Use of a run-in period to decrease loss to follow-up in the contact lens and myopia progression (CLAMP) study
Introduction
A run-in period is a time of observation prior to randomization during which potential subjects can be screened for compliance with a treatment regimen. A run-in period may increase the proportion of compliers participating in a trial, decrease losses to follow-up, improve the statistical power of a study, and allow investigators to assess the outcome measures prior to randomization [1], [2], [3]. However, run-in periods may also limit generalizability, increase the length of the study, and reduce the sample of eligible subjects [4]. The advantages and disadvantages of a run-in period must be considered prior to implementation in a clinical trial.
The Contact Lens and Myopia Progression (CLAMP) study is a randomized clinical trial to examine the effects of rigid gas permeable (RGP) contact lenses on myopia progression in children. The CLAMP study utilized a run-in period to reduce the potential for unequal loss to follow-up suffered by previous RGP contact lens myopia control studies [5], [6]. This paper describes our experience conducting a run-in period with 147 children ages 8–11 years who desired to wear contact lenses during the CLAMP study.
RGP contact lenses provide clear vision with relatively few ocular health risks, and they are a standard management option for correcting myopia. While RGP contact lenses are used to correct myopic refractive error, they may also provide a therapeutic effect and retard the progression of myopia. However, RGP contact lenses are initially less comfortable than soft contact lenses, but the long-term comfort of RGP contact lenses is comparable to soft contact lens comfort [7], [8].
Two RGP contact lens myopia control studies showed that discomfort accounted for one-fifth to one-third of the loss to follow-up [5], [6]. The absence of data from subjects who drop out of a study may compromise the validity of the results [9]. For example, if the inability to adapt to rigid contact lens wear is associated with a higher rate of myopia progression, the result may be a false impression that rigid contact lenses slow the progression of myopia. In reality, the subjects assigned to wear rigid contact lenses whose myopia progresses faster may have simply been lost to follow-up, creating the illusion of slowing the progression of myopia.
In this report, we show the benefits of a run-in period to aid retention in an RGP contact lens myopia control clinical trial; we report the percentage of children who successfully adapted to RGP contact lens wear during the run-in period of the CLAMP study; and we show the ocular characteristics and children's contact lens-related reports that are associated with successful RGP contact lens adaptation.
Section snippets
Methods
We enrolled 147 eligible children in the CLAMP study. The children were between the ages of 8 and 11 years, had between −0.75 D and −4.00 D myopia, and had not worn contact lenses previously. Successful adaptation to rigid contact lens wear was defined by the subjects' report of at least 40 hours of wearing time per week and contact lenses that were “always comfortable” or “usually comfortable.” Subjects were examined for eligibility, and follow-up visits were scheduled according to the
Results
At both the 1-year visit and the 2-year visit, 114 out of the 116 subjects (98.3%) were examined. At the 3-year visit, all of the subjects were examined, so the 3-year retention rate was 100%. Subjects were examined at 98.9% of the potential follow-up visits.
Subjects who successfully completed the run-in period are called “adapters,” and subjects who did not successfully complete the run-in period are called “nonadapters.” Boys and girls were able to adapt to RGP contact lens wear equally, and
Discussion
A careful inspection of previous rigid contact lens myopia control studies helped determine the beneficial effects of a run-in period. Because significant proportions of subjects were lost to follow-up in previous RGP contact lens myopia control studies due to poor initial comfort [5], [6], we predicted a run-in period would increase the number of compliant subjects, decrease losses to follow-up, and improve the statistical power of the study. Without the run-in period, one of every five
Acknowledgements
This work was supported by NIH/NEI grants K23-EY00383, T35-EY07151, and R21-EY12273; NIH/NHLBI grant K30-HL04162, Menicon Ltd.; CIBA Vision Corporation; SOLA Optical, USA; and an American Optometric Foundation William C. Ezell Fellowship, sponsored by Essilor.
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