Ballard 2012.

Methods	RCT, multicentre Country: United Kingdom (UK) Setting: two teaching hospitals Conducting dates: June 2007 to January 2010
Participants	Number of participants (N) = 72 Age, years (mean ± S.D.): 76.69 ± 7.4 in the BIS group, 75.16 ± 6.51 in the Control group Sex: female, n (%): 24 (71%) in the BIS group, 26 (68%) in the Control group ASA PS class: ASA III or less MMSE score: equal to or greater than 23 English literacy Surgery Type: elective surgery Orthopaedic surgery, n (%): 28 (82%) in the BIS group, 32 (84%) in the Control group Major abdominal surgery, n (%): 6 (18%) in the BIS group, 6 (16%) in the Control group Duration of surgery: 108 to 150 min in the BIS group, 110 to 159 min in the Control group Anaesthesia Premedication: not stated Induction: propofol Maintenance: isoflurane Exclusion criteria Unable to complete the outcome measures Alzheimer’s disease or other dementia Surgical procedures under regional anaesthesia, or delirium at one week post surgery
Interventions	BIS group (n = 34) using bispectral index (BIS) and cerebral oxygen saturation monitoring to enable optimizations of anaesthesia depth (BIS index of 40 to 60) and cerebral oxygen saturation Control group (n = 38) receiving usual treatment without bispectral index and cerebral oxygen saturation
Outcomes	Postoperative cognitive decline was classified at three levels — mild, moderate and severe — based on the change of ISPOCD Z score of individual participants from the baseline, as follows. Mild POCD was defined as a decline in performance in at least one of the seven cognitive domains by greater than one standard deviation (SD); Moderate POCD required an additional decline of at least 1.5 SD in an additional domain; and Severe POCD was defined as a decline of ISPOCD Z score greater than 1.96 SD in at least two domains. Note: the following seven cognitive measures were used to analyse the level of cognitive decline: MMSE, simple reaction time, digit vigilance accuracy, digit vigilance reaction time, choice reaction time accuracy, choice reaction time and cognitive reaction time.
Notes	The study was supported by the BUPA foundation. One of the authors received honoraria and expenses for meetings organized by Covidien Inc, manufacturers of the BIS and Invos monitors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "participants were randomised according to randomizations lists, generated by the study statistician in the statistical program package R, which were stratified by age group (65 to 70, 70 to 75 and over 75)."
Allocation concealment (selection bias)	Low risk	Quote: "sealed envelopes containing the randomizations codes were delivered to operating theatres, and an envelope selected randomly by the anaesthetist."
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "the nested RCT trial was double‐blinded; patients and researchers collecting outcome data were blind to treatment allocation. Only the anaesthetist delivering the intervention was aware of the treatment condition."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "the nested RCT trial was double‐blinded; patients and researchers collecting outcome data were blind to treatment allocation."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Incomplete outcome assessments in the BIS versus (vs.) Control groups as follows: 35.29% vs. 23.68% at week one, 20.58% vs. 10.52% at week twelve, and 17.64% vs. 15.78% at week 52.
Selective reporting (reporting bias)	Low risk	They reported all outcomes as indicated in the trial registration.
Learning contaminating bias	Unclear risk	The anaesthetist delivering the intervention was aware of the treatment condition.