Distler 2017.

Study characteristics
Patient sampling	Aim of the study: to analyse the negative predictive value of MRI and PSA density to rule out significant PCa Type of study: prospective cohort Selection: consecutive selection of men with a suspicion of PCa (PSA >4.0 ng/ml and/or suspicious digital rectal examination (DRE)) who were either biopsy‐naïve or after previous negative biopsy. Enrolled/eligible: 1040/1040 (597 Bx‐naïve + 443 prior‐negative Bx men) Inclusion period: October 2012‐December 2015
Patient characteristics and setting	Inclusion criteria: suspicion of PCa: PSA > 4.0 ng/mL and/or suspicious DRE, and who were Bx‐naïve or had undergone a prior‐negative Bx Exclusion criteria: none Setting: Heidelberg, Germany. University hospital Age: median 65 years (IQR 60‐71) PSA: median 7.2 ng/mL (IQR 5.3‐10.4) Prostate volume: median 45 mL (IQR 34‐64) DRE positive: 291
Index tests	Index tests: MRI only + MRI‐TBx + MRI‐pathway: a 3 Tesla MRI machine (Magnetrom Prisma or Biograph mMR (Siemens Healthcare) was used, with T2, DWI and DCE sequences. The PI‐RADS version 1 Likert 1‐5 score was used, with threshold ≥ 3 for positivity. Transperineal MRI‐TBx were taken from all positive lesions with the Biopsee system (rigid software registration). First MRI‐TBx were taken, subsequently the reference biopsies
Target condition and reference standard(s)	Target condition: GS ≥ 3+4 Reference standard: volume‐based systematic transperineal grid‐directed Bx with a median of 24 cores according to the Ginsburg protocol. Bx operators first performed the MRI‐TBx and had access to MRI data during whole procedure.
Flow and timing	All participants underwent the same reference test. All participants were included in the analysis
Comparative
Notes	Results not reported separately for the two participant groups
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Did the study avoid inappropriate exclusions?	Yes
		Low	Low
DOMAIN 2: Index Test MRI‐TBx
Was the MRI assessed without knowledge of the results of the (reference or other index) biopsies?
Were the MRI‐TBx performed independent of the (reference or other index) biopsies?	Yes
Was the performance of the SBx not influenced by the performance of the (reference or other index) biopsies?
		Low	Low
DOMAIN 2: Index Test MRI
Was the MRI assessed without knowledge of the results of the (reference or other index) biopsies?	Yes
Were the MRI‐TBx performed independent of the (reference or other index) biopsies?
Was the performance of the SBx not influenced by the performance of the (reference or other index) biopsies?
		Low	Low
DOMAIN 2: Index Test MRI‐pathway
Was the MRI assessed without knowledge of the results of the (reference or other index) biopsies?	Yes
Were the MRI‐TBx performed independent of the (reference or other index) biopsies?	Yes
Was the performance of the SBx not influenced by the performance of the (reference or other index) biopsies?
		Low	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Was the reference standard performed independent from the index test?	No
		High	Low
DOMAIN 4: Flow and Timing
Did all patients receive the same reference standard?	Yes
Were all enrolled patients included in the analysis, or were exclusions explained and not leading to a relevant bias?	Yes
		Low