Ignite Creation Date:
2025-12-24 @ 3:14 PM
Ignite Modification Date:
2026-01-02 @ 10:01 PM
Study NCT ID:
NCT03901092
Status:
COMPLETED
Last Update Posted:
2020-09-09
First Post:
2019-03-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 Positron Emission Tomography (PET) Scan Interpretation
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2020-07-16', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D000544', 'term': 'Alzheimer Disease'}], 'ancestors': [{'id': 'D003704', 'term': 'Dementia'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D024801', 'term': 'Tauopathies'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000591008', 'term': '7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clinicaloperations@avidrp.com', 'phone': '215-298-0700', 'title': 'Medical Director', 'organization': 'Avid Radiopharmaceuticals, Inc.'}, 'certainAgreement': {'restrictionType': 'LTE60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Not applicable. Adverse events were not assessed during this study.', 'description': 'Adverse events were not assessed during this study.', 'eventGroups': [{'id': 'EG000', 'title': 'All Cases', 'description': 'No study drug will be administered. Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers.', 'otherNumAtRisk': 0, 'deathsNumAtRisk': 0, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0.5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '47', 'groupId': 'OG000'}, {'value': '35', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Sensitivity of Flortaucipir vs Autopsy NFT Score', 'description': 'Subjects with a positive autopsy NFT score truth standard (NFT B3)'}, {'id': 'OG001', 'title': 'Specificity of Flortaucipir vs Autopsy NFT Score', 'description': 'Subjects with a negative autopsy NFT score truth standard (NFT B2 or lower)'}], 'classes': [{'title': 'Reader 1', 'categories': [{'measurements': [{'value': '91.5', 'groupId': 'OG000', 'lowerLimit': '80.07', 'upperLimit': '96.64'}, {'value': '77.1', 'groupId': 'OG001', 'lowerLimit': '60.98', 'upperLimit': '87.93'}]}]}, {'title': 'Reader 2', 'categories': [{'measurements': [{'value': '89.4', 'groupId': 'OG000', 'lowerLimit': '77.41', 'upperLimit': '95.37'}, {'value': '91.4', 'groupId': 'OG001', 'lowerLimit': '77.62', 'upperLimit': '97.04'}]}]}, {'title': 'Reader 3', 'categories': [{'measurements': [{'value': '87.2', 'groupId': 'OG000', 'lowerLimit': '74.83', 'upperLimit': '94.02'}, {'value': '85.7', 'groupId': 'OG001', 'lowerLimit': '70.62', 'upperLimit': '93.74'}]}]}, {'title': 'Reader 4', 'categories': [{'measurements': [{'value': '93.6', 'groupId': 'OG000', 'lowerLimit': '82.84', 'upperLimit': '97.81'}, {'value': '62.9', 'groupId': 'OG001', 'lowerLimit': '46.34', 'upperLimit': '76.83'}]}]}, {'title': 'Reader 5', 'categories': [{'measurements': [{'value': '89.4', 'groupId': 'OG000', 'lowerLimit': '77.41', 'upperLimit': '95.37'}, {'value': '77.1', 'groupId': 'OG001', 'lowerLimit': '60.98', 'upperLimit': '87.93'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': "Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem 18F-AV-1451 PET imaging for detection of a pattern of 18F-AV-1451 neocortical uptake that corresponds to neurofibrillary tangles (NFT) Score of B3 (Hyman et al., 2012; Montine et al., 2012). NFT B scores range from B0 (no NFTs in the brain) to B3 (widespread NFTs in the brain). Sensitivity and specificity are percentages that can range from 0 to 100%. The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity.", 'unitOfMeasure': 'percentage of cases correctly identified', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Analysis included all autopsy subjects with an evaluable flortaucipir PET scan interpretation (n=82). One autopsy subject scan was rated as unevaluable. n=47 were truth positive for NFTs. n=35 were truth negative for NFTs.'}, {'type': 'PRIMARY', 'title': 'Primary Objective 1 Analysis 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '41', 'groupId': 'OG000'}, {'value': '41', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Sensitivity of Flortaucipir vs NIA-AA Autopsy Diagnosis', 'description': 'Subjects with a positive truth standard (High ADNC)'}, {'id': 'OG001', 'title': 'Specificity of Flortaucipir vs NIA-AA Autopsy Diagnosis', 'description': 'Subjects with a negative truth standard (No/Low/Intermediate ADNC)'}], 'classes': [{'title': 'Reader 1', 'categories': [{'measurements': [{'value': '95.1', 'groupId': 'OG000', 'lowerLimit': '83.86', 'upperLimit': '98.65'}, {'value': '70.7', 'groupId': 'OG001', 'lowerLimit': '55.52', 'upperLimit': '82.39'}]}]}, {'title': 'Reader 2', 'categories': [{'measurements': [{'value': '95.1', 'groupId': 'OG000', 'lowerLimit': '83.86', 'upperLimit': '98.65'}, {'value': '85.4', 'groupId': 'OG001', 'lowerLimit': '71.56', 'upperLimit': '93.12'}]}]}, {'title': 'Reader 3', 'categories': [{'measurements': [{'value': '95.1', 'groupId': 'OG000', 'lowerLimit': '83.86', 'upperLimit': '98.65'}, {'value': '82.9', 'groupId': 'OG001', 'lowerLimit': '68.74', 'upperLimit': '91.47'}]}]}, {'title': 'Reader 4', 'categories': [{'measurements': [{'value': '97.6', 'groupId': 'OG000', 'lowerLimit': '87.40', 'upperLimit': '99.57'}, {'value': '58.5', 'groupId': 'OG001', 'lowerLimit': '43.37', 'upperLimit': '72.24'}]}]}, {'title': 'Reader 5', 'categories': [{'measurements': [{'value': '95.1', 'groupId': 'OG000', 'lowerLimit': '83.86', 'upperLimit': '98.65'}, {'value': '73.2', 'groupId': 'OG001', 'lowerLimit': '58.07', 'upperLimit': '84.31'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': "Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem 18F-AV-1451 PET imaging for detection of a pattern of 18F-AV-1451 neocortical uptake that corresponds to high levels of AD neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (see Hyman et al. 2012). ADNC categories are None, Low, Intermediate and High, with High indicating the most severe level of AD-related pathology changes in the brain. The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity.", 'unitOfMeasure': 'percentage of cases correctly identified', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Analysis included all autopsy subjects with an evaluable flortaucipir PET scan interpretation (n=82). One autopsy subject scan was rated as unevaluable. n=41 were truth positive. n=41 were truth negative.'}, {'type': 'PRIMARY', 'title': 'Primary Objective 2: Inter-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging', 'denoms': [{'units': 'Participants', 'counts': [{'value': '241', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Cases', 'description': 'All autopsy and non-autopsy cases'}], 'classes': [{'title': 'Reader 1 v Reader 2', 'categories': [{'measurements': [{'value': '95.0', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 3', 'categories': [{'measurements': [{'value': '93.4', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 4', 'categories': [{'measurements': [{'value': '94.6', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 5', 'categories': [{'measurements': [{'value': '97.1', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 3', 'categories': [{'measurements': [{'value': '97.1', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 4', 'categories': [{'measurements': [{'value': '91.3', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 5', 'categories': [{'measurements': [{'value': '94.6', 'groupId': 'OG000'}]}]}, {'title': 'Reader 3 v Reader 4', 'categories': [{'measurements': [{'value': '91.3', 'groupId': 'OG000'}]}]}, {'title': 'Reader 3 v Reader 5', 'categories': [{'measurements': [{'value': '93.8', 'groupId': 'OG000'}]}]}, {'title': 'Reader 4 v Reader 5', 'categories': [{'measurements': [{'value': '95.0', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': "Fleiss' kappa", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.87', 'ciLowerLimit': '0.83', 'ciUpperLimit': '0.91', 'groupDescription': "Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. The primary hypothesis to be tested was that the lower bound of two-sided 95% confidence interval of Fleiss' Kappa will be greater than or equal to 0.6.", 'nonInferiorityType': 'OTHER'}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': "As measured by Fleiss' Kappa across all scans read. Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. Fleiss' kappa can range from 0 to 1 with 1 indicating perfect agreement between the readers. Scan results binarized as positive AD pattern versus negative AD pattern. Results are displayed as percentage of agreement for individual reader pairs, computed as follows: number of images for which reader had the same interpretation divided by the total number of images evaluated, multiplied by 100%.", 'unitOfMeasure': 'percentage agreement of cases', 'reportingStatus': 'POSTED', 'populationDescription': 'Analysis included all subjects who had a valid flortaucipir PET scan in the autopsy and non-autopsy groups (n=241)'}, {'type': 'SECONDARY', 'title': 'Secondary Objective 1 Analysis 1: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect B3 NFTs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '47', 'groupId': 'OG000'}, {'value': '35', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Sensitivity of Flortaucipir tAD++ vs Autopsy NFT Score', 'description': 'Subjects with a positive autopsy NFT score truth standard (NFT B3)'}, {'id': 'OG001', 'title': 'Specificity of Flortaucipir tAD++ vs Autopsy NFT Score', 'description': 'Subjects with a negative autopsy NFT score truth standard (NFT B2 or lower)'}], 'classes': [{'title': 'Reader 1', 'categories': [{'measurements': [{'value': '87.2', 'groupId': 'OG000', 'lowerLimit': '74.83', 'upperLimit': '94.02'}, {'value': '88.6', 'groupId': 'OG001', 'lowerLimit': '74.05', 'upperLimit': '95.46'}]}]}, {'title': 'Reader 2', 'categories': [{'measurements': [{'value': '80.9', 'groupId': 'OG000', 'lowerLimit': '67.46', 'upperLimit': '89.58'}, {'value': '100.0', 'groupId': 'OG001', 'lowerLimit': '90.11', 'upperLimit': '100.00'}]}]}, {'title': 'Reader 3', 'categories': [{'measurements': [{'value': '76.6', 'groupId': 'OG000', 'lowerLimit': '62.78', 'upperLimit': '86.40'}, {'value': '94.3', 'groupId': 'OG001', 'lowerLimit': '81.39', 'upperLimit': '98.42'}]}]}, {'title': 'Reader 4', 'categories': [{'measurements': [{'value': '89.4', 'groupId': 'OG000', 'lowerLimit': '77.41', 'upperLimit': '95.37'}, {'value': '82.9', 'groupId': 'OG001', 'lowerLimit': '67.32', 'upperLimit': '91.90'}]}]}, {'title': 'Reader 5', 'categories': [{'measurements': [{'value': '83.0', 'groupId': 'OG000', 'lowerLimit': '69.86', 'upperLimit': '91.11'}, {'value': '94.3', 'groupId': 'OG001', 'lowerLimit': '81.39', 'upperLimit': '98.42'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': 'Flortaucipir F 18 PET imaging will be classified by each reader as either neocortical uptake not consistent with AD (τAD-), neocortical uptake consistent with AD (τAD+), or neocortical uptake consistent with AD with uptake beyond the temporal/occipital regions (τAD++). NFT scoring is according to Hyman, et al 2012. Truth positive is a NFT B3 score. Truth negative is NFT \\<B3 score.', 'unitOfMeasure': 'percentage cases correctly identified', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Analysis included all autopsy subjects with an evaluable flortaucipir PET scan interpretation (n=82). One autopsy subject scan was rated as unevaluable. n=47 were truth positive for NFTs. n=35 were truth negative for NFTs.'}, {'type': 'SECONDARY', 'title': 'Secondary Objective 1 Analysis 2: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect High ADNC', 'denoms': [{'units': 'Participants', 'counts': [{'value': '41', 'groupId': 'OG000'}, {'value': '41', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Sensitivity', 'description': 'Sensitivity individual Flortaucipir PET scan interpreted as τAD++ pattern versus NIA-AA autopsy Diagnosis Truth Standard'}, {'id': 'OG001', 'title': 'Specificity', 'description': 'Specificity individual Flortaucipir PET scan interpreted as τAD++ pattern versus NIA-AA autopsy Diagnosis Truth Standard'}], 'classes': [{'title': 'Reader 1', 'categories': [{'measurements': [{'value': '92.7', 'groupId': 'OG000', 'lowerLimit': '80.57', 'upperLimit': '97.48'}, {'value': '82.9', 'groupId': 'OG001', 'lowerLimit': '68.74', 'upperLimit': '91.47'}]}]}, {'title': 'Reader 2', 'categories': [{'measurements': [{'value': '85.4', 'groupId': 'OG000', 'lowerLimit': '71.56', 'upperLimit': '93.12'}, {'value': '92.7', 'groupId': 'OG001', 'lowerLimit': '80.57', 'upperLimit': '97.48'}]}]}, {'title': 'Reader 3', 'categories': [{'measurements': [{'value': '85.4', 'groupId': 'OG000', 'lowerLimit': '71.56', 'upperLimit': '93.12'}, {'value': '92.7', 'groupId': 'OG001', 'lowerLimit': '80.57', 'upperLimit': '97.48'}]}]}, {'title': 'Reader 4', 'categories': [{'measurements': [{'value': '92.7', 'groupId': 'OG000', 'lowerLimit': '80.57', 'upperLimit': '97.48'}, {'value': '75.6', 'groupId': 'OG001', 'lowerLimit': '60.66', 'upperLimit': '86.17'}]}]}, {'title': 'Reader 5', 'categories': [{'measurements': [{'value': '87.8', 'groupId': 'OG000', 'lowerLimit': '74.46', 'upperLimit': '94.68'}, {'value': '87.8', 'groupId': 'OG001', 'lowerLimit': '74.46', 'upperLimit': '94.68'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': "Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem 18F-AV-1451 PET imaging for detection of a pattern of 18F-AV-1451 neocortical uptake that corresponds to high levels of AD neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (Hyman et al. 2012). Truth positive is a High ADNC score. Truth negative is No/Low/Intermediate ADNC score.", 'unitOfMeasure': 'percentage of cases correctly identified', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Analysis included all autopsy subjects with an evaluable flortaucipir PET scan interpretation (n=82). One autopsy subject scan was rated as unevaluable. n=41 were truth positive. n=41 were truth negative.'}, {'type': 'SECONDARY', 'title': 'Secondary Objective 2: Inter-reader Reliability of Reader Interpretation of τAD++ Flortaucipir PET Images', 'denoms': [{'units': 'Participants', 'counts': [{'value': '241', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'All Cases', 'description': 'All autopsy and non-autopsy cases'}], 'classes': [{'title': 'Reader 1 v Reader 2', 'categories': [{'measurements': [{'value': '92.5', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 3', 'categories': [{'measurements': [{'value': '90.0', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 4', 'categories': [{'measurements': [{'value': '91.3', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 5', 'categories': [{'measurements': [{'value': '95.0', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 3', 'categories': [{'measurements': [{'value': '91.7', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 4', 'categories': [{'measurements': [{'value': '90.5', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 5', 'categories': [{'measurements': [{'value': '94.2', 'groupId': 'OG000'}]}]}, {'title': 'Reader 3 v Reader 4', 'categories': [{'measurements': [{'value': '88.8', 'groupId': 'OG000'}]}]}, {'title': 'Reader 3 v Reader 5', 'categories': [{'measurements': [{'value': '92.5', 'groupId': 'OG000'}]}]}, {'title': 'Reader 4 v Reader 5', 'categories': [{'measurements': [{'value': '92.9', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': "Fleiss' kappa", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.84', 'ciLowerLimit': '0.80', 'ciUpperLimit': '0.88', 'groupDescription': "Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. The primary hypothesis to be tested was that the lower bound of two-sided 95% confidence interval of Fleiss' Kappa will be greater than or equal to 0.6.", 'nonInferiorityType': 'OTHER'}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': "Overall reader agreement as measured by Fleiss' Kappa statistic. Scan results binarized as τAD++ versus τAD+/τAD-. Results are displayed as percentage of agreement for individual reader pairs, computed as follows: number of images for which reader had the same interpretation divided by the total number of images evaluated, multiplied by 100%.", 'unitOfMeasure': 'percentage agreement of cases', 'reportingStatus': 'POSTED', 'populationDescription': 'Analysis included all subjects who had a valid flortaucipir PET scan in the autopsy and non-autopsy groups (n=241)'}, {'type': 'SECONDARY', 'title': 'Secondary Objective 3: Inter-reader Reliability of Flortaucipir PET Scan Interpretation in the Population of Intended Use', 'denoms': [{'units': 'Participants', 'counts': [{'value': '159', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'A05 Cases', 'description': 'All non-autopsy cases from the Study A05 population of intended use'}], 'classes': [{'title': 'Reader 1 v Reader 2', 'categories': [{'measurements': [{'value': '97.5', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 3', 'categories': [{'measurements': [{'value': '93.1', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 4', 'categories': [{'measurements': [{'value': '95.6', 'groupId': 'OG000'}]}]}, {'title': 'Reader 1 v Reader 5', 'categories': [{'measurements': [{'value': '97.5', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 3', 'categories': [{'measurements': [{'value': '93.1', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 4', 'categories': [{'measurements': [{'value': '94.3', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2 v Reader 5', 'categories': [{'measurements': [{'value': '96.2', 'groupId': 'OG000'}]}]}, {'title': 'Reader 3 v Reader 4', 'categories': [{'measurements': [{'value': '93.7', 'groupId': 'OG000'}]}]}, {'title': 'Reader 3 v Reader 5', 'categories': [{'measurements': [{'value': '93.1', 'groupId': 'OG000'}]}]}, {'title': 'Reader 4 v Reader 5', 'categories': [{'measurements': [{'value': '96.9', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': "Fleiss' kappa", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.90', 'ciLowerLimit': '0.85', 'ciUpperLimit': '0.95', 'groupDescription': "Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. The hypothesis to be tested was that the lower bound of two-sided 95% confidence interval of Fleiss' Kappa will be greater than or equal to 0.6.", 'nonInferiorityType': 'OTHER'}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': "Reader agreement measured by Fleiss' Kappa across scans from non-autopsy cases from Study A05. Scan results binarized as positive for AD pattern versus negative for AD pattern. Results are displayed as percentage of agreement for individual reader pairs, computed as follows: number of images for which reader had the same interpretation divided by the total number of images evaluated, multiplied by 100%.", 'unitOfMeasure': 'percentage agreement of cases', 'reportingStatus': 'POSTED', 'populationDescription': 'Non-autopsy cases from Study A05'}, {'type': 'SECONDARY', 'title': 'Secondary Objective 4: Intra-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Randomly Selected Re-reads', 'description': 'Cases randomly selected to be read twice by the same reader'}], 'classes': [{'title': 'Reader 1', 'categories': [{'measurements': [{'value': '95.0', 'groupId': 'OG000'}]}]}, {'title': 'Reader 2', 'categories': [{'measurements': [{'value': '85.0', 'groupId': 'OG000'}]}]}, {'title': 'Reader 3', 'categories': [{'measurements': [{'value': '80.0', 'groupId': 'OG000'}]}]}, {'title': 'Reader 4', 'categories': [{'measurements': [{'value': '95.0', 'groupId': 'OG000'}]}]}, {'title': 'Reader 5', 'categories': [{'measurements': [{'value': '90.0', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': "Cohen's kappa", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.89', 'ciLowerLimit': '0.69', 'ciUpperLimit': '1.00', 'groupDescription': "Cohen's kappa statistic for Reader 1", 'nonInferiorityType': 'OTHER'}, {'groupIds': ['OG000'], 'paramType': "Cohen's kappa", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.71', 'ciLowerLimit': '0.41', 'ciUpperLimit': '1.00', 'groupDescription': "Cohen's kappa statistic for Reader 2", 'nonInferiorityType': 'OTHER'}, {'groupIds': ['OG000'], 'paramType': "Cohen's kappa", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.60', 'ciLowerLimit': '0.24', 'ciUpperLimit': '0.95', 'groupDescription': "Cohen's kappa statistic for Reader 3", 'nonInferiorityType': 'OTHER'}, {'groupIds': ['OG000'], 'paramType': "Cohen's kappa", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.89', 'ciLowerLimit': '0.67', 'ciUpperLimit': '1.00', 'groupDescription': "Cohen's kappa statistic for Reader 4", 'nonInferiorityType': 'OTHER'}, {'groupIds': ['OG000'], 'paramType': "Cohen's kappa", 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.79', 'ciLowerLimit': '0.52', 'ciUpperLimit': '1.00', 'groupDescription': "Cohen's kappa statistic for Reader 5", 'nonInferiorityType': 'OTHER'}], 'paramType': 'NUMBER', 'timeFrame': 'baseline scan', 'description': "Cohen's Kappa will be calculated for each of 5 readers to assess the intra-reader reliability of flortaucipir F 18 PET scan visual interpretation. The statistic takes into account the possibility of the agreement occurring by chance. Cohen's kappa values range from 0 to 1 with 1 representing perfect agreement. Results are displayed as percentage of agreement within a reader, computed as follows: number of images for which reader had the same interpretation at initial and second read divided by the total number of images evaluated twice by a reader, multiplied by 100%.", 'unitOfMeasure': 'percentage agreement of cases', 'reportingStatus': 'POSTED', 'populationDescription': '20 scans read twice to assess the intra-reader reliability'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'All Autopsy Cases', 'description': 'Cases that had a valid scan and came to autopsy in in study A16 and the A16 supplemental cohort'}, {'id': 'FG001', 'title': 'Non-Autopsy Cases', 'description': 'Mild cognitive impairment (MCI) and AD cases from the A05 confirmatory cohort'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '83'}, {'groupId': 'FG001', 'numSubjects': '159'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '83'}, {'groupId': 'FG001', 'numSubjects': '159'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Subjects were not recruited for this study. Study scans were selected from 2 previously completed imaging studies. Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) were read by 5 independent, blinded to other study information.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '242', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Cases', 'description': 'All eligible subject scans from contributing studies'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'title': 'Study A16 Autopsy Cases', 'denoms': [{'units': 'Participants', 'counts': [{'value': '83', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '81.6', 'spread': '9.91', 'groupId': 'BG000'}]}]}, {'title': 'Study A05 Non-autopsy Cases', 'denoms': [{'units': 'Participants', 'counts': [{'value': '159', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '72.9', 'spread': '9.64', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Baseline analysis includes Study A16 autopsy cases (n=83) and Study A05 Non-autopsy cases (n=159).'}, {'title': 'Sex: Female, Male', 'classes': [{'title': 'Study A16 Autopsy Cases', 'denoms': [{'units': 'Participants', 'counts': [{'value': '83', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '41', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '42', 'groupId': 'BG000'}]}]}, {'title': 'Study A05 Non-autopsy Cases', 'denoms': [{'units': 'Participants', 'counts': [{'value': '159', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '74', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '85', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Baseline analysis includes Study A16 autopsy cases (n=83) and Study A05 Non-autopsy cases (n=159).'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'title': 'Study A16 Autopsy Cases', 'denoms': [{'units': 'Participants', 'counts': [{'value': '83', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '79', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Study A05 Non-autopsy Cases', 'denoms': [{'units': 'Participants', 'counts': [{'value': '159', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '150', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Measure Analysis Population Description: Baseline analysis includes Study A16 autopsy cases (n=83) and Study A05 Non-autopsy cases (n=159).'}, {'title': 'Race (NIH/OMB)', 'classes': [{'title': 'Study A16 Autopsy Cases', 'denoms': [{'units': 'Participants', 'counts': [{'value': '83', 'groupId': 'BG000'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '81', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Study A05 Non-autopsy Cases', 'denoms': [{'units': 'Participants', 'counts': [{'value': '159', 'groupId': 'BG000'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '154', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Measure Analysis Population Description: Baseline analysis includes Study A16 autopsy cases (n=83) and Study A05 Non-autopsy cases (n=159).'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-03-21', 'size': 333138, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-06-27T14:24', 'hasProtocol': True}, {'date': '2019-04-30', 'size': 2750072, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-06-27T14:25', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'PET scans were obtained in an open-label fashion.'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Physician PET scan readers are participants, blinded to demographic and clinical data from the source PET scans.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 242}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-03-26', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-08', 'dispFirstSubmitDate': '2020-01-22', 'completionDateStruct': {'date': '2019-04-26', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-08-21', 'studyFirstSubmitDate': '2019-03-27', 'dispFirstSubmitQcDate': '2020-07-21', 'resultsFirstSubmitDate': '2020-06-27', 'studyFirstSubmitQcDate': '2019-04-01', 'dispFirstPostDateStruct': {'date': '2020-08-11', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2020-09-09', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-07-21', 'studyFirstPostDateStruct': {'date': '2019-04-03', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2020-08-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-04-26', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score)', 'timeFrame': 'baseline scan', 'description': "Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem 18F-AV-1451 PET imaging for detection of a pattern of 18F-AV-1451 neocortical uptake that corresponds to neurofibrillary tangles (NFT) Score of B3 (Hyman et al., 2012; Montine et al., 2012). NFT B scores range from B0 (no NFTs in the brain) to B3 (widespread NFTs in the brain). Sensitivity and specificity are percentages that can range from 0 to 100%. The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity."}, {'measure': 'Primary Objective 1 Analysis 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)', 'timeFrame': 'baseline scan', 'description': "Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem 18F-AV-1451 PET imaging for detection of a pattern of 18F-AV-1451 neocortical uptake that corresponds to high levels of AD neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (see Hyman et al. 2012). ADNC categories are None, Low, Intermediate and High, with High indicating the most severe level of AD-related pathology changes in the brain. The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity."}, {'measure': 'Primary Objective 2: Inter-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging', 'timeFrame': 'baseline scan', 'description': "As measured by Fleiss' Kappa across all scans read. Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. Fleiss' kappa can range from 0 to 1 with 1 indicating perfect agreement between the readers. Scan results binarized as positive AD pattern versus negative AD pattern. Results are displayed as percentage of agreement for individual reader pairs, computed as follows: number of images for which reader had the same interpretation divided by the total number of images evaluated, multiplied by 100%."}], 'secondaryOutcomes': [{'measure': 'Secondary Objective 1 Analysis 1: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect B3 NFTs', 'timeFrame': 'baseline scan', 'description': 'Flortaucipir F 18 PET imaging will be classified by each reader as either neocortical uptake not consistent with AD (τAD-), neocortical uptake consistent with AD (τAD+), or neocortical uptake consistent with AD with uptake beyond the temporal/occipital regions (τAD++). NFT scoring is according to Hyman, et al 2012. Truth positive is a NFT B3 score. Truth negative is NFT \\<B3 score.'}, {'measure': 'Secondary Objective 1 Analysis 2: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect High ADNC', 'timeFrame': 'baseline scan', 'description': "Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem 18F-AV-1451 PET imaging for detection of a pattern of 18F-AV-1451 neocortical uptake that corresponds to high levels of AD neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (Hyman et al. 2012). Truth positive is a High ADNC score. Truth negative is No/Low/Intermediate ADNC score."}, {'measure': 'Secondary Objective 2: Inter-reader Reliability of Reader Interpretation of τAD++ Flortaucipir PET Images', 'timeFrame': 'baseline scan', 'description': "Overall reader agreement as measured by Fleiss' Kappa statistic. Scan results binarized as τAD++ versus τAD+/τAD-. Results are displayed as percentage of agreement for individual reader pairs, computed as follows: number of images for which reader had the same interpretation divided by the total number of images evaluated, multiplied by 100%."}, {'measure': 'Secondary Objective 3: Inter-reader Reliability of Flortaucipir PET Scan Interpretation in the Population of Intended Use', 'timeFrame': 'baseline scan', 'description': "Reader agreement measured by Fleiss' Kappa across scans from non-autopsy cases from Study A05. Scan results binarized as positive for AD pattern versus negative for AD pattern. Results are displayed as percentage of agreement for individual reader pairs, computed as follows: number of images for which reader had the same interpretation divided by the total number of images evaluated, multiplied by 100%."}, {'measure': 'Secondary Objective 4: Intra-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging', 'timeFrame': 'baseline scan', 'description': "Cohen's Kappa will be calculated for each of 5 readers to assess the intra-reader reliability of flortaucipir F 18 PET scan visual interpretation. The statistic takes into account the possibility of the agreement occurring by chance. Cohen's kappa values range from 0 to 1 with 1 representing perfect agreement. Results are displayed as percentage of agreement within a reader, computed as follows: number of images for which reader had the same interpretation at initial and second read divided by the total number of images evaluated twice by a reader, multiplied by 100%."}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['flortaucipir F 18', 'Positron Emission Tomography', '18F-AV-1451', 'Diagnostic imaging', 'Tau imaging'], 'conditions': ['Alzheimer Disease']}, 'descriptionModule': {'briefSummary': 'This study will evaluate the performance of physician readers trained to read flortaucipir-PET (positron emission tomography) scans.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': False, 'eligibilityCriteria': 'Scan Reader Criteria (5 total):\n\n* Board-certified in radiology or nuclear medicine\n* Professional experience interpreting PET scans\n* Naive to study protocol\n* No previous training or exposure to Avid Flortaucipir F 18 read methodology\n\nScan Criteria:\n\n\\- Previous enrollment in Study A05 confirmatory cohort (NCT02016560), or A16 (NCT02516046)\n\nScan Study Population Criteria for FR01 (A05 confirmatory cohort):\n\n* Cognitively-impaired\n* mild cognitive impairment (MCI) or dementia with suspected neurodegenerative cause\n* mini-mental status exam (MMSE) score of 20-27, inclusive\n\nScan Study Population Criteria for FR01 (Study A16):\n\n* Subjects at end of life (less than or equal to 6 months)\n* Imaged with flortaucipir F18 and came to autopsy'}, 'identificationModule': {'nctId': 'NCT03901092', 'briefTitle': 'A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 Positron Emission Tomography (PET) Scan Interpretation', 'organization': {'class': 'INDUSTRY', 'fullName': 'Avid Radiopharmaceuticals'}, 'officialTitle': 'A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 PET Scan Interpretation', 'orgStudyIdInfo': {'id': '18F-AV-1451-FR01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Flortaucipir PET Scan', 'description': 'Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers.', 'interventionNames': ['Drug: flortaucipir F 18']}], 'interventions': [{'name': 'flortaucipir F 18', 'type': 'DRUG', 'otherNames': ['18F-AV-1451', '[F-18]T807', 'LY3191748'], 'description': 'No study drug will be administered.', 'armGroupLabels': ['Flortaucipir PET Scan']}]}, 'contactsLocationsModule': {'locations': [{'zip': '19103', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'American College of Radiology', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}], 'overallOfficials': [{'name': 'Study Director', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Avid Radiopharmaceuticals'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Avid Radiopharmaceuticals', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}