2.2. Outline of the Trial and Participation Issues
URTIs
To ensure a more coherent population, particularly in terms of exposure to infectious agents responsible for the URTIs, we included children from just two kindergartens in the trial. This helped to minimize potential variations in exposure and create a more homogenous study population. To increase the consistency of trial conditions further, we conducted the study in exactly the same timeframe between the end of September and mid-February, when the risk of contracting the URTIs is highest in our geographic zone. The rationale behind such a design was fully explained in the report from our previous study with medical university students [After blinding and randomization processes were completed by 29 September 2022, the parents and guardians were invited to collect the supplemented material sufficient for the entire period of the trial. The appropriate packages identifiable only by the trial ID numbers were distributed by the management of the kindergartens in which the trial was conducted. At this stage, 14 participants (2 from the COL group and 12 from the PBO group) were excluded because of not collecting the supplement despite the repeated summons. We found no rational explanation for such a disparity in the collection of supplements between the COL and the PBO group participants.Immediately after the beginning of supplementation, 3 additional participants resigned (1 from the COL group and 2 from the PBO group) without specifying any reason. After 4 months of the trial, 2 additional participants resigned (1 from the COL and 1 from the PBO groups), again without providing the reason for withdrawal. Out of the 70 participants who remained in the trial until its completion, we made the decision to exclude an additional 13 participants (5 from the COL group and 8 from the PBO group) from the final analysis, due to their poor consistency in responding to daily surveys. The minimal response rate was established at 80% of daily surveys.The trial started on 1 November 2022, upon the signal given by the administrator to all participating children. Over the first 15 days, the participants were taking 2 of the 500 mg sachets of supplementation material per day. They were supposed to take one sachet in the morning and one in the evening on an empty stomach, with water or with a teaspoon of natural yogurt. Then, for the following 30 days, the administration schedule consisted of just one sachet in the morning, and after 45 days, the supplementation period terminated.In addition to that, the parents and guardians were instructed to give 8 consecutive doses of the supplementation material (twice daily for 4 days) to their children whenever symptoms of newly developing URTI occurred until the end of the trial. The trial lasted for 147 days until 24 February 2023, when daily surveys were terminated.