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This study will investigate the performance of physician readers trained to read florbetapir-PET scans using electronic media training.
Avid has previously developed a florbetapir-PET scan binary read methodology and training program, which was successfully applied in studies 18F-AV-45-A08(NCT01565369), 18F-AV-45-A09(NCT01565382) and 18F-AV-45-A16(NCT01447719). In these previous studies, training was conducted in-person. Study 18F-AV-45-PT01 will evaluate an automated version of this training program suitable for web-based distribution. Nuclear medicine physicians will complete the automated training program then read the florbetapir-PET images from 151 subjects with repeat readings of 33 randomly selected images. Readers will rate each case as either positive for significant tracer accumulation in cortical gray matter or negative for significant tracer accumulation in cortical gray matter. The inter-rater reliability, sensitivity and specificity of the readers will be evaluated.
The primary image set for determination of inter-reader agreement is comprised of images from 119 subjects from two previous clinical studies (A07[NCT00857415]/A16[NCT01447719] and A05[NCT00702143]). This included all 59 subjects who came to autopsy in Study A07(NCT00857415) and it's follow-up study, A16(NCT01447719), and a set of 60 cases randomly selected from Study A05(NCT00702143) subjects, including 20 cognitively-normal controls, 20 with mild cognitive impairment) MCI, 20 with AD.
Subsequently, the protocol was amended to include all remaining A05(NCT00702143) MCI patients that were not used in the training program (n=32); 13 of these 32 scans presented for repeat reading (to increase the number of A05 MCI cases with repeated reads to 20). This increased the number of unique cases in the validation dataset to 151 scans with 33 scans repeated yielding a total of 184 scans reviewed by the readers.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| florbetapir F 18 | Drug | No study drug will be administered in this study - scans previously acquired in in Study A05(NCT00702143) and A07(NCT00857415) will be read |
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| Measure | Description | Time Frame |
|---|---|---|
| Inter-rater Reliability | Measure of agreement among five readers using a binary read method (amyloid positive/negative) calculated using Fleiss' kappa. All scans were read in a blinded fashion without access to clinical information. | Scan acquired 50-60 min post-injection |
| Measure | Description | Time Frame |
|---|---|---|
| Sensitivity of Florbetapir-PET to Detect Moderate to Frequent Beta-amyloid Neuritic Plaques (Probable/Definite Alzheimer's Disease) | Calculated as the percent of true positives which are correctly identified | at autopsy, within 2 years of scan |
| Specificity of Florbetapir-PET to Detect no or Sparse Beta-amyloid Neuritic Plaques (Probable/Definite Alzheimer's Disease) |
| Measure | Description | Time Frame |
|---|---|---|
| Median Sensitivity and Specificity vs. CERAD Diagnosis | Median sensitivity and specificity for 5 independent readers to detect moderate to frequent amyloid plaques (per CERAD criteria). | Baseline scan |
Eligibility for subjects scans to be used in this study is determined by subject's eligibility/enrollment in Study A05 (NCT00702143) or A07 (NCT00857415).
Alzheimer's disease (AD) group key eligibility criteria (from Study A05[NCT00702143]):
Mild cognitive impairment group key eligibility criteria (from Study A05[NCT00702143):
Cognitively normal volunteer group key eligibility criteria (from Study A05[NCT00702143]):
Autopsy cohort key eligibility criteria (from Study A07[NCT00857415]):
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| Name | Affiliation | Role |
|---|---|---|
| Chief Medical Officer | Avid Radiopharmaceuticals | Study Director |
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NO SUBJECTS WERE ENROLLED IN THIS STUDY - this study re-read scans obtained in other clinical studies
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| ID | Title | Description |
|---|---|---|
| FG000 | Florbetapir-PET Scans | All subject scans with a valid florbetapir-PET scan |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Florbetapir-PET Scans | All subjects with a valid florbetapir-PET scan (59 from study A07/A16 and 92 from study A05) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Inter-rater Reliability | Measure of agreement among five readers using a binary read method (amyloid positive/negative) calculated using Fleiss' kappa. All scans were read in a blinded fashion without access to clinical information. | 59 autopsy subjects (study A07[NCT00857415]/A16[NCT01447719]) + 20 healthy controls + 20 mild cognitive impairment + 20 AD (from study A05[NCT00702143]) | Posted | Number | 95% Confidence Interval | kappa statistic | Scan acquired 50-60 min post-injection |
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No subjects received florbetapir in this study. This study consisted of re-reads of scans previously acquired in other clinical studies (A05, A07, A16).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Florbetapir-PET Scans | All subject scans with a valid florbetapir-PET scan |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Avid Radiopharmaceuticals | 215-298-0700 | clinicaloperations@avidrp.com |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| D019636 | Neurodegenerative Diseases |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C545186 | florbetapir |
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Calculated as the percent of true negatives which are correctly identified |
| at autopsy, within 2 years of scan |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | Sensitivity of Florbetapir-PET to Detect Moderate to Frequent Beta-amyloid Neuritic Plaques (Probable/Definite Alzheimer's Disease) | Calculated as the percent of true positives which are correctly identified | Posted | Number | 95% Confidence Interval | percentage of positive cases IDed | at autopsy, within 2 years of scan |
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| Secondary | Specificity of Florbetapir-PET to Detect no or Sparse Beta-amyloid Neuritic Plaques (Probable/Definite Alzheimer's Disease) | Calculated as the percent of true negatives which are correctly identified | Posted | Number | 95% Confidence Interval | percentage of negative cases IDed | at autopsy, within 2 years of scan |
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| Post-Hoc | Inter-reader Reliability | Measure of agreement among multiple readers using binary read method (Fleiss' kappa). Where available, histopathology analysis at autopsy was the truth standard (TS). | 59 from study A07(NCT00857415)/A16(NCT01447719) and 92 from study A05(NCT00702143) | Posted | Number | 95% Confidence Interval | kappa statistic | Scan acquired 50-60 min post-injection |
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| Other Pre-specified | Median Sensitivity and Specificity vs. CERAD Diagnosis | Median sensitivity and specificity for 5 independent readers to detect moderate to frequent amyloid plaques (per CERAD criteria). | Posted | Median | Full Range | percentage of true positives/negatives | Baseline scan |
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| Post-Hoc | Individual Reader Results (All Scans With Autopsy) | Reader results (number of false negatives and number of false positives) for blinded independent readers. There were a total of 39 positive and 20 negative scans based on histopathology at autopsy. | Posted | Number | florbetapir scans | Baseline scan |
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| Post-Hoc | Individual Reader Results (Autopsy Within 1 Year of Scan) | Reader results (number of false negatives and number of false positives) for blinded independent readers. There were a total of 28 positive and 18 negative scans based on histopathology at autopsy. | Posted | Number | florbetapir scans | Baseline scan |
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| D024801 |
| Tauopathies |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
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| Reader 5 |
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| Reader 5 |
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| Title | Measurements |
|---|---|
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| AD [n=49] (29 with TS; 20 no TS) |
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| MCI [n=57] (5 with TS; 52 no TS) |
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| Cognitively normal without TS [n=20] |
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| Cognitively normal with TS [n=12] |
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| Other (non-AD) dementia with TS [n=13] |
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| Reader 2 - False Positives |
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| Reader 3 - False Negatives |
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| Reader 3 - False Positives |
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| Reader 4 - False Negatives |
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| Reader 4 - False Positives |
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| Reader 5 - False Positives |
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| Reader 2 - False Positives |
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| Reader 3 - False Negatives |
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| Reader 3 - False Positives |
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| Reader 4 - False Negatives |
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| Reader 4 - False Positives |
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| Reader 5 - False Negatives |
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| Reader 5 - False Positives |
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