Singer 2003.

Methods	RCT, 3 parallel treatment groups
Participants	Number of participants: 157 randomised (data for ITT analysis available for only 151 due to technical difficulties with actigraphy) Country: USA Setting: recruited through 36 AD research centres. Broad recruitment strategy including long‐term care facilities; number in institutional care not specified Diagnosis: probable AD (NINCDS‐ADRDA) Sleep‐related inclusion criteria: a night‐time sleep disturbance defined as averaging < 7 h of total time immobile between 8 PM and 8 AM during the screening period of at least 1 week plus 2 or more episodes/week of night‐time behaviours as reported by the caregiver on the SDI. SDI is derived from the NPI. The SDI items included difficulty falling asleep, getting up during the night (other than for toileting), night‐time wandering, awakening the caregiver, awakening and thinking it is daytime, awakening too early, and excessive daytime sleeping Gender: 88 women, 69 men Age: 77.4 ± 8.9 years Severity of dementia: MMSE 13.9 ± 8.8, ADAS‐cog 38.5 ± 18.9
Interventions	Duration of treatment: 2 to 3‐week screening and/baseline period, 8‐week treatment period, 2‐week placebo washout period Treatment group 1 (54 participants; 54 included in ITT analysis): 2.5 mg melatonin SR Treatment group 2 (51 participants; 51 included in ITT analysis): 10 mg melatonin (immediate‐release) Treatment group 3 (52 participants; 47 included in ITT analysis): Placebo All treatment groups: Route of administration: oral Time of administration: 1 h before habitual bedtime
Outcomes	Sleep outcomes all measured with actigraphy. Single actigraph records were created for the 2 to 3‐week screening and baseline and 8‐week treatment periods Primary outcome: nTST ‐ total sleep time (minutes) between 8 PM and 8 AM, as calculated by the computerized algorithm Other actigraphic sleep outcomes: dTST ‐ total sleep time (minutes) between 8 AM and 8 PM, as calculated by the computerized algorithm ratio of daytime to night‐time total sleep time time awake after sleep onset ‐ time awake (minutes) between 8 PM and 8 AM after sleep onset, until the final awakening sleep efficiency ‐ percentage of time asleep between 8 PM and 8 AM gained > 30 minutes ‐ percentage of participants with at least a 30‐minute increase in nTST Secondary outcomes: cognitive function (MMSE and ADAS‐cog) activities of daily living (ADCS‐ADL Inventory) neuropsychiatric symptoms (NPI and SDI) depression (Hamilton Depression Rating Scale) Sleep Quality Rating ‐ 5‐point sleep‐quality rating scale included in the Daily Sleep Diary that the primary caregiver completed every morning. Scores ranged from 1 (very poor night with no or little sleep) to 5 (outstanding night with no awakenings) AEs
Notes	Other psychotropic or sleep medications were allowed if use was stable Non‐commercial funding
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Subjects were randomly assigned (blocked by study site) in a double‐blind fashion to 1 of 3 groups." Randomized centrally. Likely to have been adequate
Allocation concealment (selection bias)	Low risk	No details of process given, but centrally randomised, so effective allocation concealment highly likely
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Stated to be double­blind. "Placebo and both melatonin preparations were supplied by Genzyme Limited (Boston, Mass) in identical capsules."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Actigraphic analysis conducted off site. SIte staff conducting other assessments stated to be blinded. "Sealed code breakers were distributed to each site and recovered at the end of the trial. In no instance was it necessary to break the blind."
Incomplete outcome data (attrition bias) All outcomes	Low risk	6 randomised participants excluded from sleep analyses due to technical difficulties with actigraphy. Group allocations not reported, but judged to be unlikely to introduce bias. 12 participants discontinued treatment but were included in ITT analysis, using a LOCF method. Group allocation of these participants also not reported
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Low risk	None identified