OM t of c.iii - Vision Research Coordinating Center - Washington ...

2/1/99 Chapter 2 Study Design page 2-18
and can be applied under very general assumptions which do not require the
specification of the distribution of the repeated measures. It permits missing data, the
absence of between-subject comparability of measurement times, time-dependent as
well as continuous and dichotomous covariates, and correlated outcome measures. The
CLEK Coordinating Center has experience in implementing the Liang and Zeger model
using a SAS macro prepared by Karim and Zeger (1988).
2.9.5 Analyses Keyed to Specific Aims
2.9.5a Specific Aim A
The purpose of this Aim is largely descriptive in that the primary goals are to
provide estimates of visual acuity, corneal curvature, whether keratoconus patients
wear spectacles or contact lenses and the type of contact lens, the percent of patients
with central corneal scarring and other biomicroscopic signs of keratoconus, and the
percent of patients who require corneal surgery. We will also describe the rate at which
the latter two dichotomous measures develop in patients who do not exhibit them at
baseline. (Finally, with a particular focus on those patients who develop central corneal
scarring and those patients who go to surgery during the study, we will quantify the
before/after changes in Bailey-Lovie high and low contrast visual acuity.) Ninety-five
percent confidence bounds will be placed around all parameters estimated for this
Specific Aim. Because Specific Aims B through D are focused on a detailed analysis of
these parameters with an emphasis on accounting for the correlation between two eyes
of the same patient, the descriptive Aim will simplify both the methodology and the
description of results by focusing on a single eye. Specifically, baseline estimates will be
generated with an eye of each subject chosen randomly. The rate of development of the
dichotomous parameters will be described separately using: (1) the randomly selected
eye when the condition is not present at baseline in either eye or (2) the fellow eye when
the condition is present at baseline in one eye. With the development of each
dichotomous condition between baseline and the final study measurement treated as a
yes/no variable, chi square tests will compare the rate of development of each condition
in patients who had the condition in neither eye at baseline versus patients who had the
condition in one eye at baseline. Using this same dichotomy defined by the number of
eyes (0 or 1) in which a condition is present at baseline, the rate of change in best
corrected high and low contrast visual acuity from baseline to final measurement will
be described and compared in the two groups. Thus, we will compute the mean change
in high and low contrast visual acuity in one randomly selected eye of patients with no
central corneal scarring at baseline and in the fellow eye of subjects with central corneal
scarring in only one eye at baseline. Confidence bounds will be placed around those
changes. Before/after differences in high and low contrast visual acuity will be
statistically compared using analysis of covariance with final visual acuity as the
dependent variable and with baseline visual acuity and whether central corneal scarring
was present in one eye as compared to no eyes at baseline as independent variables.
2.9.5b Specific Aim B