Evaluation of Web-based Training to Educate Physicians in the Methods of Interpreting Florbetapir-PET Scans

This study will investigate the performance of physician readers trained to read florbetapir-PET scans using electronic media training.

Study Overview

• Status: Completed
• Conditions: Neurodegenerative Diseases; Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Drug: florbetapir F 18

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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]):

• Male or female at least 50 years of age
• Have probable AD per National Institute of Neurological and Communication Disorders and Stroke (NINCDS) criteria
• Mini mental state exam (MMSE) score between 10 and 24 inclusive

Mild cognitive impairment group key eligibility criteria (from Study A05[NCT00702143):

• Male or female at least 50 years of age
• Complaints of memory or cognitive decline corroborated by an informant
• Clinical dementia rating of 0.5
• No obvious cause for cognitive impairment (eg, head trauma or stroke)
• Cognitive impairment onset within the past year
• MMSE score greater than 24

Cognitively normal volunteer group key eligibility criteria (from Study A05[NCT00702143]):

• Male or female at least 50 years of age
• MMSE score greater than or equal to 29 and cognitively normal by informant report and psychometric test battery at screening

Autopsy cohort key eligibility criteria (from Study A07[NCT00857415]):

• Male or female 18 years or older
• Projected life expectancy of less than 6 months
• Consent to brain donation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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)	Calculated as the percent of true negatives which are correctly identified	at autopsy, within 2 years of scan

Other Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Avid Radiopharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: March 6, 2012
• First Submitted That Met QC Criteria: March 7, 2012
• First Posted (Estimate): March 12, 2012

Study Record Updates

• Last Update Posted (Estimate): June 7, 2012
• Last Update Submitted That Met QC Criteria: May 3, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Diagnostic imaging; Positron Emission Tomography; Amyloid imaging; 18F-AV-45; florbetapir F 18
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Neurodegenerative Diseases
• Other Study ID Numbers: 18F-AV-45-PT01