Beta-Amyloid Imaging With [18F]NAV4694 PET in Predicting Progression to AD in Subjects MCI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Beta-Amyloid Imaging With [18F]NAV4694 PET in Predicting Progression to AD in Subjects MCI (NCT01812213), a na phase 2 study. The primary outcome is Incidence of Mild Cognitive Impairment Progression to Alzheimer's Disease.

2. Clinical Question

The stated aim was predictive: to investigate whether scan findings could separate people with MCI who later progress to AD from those who do not. This is a question about the relationship between an imaging measure and subsequent clinical progression. It is not, by itself, a question about whether the imaging procedure changes disease progression.

The primary outcome was the incidence of MCI progression to AD over 3 Years. However, the registry says the trial terminated before sufficient information was collected to evaluate that outcome and that data were not collected. Consequently, the record does not provide an observed primary-outcome result with which to assess the intended distinction.

Other listed outcomes concern PET positivity, neuro-cognitive test battery scores, and SUVR scores at specified follow-up times. They describe additional planned measurements, but the registry record does not provide numerical outcome results or analyses for them. The central clinical question therefore remains an intended question rather than one answered by the posted primary-outcome data.

3. Trial Design

The record identifies NCT01812213 as a phase 2, single-group study sponsored by Navidea Biopharmaceuticals. Its title concerns beta-amyloid imaging with [18F]NAV4694 PET in predicting progression to AD among people with MCI. The listed enrollment is 76. The study status is terminated; the record lists a start date of 2013-03 and a primary completion date of 2017-11-02.

The study is not described as a randomized comparison. Allocation is recorded as not applicable, and masking is listed as none. With a single-group model, the registry does not describe a separate control arm for a like-for-like comparison. The intervention is [18F]NAV4694, listed as a drug, and the arm description says it was administered intravenously at 8.1 mCi once every 18 months.

The primary outcome is the incidence of MCI progression to AD, with a timeframe of 3 Years. The record says the trial terminated before sufficient information was available to evaluate this measure, and that data were not collected. The listed secondary outcomes include incidence of PET-positive scans at 18 Months compared with baseline, changes in neuro-cognitive test battery scores at 6, 12, 18, 24, 30, and 36 Months compared with baseline, and change in SUVR scores at 18 Months compared with baseline.

The registry does not report the detailed eligibility criteria, the definition used to classify progression to AD, or a statistical analysis plan. It also does not report why the trial was terminated. These omissions limit how fully the intended design and its implementation can be reconstructed from the registry record alone.

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

Analysis population for the primary outcome, as defined in the registry: Trial terminated prior to collection of sufficient information to evaluate the outcome measure. Data not collected.

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 Incidence of Mild Cognitive Impairment Progression to Alzheimer's Disease, measured over 3 Years.

The primary endpoint is described as the incidence of MCI progression to AD over 3 Years. Incidence is a way to express whether the outcome of interest occurred in the study population during the stated observation period. In this study, progression to AD was the clinical event the investigators intended to relate to [18F]NAV4694 PET findings.

The endpoint is relevant to the stated predictive aim because it defines the later clinical status the imaging findings were intended to distinguish: progression versus no progression. To evaluate that question, outcome status would need to be recorded alongside the scan findings, using a sufficiently clear definition of progression and an appropriate analysis of their relationship. The registry record does not report the operational definition or adjudication process for progression.

Most importantly, the record says the trial terminated before sufficient information was collected to evaluate this endpoint and explicitly states that data were not collected. There is therefore no reported incidence estimate, comparison of scan findings between progression groups, or uncertainty measure for the primary outcome. The endpoint remains a statement of what the study set out to assess, not a result demonstrating how well the imaging measure distinguished later outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends first on distinguishing the study question from the evidence actually reported. The stated question concerns whether PET findings can distinguish people with MCI who progress to AD from those who do not. The primary measure is the incidence of progression to AD over 3 Years. Yet the registry explicitly says that the study terminated before sufficient information was collected to evaluate this outcome and that data were not collected. Statistical methods cannot recover an outcome that was not recorded.

What would an incidence measure describe?

In general, incidence describes the occurrence of a specified event in a defined population over an observation period. Here, the event is progression from MCI to AD, and the stated period is 3 Years. To interpret an incidence estimate, readers ordinarily need a clear event definition, the population contributing information, the observation period, and a method for handling participants whose outcome status is unknown or whose follow-up differs. The registry record does not report the progression definition, the analysis population, or how incomplete follow-up would have been handled. More fundamentally, it states that the primary outcome data were not collected, so no incidence estimate is available in the record.

How would prediction be evaluated?

In general, assessing whether an imaging finding distinguishes later outcome groups requires linking the imaging measure to the subsequent outcome. A statistical analysis might compare the distribution of an imaging measure across outcome groups or quantify how well the measure classifies later status. Such analyses depend on the actual observations and on prespecified definitions of positive scans and progression. The registry lists PET-positive scan incidence and SUVR change among secondary outcomes, but does not report an analysis connecting baseline imaging findings to progression. The method used for the intended predictive question is not reported in the registry record.

Measures of predictive performance also require careful interpretation. A difference between groups, if estimated, would describe an association in the studied data; it would not automatically establish that the imaging finding causes progression or that the same prediction would apply in another population. General statistical practice also distinguishes model development from validation: performance estimated in the same data used to choose or fit a model can be optimistic, so independent evaluation is often important. The registry record does not report whether any prediction model was planned, developed, or validated.

What does a confidence interval communicate?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision for that estimate than a wide interval, while neither interval alone addresses bias, measurement quality, or generalizability. The record does not provide a primary-outcome estimate or confidence interval. Thus, no conclusion about the precision of the intended primary result can be drawn from the registry entries.

A p-value, when reported, would address compatibility between data and a specified statistical model or null hypothesis; it would not measure the probability that a hypothesis is true or the clinical importance of a finding. No primary analysis or p-value is reported in the registry record for this record. The registry reports 0 analyses, and the primary outcome is explicitly marked as not collected. It would be inappropriate to infer statistical significance or lack of significance from those absences.

Why does the single-group design matter?

In general, a control group can provide a concurrent reference for a comparison, while a single-group study describes observations within the studied group. This record identifies a single-group model, allocation as not applicable, and masking as none. It therefore does not provide a randomized, like-for-like control comparison. That design is consistent with an observational predictive question, but it does not support a controlled treatment-effect interpretation. The record's stated aim is to investigate the distinguishing ability of scan findings, not to establish a treatment effect.

Masking can reduce the influence of knowledge about a participant's group or status on some study procedures and assessments. The record lists masking as none, but does not describe how progression was assessed or whether outcome assessors knew imaging findings. The possible implications cannot be resolved without those details. This is a design consideration, not evidence that any particular bias occurred.

How should planning illustrations be read?

In general, sample-size calculations describe the amount of information a future study might need under stated assumptions about the effect to detect, significance level, allocation, and statistical model. The assumptions recorded for the sample-size illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. The record also distinguishes total events for time-to-event calculations from participants per arm for other calculations.

These are planning assumptions, not a description of the completed study design. The record identifies the clinical study as single-group, so the equal-allocation, two-arm assumption in planning calculations should not be mistaken for an observed randomized comparison. Sample-size illustrations are not observed power, and they do not show that an effect was observed. In this case, the absence of primary-outcome data is decisive for interpreting the intended predictive result, regardless of what planning scenarios might imply.

The registry does not report a statistical analysis plan, sample-size justification for the actual study, interim analyses, adjustment for covariates, handling of missing data, or analysis populations. These items should remain unknown rather than being inferred from general practice or from the listed outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 0 analyses. The primary outcome concerns progression from MCI to AD; secondary outcomes include PET-positive scan incidence, neuro-cognitive test battery score changes at several follow-up times, and SUVR score change. Multiple outcomes and repeated time points can create multiple opportunities to examine patterns in the data. In general, multiplicity refers to the interpretive problem that arises when many statistical questions are tested or estimated; the chance of finding an apparently notable result can increase if no analysis strategy is specified.

The registry record does not report whether outcomes were ranked in advance for analysis, whether any adjustment for multiple testing was planned, or how secondary outcomes would be interpreted relative to the primary outcome. It also does not provide analysis results for the listed measures. No claim about multiplicity adjustment or selective reporting can therefore be made from the record alone.

Missing-data handling is especially consequential when the primary outcome itself is stated to have no collected data. The record does not describe an analysis population, the amount or pattern of missing follow-up, or a method for handling incomplete outcome information. It would be inaccurate to treat the primary result as a null finding: no primary estimate is reported because the registry says the outcome data were not collected.

The registry does not report whether analyses were planned by intention to treat, among participants with available data, or under another population definition. It also does not report a statistical analysis plan or interim analyses. Without these details and without outcome data, neither the robustness of an analysis nor the consequences of missingness can be assessed.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hip fracture (2.6%), cardiac failure congestive (1.3%), haemorrhage intracranial (1.3%), post laminectomy syndrome (1.3%), meningitis bacterial (1.3%).

The registry reports safety information for the [18F]NAV4694 group. It lists 76 at risk for serious adverse events, with 14 affected, and 76 at risk for other adverse events, with 16 affected. Deaths are recorded as 0. These are registry counts and denominators; they should be read as safety reporting rather than as evidence about the primary predictive question.

The listed serious adverse-event terms and percentages are hip fracture, 2.6%; cardiac failure congestive, 1.3%; haemorrhage intracranial, 1.3%; post laminectomy syndrome, 1.3%; meningitis bacterial, 1.3%; and headache, 1.3%. The record does not provide further details about timing, severity grading, clinical course, or whether investigators considered an event related to [18F]NAV4694. A reported event in a study does not by itself establish causation.

Because the design is single-group and the record does not identify a control group, these safety figures do not provide a like-for-like comparative estimate. They also do not indicate the background rate of these events in a comparable population. The counts should not be used to infer comparative risk or to answer whether PET findings predict progression to AD.

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

The registry record establishes the study's intended question and the fact that its primary outcome was not evaluated. It describes a phase 2, single-group study of [18F]NAV4694 PET in people with MCI, designed to investigate whether scan findings distinguish those who progress to AD from those who do not. The planned primary measure was the incidence of progression to AD over 3 Years.

The record does not establish that [18F]NAV4694 PET findings did or did not distinguish later progression groups. It reports that the trial terminated before sufficient information was collected and that primary-outcome data were not collected. There is no reported estimate, confidence interval, or primary statistical analysis with which to quantify the intended relationship. This is an absence of evaluable primary data, not a reported finding of no association.

The record also does not establish a causal effect of [18F]NAV4694 on progression, because its stated objective is predictive and the design is single-group rather than a like-for-like controlled comparison. An association between an imaging finding and a later outcome, even if one had been reported, would not by itself show that the imaging finding caused the outcome or that the intervention changed it.

The secondary outcomes and safety entries provide additional descriptions of what was listed in the registry and what was recorded in the safety information. They do not replace the absent primary outcome. The registry does not report numerical results for the listed secondary outcomes or analyses relating scans to progression.

Accordingly, the scientifically defensible conclusion from this record is limited: the study was intended to address a predictive question, but the registry reports that it did not collect sufficient primary-outcome information to answer it. Any broader conclusion about diagnostic or prognostic performance, clinical utility, treatment effects, or comparative safety is not established by these entries.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a research question and an estimable result. The objective was to evaluate whether PET findings could distinguish people with MCI who progressed to AD from those who did not. That question requires observed imaging information linked to observed progression status. The registry says that primary-outcome data were not collected, so the key quantities needed to answer the question are unavailable.

The record also highlights why study design must be matched to the intended inference. A single-group study can describe measurements and explore associations, but it does not create a randomized treatment comparison. Allocation is listed as not applicable and masking as none. The design therefore should not be interpreted as evidence from a controlled comparison of treatment effects.

Outcome lists alone do not constitute evidence. The registry includes several secondary outcomes covering scan positivity, cognitive scores, and SUVR, yet reports 0 analyses and does not provide numerical results for those measures in the record details. A prespecified outcome can clarify what investigators intended to measure, but readers still need collected data, a defined analysis, and an estimate with its uncertainty to interpret the finding.

Finally, this record shows why an absent result must not be recast as a negative result. The primary endpoint was not reported as showing no progression, no association, or no predictive ability. The stated reason is that the trial terminated before sufficient information was available and the data were not collected. Keeping that distinction clear prevents unsupported conclusions and sets an appropriate boundary on what the registry can tell readers.

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 principal limitation for interpretation is explicit: the trial terminated before sufficient information was collected to evaluate its primary outcome, and the registry states that the data were not collected. No primary estimate, uncertainty interval, or analysis is reported. Consequently, the stated predictive aim cannot be judged from the primary endpoint.

The registry identifies a single-group model, allocation as not applicable, and masking as none. It does not report a like-for-like control group. This prevents interpreting the record as a randomized comparison and limits any comparative claims. The registry also does not report details of how progression to AD was defined or assessed, whether assessors were aware of imaging findings, or how scan interpretation was standardized.

Although secondary outcomes are listed, the record does not report their numerical results or analyses. It does not provide a statistical analysis plan, a description of analysis populations, missing-data methods, covariate adjustment, or multiplicity procedures. It also does not report the reason for termination or explain whether any interim analyses took place. These details cannot be inferred from the status or outcome list.

The safety entries are limited to reported counts, denominators, and listed serious-event terms with percentages. The record does not provide further detail on event timing, relatedness, or a comparative control group. Therefore, the safety information cannot establish causation or comparative risk. These limitations concern what can be concluded from the registry record; they do not establish that unreported procedures or analyses did or did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Beta-Amyloid Imaging With [18F]NAV4694 PET in Predicting Progression to AD in Subjects MCI — NCT01812213.
• Registry record last updated 2024-08-14; status last verified 2024-07.
• Results first posted 2024-08-14.
• 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

NCT01812213 is a phase 2, single-group study sponsored by Navidea Biopharmaceuticals, with enrollment listed as 76 and status listed as terminated. It concerned [18F]NAV4694 PET in people with MCI and aimed to investigate whether imaging findings could distinguish participants who progressed to AD from those who did not.

The primary outcome was the incidence of MCI progression to AD over 3 Years. The registry says the trial terminated before sufficient information was collected to evaluate this measure and that data were not collected. It lists secondary PET, cognitive, and SUVR outcomes, but reports 0 analyses.

The safety record lists 14 affected by serious adverse events, 16 affected by other adverse events, and 0 deaths. The record does not provide an evaluable primary result or a like-for-like control comparison.