A Preliminary Study of 18F-AV-45 in Alzheimer's Disease and Healthy Elderly Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Preliminary Study of 18F-AV-45 in Alzheimer's Disease and Healthy Elderly Volunteers (NCT01565291), a non-randomized early/phase 1 study. The primary outcome is Mean Cortical to Cerebellum SUVR.

2. Clinical Question

The study was framed as a preliminary evaluation of amyloid binding properties, pharmacokinetics and safety in healthy elderly volunteers and patients with Alzheimer's disease. The primary endpoint describes tracer uptake in predefined cortical regions relative to uptake in cerebellar gray matter. It is a continuous measure, so the listed summary is a mean with a standard deviation.

The clinical question is descriptive: how the measure appeared in the two enrolled groups following tracer administration. Because participants were not randomly allocated, a difference between groups, if reported, would not by itself establish that disease status caused the difference. The record does not give the endpoint values, a between-group estimate, or an analysis result. It therefore cannot support a numerical answer about the size or precision of any group contrast.

3. Trial Design

This was an early-phase, non-randomized, unmasked, parallel-group study of florbetapir F 18, also identified as 18F-AV-45. The registry lists enrollment of 32 and describes groups of subjects with Alzheimer's disease and healthy elderly subjects. The study status is completed, with a start date of 2007-06 and primary completion in 2008-01.

The Alzheimer's disease group was described as having probable disease under NINCDS-ADRDA criteria and mild or moderate dementia, with MMSE from 10 to 24. Healthy elderly subjects were cognitively normal, had MMSE of 29 or higher, and were age 50 years or older. The record lists the study as parallel, but allocation was non-randomized and masking was none. The healthy elderly group should therefore be read as a descriptive reference, not as a randomized control group. Differences in group characteristics or other factors could contribute to any observed contrast; the record does not report an adjusted comparison that addresses such factors.

The intervention was florbetapir F 18. The brief description says the study used a PET scanner to examine how the tracer acted in the brains and bodies of the groups. The primary endpoint was assessed at 50-60 min after injection, and the endpoint description states that the total scan length was 200 min. The record notes that 4 subjects in the Alzheimer's disease group and 1 subject in the healthy elderly group were excluded from this endpoint because of poor placement and/or excessive movement during the scan.

The registry record does not report a detailed statistical analysis plan, a sample-size justification, interim analyses, or an adjusted model. It lists no statistical analyses for the outcomes. Accordingly, the design information supports describing the study groups and measurement process, but not reconstructing an unreported analysis.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 4 subjects in AD group and 1 subject in the healthy elderly group were excluded due to poor placement and/or excessive movement in the scanner during the 200-minute procedure.

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 Mean Cortical to Cerebellum SUVR, measured over 50-60 min after injection.

The primary endpoint is mean cortical-to-cerebellum SUVR at 50-60 min after injection. SUVR is defined in the record as the ratio of tracer uptake in predefined cortical regions to uptake in cerebellar gray matter. It is a continuous measure, and the planned descriptive summary is a mean with a standard deviation. The endpoint description also notes a total scan length of 200 min.

A ratio to a reference region can provide a relative measure of tracer uptake rather than describing cortical uptake in isolation. In general, such a measure can be useful when the scientific question concerns the distribution of a tracer across brain regions. Its interpretation depends on the specified regions, the timing of measurement, and the acquisition and processing methods. Those details matter because uptake can vary over the course of a scan, and the endpoint is explicitly tied to a post-injection time window.

The registry record describes the measurement but does not report the mean SUVR or standard deviation for either group. It also does not report a between-group estimate, confidence interval, or test result. Thus, the endpoint definition alone does not indicate the magnitude, direction, or precision of any observed group difference. The endpoint exclusions for placement or movement also mean the stated measure was not available for every participant described in the enrollment record; further details on missing endpoint data are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe? The primary outcome is continuous and is summarized as a mean with a standard deviation. In general, a mean describes the center of a set of measurements, while a standard deviation describes how spread out those measurements are around the mean. They answer different questions: a mean gives a typical level in the group, while a standard deviation describes variation among the measured values. Neither statistic is reported for this endpoint in the registry record, so the outcome distribution cannot be characterized from the posted information.

What does SUVR represent? The record defines SUVR as the ratio of uptake in predefined cortical regions to uptake in cerebellar gray matter. In general, a ratio expresses one measurement relative to another. It can help describe relative tracer distribution, but its interpretation depends on both the target and reference measurements, the chosen regions, and when measurements are taken. Here, the record specifies the cortical-to-cerebellum measure and the 50-60 min post-injection time window. It does not give the group values or further details about how the regions were selected or processed.

What would a group comparison estimate? In general, a comparison of group means estimates how far apart the group averages are on the outcome scale. A confidence interval, when reported, expresses the uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision; neither guarantees that an estimate is free of bias. No group contrast or confidence interval for the primary endpoint is reported in the registry record. No p-value for this outcome is reported either, so statistical significance cannot be assessed from the posted results.

Why does non-random allocation matter? Random allocation is used in general to make comparison groups more similar, on average, with respect to factors that could affect outcomes. This study is listed as non-randomized, and the two groups are defined by disease and cognitive status. A difference between their SUVR values, if it had been reported, could reflect those group characteristics or other differences in addition to the phenomenon under study. The registry record does not report an adjusted analysis to address potential confounding. The groups should therefore be treated as descriptive cohorts, not as randomized treatment arms.

How should endpoint exclusions be considered? The record says that 4 subjects in the Alzheimer's disease group and 1 subject in the healthy elderly group were excluded from the primary endpoint because of poor placement and/or excessive movement during the 200-minute scan procedure. In general, excluding measurements can affect interpretation if the availability of a usable measurement is related to the outcome or to participant characteristics. The record does not report the specific analysis population, the handling of missing measurements, or a comparison of included and excluded participants. It is therefore not possible to judge whether the endpoint exclusions could have influenced the reported estimate; the estimate itself is not reported.

What do the planning assumptions mean? The sample-size assumptions describe a planning illustration based on an observed effect, not the trial's own design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. In general, these calculations illustrate how a future study's required sample size may depend on the target effect and chosen design assumptions. They are not observed power and do not show that the completed study could or could not detect an effect. The observed effect and the numerical planning outputs are not reported in the registry record, so the illustrations cannot be evaluated numerically.

What can be concluded from the listed analysis count? The record lists 0 analyses for 2 outcome measures. That is a statement about what the registry record lists, not proof that no analysis was performed elsewhere. The statistical analysis plan, any model specifications, handling of multiple outcomes, and any interim analyses are not reported in the registry record. Without those details and the endpoint estimates, a reader cannot reproduce or evaluate the outcome analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Subjects With AD", "Healthy Elderly Subjects")
n   <- c(11, 15)
m   <- c(1.665, 1.246)
sp  <- c(0.175, 0.177)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Subjects With AD  11  1.665  0.175  1.547  1.783
CARM  Healthy Elderly Subjects  15  1.246  0.177  1.148  1.344

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary outcome of mean cortical-to-cerebellum SUVR and a secondary outcome of Precuneus to Cerebellum SUVR. It lists 2 outcome measures and 0 analyses. The statistical plan for handling multiple outcomes, including whether any adjustment for multiple testing was intended, is not reported in the registry record. No outcome-specific test results are listed, so the effect of multiplicity on interpretation cannot be assessed.

For the primary outcome, the record identifies 4 subjects in the Alzheimer's disease group and 1 subject in the healthy elderly group as excluded because of poor placement and/or excessive movement during the 200-minute scan procedure. How those exclusions were applied in analysis, whether any other measurements were missing, and whether a sensitivity analysis was performed are not reported in the registry record. A detailed analysis population and a missing-data method are also not reported in the registry record.

In general, missing-data methods matter because conclusions can depend on whether the observations that are unavailable differ systematically from those that remain. The reason stated for these exclusions relates to image acquisition, but that reason alone does not show whether the remaining endpoint measurements are representative of all enrolled participants.

The record does not report an intention-to-treat analysis, a per-protocol analysis, or another named analysis population. It also does not report interim analyses or a prespecified statistical analysis plan. These omissions limit assessment of how outcomes were selected, how missing values were handled, and whether the posted estimates followed a plan set before the results were known. No inferential claims should be made from the outcome listing alone.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists serious adverse events separately for the two groups. For subjects with Alzheimer's disease, 0 of 16 at risk were recorded with a serious adverse event. For healthy elderly subjects, 0 of 16 at risk were recorded with a serious adverse event. No serious-event terms are listed, and deaths are not reported in the registry record.

For other adverse events, the record lists 0 of 16 at risk in the Alzheimer's disease group and 2 of 16 at risk in the healthy elderly group. These are event-count summaries as recorded; the entries do not provide event descriptions, timing, severity, or the number of events per affected participant. The record does not report an exposure-adjusted comparison or a statistical analysis of safety outcomes.

In general, observing no recorded serious events does not establish that a risk is absent. The study groups are small, non-randomized cohorts, and the registry does not provide the detail needed to evaluate differences in event ascertainment or follow-up. The listed counts should be read as descriptive safety information, not as evidence that the tracer caused or prevented an adverse event or that the groups had equivalent safety profiles.

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

This study contributes a registry description of a preliminary PET evaluation of florbetapir F 18 in subjects with Alzheimer's disease and healthy elderly subjects. It specifies the primary imaging measure, the time window for that measure, and the reasons some endpoint observations were excluded. These details help define what the study set out to measure and the conditions under which the primary endpoint was collected.

However, the registry record does not report the primary endpoint means, standard deviations, or any comparison between groups. It also does not report the result for the secondary SUVR outcome. Consequently, the posted information does not establish whether the groups had similar or different uptake values, how large any difference was, or how precise an estimate might be. The endpoint definitions are not a substitute for outcome results.

The design further limits causal interpretation. The study was non-randomized and unmasked, and the groups represent people with different clinical characteristics rather than randomized alternatives. Any observed difference would be descriptive and could reflect factors other than the intended scientific contrast. No adjusted analysis is reported in the registry record.

The safety entries show no recorded serious adverse events in either group and 2 other adverse events in the healthy elderly group, with none in the Alzheimer's disease group. These counts are limited descriptive information; the registry record does not supply the event details or analyses required for a comparative safety assessment.

Overall, the record documents a preliminary measurement study and its basic design, but it does not provide the numerical outcome results needed to evaluate the primary scientific question. It cannot establish a treatment benefit, lack of benefit, or a causal effect. It also cannot establish the absence of safety risks. Those conclusions would require reported outcome estimates and sufficient methodological detail to assess the analyses.

14. Why This Trial Matters Statistically

This study is statistically instructive because its main contrast is between non-randomized groups with different clinical profiles. A healthy elderly reference group can help place an imaging measure in context, but it cannot serve as a randomized counterfactual for the Alzheimer's disease group. Statistical comparisons do not remove this limitation automatically: an unadjusted difference would remain vulnerable to confounding, and an adjusted result would require details about the model and measured covariates.

The primary endpoint also illustrates that a biomarker definition and a biomarker result are different things. The registry specifies the cortical-to-cerebellum SUVR, its measurement window, and its summary as a mean with standard deviation. It does not report the numerical values. Without the estimates and their uncertainty, readers cannot evaluate the size or precision of the observed measurement or distinguish a small, precise contrast from a larger, uncertain one.

Endpoint availability is another important issue. The registry records exclusions related to poor placement and excessive movement during a lengthy scan procedure. Such exclusions can affect who contributes to an imaging analysis. Clear reporting of the analysis population and missing-data handling would help readers judge how broadly the endpoint summaries apply.

Finally, the record separates safety counts from imaging outcomes, which is important for keeping distinct questions in view. The safety entries are descriptive and do not replace a comparative analysis. Together, these features show why careful statistical interpretation depends not only on design labels and endpoint definitions, but also on outcome estimates, uncertainty, analysis methods, and transparent reporting of exclusions.

15. 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 direct limitation of the registry record is that it does not report the primary endpoint values or statistical analyses. The mean cortical-to-cerebellum SUVR, its standard deviation, and any group contrast or confidence interval are not reported in the registry record. The secondary SUVR result is also not reported. This prevents assessment of the direction, magnitude, and precision of the imaging findings.

The design was non-randomized and unmasked. The comparison between subjects with Alzheimer's disease and healthy elderly subjects is therefore descriptive and may be influenced by differences between the groups. The registry record does not report an adjusted analysis or covariate information that could help assess this concern.

The record identifies exclusions from the primary endpoint because of poor placement and/or excessive movement during the scan. It does not report a detailed analysis population, additional missing data, the handling of excluded observations, or sensitivity analyses. These omissions make it difficult to determine how endpoint availability could affect interpretation.

The study is described as preliminary and early phase. The registry does not report a sample-size justification, statistical analysis plan, interim analyses, or the intended handling of multiple outcomes. It lists 0 analyses, leaving no outcome estimate against which to evaluate the study's questions.

Safety reporting is also limited: the registry lists counts but does not report event descriptions, timing, severity, or a formal comparison. These features constrain interpretation of both the imaging and safety information and preclude strong causal or comparative conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Preliminary Study of 18F-AV-45 in Alzheimer's Disease and Healthy Elderly Volunteers — NCT01565291.
• Registry record last updated 2012-05-18; status last verified 2012-05.
• Results first posted 2012-05-03.
• 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.

19. Record Summary

The registry record describes a completed, early-phase, non-randomized, unmasked, parallel study of florbetapir F 18 in subjects with Alzheimer's disease and healthy elderly subjects. It lists enrollment of 32, a start date of 2007-06, and primary completion in 2008-01.

The primary outcome was mean cortical-to-cerebellum SUVR at 50-60 min after injection, summarized as a mean with standard deviation. The record excludes 4 subjects in the Alzheimer's disease group and 1 subject in the healthy elderly group from this endpoint because of poor placement and/or excessive movement. Numerical results and analyses for the primary and secondary outcomes are not reported in the registry record.

The safety listing records no serious adverse events in either group, and 2 other adverse events in the healthy elderly group with none in the Alzheimer's disease group. These counts are descriptive and do not establish a comparative effect.