Assessment of Hyperphosphorylated Tau PET Binding in Primary Progressive Aphasia and Frontotemporal Dementia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of Hyperphosphorylated Tau PET Binding in Primary Progressive Aphasia and Frontotemporal Dementia (NCT02736695), a non-randomized phase 1 study. The primary outcome is Proportion of PPA Subjects That Showed Elevated Tau PET Binding Compared to Normal Controls.

2. Clinical Question

3. Trial Design

The registry describes a Phase 1, non-randomized, unmasked, single-group study sponsored by Mayo Clinic. Enrollment is listed as 81. The study status is completed, with a start date of 2016-07 and primary completion dated 2024-08-01. The stated aim was to learn more about overall tau burden in the brains of patients with PPA and frontotemporal dementia.

Participants in the tau PET scan arm received a scan using F-18 AV 1451. The record also describes a healthy-control group whose participants came from the NIH-funded Mayo Clinic Study of Aging. Those controls completed the same tau PET protocol with AV-1451, MRI, and clinical protocols, but were not consented or enrolled in this study. The record therefore combines the description of a study arm with a reference group drawn from another study; it does not describe random assignment between these groups.

The PPA participants were classified into clinical categories based on clinical features. The record lists 4 participants in lvPPA, 32 in svPPA, 24 in agPPA, 9 in PPA-U, and 0 in the healthy category for the scan arm. For the healthy controls, it lists 80 in the healthy category and 0 in each PPA category. The record does not explain how the listed subgroup counts relate to the total enrollment.

The listed secondary outcome concerns signature patterns of regional tau PET binding in clinical PPA variants. The registry record does not report the protocol’s detailed statistical plan, the criteria used to determine elevated binding, or results from the primary or secondary outcomes. It also does not report an analysis population definition or a rationale for the enrollment target.

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: We leveraged data that had already been collected on healthy controls from our NIH funded Mayo Clinic Study of Aging (U01 AG006786). That study recruited healthy subjects of which 102 were controls, who had completed the identical tau-PET protocol with AV-1451 and MRI and clinical protocols. We selected a subset of 80 age and gender match healthy controls from the 102 for use in this study. These 80 participants were not consented or enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects were subclassified into 1 of 5 categories based on clinical features. Classification for Tau PET Scan, F-18 AV 1451 arm: 4 lvPPA; 32 svPPA; 24 agPPA; 0 healthy; 9 PPA-U. Classification for Health Controls: 0 lvPPA; 0 svPPA; 0 agPPA; 80 healthy; 0 PPA-U.

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: We leveraged data that had already been collected on healthy controls from our NIH funded Mayo Clinic Study of Aging (U01 AG006786). That study recruited healthy subjects of which 102 were controls, who had completed the identical tau-PET protocol with AV-1451 and MRI and clinical protocols. We selected a subset of 80 age and gender match healthy controls from the 102 for use in this study. These 80 participants were not consented or enrolled in this study.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of PPA Subjects That Showed Elevated Tau PET Binding Compared to Normal Controls, measured over 1 week.

The primary endpoint is titled as the proportion of PPA participants who showed elevated tau PET binding compared with normal controls. Its unit is participants, and its description refers to the percentage showing elevated binding across five categories: lvPPA, svPPA, agPPA, healthy, and PPA-U. The specified timeframe is 1 week.

A proportion expresses how many participants in a defined group meet a specified condition relative to the group being considered. In this study, the condition is elevated tau PET binding, and the clinical categories provide a way to describe results across different PPA presentations. A measure organized this way can describe whether binding is observed across the clinical groups rather than treating all PPA participants as one undifferentiated category.

For a proportion to be interpretable, the record needs to make clear how the condition is defined, which participants contribute to the denominator, and how missing or unevaluable scans are handled. The registry does not report the threshold or decision rule for elevated binding, the outcome counts, or the resulting percentages. It also does not explain whether the healthy controls were used to define a reference threshold or only to provide a comparison. Consequently, the endpoint’s intended meaning is identifiable, but its observed value and operational details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is this? The primary outcome is a participant count described as a proportion or percentage. In general, a proportion is formed by counting participants who meet a defined condition and relating that count to the number of participants eligible for the calculation. The condition is elevated tau PET binding, considered across clinical categories. The registry provides neither the counts meeting the condition nor the calculated proportions, so no effect estimate can be interpreted from the record.

For the proportion to have a clear denominator, the analysis needs to specify which participants were considered eligible and whether all had usable scans and classifications. A participant with missing imaging, an incomplete assessment, or an unclassifiable result might be treated differently depending on the analysis plan. Those rules can affect the denominator and hence the estimated proportion. The registry does not report missing-data rules, the number of participants with evaluable scans, or the analysis population used for the primary endpoint.

What does a comparison with controls involve? The primary outcome refers to elevated binding “compared to normal controls.” In general, a control group can help contextualize a measurement by providing a reference distribution or comparison value. How it is used depends on a prespecified method, such as defining a threshold or comparing group-level measurements. The registry does not say which approach was used. It does not provide a control-derived threshold, a numerical reference value, or a statistical comparison.

The design is non-randomized and the healthy controls were not enrolled in the study. General statistical interpretation of an external control comparison must therefore consider whether the groups are sufficiently comparable for the question being asked. Differences in participant characteristics, recruitment, timing, or measurement circumstances can influence observed contrasts. The registry reports that the controls completed an identical tau PET protocol with AV-1451 and MRI and clinical protocols, but does not report methods to account for possible group differences. It would be inappropriate to interpret the reference group as if allocation had been randomized.

How should uncertainty be assessed? A confidence interval, in general, describes a range of values compatible with the data under the method used. For a proportion, its width depends in part on the amount of information available and on the observed proportion. An interval would help show whether the endpoint estimate is precise or uncertain. No confidence interval or other uncertainty measure is reported in the registry record. Without outcome counts, even an unadjusted interval cannot be reconstructed from the posted results.

A p-value, in general, addresses how compatible the observed data are with a specified null model under the assumptions of a statistical test. It does not measure the size or importance of an effect, and it does not replace an estimate with an uncertainty interval. The registry lists no analyses and reports no p-value. The statistical test, null hypothesis, and any adjustment for covariates are not reported in the registry record. There is therefore no basis for describing statistical significance or a modeled difference.

What does the category structure contribute? Classifying participants by PPA clinical variant allows the intended outcome to be described separately for lvPPA, svPPA, agPPA, and PPA-U, with healthy controls as a reference category in the endpoint description. The registry also names a secondary outcome for signature patterns of regional tau PET binding in clinical PPA variants. Such subgroup descriptions can address whether imaging patterns vary across clinical presentations. They also create a need for careful interpretation: smaller subgroups generally contain less information, and multiple subgroup estimates may be less precise. No subgroup outcome estimates, uncertainty measures, or analysis plan are reported.

How does multiplicity affect interpretation? In general, evaluating multiple outcomes, subgroups, or statistical tests increases the chance that at least one result appears noteworthy by chance if no adjustment or prespecified hierarchy is used. A statistical plan may address this through a defined primary outcome, testing sequence, or multiplicity adjustment. The registry identifies a primary outcome and a secondary outcome, but does not report whether there were additional planned comparisons, how the outcomes were ordered for testing, or whether any multiplicity procedure was used. No multiplicity adjustment is reported in the registry record.

The record gives enrollment as 81, but it does not state a sample-size justification or the precision the investigators sought for the primary proportion. In general, planning for a study and interpreting completed results are different tasks. A planned enrollment target does not tell readers how many participants contributed usable outcome data, and it does not establish that an estimate is precise. Since no outcome counts or analysis are posted, the precision of the primary endpoint cannot be assessed.

The study is marked completed, yet the registry record lists zero analyses. In general, a completed study can still have results that are unavailable in a registry entry. The posted information supports description of the design and intended endpoint, but not a numerical assessment of the endpoint, its uncertainty, or the evidence for a group contrast.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and a secondary outcome, but does not report a statistical analysis plan describing how multiple outcomes or subgroup comparisons were handled. Multiplicity arises when several outcomes, categories, or tests are examined: even if each test is interpreted under the same nominal threshold, the chance of at least one apparently notable result can increase. General approaches include prioritizing a primary question, using an ordered testing strategy, or adjusting inference for the number and structure of comparisons. Whether any of these approaches was used is not reported in the registry record.

Missing-data procedures are also not reported. The registry does not state how participants with absent, incomplete, or unevaluable scans would be treated, whether all enrolled participants were included in the primary analysis, or how the endpoint denominator was defined. These details matter because a proportion depends on both the number meeting the endpoint and the number assessed. The record provides classification counts but does not explain how they relate to the enrollment total.

Analysis populations, including any distinction between all enrolled participants and those with evaluable imaging, are not reported in the registry record. The record does not describe exclusions, deviations, or handling of participants who could not be assigned a clinical classification. It also does not report interim analyses or a sample-size justification. These omissions do not establish that such procedures were absent; they mean that they are not documented in the registry entry. With no posted outcome analysis, readers cannot assess how missingness, multiplicity, or analysis-population choices affected the results.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

For the F-18 AV 1451 tau PET scan group, the registry lists 81 participants at risk for serious adverse events and 0 participants with serious adverse events; it also lists 81 at risk for other adverse events and 0 affected. The registry lists 0 deaths. These are the safety figures posted for this group.

The healthy-control group is listed with 0 participants at risk for either serious or other adverse events, 0 affected, and 0 deaths. The registry says these controls were drawn from a separate study and were not consented or enrolled in this study. Their zero-at-risk entries should therefore not be interpreted as safety follow-up of an enrolled comparison arm.

Zero recorded events means that the registry reports none in the categories and groups shown. It does not establish that no events occurred outside the recorded definitions, observation period, or reporting process. The registry does not provide additional detail about event definitions, collection procedures, duration of safety follow-up, or the completeness of adverse-event reporting. The figures should be read as registry-reported counts, not as a complete characterization of safety.

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

The record establishes that investigators completed a study intended to characterize overall tau burden using F-18 AV 1451 tau PET in people with PPA and frontotemporal dementia. It identifies a primary outcome based on the proportion of PPA participants showing elevated binding compared with healthy controls, and lists a secondary outcome concerning regional binding patterns across PPA variants. It also describes how the clinical categories were assigned and where the healthy controls came from.

Those descriptions do not reveal the primary outcome’s observed value. The registry does not report the number of participants who showed elevated binding, a percentage for any category, an uncertainty interval, or an analysis of the comparison. It does not report the criterion used to define elevated binding. The posted information therefore cannot establish the size, precision, or statistical evidence of any difference between the PPA groups and healthy controls.

The study’s design also limits what can be inferred from a comparison with the controls. The study is listed as non-randomized and single-group, and the healthy controls were not enrolled in this study. Although the record says the controls completed an identical imaging and clinical protocol, it does not report whether relevant differences between the groups were assessed or adjusted for. A comparison with an external reference group should not be interpreted as a randomized treatment effect or as a causal estimate.

More generally, the registry’s endpoint and classifications are descriptive of what was intended to be measured; they are not outcome results. No claim about the presence, absence, or clinical significance of elevated binding can be drawn from the posted results alone. The safety counts likewise describe registry-reported events and do not substitute for detailed safety follow-up information.

13. Why This Trial Matters Statistically

This study raises statistical questions that are central to imaging research in clinically diverse populations. The primary endpoint is organized around whether tau PET binding is elevated across different PPA clinical variants, rather than only around an overall group summary. That structure can make the results more clinically descriptive, while also requiring transparent definitions for each category and for the meaning of “elevated.”

The use of healthy controls from a separate study is another important design feature. An external reference group may provide context for interpreting imaging measurements, but it does not have the same design protections as a concurrently randomized comparator. Readers need to know how the reference value was defined, whether the groups were comparable, and how uncertainties were handled. Those methods and the resulting estimates are not reported in the registry record.

The registry also illustrates why completion status and enrollment alone are not enough to evaluate a study’s evidence. Without the primary outcome counts, denominators, uncertainty estimates, and analysis methods, readers cannot judge the precision or robustness of the reported endpoint. Details about missing scans, analysis populations, and multiplicity are especially relevant when results are intended to be examined across several clinical categories.

Statistically, the record is informative about the question and design but does not provide the results needed to quantify the findings. That distinction matters when interpreting registry entries: a clearly stated endpoint is not itself evidence of an observed pattern, and a listed control group is not by itself proof of a valid or precise comparison.

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.

A central limitation of the posted record is that it does not report the primary endpoint results. There are no outcome counts, percentages, confidence intervals, or analysis results, despite the study being marked completed. The registry record therefore does not permit assessment of the magnitude or precision of the intended comparison.

The definition of elevated tau PET binding is not reported. The registry does not state the threshold or reference procedure used to classify a scan as elevated, or explain how the healthy-control measurements contributed to that decision. Without a clearly specified operational definition, the endpoint cannot be independently interpreted from the record.

The comparison group was not enrolled in the study. It consisted of healthy controls from the Mayo Clinic Study of Aging, so the design is not a randomized, concurrently enrolled comparison. The registry states that the controls completed an identical tau PET protocol and MRI and clinical protocols, but does not report whether differences between the study participants and controls were assessed or adjusted for.

The record lists participant classifications for the scan arm and controls but does not explain how those counts relate to total enrollment or which participants contributed evaluable imaging to the primary outcome. It does not report missing-data procedures, analysis populations, or reasons for any unavailable endpoint data. It also does not report the statistical plan, multiplicity procedures, or sample-size justification. These limitations concern what is documented in the registry; they do not establish what may have been conducted or reported elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Assessment of Hyperphosphorylated Tau PET Binding in Primary Progressive Aphasia and Frontotemporal Dementia — NCT02736695.
• Registry record last updated 2025-11-21; status last verified 2025-11.
• Results first posted 2025-11-21.
• 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.

18. Record Summary

NCT02736695 is a completed Phase 1, non-randomized, unmasked, single-group study sponsored by Mayo Clinic, with enrollment listed as 81. The record describes F-18 AV 1451 tau PET imaging in participants with PPA or frontotemporal dementia and a healthy-control reference group drawn from the Mayo Clinic Study of Aging. The controls were not consented or enrolled in this study.

The primary outcome concerns the proportion of PPA participants with elevated tau PET binding compared with healthy controls, with a stated timeframe of 1 week. The registry lists clinical classifications and a secondary outcome on regional binding patterns, but does not report primary or secondary outcome results, analyses, or the rule used to define elevated binding. Methods for missing data, analysis populations, and multiplicity are also not reported in the registry record.