Appendix 1. Embase.com search strategy

Appendix 2. CINAHL (Ebsco) search strategy

S33 S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32
S32 (MH "Quantitative Studies")
S31 TI placebo* or AB placebo*
S30 (MH "Placebos")
S29 TI random* or AB random*
S28 (MH "Random Assignment")
S27 TI (singl* blind* or singl* mask* or doubl* blind* or doubl* mask* or trebl* blind* or trebl* mask* or tripl* blind* or tripl* mask*) or AB (singl* blind* or singl* mask* or doubl* blind* or doubl* mask* or trebl* blind* or trebl* mask* or tripl* blind* or tripl* mask* )
S26 TI clinic* N1 trial* or AB clinic* N1 trial*
S25 PT clinical trial
S24 (MH "Clinical Trials+")
S23 S19 and S22
S22 S20 or S21
S21 TI (acetaminophen or acetominophen or panadol or paracetamol or tylenol) or AB (acetaminophen or acetominophen or panadol or paracetamol or tylenol)
S20 (MH "Acetaminophen")
S19 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18
S18 TI infection* N5 respiratory syncytial virus* or AB infection* N5 respiratory syncytial virus*
S17 TI respiratory syncytial virus infection* or AB respiratory syncytial virus infection*
S16 TI infection* N5 rsv or AB infection* N5 rsv
S15 TI infection* N5 influenza* or AB infection* N5 influenza*
S14 TI infection* N5 parainfluenza* or AB infection* N5 parainfluenza*
S13 TI infection* N5 adenovir* or AB infection* N5 adenovir*
S12 TI infection* N5 coronavir* or AB infection* N5 coronavir*
S11 TI infection* N5 rhinovir* or AB infection* N5 rhinovir*
S10 (MH "Influenzavirus A+") OR (MH "Influenzavirus B+") OR (MH "Influenzavirus C")
S9 (MH "Respiratory Syncytial Virus Infections")
S8 (MH "Respiratory Syncytial Viruses")
S7 (MH "Coronavirus Infections")
S6 (MH "Coronavirus")
S5 TI (coryza or acute rhinit* or rhinosinusit* or nasosinusit*) or AB (coryza or acute rhinit* or rhinosinusit* or nasosinusit*)
S4 TI upper respiratory infection* or AB upper respiratory infection*
S3 TI upper respiratory tract infection* or AB upper respiratory tract infection*
S2 TI common cold* or AB common cold*
S1 (MH "Common Cold")

Appendix 3. LILACS search strategy

(mh:"Common Cold" OR "common cold" OR "common colds" OR "Resfriado Común" OR "Resfriado Comum" OR coryza OR "Coriza Aguda" OR "upper respiratory tract infection" OR "upper respiratory tract infections" OR "upper respiratory infection" OR "upper respiratory infections" OR "Infecciones del Tracto Respiratorio Superior" OR "Infecciones de las Vías Respiratorias Superiores" OR "Infecções do Trato Respiratório Superior" OR "Infecções das Vias Respiratórias Superiores" OR "Infecções das Vias Aéreas Superiores" OR "Infecções do Sistema Respiratório Superior" OR "acute rhinitis" OR rhinosinusitis OR nasosinusitis OR rinit* OR mh:rhinovirus OR rhinovir* OR mh:coronavirus OR coronavir* OR mh:"Coronavirus Infections" OR mh:"Respiratory Syncytial Viruses" OR "respiratory syncytial virus" OR "respiratory syncytial viruses" OR rsv OR "Virus Sincitiales Respiratorios" OR "Vírus Sinciciais Respiratórios" OR mh:"Respiratory Syncytial Virus, Human" OR mh:"Respiratory Syncytial Virus Infections" OR mh:"Parainfluenza Virus 1, Human" OR mh:"Parainfluenza Virus 3, Human" OR mh:"Parainfluenza Virus 2, Human" OR mh:"parainfluenza virus 4, human" OR parainfluenza* OR mh:"Influenzavirus A" OR mh:b04.820.545.405* OR mh:b04.909.777.545.405* OR mh:"Influenzavirus B" OR mh:b04.820.545.407* OR mh:b04.909.777.545.407* OR influenza* OR mh:adenoviridae OR adenovir*) AND (mh:acetaminophen OR acetaminophen OR acetominophen OR acetaminofén OR acetaminofen OR acetamidophenol OR acetaminofeno OR acetamidofenol OR panadol OR paracetamol OR tylenol) AND db:("LILACS")

Appendix 4. Assessment of risk of bias

Criteria for a judgement of 'yes' for the sources of bias

1. Was the allocation sequence randomly generated?

Yes, low risk of bias

A random (unpredictable) assignment sequence.
Examples of adequate methods of sequence generation are computer‐generated random sequence, pre‐ordered sealed envelopes, telephone call to a central office, coin toss (for studies with two groups), rolling a dice (for studies with two or more groups), drawing of balls of different colours.

No, high risk of bias

• Quasi‐randomised approach: examples of inadequate methods are: alternation, birth date, social insurance/security number, date in which invited to participate in the study and hospital registration number.

• Non‐random approaches: allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.

Unclear

Insufficient information about the sequence generation process to permit judgement.

2. Was the treatment allocation adequately concealed?

Yes, low risk of bias

Assignment must be generated independently by a person not responsible for determining the eligibility of the participants. This person has no information about the persons included in the trial and has no influence on the assignment sequence or on the decision about whether the person is eligible to enter the trial. Examples of adequate methods of allocation concealment are: central allocation, including telephone, web‐based and pharmacy‐controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.

No, high risk of bias

Examples of inadequate methods of allocation concealment are: alternate medical record numbers; unsealed envelopes; date of birth; case record number; alternation or rotation; an open list of random numbers; or any information in the study that indicated that investigators or participants could influence the intervention group.

Unclear

Randomisation stated but no information on method of allocation used is available.

3. Blinding ‐ was knowledge of the allocated interventions adequately prevented during the study?

(a) Was the participant blinded to the intervention?

Yes, low risk of bias

The treatment and control groups are indistinguishable for the participants or if the participant was described as blinded and the method of blinding was described.

No, high risk of bias

Blinding of study participants attempted, but likely that the blinding could have been broken; participants were not blinded, and the non‐blinding of others is likely to introduce bias.

Unclear

(b) Was the care provider blinded to the intervention?

Yes, low risk of bias

The treatment and control groups are indistinguishable for the care/treatment providers or if the care provider was described as blinded and the method of blinding was described.

No, high risk of bias

Blinding of care/treatment providers attempted, but likely that the blinding could have been broken; care/treatment providers were not blinded, and the non‐blinding of others is likely to introduce bias.

Unclear

(c) Was the outcome assessor blinded to the intervention?

Yes, low risk of bias

Adequacy of blinding should be assessed for the primary outcomes. The outcome assessor was described as blinded and the method of blinding was described.

No, high risk of bias

No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding

Unclear

4. Were incomplete outcome data adequately addressed?

(a) Was the drop‐out rate described and acceptable?
The number of participants who were included in the study but did not complete the observation period or were not included in the analysis must be described and reasons given.

Yes, low risk of bias

If the percentage of withdrawals and drop‐outs does not exceed 20% for short‐term follow‐up and 30% for long‐term follow‐up and does not lead to substantial bias. (N.B. these percentages are arbitrary, not supported by literature.)

No missing outcome data

Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias).
Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Missing data have been imputed using appropriate methods.

No, high risk of bias

Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups.

Unclear

(b) Were all randomised participants analysed in the group to which they were allocated? (intention‐to‐treat (ITT) analysis)

Yes, low risk of bias

Specifically reported by authors that ITT analysis was undertaken and this was confirmed on study assessment, or not stated but evident from study assessment that all randomised participants are reported/analysed in the group to which they were allocated for the most important time point of outcome measurement (minus missing values), irrespective of non‐compliance and co‐interventions.

No, high risk of bias

Lack of ITT analysis confirmed on study assessment (patients who were randomised were not included in the analysis because they did not receive the study intervention, they withdrew from the study or were not included because of protocol violation) regardless of whether ITT reported or not.
'As‐treated' analysis done with substantial departure from the intervention received compared to that assigned at randomisation; potentially inappropriate application of simple imputation.

Unclear

Described as ITT analysis, but unable to confirm on study assessment, or not reported and unable to confirm by study assessment.