Smith 1999.

Study characteristics
Patient Sampling	Inclusion/exclusion criteria Inclusion criteria: diffuse gliomas Prior testing Histopathological diagnosis according to WHO 1993 classification.
Patient characteristics and setting	Number of participants/tumours with results for 1p/19q status by ≥ 2 DNA‐based tests: 79 Country: USA Population source and setting: Mayo Clinic in Rochester, MN, Johns Hopkins Hospital in Baltimore, Maryland, USA, and the University of California at San Francisco, USA. Time period NR. Cases subsequently included in Hatanpaa 2003a and Hatanpaa 2003b were removed. Age: NR Gender: NR Karnofsky performance status: NR First diagnosis/recurrent disease: 72.2% (57/79) primary glioma specimens; 27.8% (22/79) recurrent glioma specimens
Index tests	3 tests: CGH, FISH and PCR CGH Tumour sample type: NR Region(s) analysed: NR Cut‐off: reference Mohapatra G, Kim DH, Feuerstein BG. Detection of multiple gains and losses of genetic material in ten glioma cell lines by comparative genomic hybridization. Genes, Chromosomes & Cancer 1995;13;86‐93. In this publication: "Definition of CGH ratio thresholds to define ratios that were indicative of changes in DNA copy number, we performed 21 CGH experiments using normal control DNA. We calculated average ratio changes and standard deviations by using the software program cghprofstats.new (Piper et al., 1994). The average ratio for all 21 hybridizations was 0.99 (range 0.9‐1.1). The average standard deviation was 0.04 (range 0.02‐0.06). Taking these findings into consideration, we chose upper and lower ratio thresholds of 1.2 and 0.8, respectively. Any change in ratio in excess of these thresholds was interpreted as indicative of DNA copy number changes only if found in both forward and reverse experiments. Amplifications were defined both by a ratio >2.0 and by visual inspection". Piper J, Rutovitz D, Sudar D, Kallioniemi A, Kallioniemi O, Waldman FM, et al. Computer image analysis of comparative genomic hybridization. Cytometry 1995;19:10‐26 also cited. FISH Tumour sample type: NR Region(s) analysed: 1p36, 1q24, 19p13.1, 19q13.1‐q13.2 and 19q13.3. Cut‐off: we defined codeletion as hemizygous deletion of 1p36, 1q13.1‐q13.2 and 19q13.3. What defined hemizygous deletion NR. Also cited Qian J, Bostwick DG, Takahashi S, Borell TJ, Herath JF, Lieber MM et al. Chromosomal anomalies in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization. Cancer Research 1995;55:5408‐14. In this paper (quote) "abnormal autosomal loss required ≥55% nuclei with zero or one signal". Unclear if this threshold was used. PCR Tumour sample type: NR Region(s) analysed: 1p: D1S468, D1S1612, D1S1597, D1S199, D1S1665, D1S1728, D1S1588, D1S1675, D1S187; 19q: D19S213, D19S569, D19S422. D19S219, SM, S19S112, S19S412, D19S596, HRC, D19S589, D19S218 Cut‐off: we defined codeletion as all markers showing confirmed allelic loss, presumed allelic loss, were homozygous or were indeterminant.
Target condition and reference standard(s)	Target condition was absolute 1p/19q deletion. FISH or PCR‐based LOH used as reference standard in some of our analyses.
Flow and timing	We presumed that all tests were performed on biopsied tumour material collected on 1 occasion.
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (NanoString)
DOMAIN 2: Index Test (aCGH)
DOMAIN 2: Index Test (NGS)
DOMAIN 2: Index Test (G‐banding)
DOMAIN 2: Index Test (FISH (variant 4))
DOMAIN 2: Index Test (SNP array)
DOMAIN 2: Index Test (PCR (with comparison to normal DNA))
DOMAIN 2: Index Test (PCR (without comparison to normal DNA))
DOMAIN 2: Index Test (CISH)
DOMAIN 2: Index Test (MS)
DOMAIN 2: Index Test (RFLP)
DOMAIN 2: Index Test (PCR‐based LOH)
If a threshold was used, was it pre‐specified?	Unclear
Were the index test results interpreted without knowledge of the results of the other tests being compared?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 2: Index Test (NGS or aCGH (or both))
DOMAIN 2: Index Test (Methylation array)
DOMAIN 2: Index Test (FISH)
If a threshold was used, was it pre‐specified?	Unclear
Were the index test results interpreted without knowledge of the results of the other tests being compared?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 2: Index Test (FISH (variant 1))
DOMAIN 2: Index Test (FISH (variant 2))
DOMAIN 2: Index Test (FISH (variant 3))
DOMAIN 2: Index Test (Real‐time PCR)
DOMAIN 2: Index Test (MLPA)
DOMAIN 2: Index Test (CGH)
If a threshold was used, was it pre‐specified?	Unclear
Were the index test results interpreted without knowledge of the results of the other tests being compared?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk