In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
The study is a retrospective study design where a randomly selected, stratified sample of 200
practitioners will be identified to determine their patients fit with duration of lens wear, and establish the presence or absence of a history of microbial keratitis. For practitioners who ordered less than 25 pairs of the lenses in 2004 and 2005, all patients will contribute to the analysis and those who ordered 25 or more, no more than 50 patients will contribute to the analysis. This post-approval study condition of approval is being fulfilled by a 522 study that was already proposed when this device was approved.
Study Population Description
Study population is as per approved device indication: The lenses are indicated for use in
the reduction of myopic refractive error in non-diseased eyes. The lenses are indicated for overnight wear in a Contact Lens Corneal Refractive Therapy fitting program for the temporary reduction of myopia up to 6.00 diopters in eyes with astigmatism up to 1.75 diopters. The lenses may be disinfected using only a chemical disinfection system. Practitioners were surveyed and asked if they had observed microbial keratitis cases among the patients who received the device.
Approximately 1,000 pediatrics and 1,000 Adults. A total of 2,000 patient-years had to be accrued
Cases of microbial keratitis (MK)
Followup Visits and Length of Followup
On average each subject was to be followed for 1 year
Final Study Results
Actual Number of Patients Enrolled
Actual Number of Sites Enrolled
Patient Followup Rate
Final Safety Findings
Incidence of microbial keratitis was the main study endpoint.
A total of 2,599 patient-years of
lens wear for 1,317 patients were included in the analysis. At the original fitting date the mean age of the pediatric group was 12.2_+ 2.5 years and for adults was 38.0 + 11.1 years. The mean follow-up for the pediatric group was 2.1+0.8 years, with 620 (92%) having at least 12 months of follow-up, for adults the mean follow-up was 1.8+10 years, with 497 (78%) having at least 12 months of follow-up.
The outcome Assessment Panel identified two cases of microbial keratitis within 2,599 patient years of overnight corneal reshaping lens wear. Both cases of microbial keratitis occurred at least one year after fitting and neither resulted in any documented long-term loss of best corrected visual acuity. The overall estimated incidence of microbial keratitis is 0.00077 per patient-year including the estimated incidence of 0.00139 per patient-year for the pediatric group, and 0.0 per patient-year for adults. The two-sided 95% confidence interval for difference in risk between the two age groups was -0.00139 to 0.00509.
A conservative analysis of 685 patients who began wear of overnight corneal reshaping lenses after January 2005 and had at least one year of document lens wear shows a total of 1,415 patient-years of lens wear (794 pediatric and 621 adult). The two-sided 95% confidence interval for difference in risk between the two age groups was -0.00341 to 0.00927.
Final Effectiveness Findings
Study Strengths and Weaknesses
Due to the nature of retrospective study design, the study was conducted in relatively short
period of time, achieving the required number of patient years, as per protocol. However, there are certain study limitations: loss of follow-up of patients with the event of interest, who could seek medical care elsewhere, may introduce bias that could result in no difference between the comparison groups. Additionally, there was low participation rate among the practitioners who were asked to participate in the study, only 86 out of 200 participated.
Recommendations for Labeling Changes
The recommended labeling change includes a summary of the 522 study including: introduction, study
objective, study design, results, conclusions and strengths and limitations.