Sas version 9.4 or higher

This was an exploratory study. The numbers of subjects per cohort are consistent with common practice for this study type and were considered suitable to achieve the study objectives. Descriptive statistics for safety data are presented as cases (%). PK parameters, C_max, AUC, t_1/2, CL or CL/F, Vd_(area), and F are presented as arithmetic means with standard deviation (SD). T_max is expressed as the median (range). Subject disposition (age and BMI) is presented as median (range). All statistical analyses were performed using SAS version 9.4 or higher (SAS Institute, Cary, North Carolina), and/or Phoenix WinNonlin version 8 software.

A non-inferiority analysis was carried out on the assumption that there would be no inferiority between pre- and post-surgery values for monocular and binocular CDVA. The sample size was calculated based on an expected difference between the pre- and postoperative follow-ups of at least 0.1 logMAR, a power of 80% and a significance level of 0.025. The minimal recommended number of bilaterally implanted patients was 30. Taking into account possible screening failures, 36 patients were planned to be recruited.
Quantitative variables are presented as the number of non-missing observations (n), the arithmetic mean ± the standard deviation (SD), the minimum (min), and the maximum (max). For categorical variables, the number (n) and percentage (%) of subjects per category are presented. In addition to the standard summary statistics, the mean CDVA differences between the preoperative visit and the 4 to 12-month follow-up visit was analysed in a confirmatory manner using a one-sided paired t-test on a 2.5% significance level. All descriptive p-values were calculated on the assumption of a t-distribution. Statistical analysis was performed using SAS Version 9.4 or higher (SAS Institute Inc., Cary, USA).

The data were analyzed by Statiza Statistical Services, India. The sample size was calculated with a two-sided 95% confidence interval (CI), assuming a sensitivity of 80% and target width of 0.5 using the Clopper-Pearson Interval (Exact) Method. Considering a breast cancer prevalence of 4% in the tertiary-care center (institutional data, unpublished), ~450 women were estimated to be recruited. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Thermalytix test in identifying breast malignancy were calculated. All statistical analyses were performed using R Software version 3.5.0 and SAS^® Version 9.4 or higher [SAS Institute Inc., USA].
The study was fundd by Niramai Health Analytix Pvt. Ltd., Bangalore, India, and Niramai Health Analytix is the creator of the Thermalytix software. The company was not responsible for data collection, nor did it have access to or control of the data or its analysis prior to manuscript preparation.

All derivations, statistical analyses, summaries, and listings were generated using SAS version 9.4 or higher (SAS Institute, Inc., Cary, North Carolina, United States). There were two analysis populations, the safety population and the PK population. The safety population included all randomized participants who received any amount of study treatment (COVID-HIGIV or placebo). All safety analyses were based on the safety population. The PK population included all randomized participants who received any amount of study treatment (COVID-HIGIV) according to the protocol and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample). A validated binding IgG immunoassay targeting anti-SARS-CoV-2 antibodies was used for the principal PK analyses. Serum concentration versus time data was analyzed by standard noncompartmental methods (i.e., linear trapezoidal method for consecutive time points with level or increasing concentrations and log-linear trapezoidal method for consecutive time points with decreasing concentrations) done manually using SAS software. Actual sample collection times and not nominal times were used in PK parameter estimates.

After submitting a written informed consent for study participation at Visit 1, the participants were assigned a screening number. If determined to be eligible for study participation based on inclusion/exclusion criteria in accordance with the study protocol at screening, participants were not allowed to use eye drops, including treatment agents for DED, during the 2-week pre-study washout period. Any participant who did not use other eye drops before randomization and met inclusion/exclusion criteria at Visit 2 was randomized to either of three treatment arms, such as the 1% rebamipide, 2% rebamipide, and placebo groups. Each of the eye drop formulations was instilled four times daily for 12 weeks. Packages of clinical trial drugs was established and the randomization scheme was generated using SAS Version 9.4 or higher (SAS Institute, Cary, NC, USA), and the list was delivered to the interactive web response system (IWRS) developer and personnel who were responsible for the packaging of the clinical trial drugs. The randomization number and the batch number of clinical trial drugs were confirmed by the IWRS.
All the randomized participants were allowed to receive study treatments for 12 weeks, and were instructed to visit each study center at 4, 8 and 12 weeks for assessment of efficacy, safety, and eye tolerability.