Avidan 2008.

Methods	Study design: randomized parallel groups Study dates: September 2005 to October 2006
Participants	Country: USA Sex: both Age: mean age 59.5 to 59.2 at high risk of awareness ASA: I‐IV Procedure: not identified Study size: 2000 entered study and 1941 completed possible interviews
Interventions	Randomized portion of anaesthetic: volatile agent types ADM BIS vs ETAG Intervention 1: BIS guided anaesthesia (target BIS range, 40 to 60), N = 1000 Intervention 2: ETAG guided anaesthesia (target ETAG 0.7 to 1.3 MAC), enrolled 2000, completed study 1941
Outcomes	Primary outcomes: awareness/wakefulness as defined using our "Classification of intra‐operative cognitive states" Table 1: class 4 Comment: 16 awareness reports by patients = 4 definite + 5 possible + 7 no awareness: expert panel classification.1 2/16 patient awareness reports NOT used in calculation of awareness rate (definite awareness) Definite and possible BIS 10/967 vs SCP 6/974 Definite: BIS 2/967 vs SCP 2/974
Notes	Non‐randomized portion of anaesthetic: parts of volatile agent: N2O unclear/narcotics/hypnotics/muscle relaxants induction unclear/maintenance unclear Anaesthesia induction: left to discretion of anaesthetist Anaesthesia maintenance: left to discretion of anaesthetist Comment: high risk of anaesthesia awareness/isoflurane, sevoflurane or desflurane/supplemental N2O permitted Time of outcome determination: within 24 h, 1 to 3 days, and 72 days postoperative period Survey response: 27 September 2011 Michael Avidan, avidanm@anest.wustl.edu Email sent to author to clarify missing data issues: 7 December 2013: Michael Avidan, avidanm@anest.wustl.edu. Dr Avidan responded. Senior authors developed consensus on ROB domain emailed to authors and response acknowledging our assessment sent/received 28 December 2013. Email sent 21 October 2014 adjudicated awareness reports and response 21 October 2014; 14 November 2014 adjudicated awareness reports for review copies of reports not published in RCT. Dr Avidan responded 14 November 2014
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The design was a single‐center, prospective study, in which 2000 patients underwent pre‐randomization electronically in blocks of 100, with 50 patients assigned to a BIS‐guided protocol and 50 to an ETAG‐guided protocol" Quote from survey: "Computer generated randomization. Block randomized in blocks of 100 (50 in each group per block). Unique case identifier and information on group allocation (BIS or ETAG) was sealed in opaque envelopes"
Allocation concealment (selection bias)	Low risk	Quote from survey: "The opaque envelope was opened by a research coordinator only after the patient (who had already signed consent) was transferred to the operating room"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "The anesthesiologists were not blinded to treatment allocation to ensure safe anaesthetic care" Quote from paper: "formed consent. The anesthesia practitioners were aware of the assignments of the patients, but the patients, the postoperative interviewers, the expert reviewers, and the statistician were not"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Patient, Awareness outcome assessor (interviewer), Statistician, expert reviewers who determined whether awareness was definite, possible or not awareness"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 2000 patients enrolled, in table 1, trial enrolment, there were 33 BIS and 26 ETAG patients excluded after randomization. 1905/1941 (98%) completed 1 to 3 awareness interviews and 36/1941 (2%) completed no awareness interviews Senior authors' consensus: ... because of the balanced event rates and sample sizes, even though the reasons for a portion of the dropouts are not known, there would be little impact on the reported outcome from the study if these patients had been interviewed for awareness 33/2000 vs 26/2000, Peto OR 1.27 (0.76 to 2.13) Email sent to author to clarify these issues: 7 December 2013: Michael Avidan, avidanm@anest.wustl.edu
Selective reporting (reporting bias)	Low risk	Quote: "The study protocol was not published in the public domain. The trial was registered on clinical trials.com (NCT00281489)"
Other bias	Low risk	Quote: "We know of no bias related to the study design"