| [Background]Soft hydrophilic contact lens is a type of implantable medical device which has high requirements of technical performance. It had been widely accepted and applied, and it has a broad market. Currently, the relevant new products can be launched in China only after performing strict non-inferiority clinical trial to verify the effectiveness and safety, and the key for confirming test sample size and proper test conclusion is the confirmation of the main indicators and non-inferiority margin. Until now, no systematic study has been reported in this aspect.[Objective]The goal is to consult experts by designing two rounds of Delphi surveys, where in the first round is to confirm the main parameters of the clinical study of soft hydrophilic contact lens, and the second round is to confirm the non-inferiority margin by referring to previous test data.This study will provide references for the designing and conclusion assessment of non-inferiority clinical study of soft hydrophilic contact lens, and will offer scientific evidence for confirmation of test sample size.[Methods]1. The study consulted advices from 16 domestic authoritative ophthalmological clinical experts. These experts were all from the Class III Grade I general hospitals or well-known ophthalmology hospitals, had a more than sub-senior title, and participated in guiding soft hydrophilic contact lens clinical experimental work. Among them, there were 6 males and 10 females with a mean age of 42.29 ± 5.14 years old, a mean working length of 18.36 ± 6.30 years and a mean working life working on ophthalmological medical science of 16.71 ± 7.39 years.2. The basic method of this study was Delphi expert consultation method, in which two rounds of surveys and expert discussions were designed to consult ophthalmology specialists. Both rounds of survey data were used to establish EpiData database before double entry and validation. Then SAS 9.3 was imported for statistical analysis, and Stata 12.0 was applied for Meta-analysis of previous data. In the first round survey, the relative importance evaluation of the grade two clinical study parameters of soft hydrophilic contact lens had been assessed by experts. After corrections by authority coefficient from experts, the average correction scoring was obtained for confirming main grade two parameters; in the second round survey, the grade two clinical study γ value of soft hydrophilic contact lens had been quantitative estimated by experts. After corrections by authority coefficient from experts, the non-inferiority margin formula based on previous clinical data and yield spread was performed to calculate the non-inferiority margin.The contents of the first round of the questionnaire were as follows: research background materials, basic expert condition sheet, expert authoritative degree self-assessment and score sheet of expert for soft hydrophilic contact lens clinical trial secondary indicator relative important degree. Research projects included: positive coefficient of experts, authoritative degree of experts, concentration degree of expert opinion(to determine main indicators) and coordination degree of expert advice.The contents of the second round of the questionnaire were as follows: research background materials and quantitative estimation of experts to secondary clinical trial indicator γ value of the soft hydrophilic contact lens. Research projects included: positive coefficient of experts, estimation condition of expert to the γ value(to determine main indicators for non-inferiority margin) and coordination degree of expert advice.[Results]1. The positive coefficient of experts: the first round of surveys issued a total of 20 questionnaires and 20 copies of the questionnaires were recycled. Among them, 4 copies were excluded due to the fact that they do not meet the inclusion criteria with a positive factor of 100%.The second round of surveys issued 16 questionnaires and 15 copies were recycled with a positive factor of 93.75%.2. The authoritative degree of experts: after the expert self-assessment in a first round of the questionnaire, the overall mean score was 0.86 ± 0.13(full mark was 0.95) of each expert for each level of test indicators.3. The concentration degree of expert opinion: in the first round of the questionnaire, for the optical corrected soft hydrophilic contact lens, the highest mean correction score for three secondary efficacy indicators were 8.29 ± 1.52 points of corrected visual acuity, 8.03 ± 1.29 points of visual stability and visual 8.02 ± 1.18 points of clear degree and the highest mean correction score for three secondary safety indicators were 8.25 ± 1.49 points of limbal hyperemia, 8.23 ± 1.48 points of corneal punctate staining and 7.84 ± 1.46 points of corneal edema. For the decorated soft hydrophilic contact lens, the highest mean correction score for three secondary efficacy indicators were 7.99 ± 1.52 points of corrected visual acuity, 7.96 ± 1.22 points of foreign body sensation and 7.73 ± 1.41 points of centralized positioning and the highest mean correction score for three secondary safety indicators were 8.30 ± 1.55 points of corneal infiltrates, 8.14 ± 1.57 points of limbal hyperemia and 8.09 ± 1.61 points of corneal punctate staining.4. The estimation condition of expert to the γ value and determination of non-inferiority margin: in the second round of the questionnaire, for the optical corrected soft hydrophilic contact lens, the mean γ value of the main secondary indicators of expert authoritative degree were as follows: corrected visual acuity(90.74 ± 6.79), eyesight stability(90.88 ± 7.29), visual clear degree(90.71 ± 6.65), limbal hyperemia(89.14 ± 10.02), corneal punctate staining(90.89 ± 10.46) and cornea edema(91.68 ± 10.93).For the decorated soft hydrophilic contact lens, the mean γ values of the main secondary indicators of expert authoritative degree were: corrected visual acuity(90.15 ± 6.12), foreign body sensation(90.14 ± 6.41), centralized positioning(90.03 ± 10.24), corneal infiltration(91.10 ± 10.82), limbal hyperemia(90.24 ± 10.56) and corneal punctate staining(91.76 ± 10.71).The mean correction value of the γ value was used to calculate non-inferiority margin as follows:(1) For the optical corrected soft hydrophilic contact lens: vision correction(-9.25%), visual stability(-8.91%), visual clear degree(-8.80%), limbal hyperemia(-10.93%), corneal punctate staining(-8.95%) and corneal edema(-8.34%);(2) For the decorated soft hydrophilic contact lens: corrected visual acuity(-9.79%), foreign body sensation(-10.41%), centralized positioning(-9.85%), corneal infiltrates(-8.90%), limbal hyperemia(-9.74%) and corneal punctate staining(-8.28%).5. The degree of coordination of the opinions from experts: the coordination coefficient of surveys from the first round and the second round were 0.354(χ2=43.69, P<0.05)and 0.517(χ2=65.33, P<0.05) respectively, and they were both statistically significant.[Conclusions]1. The positive coefficient and authoritative coefficient of the study were high and the coordination coefficient was also relatively high. Thus the study results were more accurate and reliable.2. The main clinical trial indicators of the optical corrected soft hydrophilic contact lens were corrected visual acuity, visual clear degree, vision stability, limbal hyperemia, corneal punctate staining and corneal edema. The main clinical trial indicators of the decorated soft hydrophilic contact lens were corrected visual acuity, centralized positioning, foreign body sensation, corneal infiltration, limbal hyperemia and corneal punctate staining.3. The non-inferiority margins of all parameters were within the range of-11%~-8%, which were close to the mainstream reference value of current non-inferiority clinical study of soft hydrophilic contact lens in China(such as-10%,-8%,-12% and so on), and the non-inferiority margin of different parameters had certain variations. Considering the actual test sample size and the requirements of labor and material costs, as well as the opinions from statisticians, it is more reasonable and feasible to set the non-inferiority margin of the main parameters into-12%~-10%. |
