Doraiswamy 2014.

Study characteristics
Patient sampling	There were 52 MCI at time of performing the test planned as evaluable for efficacy participants. The participants were 50 years old or older with memory complaint or cognitive impairment corroborated by an informant, CDR 0.5, and MMSE > 24, no episodic memory cut‐off was required. No further details of participant sampling and recruitment were reported
Patient characteristics and setting	52 MCI participants diagnosed by CDR 0.5, but the following data related to those reported in the study as the 'efficacy data set'. Therefore we reported data on 47 participants of 52 participants at baseline. The mean age was 74.47 (+ 7.72) years for those with Aβ (+) and 70.40 (+ 10.72) years old for those with Aβ (‐). 25 of the 47 in the efficacy data set of participants were women. APOE ϵ4 carrier: 11 of 17 participants in the Aβ (+) group, and 4 of 30 in the Aβ (‐) were positive to APOE ϵ4. MMSE: the mean MMSE for those in the Aβ (+) group was 27.29 (+ 2.14) and 27.53 (+ 1.63) for those in Aβ (‐) group. Years of education: the mean for those in Aβ (+) group was 14.47 (+ 2.18) years and 15.27 (+ 2.42) years for those in Aβ (‐) group. Sources of referral: not reported. Setting: 21 sites in the United States of America, no data regarding the specific setting were reported.
Index tests	Site PET scanners were qualified with a Hoffman brain phantom. Time between the 18F‐florbetapir injection and PET acquisition: fifty minutes after injection and, a 10‐min emission scan (acquired in 2 × 5 min frames) was obtained. 18F‐florbetapir administration mCi (MBq) dose: 10 mCi (370 MBq). PET scanners included Discovery LS PET/CT (GE, Fairfield, CT, USA), Advance PET (GE), ECAT HR+ (Siemens, Washington DC, USA) and Biograph PET/CT (Siemens) models. Image reconstruction utilized an iterative algorithm (4 iterations, 16 subsets) and a post‐reconstruction Gaussian filter of 5 mm. Semiquantitative visual rating: After a training session, three nuclear medicine physicians with no access to clinical information, independently rated each PET image for amyloid burden based on successive levels of florbetapir retention from 0 to 4 as follows: (0) None: predominantly white matter tracer retention with no appreciable cortical gray matter retention above cerebellar grey matter levels; (1) Low: evidence of increased tracer retention above cerebellar grey levels in 1 or 2 cortical grey regions; (2) Low‐moderate: either (a) predominantly white matter pattern, but at least 2 cortical regions with increased retention relative to cerebellar grey, or (b) predominantly a cortical gray matter pattern, with most cortical areas mildly positive relative to cerebellum; (3) Moderate‐high: specific cortical retention generally greater than or equal to white matter retention and at least one cortical area with greatly increased retention relative to cerebellar grey; (4) High: Specific cortical uptake greater than or equal to white matter background and multiple cortical areas with greatly increased retention relative to cerebellar grey. Binary Classification: The visual reads were used to classify each data set as either visually positive for Aβ or visually negative for Aβ Visual rating scores of 2 to 4 were considered positive and 0 to 1 were considered negative. Cerebellum was used as the reference region.
Target condition and reference standard(s)	Target condition: Alzheimer’s disease dementia Reference standard: not explicitly stated, although NINCDS‐ADRDA criteria for ADD (McKhann 1984) were baseline diagnostic criteria, and clinical diagnoses were generated without knowledge of the 18F‐florbetapir scan results.
Flow and timing	Duration of follow‐up: 3 years Number included in analysis: 47 participants with at least one post baseline measurement; 17 18F‐florbetapir (+) and 30 18F‐florbetapir (‐) Progression from MCI to ADD: 18F‐florbetapir (+): 6 MCI converted to ADD and 11 MCI not converted to ADD; 18F‐florbetapir (‐): 3 MCI converted to ADD and 27 MCI not converted to ADD TP = 6; FP = 11; FN = 3; TN = 27 Loss to follow‐up including those without any post‐baseline measurement: 15 MCI participants. No further information was given on the MCI group reasons. There were data regarding all groups (ADD, MCI, normal controls) where it was described that the most common reasons for termination were withdrawal of consent (n = 38) and loss of follow‐up (n = 8). Financial support from the manufacturer of 18F‐florbetapir tracer and six authors were employees
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
		Unclear	Low
DOMAIN 2: Index Test All tests
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Was the PET scan interpretation done by a trained reader physician?	Yes
Was there a clear definition of a positive result?	Yes
		Low	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
		Unclear	Unclear
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Unclear
Were all patients included in the analysis?	Yes
Was the study free of commercial funding?	No
		High