Cognitive Impairment
Conditions
Keywords
Vizamyl, flutemetamol, Alzheimer's disease, cognitive impairment, dementia
Brief summary
This is a study to determine the effectiveness of the VIZAMYL™ reader training programme in clinical practice in Europe
Detailed description
This study is a combination of Prospective and Retrospective models.
Interventions
None listed
Sponsors
ICON plc
GE Healthcare
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The subject is an adult (aged 18 years or older) of any race or gender and has been referred for a VIZAMYL™ PET brain scan as part of the assessment of his/her cognitive impairment. * The VIZAMYL™ scan was ordered as part of the clinical care of the subject and is not exclusively for a clinical trial. * If informed consent is required by the local IEC, the subject, or his/her legally authorised representative, is willing and able to sign consent for use of their de-identified VIZAMYL™ PET images and associated anatomic images (brain CT and/or MRI) used in the interpretation of the VIZAMYL™ images as well as de-identified demographic information.
Exclusion criteria
* If informed consent is required by the local IEC, the subject (or representative) is not willing to consent to their de-identified images and other data being used in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | Up to 1093 days | Accuracy was estimated as 100 percent (%) \*(number of true positives \[TP\] + number of true negatives \[TN\]) / (number of TP + number of TN + number of false positives \[FP\] + number of false negatives \[FN\]). The data presented are the point estimates representing percentage of accuracy, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method. |
| Sensitivity of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | Up to 1093 days | Sensitivity was defined as 100%\*number of TP / (number of TP + number of FN). The data presented are the point estimates representing percentage sensitivity, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method. |
| Specificity of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | Up to 1093 days | Specificity was defined as 100%\*number of TN / (number of TN + number of FP). The data presented are the point estimates representing the percentage specificity, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method. |
| Positive Predictive Value (PPV) of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | Up to 1093 days | The PPV was defined as 100%\*number of TP / (number of TP + number of FP). The data presented are the point estimates representing percentage PPV, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method. |
| Negative Predictive Value (NPV) of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | Up to 1093 days | The NPV was defined as 100%\*number of TN/ (number of TN + number of FN). The data presented are the point estimates representing percentage NPV, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Coefficient Between Clinical Reader Age and Accuracy | Up to 1093 days | Correlation coefficient was used to assess the correlation between clinical reader age and accuracy. A scatterplot of clinical reader accuracy vs. reader age was plotted to check correlation (coefficient) between accuracy and age. |
| Time From Last Training | Retrospective data covering up to 8.1 years | Time from last training was reported. Number of readers remaining at timepoint was number of readers with accuracy greater than or equal to 0.9333. All readers met this criterion at time 0 hence, data for all clinical reader is reported. All 18 readers were trained in interpretation of Vizamyl images & as part of their training, had their interpretation accuracy tested using 15 test images. To pass test, a reader had to interpret atleast 14 of 15 images correctly. 14 represents 0.9333 of 15, so each reader had to have an accuracy of atleast 0.9333 in order to pass test. Date on which a reader took his/her test is considered to be Time 0. Each reader's accuracy at a later time was assessed in study. |
| Number of Participants With Accuracy Less Than (<) 0.9333 or Greater Than Equal to (>=) 0.9333 in Terms of Sex of Clinical Readers | Up to 1093 days | Number of participants with accuracy \< 0.9333 or \>= 0.9333 in terms of sex of clinical readers were reported. |
| Number of Participants With Association of Electronic Training (With or Without In-Person Training) With Clinical Reader Accuracy | Up to 1093 days | Number of participants with association of electronic training (with or without In-person training) with clinical reader accuracy were reported. |
| Number of Participants With Association of In-Person Training (With or Without Electronic Training) With Clinical Reader Accuracy | Up to 1093 days | Number of participants with association of In-person training (with or without electronic training) with clinical reader accuracy were reported. |
| Number of Participants With Association of Training Type With Clinical Reader Accuracy (Excluding Readers Who Took Both Types) | Up to 1093 days | Number of participants with association of training type with clinical reader accuracy (excluding readers who took both types) were reported. |
Countries
Austria, Finland, Italy, Netherlands, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VIZAMYL™ Participants who received a single VIZAMYL™ injection intravenously prior to PET brain imaging, as per the clinical practice. | 209 |
| All Clinical Readers Clinical readers had been trained to interpret VIZAMYL™ images using an in-person training programme. They read the Vizamyl images. | 18 |
| Total | 227 |
Baseline characteristics
| Characteristic | VIZAMYL™ | All Clinical Readers | Total |
|---|---|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 8.81 | 51.3 years STANDARD_DEVIATION 98.4 | NA years |
| Race/Ethnicity, Customized Missing | 30 Participants | 2 Participants | 32 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 176 Participants | 15 Participants | 191 Participants |
| Sex: Female, Male Female | 101 Participants | 7 Participants | 108 Participants |
| Sex: Female, Male Male | 108 Participants | 11 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 209 |
| other Total, other adverse events | 0 / 209 |
| serious Total, serious adverse events | 0 / 209 |
Outcome results
Primary
Accuracy of VIZAMYL™ PET Image Interpretations Made by Clinical Readers
Accuracy was estimated as 100 percent (%) \*(number of true positives \[TP\] + number of true negatives \[TN\]) / (number of TP + number of TN + number of false positives \[FP\] + number of false negatives \[FN\]). The data presented are the point estimates representing percentage of accuracy, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method.
Time frame: Up to 1093 days
Population: The efficacy population included participants who had an interpretable image that had an available standard of truth (SOT) classification (expert majority image interpretation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIZAMYL™ | Accuracy of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | 83.25 Percentage of image interpretations |
Primary
Negative Predictive Value (NPV) of VIZAMYL™ PET Image Interpretations Made by Clinical Readers
The NPV was defined as 100%\*number of TN/ (number of TN + number of FN). The data presented are the point estimates representing percentage NPV, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method.
Time frame: Up to 1093 days
Population: The efficacy population included participants who had an interpretable image that had an available SOT classification (expert majority image interpretation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIZAMYL™ | Negative Predictive Value (NPV) of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | 88.16 Percentage of image interpretations |
Primary
Positive Predictive Value (PPV) of VIZAMYL™ PET Image Interpretations Made by Clinical Readers
The PPV was defined as 100%\*number of TP / (number of TP + number of FP). The data presented are the point estimates representing percentage PPV, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method.
Time frame: Up to 1093 days
Population: The efficacy population included participants who had an interpretable image that had an available SOT classification (expert majority image interpretation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIZAMYL™ | Positive Predictive Value (PPV) of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | 80.45 Percentage of image interpretations |
Primary
Sensitivity of VIZAMYL™ PET Image Interpretations Made by Clinical Readers
Sensitivity was defined as 100%\*number of TP / (number of TP + number of FN). The data presented are the point estimates representing percentage sensitivity, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method.
Time frame: Up to 1093 days
Population: The efficacy population included participants who had an interpretable image that had an available SOT classification (expert majority image interpretation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIZAMYL™ | Sensitivity of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | 92.24 Percentage of image interpretations |
Primary
Specificity of VIZAMYL™ PET Image Interpretations Made by Clinical Readers
Specificity was defined as 100%\*number of TN / (number of TN + number of FP). The data presented are the point estimates representing the percentage specificity, with Measure Type Number and 95% exact binomial confidence interval. These have been estimated using Clopper-Pearson method.
Time frame: Up to 1093 days
Population: The efficacy population included participants who had an interpretable image that had an available SOT classification (expert majority image interpretation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIZAMYL™ | Specificity of VIZAMYL™ PET Image Interpretations Made by Clinical Readers | 72.04 Percentage of image interpretations |
Secondary
Correlation Coefficient Between Clinical Reader Age and Accuracy
Correlation coefficient was used to assess the correlation between clinical reader age and accuracy. A scatterplot of clinical reader accuracy vs. reader age was plotted to check correlation (coefficient) between accuracy and age.
Time frame: Up to 1093 days
Population: The efficacy clinical reader population consisted of 18 clinical readers who had interpreted the images included from his/her institution and had at least one of their image interpretations classified as TP, TN, FP, or FN through comparison with the SOT (the expert blinded reader majority interpretation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIZAMYL™ | Correlation Coefficient Between Clinical Reader Age and Accuracy | -0.2415 Correlation coefficient |
Secondary
Number of Participants With Accuracy Less Than (<) 0.9333 or Greater Than Equal to (>=) 0.9333 in Terms of Sex of Clinical Readers
Number of participants with accuracy \< 0.9333 or \>= 0.9333 in terms of sex of clinical readers were reported.
Time frame: Up to 1093 days
Population: The efficacy clinical reader population consisted of 18 clinical readers who had interpreted the images included from his/her institution and had at least one of their image interpretations classified as TP, TN, FP, or FN through comparison with the SOT (the expert blinded reader majority interpretation).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIZAMYL™ | Number of Participants With Accuracy Less Than (<) 0.9333 or Greater Than Equal to (>=) 0.9333 in Terms of Sex of Clinical Readers | Accuracy < 0.9333: Male | 6 Participants |
| VIZAMYL™ | Number of Participants With Accuracy Less Than (<) 0.9333 or Greater Than Equal to (>=) 0.9333 in Terms of Sex of Clinical Readers | Accuracy < 0.9333: Female | 5 Participants |
| VIZAMYL™ | Number of Participants With Accuracy Less Than (<) 0.9333 or Greater Than Equal to (>=) 0.9333 in Terms of Sex of Clinical Readers | Accuracy >= 0.9333: Male | 5 Participants |
| VIZAMYL™ | Number of Participants With Accuracy Less Than (<) 0.9333 or Greater Than Equal to (>=) 0.9333 in Terms of Sex of Clinical Readers | Accuracy >= 0.9333: Female | 2 Participants |
p-value: 0.6371Fisher Exact
Secondary
Number of Participants With Association of Electronic Training (With or Without In-Person Training) With Clinical Reader Accuracy
Number of participants with association of electronic training (with or without In-person training) with clinical reader accuracy were reported.
Time frame: Up to 1093 days
Population: The efficacy clinical reader population consisted of 18 clinical readers who had interpreted the images included from his/her institution and had at least one of their image interpretations classified as TP, TN, FP, or FN through comparison with the SOT (the expert blinded reader majority interpretation). Here, 'number analyzed' included all clinical readers who were trained or not trained type with clinical reader accuracy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIZAMYL™ | Number of Participants With Association of Electronic Training (With or Without In-Person Training) With Clinical Reader Accuracy | Accuracy >= 0.9333: Trained electronically | 2 Participants |
| VIZAMYL™ | Number of Participants With Association of Electronic Training (With or Without In-Person Training) With Clinical Reader Accuracy | Accuracy >= 0.9333: Not Trained electronically | 5 Participants |
| VIZAMYL™ | Number of Participants With Association of Electronic Training (With or Without In-Person Training) With Clinical Reader Accuracy | Accuracy < 0.9333: Trained electronically | 8 Participants |
| VIZAMYL™ | Number of Participants With Association of Electronic Training (With or Without In-Person Training) With Clinical Reader Accuracy | Accuracy < 0.9333: Not Trained electronically | 3 Participants |
p-value: 0.1448Fisher Exact
Secondary
Number of Participants With Association of In-Person Training (With or Without Electronic Training) With Clinical Reader Accuracy
Number of participants with association of In-person training (with or without electronic training) with clinical reader accuracy were reported.
Time frame: Up to 1093 days
Population: The efficacy clinical reader population consisted of 18 clinical readers who had interpreted the images included from his/her institution and had at least one of their image interpretations classified as TP, TN, FP, or FN through comparison with the SOT (the expert blinded reader majority interpretation). Here, 'Number analyzed' included all clinical readers who were trained or not trained type with clinical reader accuracy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIZAMYL™ | Number of Participants With Association of In-Person Training (With or Without Electronic Training) With Clinical Reader Accuracy | Accuracy >= 0.9333: Trained in person | 6 Participants |
| VIZAMYL™ | Number of Participants With Association of In-Person Training (With or Without Electronic Training) With Clinical Reader Accuracy | Accuracy >= 0.9333: Not trained in person | 1 Participants |
| VIZAMYL™ | Number of Participants With Association of In-Person Training (With or Without Electronic Training) With Clinical Reader Accuracy | Accuracy < 0.9333: Trained in person | 5 Participants |
| VIZAMYL™ | Number of Participants With Association of In-Person Training (With or Without Electronic Training) With Clinical Reader Accuracy | Accuracy < 0.9333: Not trained in person | 6 Participants |
p-value: 0.1507Fisher Exact
Secondary
Number of Participants With Association of Training Type With Clinical Reader Accuracy (Excluding Readers Who Took Both Types)
Number of participants with association of training type with clinical reader accuracy (excluding readers who took both types) were reported.
Time frame: Up to 1093 days
Population: Efficacy clinical reader population. Here 'Overall number of participants analyzed' included all clinical readers who were trained type with clinical reader accuracy and 'number analyzed' signifies who were trained with clinical reader accuracy at specific category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIZAMYL™ | Number of Participants With Association of Training Type With Clinical Reader Accuracy (Excluding Readers Who Took Both Types) | Accuracy >= 0.9333: Trained electronically only | 1 Participants |
| VIZAMYL™ | Number of Participants With Association of Training Type With Clinical Reader Accuracy (Excluding Readers Who Took Both Types) | Accuracy >= 0.9333: Trained in person only | 5 Participants |
| VIZAMYL™ | Number of Participants With Association of Training Type With Clinical Reader Accuracy (Excluding Readers Who Took Both Types) | Accuracy < 0.9333: Trained electronically only | 6 Participants |
| VIZAMYL™ | Number of Participants With Association of Training Type With Clinical Reader Accuracy (Excluding Readers Who Took Both Types) | Accuracy < 0.9333: Trained in person only | 3 Participants |
p-value: 0.1189Fisher Exact
Secondary
Time From Last Training
Time from last training was reported. Number of readers remaining at timepoint was number of readers with accuracy greater than or equal to 0.9333. All readers met this criterion at time 0 hence, data for all clinical reader is reported. All 18 readers were trained in interpretation of Vizamyl images & as part of their training, had their interpretation accuracy tested using 15 test images. To pass test, a reader had to interpret atleast 14 of 15 images correctly. 14 represents 0.9333 of 15, so each reader had to have an accuracy of atleast 0.9333 in order to pass test. Date on which a reader took his/her test is considered to be Time 0. Each reader's accuracy at a later time was assessed in study.
Time frame: Retrospective data covering up to 8.1 years
Population: The efficacy clinical reader population consisted of 18 clinical readers who had interpreted the images included from his/her institution and had at least one of their image interpretations classified as TP, TN, FP, or FN through comparison with the SOT (the expert blinded reader majority interpretation).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VIZAMYL™ | Time From Last Training | 3.45 Years |