Herring 2020.

Study characteristics
Methods	RCT, 2 parallel treatment groups
Participants	Number of participants: 285 Country: 8 countries Setting: 35 centres, quote: "primarily memory clinics and contract research clinics with experience in neurology studies" Diagnosis: NIA‐AA and DSM‐5 clinical criteria for probable AD dementia Sleep‐related inclusion criteria: DSM‐5 criteria for insomnia, quote: "confirmed by a mean total sleep time (TST) of <6 hours over screening and (by) baseline sleep laboratory polysomnography (PSG) visits, with neither night >6.5 hours." Gender: 65% women Age: 71% ≥ 65 years Severity of dementia: 79% AD of mild severity (MMSE 21–26); 21% moderate severity (MMSE 12–20)
Interventions	Duration of treatment: 4 weeks (3‐week screening period, 2‐week single‐blind placebo run‐in, 4‐week double‐blind randomised treatment period). Treatment group 1 (n = 142): suvorexant 10 mg once a day. Quote: "At the week 2 clinic visit, this dose could be escalated, in a blinded fashion, to the maximum recommended dose of 20 mg (or matching placebo) if there was insufficient response as indicated by a Clinical Global Impression – Severity (CGI‐S) for insomnia of mildly ill or worse and the tolerability of the current dose was acceptable in the investigator's judgment." Treatment group 2 (n = 143): matching placebo Route of administration: oral Time of administration: 30 minutes before bedtime
Outcomes	Overnight PSG in a sleep laboratory for 8 h starting at participant's usual bedtime Outcome time points: baseline (7 days before randomisation) and at the end of the 4‐week treatment period Primary: TST Secondary: WASO (amount of time awake during recording period after the first period of continuous sleep lasting ≥ 10 minutes) "Exploratory": percentage of responders achieving an improvement in TST ≥ 50 minutes TST and WASO by thirds of the night sleep efficiency latency to persistent sleep number of arousals adjusted for TST number of awakenings adjusted for TST PSG sleep architecture (%TST in REM, N1, N2, N3, and REM sleep latency) partner‐rated assessments of the patient's sleep (daily e‐diary including SQR) total score on the SDI (weekly, trial‐partner assessed), CGI‐S, and partner‐rated assessment of their own sleep quality and distress (SSQC) NPI MMSE Digit Symbol Quote: "Actigraphy measures were also recorded via an activity/sleep watch worn by the patient and will be the subject of a separate report." Safety assessed by AE reports, laboratory analyses, electrocardiography, and physical examinations. Quote: "A guidance document listing adverse events pre‐specified as events of clinical interest for which additional information was to be collected was provided to investigators."
Notes	Sponsored by MSD. Conflict of interest declarations: 8/9 authors are current or former employees of MSD, a subsidiary of Merck & Co., Inc. and own or owned stock options in Merck & Co., Inc. The 9th author has acted as a consultant for Merck & Co., Inc., Jazz, Eisai, and Ferring.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "An interactive response system randomly assigned patients to suvorexant or placebo in a 1:1 ratio according to a computer‐generated assignment schedule. Randomization was stratified according to dementia severity as indexed by screening MMSE score (moderate = 12–20, mild = 21–26), with the intention to enroll ≈30% of patients in the moderate stratum."
Allocation concealment (selection bias)	Low risk	Quote: "An interactive response system randomly assigned patients to suvorexant or placebo …" From protocol: quote: "The Clinical Biostatistics department will generate the randomized allocation schedule(s) for trial medication assignment. Randomization will be implemented by an interactive voice response system (IVRS)."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "All treatments were administered as identical‐appearing tablets." Quote: "At the week 2 clinic visit, this dose could be escalated, in a blinded fashion, to the maximum recommended dose of 20 mg (or matching placebo) if there was insufficient response … The patient and caregiver were not told if the dose was increased." From protocol: quote: "5.2.3 Trial Blinding/Masking: The subject, the investigator and Sponsor personnel or delegate(s) who are involved in the treatment or clinical evaluation of the subjects are unaware of the group assignments."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Sleep stage scoring of the PSG recordings was performed for each 30 second epoch … by a certified sleep technician at a central sleep scoring laboratory." AEs: quote: "An independent committee blind to treatment assignment comprising three experts in neurology, psychiatry, and sleep, respectively, adjudicated all events of clinical interest." From protocol: quote: "5.2.3 Trial Blinding/Masking: The subject, the investigator and Sponsor personnel or delegate(s) who are involved in the treatment or clinical evaluation of the subjects are unaware of the group assignments."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "The modified intent‐to‐treat approach was used for the primary and secondary efficacy endpoints, in which treated patients with both a baseline measurement and at least one post‐randomization observation were included." Suvorexant: randomised n = 142; treated n = 142; discontinued n = 6 (participant withdrew n = 5, screen failure n = 1); completed trial n = 136; analysed efficacy n = 135, safety n = 142. Placebo: randomised n = 143; treated n = 143; discontinued n = 2 (participant withdrew n = 2); completed trial n = 141; analysed efficacy n = 139, safety n = 143. Quote: "The number of patients in the full‐analysis‐set for the primary endpoint of change from baseline in TST at week 4. In the suvorexant group, seven patients were excluded due to missing PSG data. In the placebo group, two patients were excluded due to missing PSG data and two patients were excluded due to Good Clinical Practice noncompliance issues at one site."
Selective reporting (reporting bias)	Low risk	Data on actigraphy outcomes not yet available although paper stated that these will be published elsewhere.
Other bias	Low risk	None identified.