Bjarnason 2009.

Methods	Location of trial: Canada. Number of centres: 12. Funding: National Cancer Institute of Canada. Trial ID: not stated.
Participants	Inclusion criteria: histologically proven squamous cell carcinomas of oral cavity, pharynx, larynx were eligible to receive radiotherapy without chemotherapy, 2 or more visible areas of oral mucosa in target area, ECOG performance status 0‐1, adequate haematological function. T1‐T4 included. Exclusion criteria: shift workers, patients with abnormal sleep habits, previous radiotherapy or chemotherapy within 6 months, planned use of radioprotective agents, connective tissue disease or AIDS. Recruitment period: August 1999 to November 2002. OC: 40/216 (19%). OP: 76/216 (35%). OC+OP: 116/216 (54%). Number randomised: 216. Number analysed: 216 (for overall survival); 205 (for toxicity).
Interventions	Morning radiotherapy versus afternoon radiotherapy Morning (n = 108 ): radiotherapy between 8 &10 am. Afternoon (n = 108 ): radiotherapy between 4 & 6 pm. 4 different schedules were used, either 50 Gy in 25 fractions, or 60 Gy in 25‐30 fractions or 66 Gy in 33 fractions of 70 Gy in 25 fractions. Randomisation was stratified on planned total dose.
Outcomes	Primary: oral mucositis incidence of grade 3 or higher. Secondary: interval to development of grade 2 mucositis, duration of various grades of mucositis, treatment days lost due to toxicity, other acute/late toxicities, quality of life, weight loss during/after treatment, overall survival, locoregional control. Duration of follow‐up: maximum 5 years, 7 months.
Notes	Sample size calculation: hypothesised that incidence of grade 3 or greater mucositis with afternoon RT would be 35% and 17.5% for morning RT and it was estimated that 216 patients would be required to detect this difference with 80% power at a 2‐sided 0.05 level, after taking into account a potential 5% withdrawal rate. HR presented in text.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	A minimisation procedure was used to randomise patients. Patients were stratified by treatment centre, pretreatment smoking status and planned total radiation dose.
Allocation concealment?	Unclear risk	Insufficient information.
Blinding ‐ Outcome Assessors	High risk	Not mentioned.
Incomplete outcome data addressed?	Low risk	Gr A 4/108 (4%) patients and Gr B 3/108 (3%) were found to be ineligible. In addition, Gr B 3/108 did not receive RT & 1/108 had no mucositis assessments recorded (4%). All randomised patients were included in survival outcome.
Free of selective reporting?	Low risk	Primary endpoint of study is toxicity, overall survival is a secondary outcome.
Free of other bias?	Low risk	Groups appear comparable at baseline. Possible co‐interventions clearly proscribed.