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

• Sponsor: Avid Radiopharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03901092
• Collaborator: (none)
• Enrollment: 242
• Location: 1
• Arm: 1
• Actual Duration (Months): 1
• Patients Per Site Per Month: 237.6

Study Details

Study Description

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

• Study Type: Interventional
• 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.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: Mar 26, 2019
• Actual Primary Completion Date: Apr 26, 2019
• Actual Study Completion Date: Apr 26, 2019

Arms and Interventions

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

Primary Outcome Measures

1. Primary Objective 1 Analysis 1: Diagnostic Performance of Individual Readers (NFT Score) [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) [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 [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 [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 [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 [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 [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 [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

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	American College of Radiology	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• Avid Radiopharmaceuticals

Investigators

• Study Director: Study Director, Avid Radiopharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Mar 21, 2019
• Statistical Analysis Plan - Apr 30, 2019

More Information

Publications

None provided.

• Responsible Party: Avid Radiopharmaceuticals
• ClinicalTrials.gov Identifier: NCT03901092
• Other Study ID Numbers: 18F-AV-1451-FR01
• First Posted: Apr 3, 2019
• Last Update Posted: Sep 9, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Alzheimer Disease

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	All Autopsy Cases	Non-Autopsy Cases
Arm/Group Description	Cases that had a valid scan and came to autopsy in in study A16 and the A16 supplemental cohort	Mild cognitive impairment (MCI) and AD cases from the A05 confirmatory cohort
Period Title: Overall Study
STARTED	83	159
COMPLETED	83	159
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Cases
Arm/Group Description	All eligible subject scans from contributing studies
Overall Participants	242
Age (years) [Mean (Standard Deviation) ]
Study A16 Autopsy Cases	81.6 (9.91)
Study A05 Non-autopsy Cases	72.9 (9.64)
Sex: Female, Male (Count of Participants)
Female	41 16.9%
Male	42 17.4%
Female	74 30.6%
Male	85 35.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 1.7%
Not Hispanic or Latino	79 32.6%
Unknown or Not Reported	0 0%
Hispanic or Latino	9 3.7%
Not Hispanic or Latino	150 62%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 0.4%
White	81 33.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
American Indian or Alaska Native	0 0%
Asian	2 0.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 1.2%
White	154 63.6%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Sensitivity of Flortaucipir vs Autopsy NFT Score	Specificity of Flortaucipir vs Autopsy NFT Score
Arm/Group Description	Subjects with a positive autopsy NFT score truth standard (NFT B3)	Subjects with a negative autopsy NFT score truth standard (NFT B2 or lower)
Measure Participants	47	35
Reader 1	91.5	77.1
Reader 2	89.4	91.4
Reader 3	87.2	85.7
Reader 4	93.6	62.9
Reader 5	89.4	77.1

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Sensitivity of Flortaucipir vs NIA-AA Autopsy Diagnosis	Specificity of Flortaucipir vs NIA-AA Autopsy Diagnosis
Arm/Group Description	Subjects with a positive truth standard (High ADNC)	Subjects with a negative truth standard (No/Low/Intermediate ADNC)
Measure Participants	41	41
Reader 1	95.1	70.7
Reader 2	95.1	85.4
Reader 3	95.1	82.9
Reader 4	97.6	58.5
Reader 5	95.1	73.2

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis included all subjects who had a valid flortaucipir PET scan in the autopsy and non-autopsy groups (n=241)

Arm/Group Title	All Cases
Arm/Group Description	All autopsy and non-autopsy cases
Measure Participants	241
Reader 1 v Reader 2	95.0
Reader 1 v Reader 3	93.4
Reader 1 v Reader 4	94.6
Reader 1 v Reader 5	97.1
Reader 2 v Reader 3	97.1
Reader 2 v Reader 4	91.3
Reader 2 v Reader 5	94.6
Reader 3 v Reader 4	91.3
Reader 3 v Reader 5	93.8
Reader 4 v Reader 5	95.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sensitivity of Flortaucipir vs Autopsy NFT Score
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Fleiss' kappa
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.83 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Sensitivity of Flortaucipir tAD++ vs Autopsy NFT Score	Specificity of Flortaucipir tAD++ vs Autopsy NFT Score
Arm/Group Description	Subjects with a positive autopsy NFT score truth standard (NFT B3)	Subjects with a negative autopsy NFT score truth standard (NFT B2 or lower)
Measure Participants	47	35
Reader 1	87.2	88.6
Reader 2	80.9	100.0
Reader 3	76.6	94.3
Reader 4	89.4	82.9
Reader 5	83.0	94.3

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Sensitivity	Specificity
Arm/Group Description	Sensitivity individual Flortaucipir PET scan interpreted as τAD++ pattern versus NIA-AA autopsy Diagnosis Truth Standard	Specificity individual Flortaucipir PET scan interpreted as τAD++ pattern versus NIA-AA autopsy Diagnosis Truth Standard
Measure Participants	41	41
Reader 1	92.7	82.9
Reader 2	85.4	92.7
Reader 3	85.4	92.7
Reader 4	92.7	75.6
Reader 5	87.8	87.8

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis included all subjects who had a valid flortaucipir PET scan in the autopsy and non-autopsy groups (n=241)

Arm/Group Title	All Cases
Arm/Group Description	All autopsy and non-autopsy cases
Measure Participants	241
Reader 1 v Reader 2	92.5
Reader 1 v Reader 3	90.0
Reader 1 v Reader 4	91.3
Reader 1 v Reader 5	95.0
Reader 2 v Reader 3	91.7
Reader 2 v Reader 4	90.5
Reader 2 v Reader 5	94.2
Reader 3 v Reader 4	88.8
Reader 3 v Reader 5	92.5
Reader 4 v Reader 5	92.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sensitivity of Flortaucipir vs Autopsy NFT Score
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Fleiss' kappa
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.80 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Non-autopsy cases from Study A05

Arm/Group Title	A05 Cases
Arm/Group Description	All non-autopsy cases from the Study A05 population of intended use
Measure Participants	159
Reader 1 v Reader 2	97.5
Reader 1 v Reader 3	93.1
Reader 1 v Reader 4	95.6
Reader 1 v Reader 5	97.5
Reader 2 v Reader 3	93.1
Reader 2 v Reader 4	94.3
Reader 2 v Reader 5	96.2
Reader 3 v Reader 4	93.7
Reader 3 v Reader 5	93.1
Reader 4 v Reader 5	96.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sensitivity of Flortaucipir vs Autopsy NFT Score
	Comments	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.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Fleiss' kappa
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.85 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

20 scans read twice to assess the intra-reader reliability

Arm/Group Title	Randomly Selected Re-reads
Arm/Group Description	Cases randomly selected to be read twice by the same reader
Measure Participants	20
Reader 1	95.0
Reader 2	85.0
Reader 3	80.0
Reader 4	95.0
Reader 5	90.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sensitivity of Flortaucipir vs Autopsy NFT Score
	Comments	Cohen's kappa statistic for Reader 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's kappa
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sensitivity of Flortaucipir vs Autopsy NFT Score
	Comments	Cohen's kappa statistic for Reader 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's kappa
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.41 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sensitivity of Flortaucipir vs Autopsy NFT Score
	Comments	Cohen's kappa statistic for Reader 3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's kappa
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sensitivity of Flortaucipir vs Autopsy NFT Score
	Comments	Cohen's kappa statistic for Reader 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's kappa
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Sensitivity of Flortaucipir vs Autopsy NFT Score
	Comments	Cohen's kappa statistic for Reader 5
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cohen's kappa
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Not applicable. Adverse events were not assessed during this study.
Adverse Event Reporting Description	Adverse events were not assessed during this study.
Arm/Group Title	All Cases
Arm/Group Description	No study drug will be administered. Scans previously acquired from Study A16 (NCT02516046) and A05 (NCT02016560) will be read by independent, blinded readers.
All Cause Mortality
	All Cases
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	All Cases
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	All Cases
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.