Gordon 1990.

Clinical features and settings	Inclusion period: January 1986 to March 1988. Patient population: 44 unselected eligible patients with histologically proven neuroblastoma and with a ¹²³I‐MIBG scan; 9mTc‐MDP and ¹²³I‐MIBG scans were completed within four weeks of each other. Three patients were excluded due to incorrect timing of the studies and another five because the images were missing from the file. So 36 of 44 patients were included, of which 28 had a ¹²³I‐MIBG scan at diagnosis and thus were included in this review. Consecutive series: n.r. Diagnostic work‐up: n.r. Time spans symptoms‐index test, symptoms‐reference standard and index test‐reference standard: n.r. Treatment between index test‐reference standard: n.r.
Participants	Included patients: 28 children with a neuroblastoma and a ¹²³I‐MIBG scan at first diagnosis. Median age at diagnosis: n.r. for these 28 included patients; for all 36 patients: 3.0 years (range 1 week to 11.5 years). Sex distribution: n.r. for these 28 included patients; for all 36 patients: 23 boys (62%), 13 girls (38%). INSS stage: six stage 1 to 3 and 22 stage 4.
Study design	Case series with pathologically proven neuroblastoma (histopathology not known at the time of MIBG‐scintigraphy).
Target condition and reference standard(s)	Target condition: Newly diagnosed neuroblastoma. Reference standard: histopathology or bilateral aspirates of bone marrow and trephine biopsy.
Index and comparator tests	Assessed primary objective 1.1: to determine the diagnostic accuracy of ¹²³I‐MIBG (SPECT‐CT) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. Index test: ¹²³I‐MIBG scintigraphy. Radiofarmacon: ¹²³I‐MIBG. Dose: 120 MBq for children aged under two years and 160 MBq for those over two years. Collimator: n.r. Matrix: n.r. Acquisition protocol: WB scans. The children were sedated, if necessary. Acquisition time: 18 to 24 hours after injection. Acquisition duration: 5 minutes for WB scans. Interfering medication: n.r.; parents received a list of drugs known to inhibit ¹²³I‐MIBG uptake. Thyroid prophylaxis: oral potassium iodide three days before the examination. Positive test result: n.r. Number of observers: one author blinded for the results of the 99mTc‐MDP scan. Expertise of observers: n.r. Interobserver concordance: n.r.
Follow‐up	n.r.; some patients were followed up to 64 months.
Notes	The sensitivity and specificity of the diagnosis neuroblastoma could be analysed for 19 of the 28 eligible patients. The remaining nine patients could be analysed concerning sensitivity and specificity of metastases only. These patients had false positive results for neuroblastoma based just on negative bone marrow biopsies which is not a valid method to detect neuroblastoma, but only to detect metastases. As stated in the methods, neuroblastoma was assumed not present if all three reference tests were negative.
Table of Methodological Quality
Item	Authors' judgement	Description
Representative spectrum? All tests	Yes	Patients with a neuroblastoma at first diagnosis, age 1 week to 11.5 years and stage distribution is reported.
Acceptable reference standard? All tests	Yes	Histopathology.
Acceptable delay between tests? All tests	Unclear	n.r.
Partial verification avoided? All tests	Yes	Diagnosis confirmed by histopathology in all patients.
Differential verification avoided? All tests	Yes	Diagnosis confirmed by histopathology in all patients.
Incorporation avoided? All tests	Yes	Index test not a part of the reference test.
Reference standard results blinded? All tests	Unclear	n.r.
Index test results blinded? All tests	Unclear	n.r.
Relevant clinical information? All tests	Unclear	n.r.
Uninterpretable results reported? All tests	Unclear	n.r.
Withdrawals explained? All tests	Unclear	n.r.
Selection criteria clearly described? All tests	Yes	Patients with histologically proven neuroblastoma and with a ¹²³I‐MIBG scan. Three patients were excluded due to incorrect timing of the studies and another five because the images were missing from the file.
Sufficient detail for replication index test? All tests	Yes	Radiofarmacon, dose, acquisition protocol, acquisition time and acquisition duration were reported.
Sufficient detail for replication reference test? All tests	No	n.r.
Clear definition of positive result index test? All tests	No	n.r.
Interobserver variation reported and acceptable? All tests	Unclear	n.r.