Question | Response and weighting | Explanation |
Patient selection | ||
Was the sampling method appropriate? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | Where sampling is used, the designs least likely to cause bias are consecutive sampling or random sampling. Sampling that is based on volunteers or selecting subjects from a clinic or research resource is prone to bias. |
Was a case‐control or similar design avoided? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | Designs similar to case‐control that may introduce bias are those designs where the study team deliberately increase or decrease the proportion of subjects with the target condition, which may not be representative. Some case‐control methods may already be excluded if they mix subjects from various settings. |
Are exclusion criteria described and appropriate? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | We automatically graded the study as unclear if the study authors did not detail exclusions (pending contact with study authors). Where a study details exclusions, we graded the study as 'low risk' if we considered exclusions to be appropriate. Certain exclusions common to many studies of dementia are: medical instability; terminal disease; alcohol/substance misuse; concomitant psychiatric diagnosis; other neurodegenerative conditions. Exclusions are not appropriate if they comprise ‘difficult to diagnose’ patients. We labelled post‐hoc and inappropriate exclusions as at 'high risk' of bias. |
Index test | ||
Was the 18F‐florbetapir PET ligand for Aβ biomarker's assessment/interpretation performed without knowledge of clinical dementia diagnosis? |
No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | Terms such as 'blinded' or 'independently and without knowledge of' are sufficient and full details of the blinding procedure are not required. Interpretation of the results of the index test may be influenced by knowledge of the results of the reference standard. If the index test is always interpreted prior to the reference standard, then the person interpreting the index test cannot be aware of the results of the reference standard and so this item could be rated as ‘yes’. For certain index tests, the result is objective and knowledge of the reference standard should not influence the result, e.g. level of protein in cerebrospinal fluid; in this instance, the quality assessment may be 'low risk' even if blinding was not achieved. |
Was the 18F‐florbetapir PET ligand for Aβ biomarker's threshold prespecified? |
No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | For scales and biomarkers, there is often a reference point (in units or categories) above which subjects are classified as 'test‐positive'; this may be referred to as the threshold, clinical cut‐off, or dichotomisation point. A study is classified at high risk of bias if the study authors define the optimal cut‐off post‐hoc based on their own study data because selecting the threshold to maximise sensitivity and/or specificity may lead to overoptimistic measures of test performance. Certain papers may use an alternative methodology for analysis that does not use thresholds and these papers should be classified as not applicable. |
Was the 18F‐florbetapir PET ligand for Aβ scan interpretation done by a trained reader physician? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | If a trained reader physician performed the scan interpretation, we scored this item as ’yes’. If no definition of trained reader was done, we scored this item as ’unclear’. If a nontrained reader physician performed the scan interpretation, we scored this item as ’no’. |
Did the study provide a clear definition of what was considered to be a 18F‐florbetapir PET ligand for Aβ biomarker’s positive result? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | If the study clearly stated the definition of a positive result (e.g. SUV), we scored this item as ’yes’. If the study did not give a definition of what it considered a positive result or the definition of a positive result varied between the participants, we scored this item as ’no’. If the study gave insufficient information to permit judgement, we scored the item as ’unclear’. |
Reference standard | ||
Is the assessment used for clinical diagnosis of dementia acceptable? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | Commonly used international criteria to assist with clinical diagnosis of dementia included those detailed in DSM‐IV and ICD‐10. Criteria specific to dementia subtypes included but were not limited to NINCDS‐ADRDA criteria for Alzheimer’s dementia; McKeith criteria for Lewy body dementia; Lund criteria and International Behavioural Variant FTD Criteria Consortium for frontotemporal dementia; and the NINDS‐AIREN criteria for vascular dementia. Where the criteria used for assessment were not familiar to the review authors or the Cochrane Dementia and Cognitive Improvement group (‘unclear’), we classified this item as 'high risk of bias'. |
Were clinical assessments for dementia performed without knowledge of the 18F‐florbetapir PET ligand for Aβ biomarker? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | Terms such as 'blinded' or 'independently and without knowledge of' were sufficient and full details of the blinding procedure were not required. Interpretation of the results of the reference standard may be influenced by knowledge of the results of the index test. |
Patient flow | ||
Was there an appropriate interval between 18F‐florbetapir PET ligand for Aβ biomarker and clinical dementia assessment? |
No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | As we test the accuracy of the 18F‐florbetapir PET ligand for Aβ biomarker for MCI progression to dementia, there will always be a delay between the index test and the reference standard assessments. The time between the reference standard and the index test will influence the accuracy (Geslani 2005; Okello 2007; Visser 2006), and therefore we noted time as a separate variable (both within and between studies) and will test its influence on the diagnostic accuracy. We have set a minimum mean time to follow‐up assessment of 1 year. If more than 16% of subjects have assessment for MCI progression before nine months, this item was scored ‘no’. |
Did all subjects get the same assessment for dementia regardless 18F‐florbetapir PET ligand for Aβ biomarker? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | There may be scenarios where participants who score 'test‐positive' on the index test have a more detailed assessment. Where dementia assessment differs between participants, this should be classified as high risk of bias. |
Were all patients who received 18F‐florbetapir PET ligand for Aβ biomarker’s assessment included in the final analysis? |
No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | If the number of patients enrolled differs from the number of patients included in the 2 × 2 table, then there is the potential for bias. If patients lost to dropouts differ systematically from those who remain, then estimates of test performance may differ. If there are dropouts, these should be accounted for; a maximum proportion of dropouts for a study to remain at low risk of bias has been specified as 20%. |
Were missing 18F‐florbetapir PET ligand for Aβ biomarker's results reported? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | Where missing or uninterpretable results are reported, and if there is substantial attrition (we have set an arbitrary value of 50% missing data), we will score this as ‘no’. If the study did not report these results, we scored this as ‘unclear’ and we contacted the study authors. |
Was the study with 18F‐florbetapir PET ligand for Aβ biomarker free of commercial funding? | No = high risk of bias Yes = low risk of bias Unclear = unclear risk of bias | If the funding source is clearly stated and is not commercial, this should be scored as ‘no’. If the funding source is clearly stated and is commercial, this should be scored as ’yes ’. If not enough information is given to assess whether the funding source is commercial, the scored is ’unclear’. |
Anchoring statements to assist with assessment for applicability | ||
Question | Explanation | |
Were included patients representative of the general population of interest? | The included patients should match the intended population as described in the review question. The review authors should consider population in terms of symptoms; pretesting; potential disease prevalence; setting. If there is a clear ground for suspecting an unrepresentative spectrum, the item should be rated poor applicability. | |
Index test | ||
Were sufficient data on 18F‐florbetapir PET ligand for Aβ biomarker’s application given for the test to be repeated in an independent study? | Variation in technology, test execution, and test interpretation may affect estimate of accuracy. In addition, the background, and training/expertise of the assessor should be reported and taken in consideration. If 18F‐florbetapir PET ligand for Aβ biomarker was not performed consistently, this item should be rated poor applicability. | |
Reference standard | ||
Was clinical diagnosis of dementia made in a manner similar to current clinical practice? | For many reviews, inclusion criteria and 'Risk of bias' assessments will already have assessed the dementia diagnosis. For certain reviews, an applicability statement relating to the reference standard may not be applicable. There is the possibility that a form of dementia assessment, although valid, may diagnose a far larger proportion of people with disease than usual clinical practice. In this instance, the item should be rated poor applicability. |