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A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 Positron Emission Tomography (PET) Scan Interpretation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03901092
Recruitment Status : Completed
First Posted : April 3, 2019
Results First Posted : August 11, 2020
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Avid Radiopharmaceuticals

Study Description
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Brief Summary:
This study will evaluate the performance of physician readers trained to read flortaucipir-PET (positron emission tomography) scans.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: flortaucipir F 18 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 242 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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.
Primary Purpose: Diagnostic
Official Title: A Reader Study to Assess Accuracy and Reliability of Flortaucipir F 18 PET Scan Interpretation
Actual Study Start Date : March 26, 2019
Actual Primary Completion Date : April 26, 2019
Actual Study Completion Date : April 26, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Nuclear Scans

Arms and Interventions
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Arm Intervention/treatment
Experimental: Flortaucipir PET Scan
Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers.
 Drug: flortaucipir F 18
No study drug will be administered.
Other Names:
  • 18F-AV-1451
  • [F-18]T807
  • LY3191748


Outcome Measures
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Primary Outcome Measures :
  1. Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score) [ Time Frame: baseline scan ]
    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.

  2. Primary Objective 1 Analysis 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis) [ Time Frame: baseline scan ]
    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.

  3. Primary Objective 2: Inter-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging [ Time Frame: baseline scan ]
    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 :
  1. Secondary Objective 1 Analysis 1: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect B3 NFTs [ Time Frame: baseline scan ]
    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.

  2. Secondary Objective 1 Analysis 2: Diagnostic Performance of τAD++ Flortaucipir PET Images to Detect High ADNC [ Time Frame: baseline scan ]
    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.

  3. Secondary Objective 2: Inter-reader Reliability of Reader Interpretation of τAD++ Flortaucipir PET Images [ Time Frame: baseline scan ]
    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%.

  4. Secondary Objective 3: Inter-reader Reliability of Flortaucipir PET Scan Interpretation in the Population of Intended Use [ Time Frame: baseline scan ]
    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%.

  5. Secondary Objective 4: Intra-reader Reliability of Reader Interpretation of Flortaucipir-PET Imaging [ Time Frame: baseline scan ]
    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%.


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03901092


Locations
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United States, Pennsylvania
American College of Radiology
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Avid Radiopharmaceuticals
Investigators
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Study Director: Study Director Avid Radiopharmaceuticals
  Study Documents (Full-Text)

Documents provided by Avid Radiopharmaceuticals:
Study Protocol  [PDF] March 21, 2019
Statistical Analysis Plan  [PDF] April 30, 2019

More Information
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Responsible Party: Avid Radiopharmaceuticals
ClinicalTrials.gov Identifier: NCT03901092    
Other Study ID Numbers: 18F-AV-1451-FR01
First Posted: April 3, 2019    Key Record Dates
Results First Posted: August 11, 2020
Last Update Posted: September 9, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Avid Radiopharmaceuticals:
flortaucipir F 18
Positron Emission Tomography
18F-AV-1451
Diagnostic imaging
Tau imaging
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders