Impact of Attributing Cause of Abnormality to POAG on Endpoint Rate and Statistical Power in the Ocular Hypertension Treatment Study

Abstract

 

Purpose:

 

1). to report the proportion of confirmed abnormalities in OHTS due to POAG or to "other causes" and 2). To assess statistical power of OHTS with "POAG" or "all cause" endpoints.

 

Methods:

 

A masked Endpoint Committee (DH, EH, RP) reviewed all confirmed visual field abnormalities and confirmed disc progression to determine whether the change was "most probably due to POAG", "most probably not due to POAG" or, in the case of disc progression, whether the progression was "not clinically significant" or an artifact. Endpoint committee members, masked as to treatment history, reviewed baseline and follow-up case report forms, visual fields and stereoscopic disc photographs of both eyes. Analysis dataset for this report includes the first confirmed abnormality of participants from the start of the study 2/94 to approximately 6/02.

 

Results:

 

The endpoint committee reviewed 509 confirmed abnormalities, 282 visual field abnormalities and 227 optic disc progressions. The endpoint committee attributed only 34% (97 of 282) of the visual field abnormalities and 45% (101 of 227) of the optic disc progression to POAG. Statistical power of OHTS to detect a treatment effect would have been 82% for all abnormalities compared to 99% for abnormalities due to POAG, 29% for all VF abnormalities compared to 96% for VF abnormalities due to POAG, and 99% for all optic disc progression and 99.9% for disc progression due to POAG.

 

Conclusions:

 

To protect the internal validity and statistical power of a clinical trial, the cause of visual field abnormalities and the cause and clinical significance of optic disc changes must be ascertained.  

 

Clinical Trial:

 

www.clinicaltrials.gov nct00000125

 

Keywords: clinical research methodology • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • clinical (human) or epidemiologic studies: biostatistics/epidemiology methodology