This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Phase II Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid. (NCT00928304), a na phase 2 study. The primary outcome is Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00928304 |
| Phase | Phase 2 |
| Condition | Down Syndrome, Amyloid Beta-protein |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 109 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Lantheus Biosciences Ltd. |
| Results posted | Yes |
2. Clinical Question
Population
Individuals with Down syndrome and healthy volunteers without Down syndrome. The registry reports enrollment of 109. The primary analysis was described as including all subjects in the Down syndrome population and healthy volunteers.
Intervention
Florbetaben, also identified as BAY94-9172, administered for positron emission tomography imaging. The registry describes visual assessment of brain uptake in PET images obtained 100-120 min post-injection.
Comparator
The study was open-label, non-randomized, and listed as a single-group model. The two populations serve different diagnostic roles rather than forming randomized treatment arms: Down syndrome status is used as the reference for sensitivity, while healthy volunteers are used to assess specificity.
Primary question
How often did the majority visual reading identify cerebral β-amyloid in the Down syndrome group, and how often did it classify healthy volunteers as negative? The registry describes these measures as sensitivity and specificity, respectively.
The clinical question concerns the diagnostic classification of PET images, not a comparison of treatment effects. The study aimed to assess whether visual interpretation of florbetaben images could detect cerebral β-amyloid in individuals with Down syndrome and provide negative classifications in healthy volunteers without Down syndrome. The registry states that clinical diagnosis of Down syndrome served as the standard of truth, noting that β-amyloid pathology develops over the age of 40 in individuals with Down syndrome. The endpoint description specifies a majority reading by three independent blinded readers. Although the registry gives the intended measures and imaging window, it does not report the observed sensitivity, specificity, confidence interval limits, or the underlying numbers of positive and negative classifications. Those omissions mean that the diagnostic performance cannot be quantified from the registry record.
3. Trial Design
This was a Phase II, open-label, non-randomized study listed as a single-group model. Its official title describes an evaluation of BAY94-9172 PET for detecting cerebral β-amyloid in individuals with Down syndrome compared with individuals without Down syndrome. Florbetaben (BAY94-9172) is the listed intervention. The registry records enrollment of 109 and a completed status, with study start recorded as 2009-06 and primary completion as 2011-01.
The study’s diagnostic aim involved two populations and two related but distinct measures. Sensitivity was defined for the Down syndrome group as the percentage positive for cerebral β-amyloid. Specificity was defined for healthy volunteers as the percentage negative. These are not randomized treatment arms, and the registry explicitly cautions that the groups are not a like-for-like control comparison. Group membership therefore should not be interpreted as treatment allocation or as evidence of a causal contrast.
For the primary assessment, PET images obtained 100-120 min post-injection were read visually by three independent blinded readers. The endpoint description specifies use of their majority read. The trial-level masking field is listed as none; the registry does not explain how that designation relates to the endpoint’s description of blinded readers. The registry also does not report further details of image acquisition, reader training, adjudication procedures, or how disagreements were handled beyond the majority-read approach.
Secondary outcomes included sensitivity results in Down syndrome age subgroups, quantitative standard uptake value ratio parameters, and consistency between visual and quantitative efficacy. The registry lists four outcome measures but no analyses. It does not report the secondary outcome findings or give further detail about the fourth measure. Randomization, allocation concealment, a concurrent randomized control group, and a statistical analysis plan are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: A total of 130 subjects were screened. 21 subjects were considered as screen failures and were not enrolled into the study. 9 subjects did not meet the inclusion/exclusion criteria. 10 subjects withdrew their consent. 1 subject was lost to follow-up and 1 subjected exceeded the weight limit for the camera.
Overall Study
| Stage | Down Syndrome Group | Healthy Volunteer Group |
|---|---|---|
| STARTED | 39 | 70 |
| COMPLETED | 39 | 70 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All subjects in the down syndrome population and healthy volunteers were included in this analysis.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: All Down Syndrome subjects and healthy volunteers enrolled into the study were included in the Baseline Analysis Population
| Characteristic | Unit | Subjects Enrolled in Study |
|---|---|---|
| Participants analysed | 109 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 109 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous: Down Syndrome Group | years | 46.3 (SD 4.7) |
| Age, Continuous: Healthy Volunteer Group | years | 27.7 (SD 5.1) |
| Sex: Female, Male: Female | Participants | 60 |
| Sex: Female, Male: Male | Participants | 49 |
| Region of Enrollment: United States | participants | 109 |
6. Primary Endpoint
The registry lists the primary outcome as Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome, measured over 100-120 min.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of subjects |
| Endpoint classification | Binary Endpoint |
The primary endpoint comprised sensitivity and specificity, expressed as percentages of subjects. Sensitivity refers to the proportion of individuals in the Down syndrome population classified as positive for cerebral β-amyloid by the visual assessment. Specificity refers to the proportion of healthy volunteers classified as negative. The endpoint was based on the majority reading by three independent blinded readers of florbetaben PET images obtained 100-120 min post-injection. The registry states that clinical diagnosis of Down syndrome served as the standard of truth.
These measures address different aspects of diagnostic classification. Sensitivity describes positive classifications in the population designated for detection; specificity describes negative classifications in the population designated for exclusion. Neither measure alone captures every aspect of test performance, and interpretation depends on the populations and reference standard used. As a general statistical point, a confidence interval communicates uncertainty around an estimated proportion: narrower intervals indicate greater precision, while wider intervals indicate less precision. The endpoint specifies a 95% confidence interval, but its limits and the underlying results are not reported in the registry record.
The registry gives the endpoint’s definition and timeframe, but does not provide the observed sensitivity or specificity, the number of classifiable images, or the handling of indeterminate readings. Consequently, the endpoint can be described but its numerical performance and precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a diagnostic imaging study designed to estimate sensitivity in individuals with Down syndrome and specificity in healthy volunteers. Its primary endpoint is clearly named, and the record specifies that the assessment used a majority visual reading by three independent blinded readers of PET images obtained 100-120 min post-injection. However, it does not report the actual sensitivity or specificity estimates, their 95% confidence intervals, or the counts underlying those estimates. The main diagnostic findings therefore cannot be interpreted quantitatively from the registry record.
Enrollment is recorded as 109. The safety entries list 39 participants at risk in the Down Syndrome Group and 70 in the Healthy Volunteer Group. These are denominators in the safety records and should not be assumed to be the exact analysis denominators for the primary endpoint. The primary analysis population is described broadly as all subjects in the Down syndrome population and healthy volunteers, but the registry does not state how many contributed usable images or were included in each endpoint calculation.
The two populations have different roles in the endpoint and were not randomized treatment arms. Sensitivity in the Down syndrome population and specificity in healthy volunteers are distinct quantities. They should not be treated as a direct, like-for-like comparison of groups or as evidence that one group’s outcome was caused by a treatment difference. The study was open-label and non-randomized; the reader-level description of blinding is a separate feature of image assessment, not evidence that the overall study was masked.
The endpoint specifies confidence intervals, but no interval limits are posted. Without estimates and intervals, neither the magnitude of observed diagnostic performance nor its precision can be judged. The registry also lists no analyses, although it names secondary outcomes involving age subgroups, quantitative uptake ratios, and consistency between visual and quantitative assessment. The findings for these outcomes are not reported in the registry record.
The completed status indicates that the registry marks the study as completed; it does not substitute for posted results. The record does not report a statistical analysis plan, missing-data procedures, reader-level results, or details of the reference-standard classification beyond its description of clinical diagnosis of Down syndrome as the standard of truth. Accordingly, conclusions should stay limited to the stated objective, design, and available safety counts rather than infer diagnostic accuracy or clinical utility.
9. Statistical Methods Explained
Sensitivity and specificity. In general, sensitivity is the proportion of people with the condition of interest who are classified as positive by a test. Specificity is the proportion without the condition who are classified as negative. The study defined sensitivity in the Down syndrome population and specificity in healthy volunteers. These measures answer complementary questions, so one cannot be substituted for the other. Their values depend on the populations studied and on the reference standard used to decide the condition status. The registry states that clinical diagnosis of Down syndrome served as the standard of truth, but does not give further details about how cerebral β-amyloid status was established for individual participants.
Visual reading and majority classification. The primary assessment used a majority reading by three independent blinded readers. In general, a majority rule converts multiple reader judgments into one classification by using the judgment shared by most readers. This may reduce reliance on a single reader, but does not by itself describe the degree of agreement or show how accurate each reader was. The registry does not report individual reader results, agreement statistics, an adjudication process, or the handling of ties or indeterminate readings. It describes the readers as blinded while the overall masking field is listed as none; the record does not clarify this distinction.
Confidence intervals. A confidence interval expresses the uncertainty associated with an estimate. For a percentage such as sensitivity or specificity, the interval helps readers assess how precisely the estimate is supported by the observations. In general, precision depends on the amount and distribution of relevant information, not just on the point estimate. The primary endpoint specifies a 95% confidence interval, but its limits and calculation method are not reported in the registry record. It is therefore not possible to assess the precision of either diagnostic measure from the record.
Reference standard and interpretation. Diagnostic accuracy is assessed by comparing a test classification with a reference standard. Here, the registry identifies clinical diagnosis of Down syndrome as the standard of truth and assigns sensitivity and specificity to different populations. Those definitions should be read as the study’s stated approach, not as evidence that the groups were randomized or that their results estimate a treatment effect. The registry does not explain whether another reference assessment was used for cerebral β-amyloid or how discrepancies between image readings and reference classifications were resolved.
Quantitative measures and secondary outcomes. The registry names quantitative standard uptake value ratio parameters and consistency between visual and quantitative efficacy among the secondary outcomes. In general, a quantitative imaging measure expresses image uptake numerically, while consistency analysis examines how two assessment approaches relate. The record does not provide the quantitative values, analysis methods, or findings. It also names sensitivity results in Down syndrome age subgroups without reporting subgroup definitions or estimates. No interpretation of these secondary outcomes can be made from the registry record.
Planning illustrations. The record describes sample-size planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a specified fraction of the observed effect and that the figures are planning illustrations, not the trial’s own design. Such illustrations are prospective planning calculations, not observed power and not evidence that a study had a particular probability of detecting an effect. Because this study is described as non-randomized and not a like-for-like arm comparison, the stated equal-allocation framework should not be mistaken for the study design. The numerical planning results and effect fractions are not reported in the registry record.
Over-dispersion. In general, over-dispersion occurs when observed variability is greater than assumed by a statistical model. If a model does not allow for that extra variability, uncertainty may be understated and intervals or tests may be misleading. The registry does not report whether over-dispersion was relevant to any analysis or how it was assessed. No conclusion about its presence or handling can be drawn from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists secondary outcomes for sensitivity in Down syndrome age subgroups, quantitative standard uptake value ratio parameters, and consistency between visual and quantitative efficacy. It also lists four outcome measures, but reports no analyses. The record does not describe a multiplicity adjustment, a hierarchy of hypotheses, or which outcomes were designated for confirmatory interpretation. It is therefore not reported in the registry record whether or how the risk of chance findings across multiple analyses was addressed.
The primary analysis population is described as all subjects in the Down syndrome population and healthy volunteers. The record does not give endpoint-specific denominators or explain whether all enrolled participants had usable PET images, completed the visual assessment, or contributed to both sensitivity and specificity calculations. Missing-data rules, exclusions, withdrawals, and handling of indeterminate or unreadable images are not reported in the registry record. The safety denominators should not be assumed to equal the endpoint analysis denominators.
The registry does not report an analysis plan, the statistical methods used to calculate the primary confidence intervals, or whether any analyses were adjusted for participant characteristics. The recorded endpoint timeframe is 100-120 min post-injection, but the record does not describe deviations from that window or their treatment in analysis. As a result, it is not possible to determine from the registry record how missing observations, multiple outcomes, or analysis-population decisions may have affected the reported findings. The primary sensitivity and specificity results themselves are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Down Syndrome Group | 0 | 39 | 0.0% |
| Healthy Volunteer Group | 0 | 70 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Down Syndrome Group | 2 of 39 |
| Healthy Volunteer Group | 5 of 70 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Down Syndrome Group | Healthy Volunteer Group |
|---|---|---|---|
| Headache | Nervous system disorders | 0 of 39 | 5 of 70 |
| Injection site hematoma | General disorders | 2 of 39 | 1 of 70 |
The safety entries are presented separately for the Down Syndrome Group and the Healthy Volunteer Group. In the Down Syndrome Group, the registry lists 39 at risk for serious adverse events and 0 with a serious adverse event; it lists 39 at risk for other adverse events and 2 affected. In the Healthy Volunteer Group, it lists 70 at risk for serious adverse events and 0 with a serious adverse event; it lists 70 at risk for other adverse events and 5 affected.
These are counts and denominators recorded for the safety outcomes, not estimates of diagnostic performance. The registry does not provide event descriptions for the other adverse events in these entries, and the top serious terms list is empty. Deaths are not reported in the registry record. The record does not give further detail about event definitions, severity grading, timing, relatedness to florbetaben, or how participants were monitored.
Zero recorded serious adverse events in these entries should be read narrowly as the posted count for the listed groups. It does not establish that no serious events could occur, and it does not provide a comparative risk estimate. The study was non-randomized, and the population groups were not like-for-like control arms. The safety counts therefore do not support a causal comparison between the groups.
12. What the Result Does, and Does Not, Mean
The record establishes that the study was designed to evaluate visual assessment of florbetaben PET images for detecting cerebral β-amyloid in individuals with Down syndrome and classifying healthy volunteers as negative. It specifies the primary measures, the reader approach, and the imaging window. These details describe what the investigators intended to assess; they do not supply the observed diagnostic results.
Because the registry does not report sensitivity, specificity, confidence interval limits, or the numbers of positive and negative classifications, it is not possible to say how often the image assessment produced either classification or how precisely those percentages were estimated. The endpoint description alone cannot establish diagnostic accuracy. Nor can the named secondary outcomes be interpreted, because their results are not reported in the registry record.
The study’s two populations serve different roles, and the registry identifies the trial as open-label, non-randomized, and single-group. They should not be treated as randomized intervention and control groups. The design does not support a causal treatment comparison based on the group labels. Although the endpoint description refers to blinded independent readers, the registry’s overall masking field is none, and the relationship between those statements is not explained.
The safety entries report no serious adverse events in either listed group and report other adverse events in both. These counts describe the posted safety record; they do not establish the absence of risk or permit a causal comparison. The record does not report event details or deaths.
Overall, the registry supports a description of the diagnostic objective and study procedures, but not a conclusion about the magnitude, precision, or clinical implications of diagnostic performance. The completed status does not fill the gap left by the unreported outcome results. Any interpretation beyond the design and posted counts would go beyond what the registry record reports.
13. Why This Trial Matters Statistically
This study is statistically notable for framing a PET imaging question in terms of diagnostic classification rather than treatment efficacy. Sensitivity and specificity are distinct measures, and the record assigns them to different populations: individuals with Down syndrome for detection and healthy volunteers for exclusion. That separation matters because the results would answer different questions and should not be collapsed into one overall performance claim.
The majority reading by three independent blinded readers also highlights the role of measurement procedures in diagnostic studies. A test result depends not only on image acquisition but also on how images are interpreted and how reader judgments are combined. The registry specifies a majority assessment and an imaging window of 100-120 min post-injection, while leaving reader agreement and adjudication details unreported. Those omissions limit assessment of reproducibility from the record.
The study also illustrates why a completed registry record and a defined endpoint are not sufficient for evaluating a result. Without the estimates, confidence intervals, and analysis denominators, readers cannot assess either the size or precision of diagnostic performance. The named secondary outcomes likewise cannot be evaluated without their findings and methods.
Finally, the non-randomized design and the different roles of the populations matter for interpretation. A comparison between these groups is not a randomized treatment contrast. Clear distinction between diagnostic accuracy, reader reliability, and causal treatment effects helps prevent claims that the design and available record cannot support.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record leaves the primary diagnostic results unreported. It provides no sensitivity or specificity estimates, 95% confidence interval limits, or numbers of positive and negative classifications. The endpoint analysis denominators are also not reported, so the safety-group denominators cannot be assumed to represent the endpoint populations.
The study is listed as open-label, non-randomized, and single-group, and the registry cautions that the groups are not a like-for-like control comparison. The two populations have different roles in the sensitivity and specificity measures. This design does not provide a randomized comparison of treatment effects. The record does not explain how the overall masking designation relates to the description of independent blinded readers.
Important methods details are not reported in the registry record, including the statistical analysis plan, confidence interval calculation method, missing-data rules, treatment of unreadable or indeterminate images, and procedures for resolving reader disagreement. The reference-standard description is limited to the statement that clinical diagnosis of Down syndrome served as the standard of truth. The record does not clarify the reference assessment for individual amyloid classifications.
Although the registry names secondary outcomes, it does not report their results or analysis methods. It also does not provide further safety-event descriptions, relatedness, or deaths. These gaps prevent a full assessment of diagnostic performance, precision, reproducibility, missingness, and safety from the registry record alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase II Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid. — NCT00928304.
- Registry record last updated 2014-03-05; status last verified 2014-01.
- Results first posted 2014-01-28.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00928304 is a completed Phase II, open-label, non-randomized study of florbetaben (BAY94-9172) PET imaging. The registry records enrollment of 109, a study start of 2009-06, and primary completion of 2011-01. The study aimed to assess visual detection of cerebral β-amyloid in individuals with Down syndrome and negative classification in healthy volunteers without Down syndrome.
The primary endpoint was sensitivity and specificity based on the majority visual reading by three independent blinded readers of PET images obtained 100-120 min post-injection. The registry specifies a 95% confidence interval but does not report the primary estimates, interval limits, or endpoint denominators. It lists secondary outcomes involving age subgroups, quantitative uptake ratios, and consistency between visual and quantitative assessments, but no analyses are reported.
Safety records list 0 serious adverse events in each group, with 2 other adverse events in the Down Syndrome Group and 5 in the Healthy Volunteer Group. Deaths are not reported in the registry record.