about the effects of this study as major limitations were identified. Authors did not conduct a comprehensive search of the literature to ensure that relevant studies were not omitted in the review. As such, this review may be prone to publication bias. Authors did not use appropriate methods to screen studies for inclusion, to extract data or to appraise the methodological quality of included studies.