Willems 2006.

Study characteristics
Methods	Randomised controlled trial. Randomisation: stratified by age (< 45 or ≥ 45 years) and KPS (≤ 70 or > 70), and they were evenly randomised to SS (without neuronavigation) or SN (with neuronavigation) using a computer‐generated list with allocation codes in random order, balanced for each stratum using blocks of 4. Sample size: based on the results of a power analysis (details not specified in the paper), the authors planned to include 182 participants in the study, but the trial was stopped at 45 participants after an early pilot analysis. There was no blinding.
Participants	Inclusion criteria: solitary intracerebral space‐occupying lesion with (partial) contrast enhancement eligible for surgical debulking with the intention of gross total resection. Exclusion criteria: previous neurosurgical treatment or any other known primary tumour elsewhere in the body.
Interventions	Intervention: neuronavigation was performed with bone fiducial markers. Preoperative magnetic resonance images were obtained using a 0.5‐T system with contrast‐enhanced T1 weighted images. Volumetric measurements were performed to assess total lesion volume. Functional grading was recorded according to the MD Anderson scheme (Sawaya 1998). Planning involved localisation using fiducial markers, trajectory planning, and segmentation of the tumour boundary. Tools included an infrared pointer or mechanically tracked operating microscope.
Outcomes	Primary outcome: extent of resection and survival. Other outcomes: procedure duration, usefulness of neuronavigation, extent of resection, quality of life, and postoperative course (including neurological status and adverse events).
Notes	There were 3 early deaths in the navigation arm from systemic causes, which, with the low numbers in each arm, skewed the results. Interim analysis/abbreviated study. Definitions: Postoperative magnetic resonance images were obtained within 72 hours and subject to volumetric analysis. Clinical assessment was performed postoperatively within 3 days, 1 week, 6 weeks, and 3 months to assess adverse events and neurological status (using KPS and Barthel Index scores). Quality of life questionnaires (EORTC QLQ‐C30 questionnaire with BN20 brain tumour module, and EQ‐5D questionnaire) were filled out preoperatively and approximately 3 months after surgery.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised to SS (without neuronavigation) or SN (with neuronavigation) using a computer‐generated list with allocation codes in random order, balanced for each stratum using blocks of 4. However, groups were not evenly distributed at baseline, with more eloquently located tumours in the standard surgery arm and histology with more metastasis in the navigation arm (although the latter was a variable that could not have been determined preoperatively).
Allocation concealment (selection bias)	Unclear risk	Unclear risk.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not blinded.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	1 participant was excluded due to an alternative diagnosis (meningioma). Postoperative imaging was only assessed in 34/45 participants for tumour volume and 40/45 for contrast‐enhancing volume. Data for quality of life at 3 months were only reported on 64.5% of the total eligible population.
Selective reporting (reporting bias)	High risk	All outcome measures were reported to a degree. However, full data with suitable presentation and analysis were not available for survival (no Kaplan‐Meier plots), quality of life (no statistical analysis), and adverse events (no presentation of numbers of events).
Other bias	High risk	Trial was significantly underpowered and was terminated prematurely. Out of 280 potentially eligible participants, only 46 participants were included, with a planned target of 182.

ASA: American Society of Anesthesiologists; EORTC QLQ‐C30: European Organisation for Research and Treatment of Cancer quality of life assessment; EQ‐5D: European Quality of Life‐5 Dimensions; KPS: Karnofsky performance score; iMRI: intraoperative magnetic resonance imaging; MRI: magnetic resonance imaging; NIHSS: National Institutes of Health Stroke Scale; PFS: progression‐free survival; RTV: residual tumour volume; WHO: World Health Organization.