The Feasibility of Florbetapir Quantitation in Europe: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Feasibility of Florbetapir Quantitation in Europe (NCT02107599), a na phase 4 study. The primary outcome is Change in Reader Accuracy After Application of Quantitation Software.

2. Clinical Question

3. Trial Design

This is a completed Phase 4 study titled “The Feasibility of Florbetapir Quantitation in Europe.” The registry lists an enrollment of 96, a start date of 2014-03, and a primary completion date of 2014-05. Avid Radiopharmaceuticals is listed as the sponsor, and Alzheimer's Disease is listed as a condition.

The study is described as single group, with allocation listed as NA and masking listed as single. The reader process is sequential: physician readers interpret Amyvid scans using qualitative analysis, followed by use of quantitation. The stated purpose is to assess whether adding quantitative analysis software improves interpretation accuracy. This is not a comparison of parallel randomized arms, and the registry record does not describe an independent control group.

The primary outcome is change in reader accuracy after application of quantitation software, expressed as a net reclassification index. Its timeframe is described as scans acquired 50-60 minutes post injection. The primary outcome description specifies that only the 46 scans with autopsy from A16 are used for this measure. A secondary outcome concerns change in scan interpretation reliability after application of the software. The record lists two outcome measures and four analyses, but does not report their detailed analysis methods or numerical results.

The intervention list names Florbetapir (18F), while the arm description explicitly states that no subjects will be exposed to it as part of the study. The intervention under evaluation is the use of quantitation software in reading scans, not administration of the drug to study subjects.

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.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in Reader Accuracy After Application of Quantitation Software, measured over Scan acquired 50-60 minutes post injection.

The primary endpoint is the change in reader accuracy after application of quantitation software, measured with the net reclassification index (NRI). The index summarizes whether classifications move in directions that are correct when the added information is used. In this record, “up” means a scan changes from negative to positive, and “down” means it changes from positive to negative. Events are true positive cases, while nonevents are true negative cases.

The NRI combines movement among events with movement among nonevents. For events, upward reclassification contributes positively and downward reclassification negatively. For nonevents, the direction is reversed: downward reclassification contributes positively, while upward reclassification contributes negatively. Thus, the measure reflects whether changes in classification align with the true positive and true negative status used for evaluation. The registry defines values greater than zero as indicating improved scan interpretation accuracy and values less than zero as indicating a decline.

This endpoint is used because the study asks whether adding a marker—in this case, quantitative analysis—changes reader classifications in a useful direction. It is not a direct measure of clinical outcomes. The endpoint description limits the analysis to 46 scans with autopsy from A16. Although the registry defines the measure and its interpretation, it does not report the numerical NRI, its uncertainty, or the underlying reclassification counts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a net reclassification index, a measure of how predicted classifications move after adding information. In this study, the information being added is quantitative scan analysis used alongside visual interpretation. The registry defines upward movement as a change from negative to positive and downward movement as a change from positive to negative. It defines events as true positive cases and nonevents as true negative cases.

How the NRI summarizes movement

For true positive cases, moving from a negative to a positive classification counts in the favorable direction, while moving from positive to negative counts in the unfavorable direction. For true negative cases, retaining or moving toward a negative classification is favorable, while movement from negative to positive is unfavorable. The NRI combines the difference in favorable and unfavorable movements for events with the corresponding difference for nonevents. This construction is intended to assess whether classifications change in directions consistent with the reference status.

As a general statistical point, a reclassification measure focuses on changes in categories or predicted classifications, rather than simply comparing average values between reading approaches. Its interpretation depends on how classifications are defined and on the reference status used to judge whether movements are correct. The registry explains the direction of movement and identifies the autopsy scans used, but does not report the classification thresholds, counts of movements, or the resulting NRI value. Those details are important for understanding how the estimate was formed and what patterns of reclassification contributed to it.

What a positive or negative value means

The registry states that an NRI greater than zero indicates improved scan interpretation accuracy and an NRI less than zero indicates a decline after applying quantitation software. This describes the direction of the index under the stated definition. It does not by itself describe the precision of the estimate or establish how much evidence supports a particular direction. An estimate can be considered together with an uncertainty interval to assess the range of values consistent with the data, but no such interval is reported in the registry record.

More generally, confidence intervals help distinguish a precise estimate from one that remains uncertain. They do not guarantee that the analysis is unbiased, and their interpretation depends on the statistical method and assumptions used. The registry record does not report an interval for the NRI, a standard error, or the method used to estimate uncertainty. It is therefore not possible to evaluate the primary estimate’s precision from the posted results.

Sequential reader assessment

The reader procedure is qualitative interpretation followed by use of quantitation. Statistically, this creates a before-and-after comparison of interpretations rather than a comparison between separate randomized arms. A paired assessment can use information from both readings of the same scan, but the registry record does not state how observations were paired, how multiple readers were handled, or what statistical model was used. The general benefit of pairing is that each scan can serve as its own point of comparison; the analysis still needs to account appropriately for the structure of the reader and scan data.

The record describes masking as single but does not explain who was masked or what information was concealed. It also does not report whether readers had access to earlier interpretations while using quantitation. These details matter for evaluating the potential influence of the sequence of readings, but no further procedural assumptions can be made from the registry entry.

Scope of the analyzed scans

The primary outcome description restricts the analysis to 46 scans with autopsy from A16. The enrollment is listed as 96, but the registry does not explain why the primary measure uses this subset, how the scans were selected, or whether other scans contributed to other analyses. This distinction matters because an estimate calculated from a defined subset describes that subset directly. Its relevance to a broader scan population depends on selection and other study features that are not reported in the record.

General statistical interpretation also depends on how the reference status was established, how missing or indeterminate classifications were handled, and whether all relevant observations were included. The endpoint description identifies true positive and true negative status but does not report operational details for these determinations beyond specifying scans with autopsy. The missing details prevent a more complete appraisal of the endpoint construction.

Planning calculations and observed results

Sample-size calculations based on an observed effect are planning illustrations, not evidence that a study had a particular probability of detecting an effect. The registry record does not report a sample-size justification or its own design assumptions. No numerical planning estimates are reported in the registry record. Such calculations should not be confused with observed results or treated as observed power.

The record lists four analyses but does not describe their methods. It does not report whether analyses were adjusted, how uncertainty was calculated, or whether the NRI was assessed using additional statistical tests. These omissions mean that the endpoint definition can be explained, but the specific inferential procedure behind any numerical conclusion cannot be reconstructed from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and four analyses. It identifies the primary outcome as change in reader accuracy and the secondary outcome as change in scan interpretation reliability after application of quantitation software. The record does not report how the four analyses correspond to those outcomes, whether they represent separate analysis populations or methods, or whether any multiplicity procedure was used.

Multiplicity concerns arise when several outcomes or analyses may contribute to interpretation. As a general statistical matter, examining multiple results can increase the chance that at least one appears notable by chance. Researchers may address this through a prespecified hierarchy or adjustment, but the registry record does not report such a plan. It is not possible to determine whether or how multiplicity was handled.

The primary endpoint description specifies 46 scans with autopsy from A16, while overall enrollment is 96. The record does not describe missing data, exclusions, indeterminate readings, or the reasons this subset was used. It also does not state whether all observations in the specified subset were analyzed or how any unavailable classifications were handled. These details are not reported in the registry record.

The analysis populations are not described beyond the stated scan subset for the primary outcome. The registry does not report a participant flow, reader-level analysis population, or rules for inclusion in the reliability outcome. The number of readers and the handling of repeated readings are also not reported. Without this information, it is difficult to assess which observations contributed to each analysis or whether the analyses used consistent populations.

No interim analyses or statistical analysis plan are reported in the registry record. Their absence from the registry entry does not establish whether they existed elsewhere; it means that the posted record does not permit assessment of those procedures.

11. What the Result Does, and Does Not, Mean

The record establishes that the study evaluated the use of quantitative analysis software as an adjunct to visual interpretation of Amyvid scans. It defines the primary measure, the direction of scan reclassification, and the meaning assigned to positive and negative NRI values. It also specifies that the primary measure uses 46 scans with autopsy from A16. These details clarify the intended statistical question and the scope of the primary outcome.

However, the numerical primary result is not reported in the registry record. The record therefore does not show whether the NRI was positive or negative, its magnitude, or how precisely it was estimated. No uncertainty interval or underlying reclassification counts are reported. The outcome definition alone cannot establish the direction or strength of the observed result.

The study’s sequential design compares qualitative interpretation with interpretation after quantitation, rather than randomized groups. It can address changes in reader classifications under the described process, but the registry entry does not provide enough detail to assess all features of implementation or the statistical handling of repeated scan and reader observations. Nor does the record report enough information to judge whether the analyzed scans represent a broader population of scans.

As a general distinction, a statistical measure of classification change is not itself a direct measure of patient outcomes. The primary endpoint concerns reader accuracy as defined through the study’s reclassification framework. The record does not report clinical outcomes, nor does it establish conclusions beyond the scan-interpretation question described.

The registry lists a reliability outcome as secondary but does not provide its result. It also does not report details of multiplicity, missing-data handling, analysis populations, or a statistical analysis plan. Accordingly, the posted information supports an account of the study question and endpoint definition, but not a conclusion about the observed effect or its certainty.

12. Why This Trial Matters Statistically

This study is statistically notable for asking how an added quantitative marker changes classifications, rather than only whether readers agree with one another or whether average measurements differ. The net reclassification index is designed to summarize whether movements in predicted classifications align with true positive and true negative status. That makes the direction of movement central to the endpoint’s interpretation.

The sequential design also highlights an important distinction in interpreting clinical research. Readers assess scans qualitatively and then use quantitation, so the comparison concerns readings at different stages of a process. It is not a randomized, like-for-like comparison between separate treatment groups. Understanding that structure is necessary before interpreting any estimated change.

The endpoint is restricted to 46 scans with autopsy from A16, while the overall enrollment is 96. That distinction illustrates why the analysis population matters: the size and selection of the set used for an outcome affect what the estimate directly describes. The registry does not explain the selection process or the relationship between those scans and the full enrollment.

Finally, statistical interpretation requires both an estimate and information about its uncertainty. The registry defines the NRI’s direction but does not report its numerical value or precision. This makes the record useful for identifying the analytical question and intended measure, while leaving the size and reliability of any observed change unresolved. The distinction between an endpoint definition and a reported result is essential when reading registry outcomes.

13. 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 most consequential limitation of the registry record for statistical interpretation is that it does not report a numerical result for the primary NRI outcome. It also does not report an uncertainty interval, standard error, or the reclassification counts that would show how the estimate was constructed. The direction and precision of the primary finding therefore cannot be assessed from the posted record.

The primary outcome uses only 46 scans with autopsy from A16, while enrollment is listed as 96. The record does not explain the selection of those scans, the relationship between them and the enrolled group, or whether missing or indeterminate readings affected inclusion. As a result, the scope of the primary estimate and the potential for selection effects cannot be evaluated from the registry entry.

The design is single group and sequential: qualitative reading is followed by use of quantitation. The record does not describe the number of readers, how reader-level observations were combined, whether earlier readings remained available, or how the analysis accounted for repeated assessments. Masking is listed as single, but the identity of the masked party and the masked information are not reported.

The registry lists a secondary reliability outcome and four analyses, but does not provide their numerical results or detailed methods. It does not report multiplicity procedures, missing-data methods, analysis populations beyond the specified scan subset, or a statistical analysis plan. These omissions limit assessment of analytic choices and robustness. They do not establish that a particular method was or was not used outside the registry record.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: The Feasibility of Florbetapir Quantitation in Europe — NCT02107599.
• Registry record last updated 2015-07-09; status last verified 2015-06.
• Results first posted 2015-07-09.
• 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.

17. Record Summary

The completed Phase 4 study evaluated whether quantitative analysis software, used after qualitative interpretation, changes physician readers’ accuracy for Amyvid scans. Avid Radiopharmaceuticals is listed as sponsor; enrollment is 96, with dates of 2014-03 to 2014-05. The primary outcome is a net reclassification index, with the primary analysis specified for 46 scans with autopsy from A16. The registry defines positive NRI values as indicating improved accuracy and negative values as indicating a decline.

The record also lists change in scan interpretation reliability as a secondary outcome. It describes a single-group reader process, lists allocation as NA, and states that no subjects will be exposed to Florbetapir (18F) as part of the study. Numerical results for the primary and secondary outcomes, uncertainty estimates, and detailed analysis methods are not reported in the registry record.