Sample Size Justification Clause Samples

Sample Size Justification. Given the early pilot nature of the study, sample size/power calculation is not relevant.

Sample Size Justification. Sample size calculation is based on a prior clinical study which evaluated performance of DT1 and Infuse. To demonstrate noninferiority (margin = 0.05 in logMAR; ½ line in Snellen) in distance VA as a one-tailed hypothesis with α=0.05, and using a standard deviation of 0.0497 for paired differences, 80% power can be attained with a sample size of 8 (4 per sequence).

Sample Size Justification. Sample size calculations for distance VA at 80% power, are summarized below: Endpoint Assumptions Type I error N Distance VA Habitual lens care and rewetting/lubricating drops as applicable will be used during the wear of habitual lenses. No lens care will be needed during daily disposable study lens (test and control) exposure. Artificial tears and re-wetting drops will not be permitted to be used with study lenses (test and control). Contact lens, vision correction, visual acuity, daily disposable contact lens, eye fatigue, digital devices, CVS-Q One-sided 0.05 SD (paired difference) = 0.075 NI margin = 0.05 Primary Digital Use Time ✓ - ✓ - ✓ - ✓ - - Symptomatology Question ✓ - ✓ - - - - - - CVS-Q ✓ - ✓ - ✓ - ✓ - - Informed Consent - ✓ - - - - - - - Demographics - ✓ - - - - - - - Habitual Lens (brand and wear schedule), Lens Care, Drops - ✓ - - - - - - - Medical History - ✓ ✓ - ✓ - ✓ ✓ ✓ Concomitant Medications - ✓ ✓ - ✓ - ✓ (✓) ✓ Inclusion/Exclusion - ✓ ✓ - - - - - - VA (OD, OS,OU logMAR distance with habitual contact lenses) - ✓ - - - - ✓ - (✓) Subjective (manifest) refraction* - ✓ (✓) (✓) (✓) (✓) (✓) (✓ ) (✓) BCVA (OD, OS, OU, logMAR distance with manifest refraction)* - ✓ (✓) (✓) (✓) (✓) (✓) (✓ ) (✓) Habitual contact lens power optimization (if needed) - ✓ - - - - - - - Biomicroscopy - ✓ ✓ - ✓ - ✓ (✓ ) ✓ Dispense new (optimized) habitual contact lenses - ✓ - - - - - - -

Sample Size Justification. To enroll more than or equal to 30 eligible T2 eyes used for analysis, at least 30 subjects will be evaluated by a new Alcon Toric calculator that incorporates ocular trends in Toric IOL planning and unilaterally or bilaterally implanted with the AcrySof IQ PanOptix IOL (TFNT20). Using a new Alcon calculator that incorporates ocular trends in Toric IOL planning, percentage of eyes with ≤ 0.25 D refractive cylinder at Visit 3/3A (Day 30-60) in T2 group was estimated as 60.9% based on a previous (T2) study conducted in US. Using the same calculator, the percentage in T0 group was recalculated as 29.2% from the combined result of studies (non-Toric T0 lenses) conducted in Japan . Statistical test will be conducted to compare percentage of T2 with a constant of 29.2% as percentage of T0. With 30 eyes from 30 subjects in T2 group, assuming the percentage of T2 is equal to 60.9% , the statistical power to demonstrate superiority of T2 to T0 is 91.6% with one-sided alpha of 2.5%, using an exact test of binomial proportion.

Sample Size Justification. Sample size calculation is based on a prior clinical study (M-14-010) which partly evaluated performance of DACP Multifocal and DACP lenses. To demonstrate noninferiority (margin = 0.05 logMAR) as a one-tailed hypothesis with α=0.05, and using a standard deviation of 0.098 for paired differences, 80% power can be attained with a sample size of 36 (18 per sequence group). To demonstrate noninferiority (margin = 1.0) as a one-tailed hypothesis with α=0.05, and using a standard deviation of 2.29 for paired differences, 80% power can be attained with a sample size of 48 (24 per sequence group).

Sample Size Justification. For VA with a sample size of 15 in each treatment group, a two-sided 95% confidence interval for the difference of 2 means will extend 0.05 from the observed difference in means with an assumed common standard deviation of 0.07.

Sample Size Justification. Sample size calculations are based on prior clinical study (CLD523-C001) which evaluated performance of DACP Digital and DACP sphere, preliminary results from IIT #42145213, as well as other publications. To demonstrate noninferiority (margin = 0.05 in logMAR; ½ line in Snellen) in mean distance VA as a one-tailed hypothesis with α=0.05, and using a standard deviation of 0.075 for paired differences based on CLD523-C001, 80% power can be attained with a sample size of 16 (8 per sequence). The Study Sponsor may release anonymized study data to external researchers for purposes of future research directly related to the study objectives, or future research that is beyond the scope of the current study objectives. The Informed Consent Form explains this to study subjects. Anonymization means that all identifiable information will be removed from the dataset and all links to the subjects in the study will be removed. Anonymization of the data will maintain confidentiality of the subjects who participate in the study so that they cannot be identified by external researchers. The anonymized data set will contain records from all of the subjects in the current study, but the anonymization process might change the data set in some ways, so external researchers will be informed that they might not be able to duplicate some of the results from this study.

Sample Size Justification. Sample size calculation is based on published results regarding response time for distance and near visual acuity, with high and low contrast. To demonstrate noninferiority (margin = 0.5 seconds) as a one-tailed hypothesis with α = 0.05, and using a common standard deviation of 0.456, 80% power can be attained with a sample size of 48 (12 per group). For a comparison using a 3:1 ratio, required sample sizes for 80% power are 24:8 (test:control).

Sample Size Justification. Sample size calculation for each of the relevant efficacy endpoints is described below. Sample size calculation for the primary efficacy hypothesis on decrease in symptomatology is based on published data (Chalmers 2012). With an assumed SD for paired differences of 10, a sample size of 36/sequence will provide 80% power to detect a difference of 3 at one-sided α=0.05.