Back to resultsA Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 Positron Emission Tomography (PET) Scan Interpretation
Primary Purpose
Alzheimer Disease
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
flortaucipir F 18
Sponsored by
About this trial
This is an interventional diagnostic trial for Alzheimer Disease focused on measuring flortaucipir F 18, Positron Emission Tomography, 18F-AV-1451, Diagnostic imaging, Tau imaging
Eligibility Criteria
Scan Reader Criteria (5 total):
- Board-certified in radiology or nuclear medicine
- Professional experience interpreting PET scans
- Naive to study protocol
- No previous training or exposure to Avid Flortaucipir F 18 read methodology
Scan Criteria:
- Previous enrollment in Study A05 confirmatory cohort (NCT02016560), or A16 (NCT02516046)
Scan Study Population Criteria for FR01 (A05 confirmatory cohort):
- Cognitively-impaired
- mild cognitive impairment (MCI) or dementia with suspected neurodegenerative cause
- mini-mental status exam (MMSE) score of 20-27, inclusive
Scan Study Population Criteria for FR01 (Study A16):
- Subjects at end of life (less than or equal to 6 months)
- Imaged with flortaucipir F18 and came to autopsy
Sites / Locations
- American College of Radiology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Flortaucipir PET Scan
Arm Description
Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers.
Outcomes
Primary Outcome Measures
Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score)
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.
Primary Objective 1 Analysis 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)
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.
Primary Objective 2: Inter-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging
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%.
Secondary Outcome Measures
Secondary Objective 1 Analysis 1: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect B3 NFTs
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.
Secondary Objective 1 Analysis 2: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect High ADNC
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.
Secondary Objective 2: Inter-reader Reliability of Reader Interpretation of τAD++ Flortaucipir PET Images
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%.
Secondary Objective 3: Inter-reader Reliability of Flortaucipir PET Scan Interpretation in the Population of Intended Use
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%.
Secondary Objective 4: Intra-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging
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%.
Full Information
NCT ID
NCT03901092
First Posted
March 27, 2019
Last Updated
August 21, 2020
Sponsor
Avid Radiopharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03901092
Brief Title
A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 Positron Emission Tomography (PET) Scan Interpretation
Official Title
A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 PET Scan Interpretation
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
March 26, 2019 (Actual)
Primary Completion Date
April 26, 2019 (Actual)
Study Completion Date
April 26, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Avid Radiopharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study will evaluate the performance of physician readers trained to read flortaucipir-PET (positron emission tomography) scans.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
flortaucipir F 18, Positron Emission Tomography, 18F-AV-1451, Diagnostic imaging, Tau imaging
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Physician PET scan readers are participants, blinded to demographic and clinical data from the source PET scans.
Masking
None (Open Label)
Masking Description
PET scans were obtained in an open-label fashion.
Allocation
N/A
Enrollment
242 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Flortaucipir PET Scan
Arm Type
Experimental
Arm Description
Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers.
Intervention Type
Drug
Intervention Name(s)
flortaucipir F 18
Other Intervention Name(s)
18F-AV-1451, [F-18]T807, LY3191748
Intervention Description
No study drug will be administered.
Primary Outcome Measure Information:
Title
Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score)
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.
Time Frame
baseline scan
Title
Primary Objective 1 Analysis 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)
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.
Time Frame
baseline scan
Title
Primary Objective 2: Inter-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging
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%.
Time Frame
baseline scan
Secondary Outcome Measure Information:
Title
Secondary Objective 1 Analysis 1: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect B3 NFTs
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.
Time Frame
baseline scan
Title
Secondary Objective 1 Analysis 2: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect High ADNC
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.
Time Frame
baseline scan
Title
Secondary Objective 2: Inter-reader Reliability of Reader Interpretation of τAD++ Flortaucipir PET Images
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%.
Time Frame
baseline scan
Title
Secondary Objective 3: Inter-reader Reliability of Flortaucipir PET Scan Interpretation in the Population of Intended Use
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%.
Time Frame
baseline scan
Title
Secondary Objective 4: Intra-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging
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%.
Time Frame
baseline scan
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Scan Reader Criteria (5 total):
Board-certified in radiology or nuclear medicine
Professional experience interpreting PET scans
Naive to study protocol
No previous training or exposure to Avid Flortaucipir F 18 read methodology
Scan Criteria:
- Previous enrollment in Study A05 confirmatory cohort (NCT02016560), or A16 (NCT02516046)
Scan Study Population Criteria for FR01 (A05 confirmatory cohort):
Cognitively-impaired
mild cognitive impairment (MCI) or dementia with suspected neurodegenerative cause
mini-mental status exam (MMSE) score of 20-27, inclusive
Scan Study Population Criteria for FR01 (Study A16):
Subjects at end of life (less than or equal to 6 months)
Imaged with flortaucipir F18 and came to autopsy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Avid Radiopharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
American College of Radiology
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 Positron Emission Tomography (PET) Scan Interpretation
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