Bridging Study of C11 Pittsburgh Compound B (PiB) and F18 Flutemetamol Brain Positron Emission Tomography (PET): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bridging Study of C11 Pittsburgh Compound B (PiB) and F18 Flutemetamol Brain Positron Emission Tomography (PET) (NCT01607476), a non-randomized phase 2 study. The primary outcome is Global Distribution of C11 PiB in the Brain.

2. Clinical Question

The protocol's stated aim is to test equivalency between C11 PiB and F18 Flutemetamol imaging. Its rationale is that differences in nonspecific accumulation, including in white matter, could affect image performance. The brief summary notes earlier observations of similar distribution in people with Alzheimer's disease or mild cognitive impairment, while stating that comparison data in normal subjects had not been published. These statements describe the motivation for the research, not the study's numerical findings.

The registry record does not report a primary-outcome estimate, an uncertainty interval, or a statistical test result. It therefore does not establish from the posted numerical results whether uptake distributions were similar or different. The stated question and the results available in the record should be kept separate: the former describes what investigators set out to examine, while the latter would be needed to quantify the comparison.

3. Trial Design

NCT01607476 is listed as a completed Phase 2 study sponsored by Mayo Clinic. The registry lists enrollment of 89. The study started in 2012-07 and had primary completion in 2014-12. The design is recorded as non-randomized, with no masking and a parallel model.

The listed groups are Alzheimer's disease, Cognitive Normal Elderly, and Cognitive Normal Young. Their descriptions identify clinical or cognitive status and age characteristics. The descriptions state that participants in each group receive C11 PiB PET/CT and F18 Flutemetamol PET/CT, with C11 PiB performed first. The registry also lists both imaging agents as interventions. The record does not describe randomized assignment to the disease or age groups, and these groups should not be interpreted as randomized treatment arms.

The non-randomized designation matters for interpretation. Randomization is a method for creating treatment groups that are comparable, on average, with respect to measured and unmeasured characteristics. It is not the design recorded. Differences between the clinical and cognitive groups could reflect group characteristics as well as imaging-agent distribution. The posted design therefore does not support treating the group labels as interchangeable control conditions.

The study's stated purpose is a bridging comparison of two amyloid imaging drugs. The order is specified, with C11 PiB first, but the registry record does not report whether order effects were assessed or how they were handled analytically. It also does not report a detailed statistical analysis plan, eligibility criteria beyond those in the arm descriptions, or the number of participants contributing usable data to each endpoint. Enrollment describes the registered study size; it does not, by itself, establish the analysis population for any particular measure.

Although the record identifies a primary outcome and lists additional outcome and analysis entries, numerical primary-outcome estimates are not reported in the registry record. The design can be described, but the size and precision of the imaging comparison cannot be evaluated from the posted numerical results.

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: 89 subjects were consented, but 1 subject was a screen failure prior to assignment.

Overall Study

Reasons for not completing this period:

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 Global Distribution of C11 PiB in the Brain, measured over Approximately one hour after injection of positron emission tomography (PET) drug.

The primary endpoint is titled Global Distribution of C11 PiB in the Brain. It measures mean global uptake as a standard uptake value ratio (SUVR), with standard deviation specified as the dispersion measure. The stated timeframe is approximately one hour after injection of the PET drug.

According to the endpoint description, imaging analysts use a global brain atlas to measure tracer uptake, or image brightness, across the brain. That global uptake is normalized to uptake in the cerebellar crus. The SUVR is described as a ratio of SUV from two regions in the same PET image. The description explains that injected activity, body weight, and the volume-to-mass conversion factor cancel in this ratio.

As a general statistical matter, normalization can help express uptake relative to a reference region rather than as an unscaled signal. It does not remove every possible source of measurement variation, and interpretation depends on the chosen regions, image processing, and the properties of the reference signal. The registry description identifies the cerebellar crus as the reference but does not report additional validation or processing details.

The endpoint is relevant to the study's stated interest in how the imaging agent distributes across brain structures. However, the record does not report a mean SUVR, standard deviation, comparison estimate, or uncertainty interval. The endpoint definition explains what was intended to be measured; it cannot by itself show the observed distribution or establish how precisely it was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical concepts help explain what would be needed to assess this study's stated comparison. The registry identifies a continuous primary measure: mean global SUVR, with standard deviation as its dispersion summary. It does not report the numerical outcome summaries or the model used to analyze them. The explanations below describe general principles, not analyses confirmed for this study.

What does a mean describe?

For a continuous measure, a mean describes the arithmetic center of the observed values. It is useful for summarizing average uptake, but it does not show how values are distributed around that center. The standard deviation describes spread among observations on the scale of the measure. A mean and standard deviation together can aid description, but they do not reveal the shape of the distribution, influential observations, or uncertainty in the mean unless the sample size and relevant assumptions are also known.

For imaging-agent comparisons, a mean alone would not establish that two agents produce equivalent distributions. An analysis would need a defined contrast, such as a difference in means or another prespecified agreement measure, and a measure of uncertainty around that contrast. The registry record does not give these results. It also does not report whether the primary comparison was made within participants, between groups, or using another analysis structure.

What does a confidence interval add?

General: a confidence interval expresses statistical uncertainty around an estimate under the assumptions of the method used. A narrow interval indicates greater precision than a wide interval, but precision is not the same as clinical or imaging importance. Whether an interval supports equivalence depends on a prespecified acceptable range for the contrast. The record does not report an interval or an equivalence margin, so the degree of precision and the equivalence question cannot be evaluated from its numerical results.

A test of a null hypothesis and an equivalence assessment have different aims. A conventional test can evaluate evidence against a specified null value. Failing to reject that null does not demonstrate that the true difference is sufficiently small. Equivalence methods instead ask whether the uncertainty around the difference lies within a defensible margin. This is a general distinction; the registry record does not state which formal method was used for the study's equivalency aim.

Why does the design affect analysis?

General: a non-randomized comparison can be affected by differences in participant characteristics, selection, measurement conditions, and other factors associated with group membership. Adjustment can address measured covariates when an appropriate model and data are available, but it cannot guarantee removal of unmeasured differences. The registry record does not describe covariate adjustment or a detailed statistical model.

The arm descriptions say both imaging procedures are performed and that C11 PiB comes first. If outcomes are collected from the same participant under both imaging conditions, a paired analysis can account for within-person correlation. Treating paired measurements as independent would generally misrepresent their uncertainty. However, the registry record does not report the analysis population, the linkage of measurements, or whether the posted analysis used a paired method. Thus, this is a general consideration rather than a claim about the analysis actually performed.

Order can also matter in repeated measurement settings. A general analysis might consider whether sequence, timing, or carryover could influence the result, depending on the imaging procedures and protocol. The record specifies the order but does not report an order-effect assessment or protocol details sufficient to characterize such effects.

What is the role of dispersion and model choice?

General: statistical models translate observed data into estimates and uncertainty statements. Their suitability depends on the outcome scale, distribution, dependence structure, and study design. For a continuous SUVR outcome, an analysis might use a model for means, but the appropriate approach cannot be determined from the endpoint label alone. The registry record does not identify the specific model, diagnostic checks, or transformations, if any.

Over-dispersion is a general concern when the observed variability exceeds what a model assumes. In count-data analyses, for example, over-dispersion can make standard errors too small if the model does not allow extra variability. That concept does not establish that over-dispersion applies to this continuous imaging endpoint; the record provides no diagnostic evidence of it. More broadly, uncertainty estimates depend on whether the model captures the actual variability and dependence in the data.

How should planning illustrations be read?

General: sample-size planning uses assumptions about the target effect, variability, significance level, allocation, and statistical method. The planning assumptions described for this study use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. Such illustrations are planning calculations, not observed trial findings and not observed power. They do not establish the study's original design rationale or show that the trial was planned using those assumptions.

The registry record does not report a sample-size justification for the original study. Nor does it provide enough numerical primary-outcome information in this record to independently assess the precision of the imaging comparison. A planning calculation based on an observed effect cannot replace the observed estimate and its uncertainty, and it should not be interpreted as proof that a result is reliable or that a null finding demonstrates equivalence.

Overall, statistical interpretation requires the outcome summaries, contrast estimate, uncertainty, analysis population, and analytic method. Those details are not reported in the registry record. General statistical principles can clarify what to look for, but they cannot fill in absent trial results.

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("Alzheimer's Disease", "Cognitive Normal Elderly", "Cognitive Normal Young")
n   <- c(24, 30, 30)
m   <- c(2.5, 1.47, 1.23)
sp  <- c(0.53, 0.28, 0.08)
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  Alzheimer's Disease  24  2.500  0.530  2.276  2.724
CARM  Cognitive Normal Elderly  30  1.470  0.280  1.365  1.575
CARM  Cognitive Normal Young  30  1.230  0.080  1.200  1.260

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and six analyses, but the numerical results and detailed analysis descriptions are not reported in the information available for this account. The record does not state how the outcomes or analyses relate to one another, which analyses were primary or secondary beyond the named primary measure, or whether any adjustment for multiple testing was applied.

General: when several outcomes, comparisons, or subgroup analyses are tested, the chance of at least one apparently unusual result can increase if each test is interpreted independently. Multiplicity procedures can manage that issue, but their choice depends on the questions and analysis plan. No multiplicity method is reported in the registry record, so no claim can be made about whether or how it was handled.

The missing-data approach is also not reported in the registry record. The endpoint description does not state how unavailable, incomplete, or technically unusable imaging measurements were treated. The number contributing to each outcome analysis and the reasons for any missing observations are not reported. Enrollment of 89 should not be read as confirmation that every enrolled participant contributed data to every analysis.

Analysis populations are not defined in the registry record. It does not identify whether analyses included all enrolled participants, only participants with evaluable scans, or another specified population. These choices can affect interpretation, especially when incomplete data or exclusions are related to participant characteristics or scan quality.

The record also does not report a detailed statistical analysis plan, prespecified model, or handling of deviations from the planned measurement process. Without these details, readers cannot assess whether the analyses were prespecified or how robust the results are to alternative reasonable choices. These are reporting gaps, not evidence that a particular procedure was or was not used.

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 lists serious adverse events by group. It reports 0 affected participants among 24 at risk in Alzheimer's disease, 0 among 30 at risk in Cognitive Normal Elderly, and 0 among 30 at risk in Cognitive Normal Young. It also lists other adverse events: 1 affected participant among 24 at risk in Alzheimer's disease, 4 among 30 at risk in Cognitive Normal Elderly, and 2 among 30 at risk in Cognitive Normal Young.

These are descriptive registry counts. They should be read with their listed group denominators and event categories, rather than as estimates of comparative risk between randomized treatments. The study is non-randomized, and the group descriptions represent different clinical or cognitive populations. The registry record does not report deaths for these groups, and no serious-event terms are listed in the available information.

General: an observed count of zero does not establish that an event is impossible or that the underlying risk is zero. The precision of safety estimates depends on the number observed, follow-up, event definitions, and completeness of reporting. The registry record does not provide further detail about event timing, attribution, severity criteria, or exposure-specific safety comparisons. These counts therefore describe what is listed, not a complete characterization of safety or a causal comparison between agents.

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

The record establishes that a completed Phase 2 study was registered to examine C11 PiB and F18 Flutemetamol brain PET imaging. It describes three clinical or cognitive groups, identifies the scan order, and defines a primary global C11 PiB SUVR measure. These registry entries explain the purpose and structure of the research.

The posted information does not report numerical primary-outcome estimates, a direct comparison, confidence intervals, or a statistical test result. As a result, it does not quantify how similar or different the observed imaging distributions were, nor how precisely they were estimated. The stated hypothesis that there would be no significant difference is a study rationale, not a reported result.

The word equivalency requires particular care. General: evidence that two measurements are equivalent requires an acceptable difference to be defined and the estimated uncertainty to be sufficiently contained within that margin. A lack of a statistically significant difference, if one were reported, would not alone establish equivalence. The registry record does not report the margin or the numerical analysis needed to assess equivalence.

The study is non-randomized and lists groups with different clinical and age characteristics. It should not be interpreted as a randomized comparison of treatment assignments. The arm descriptions state that both imaging procedures are performed, with C11 PiB first, but the record does not provide the numerical within-person results or analysis details needed to assess agreement.

The adverse-event counts are descriptive and belong to a separate safety question. They do not resolve the primary imaging question. The registry record supports a description of intent, design, endpoint, and listed adverse events; it does not support a conclusion about the observed magnitude, direction, or precision of the primary imaging comparison.

14. Why This Trial Matters Statistically

This study matters statistically because it asks a measurement-comparison question framed in terms of equivalency. In imaging research, similar average uptake is not necessarily the same as interchangeable measurement. A meaningful assessment needs a defined comparison, an acceptable margin for differences, and uncertainty estimates that are precise enough to evaluate that margin. The registry record describes the intent to test equivalency but does not report the estimates or margin needed to judge it.

The endpoint also illustrates the importance of measurement definition. Global uptake is normalized to uptake in the cerebellar crus, producing an SUVR from two regions in the same PET image. This makes the reference region part of the meaning of the outcome. Statistical interpretation depends not only on the arithmetic comparison but also on what the measurement represents and how reliably it is constructed.

The record's non-randomized design is another central statistical feature. Group comparisons across Alzheimer's disease and cognitively normal participants may reflect differences in the groups as well as imaging distributions. The described sequence, with C11 PiB first, is relevant to interpreting repeated imaging, but the registry does not say how sequence was addressed analytically.

Finally, this record illustrates the difference between a completed study and a fully interpretable numerical result. Completion status and enrollment establish aspects of study conduct, not the effect estimate or its precision. Clear reporting of analysis populations, missing-data handling, comparison methods, and uncertainty would be needed to judge the strength and scope of the imaging evidence. In their absence, the study's statistical importance lies in the question it set out to address and in the limits on what can be concluded from the registered information.

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 primary limitation for statistical interpretation is that numerical primary-outcome results are not reported in the registry record. No mean SUVR, comparison estimate, uncertainty interval, or test result is available in the information. Thus, the magnitude, direction, and precision of the imaging comparison cannot be assessed.

The study's equivalency aim is not accompanied by a reported equivalence margin or analysis method. Without those details, the intended standard for concluding that distributions are sufficiently similar is unclear. The registry's statement of a hypothesis of no significant difference cannot substitute for an equivalence analysis.

The design is non-randomized, with clinically and cognitively distinct groups. This limits direct causal interpretation of differences between groups. The record specifies that C11 PiB is performed first, but does not report whether order effects were evaluated, how the repeated procedures were modeled, or whether the comparison used paired observations.

Other relevant analytic details are not reported in the registry record: endpoint-specific analysis populations, missing-data handling, model specification, covariate adjustment, multiplicity procedures, or the number of evaluable observations for each outcome. The record lists two outcome measures and six analyses without providing the numerical findings needed to interpret them.

The endpoint description explains the SUVR and its reference region, but does not report additional measurement validation or image-processing details. The safety summaries list event counts, yet do not provide further information about attribution, timing, or exposure-specific comparison. These limitations concern what the registry record reports; they do not establish what procedures were or were not conducted outside that record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bridging Study of C11 Pittsburgh Compound B (PiB) and F18 Flutemetamol Brain Positron Emission Tomography (PET) — NCT01607476.
• Registry record last updated 2017-04-18; status last verified 2016-11.
• Results first posted 2016-11-01.
• 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

NCT01607476 is a completed Phase 2, non-randomized study sponsored by Mayo Clinic, with enrollment listed as 89. The record gives a start of 2012-07 and primary completion of 2014-12. It describes Alzheimer's disease, Cognitive Normal Elderly, and Cognitive Normal Young groups, with C11 PiB PET/CT performed before F18 Flutemetamol PET/CT.

The primary endpoint is mean global C11 PiB SUVR, normalized to uptake in the cerebellar crus, with standard deviation as the stated dispersion measure and measurement approximately one hour after injection. The study's stated purpose is to examine equivalency and distribution of the imaging agents.

Numerical primary-outcome results and detailed analysis methods are not reported in the registry record. Listed adverse-event counts include no serious events in the described groups and other-event counts of 1, 4, and 2, respectively. The registered information supports describing the study's design and aims, but not quantifying the primary imaging comparison.