Hemilä 2020.

Study characteristics
Methods	Study design: parallel randomised controlled trial Prevention or treatment trial: treatment Concomitant treatments explicitly allowed or forbidden: "Participation in the trial did not limit the use of usual healthcare services or over‐the‐counter medicines during the study." Describe any investigation of ability to distinguish between zinc and placebo: "On the first follow‐up day, the participants were asked to guess whether they received zinc or placebo lozenges (table2). Sixty‐five percent of participants did not guess the kind of lozenge that they were taking. Of those who responded either zinc or placebo, about half responded incorrectly, consistent with guessing" Duration of follow‐up: until the participant recovered or until the 10th follow‐up day when the follow‐up recording was terminated Duration of intervention: 5 days after first symptoms Duration of run‐in or washout period: NA Describe how participants were identified as having colds/URTI at baseline (treatment trial): their personal consideration that they have the common cold Outcomes measured: the primary outcome was the self‐reported recovery from the common cold, based on the patient’s own interpretation of when he or she recovered. Outcomes were duration of cold, global severity of the cold (noted as collected but not clearly reported), severity of individual cold symptoms (noted as collected but not clearly reported), and adverse events.
Participants	Setting: working population in Finland, community Country: Finland Zinc acetate 78 mg/d lozenge Number: 45 Percentage female: 87% Age (mean (SD)): 46 (10) Placebo lozenge Number: 42 Percentage female: 93 Age (mean (SD)): 48 (9) Overall Number: 87 Percentage female: 90% Age (mean (SD)): 47 (9.5) Inclusion criteria: "Participants were recruited from the employees of City of Helsinki, Finland in collaboration with occupational health unit. We included male and female employees, age ≥18 years and with a self‐report that they usually have had ≥1 colds per winter" Exclusion criteria: "Exclusion criteria were pregnancy, lactation, chronic runny nose or chronic cough." Group differences: "Differences in the baseline characteristics were small between the treatment groups except for the occurrence of sinusitis, which was twice as common in the placebo group as in the zinc lozenge group." Condition studied: common cold Description of recruitment: "The randomised controlled trial was conducted from 1 December 2017 to 30 April 2018. Participants were recruited from the employees of City of Helsinki, Finland in collaboration with occupational health unit." "Initial invitation to the study was sent by email to approximately 6000 employees (figure 1). Of them, 253 met the inclusion and exclusion criteria, were willing to participate, gave signed informed consent and were randomised..." Diagnostic criteria for condition: "The participants were instructed to start taking lozenges as soon as they started to suffer from the first symptoms of the common cold, defined as their personal consideration that they have the common cold..." Number of study centres: web‐based (1) Number of withdrawals: 1 Total number screened/eligible/randomised: 6000/253/87
Interventions	Zinc acetate 78 mg/d lozenge Study description of intervention and administration: "The zinc lozenge was a commercially available zinc acetate lozenge with 13mg elemental zinc per lozenge (University Pharmacy, Helsinki, Finland). The lozenge weighed 0.9g and had a diameter of 13mm. The lozenges contained isomaltulose, sorbitol, magnesium stearate, orange and peppermint flavours and sucralose. The instruction of the commercial package for patients with common cold is to dissolve slowly six lozenges per day in the mouth, which totals to 78mg/day of elemental zinc, at most for 5 days. The same instruction was used in this trial. Each package contained 30 lozenges." Form of product (tablet, lozenge, syrup, intranasal, other (specify)): lozenge Type of zinc (zinc sulfate, zinc gluconate, zinc acetate, other (specify)): acetate Frequency of dose: 6/d Dose per day (elemental zinc in mg): 78 mg/d Duration of treatment: 5 days Placebo lozenge Study description of intervention and administration: "The placebo lozenges, formulated by University Phar‐macy, contained 0.13mg sucrose octa‐acetate, which has previously been used in the construction of slightly bitter placebo lozenges to imitate zinc acetate lozenges. The placebo lozenges were closely similar with the zinc lozenges in visual appearance and in taste.When allowing the zinc and placebo lozenges to slowly dissolve in the mouth, they dissolved in about 8min." Form of product (tablet, lozenge, syrup, intranasal, other (specify)): lozenge Frequency of dose: 6/d Duration of treatment: 5 days
Outcomes	Duration of cold symptoms (n) Outcome type: dichotomous outcome Reported as: number of participants with event (n, N) Notes: "The median duration of colds was 5 days in the placebo group and 7 days in the zinc lozenge group." Supplementary tables included data, which were used to calculate the mean and SD for duration. Adverse events Outcome type: dichotomous outcome Reported as: number of participants with event (n, N)
Identification	Author's name: Dr Harri Hemilä Institution: Department of Public Health, University of Helsinki, Helsinki, Finland Email: harri.hemila@helsinki.fi Address: University of Helsinki Trial registration identifier: NCT03309995 Year study recruitment began: 2017
Notes	Declaration of interest: "Competing interests: None declared." Funding source: "This study was investigator‐initiated trial, which was supported by NordForsk (75021) and Academy of Finland (311492). Zinc and placebo lozenges were donated by the University Pharmacy, Helsinki, Finland." Contact with study authors for additional information: none Other: supplementary tables include raw data, much of it is in Finnish. Link to data: https://bmjopen.bmj.com/content/bmjopen/10/1/e031662/DC3/embed/inline-supplementary-material-3.xlsx?download=true
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation code was generated at the University Pharmacy and the code was maintained by them until the end of the trial period." Judgement comment: central randomisation done by a pharmacy and although the source of the sequence was not specified, it was almost certainly a random number table or computer program. No possibility of quasi‐randomisation.
Allocation concealment (selection bias)	Low risk	Quote: "The lozenge packages were numbered with 3‐ digit codes that were used in the identification of the packages (zinc vs placebo). The packages were distributed to participants without the participants and the researchers knowing the contents of the packages. Thus, both participants and researchers were blinded of the type of lozenge during the trial." Judgement comment: pharmacy‐controlled randomisation with 3‐digit code identifiers.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "After the trial was concluded, we asked for the group data as coded to A and B after cleaning the data and the actual group identification (zinc or placebo) after carrying out the primary analyses of the primary outcome." Judgement comment: attention was paid to making the zinc lozenge imitate the taste of the zinc lozenge and when blinding was tested it was found to be successful.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The primary outcome was the self‐reported recovery from the common cold, based on the patient’s own interpretation when he or she recovered." Judgement comment: participants assessed their own recovery and they were blinded to treatment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "In our primary analysis, we included 87 participants who contracted the common cold during the follow‐up (figure 1)." Judgement comment: primary outcome reported for 87/88 (99%) participants after 1 participant withdrew due to an adverse event.
Selective reporting (reporting bias)	Low risk	Judgement comment: trial registration number NCT03309995 and it was registered prior to study start date. Outcomes and analysis correspond to study report. Aligns with NCT report for outcome measures. https://clinicaltrials.gov/ct2/show/NCT03309995.
Other bias	Low risk	Judgement comment: no other apparent sources of bias.