- Scope
This document describes the requirements of the regulations and rules for full pre-marketing
clinical trials.
This document applies only to clinical trials for Rigid Gas Permeable Contact Lens products that
use a re-shaping method to alter the corneal topography to achieve a temporary correction of
refractive error.
The pre-marketing clinical trial plan for Orthokeratology lens products must demonstrate
characteristics based on the claims of the declared product. Generally, the characteristics of the
trial should not be lower than the requirements of this guidance. - Principles
The applicant shall design, implement, monitor, record and summarize the clinical test results in
accordance with the relevant requirements of the Quality Management Standards for Clinical
Trials of Medical Devices, and ensure that the clinical trial process is standardized, and the
results are true, scientific, reliable and traceable. - Clinical Trial Plan
3.1 Clinical trial objectives and precautions
Clinical trial of Orthokeratology products is designed to evaluate whether the declared
product has the expected safety and effectiveness. The LogMAR visual acuity chart (also
known as the EDTRS eye chart) is recommended for the clinical trial, but a standard
logarithmic visual acuity chart can also be used. Visual acuity measurements should be
checked using standard methods. For multi-center clinical trials, the visual acuity methods
used in different clinical trial sites must be consistent. If refractive error is one of the testing
criteria, the subjects’ subjective refractive measurements (including degree of sphere and
degree of cylinder) should be the endpoint; the objective optometry values (including
degree of sphere and degree of cylinder) should be considered as reference only.
3.2 Clinical trial design
The design of the clinical trial for Orthokeratology (Ortho-K) should be a prospective,
randomized and have a control arm. Clinical trials should be conducted in two or more
clinical trial centers. If the clinical trials are conducted by following the same clinical trial
protocol in three or more sites, this would be considered a multi-center trial. The medical
device which is selected as the control device should be a similar product, and have been
approved for listing in China. The functionality and wearing schedule should be the same as
test product. Historical control or non-parallel control is not recommended.
3.3 Sample size of clinical trials
Major evaluation indicators: 30 days of product efficiency. Effective definition: “effective”
when both uncorrected visual acuity (UCVA) and refractive error should meet the following
requirements:
a. UCVA: The uncorrected visual acuity should be greater than or equal to 0.8.
b. Residual diopter: The residual refractive error should be 0.00D ±0.50D
The test hypothesis should be created, and the sample size should be calculated based on
the evidence-based medical related data of the corresponding indicators of the Ortho-K
product. Determination of the sample size is related to the type of hypothesis test selected
(superior, non-inferiority, equivalence test) and type I and II errors, as well as clinically
significant cut-off values (poor efficacy). The exclusion and the number of subjects lost to
follow-up should also be considered while determining sample size.
The clinical trial sample size should be determined in accordance with the purpose and
statistical requirements of the clinical trial, and the subjects who completed all visits should
not be less than the minimum sample size specified in this guidance. Currently, the
keratoconus randomized controlled trial is a clinical trial of 1:1 with no less than 100
subjects in each arm fitted bilatereally (200 subjects total) with the control and test
product. Both subjects are required to be enrolled in both eyes, and both eyes must be
included into statistical analysis. Monocular patients are not recommended for enrollment.
3.4 Clinical trial follow-up time
Currently the follow-up visit schedules for clinical trials of different contact lenses is not
completely consistent. The determination of follow-up visit should be supported by
literatures and should be based on medical consensus.
Currently, the follow-up period is up to 12-month. At the same time, the interval of visit
schedule should be set as 1 day, 1 week, 2 weeks, 30 days, 3 months, 6 months, 9 months,
12 months after wearing the lenses.
