This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase II Trial of Florbetapir (18F) Positron Emission Tomography (PET) Imaging in Japan of Healthy Volunteers, Patients With Mild Cognitive Impairment (MCI) and Patients With Alzheimer's Disease (AD) (NCT01662882), a non-randomized phase 2, phase 3 study. The primary outcome is Qualitative Amyloid Image Assessment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01662882 |
| Phase | Phase 2, Phase 3 |
| Condition | Alzheimer's Disease, Mild Cognitive Impairment |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 48 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Avid Radiopharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned Japanese healthy volunteers, participants with mild cognitive impairment (MCI), and participants with Alzheimer's disease (AD). The record lists an enrollment of 48. The safety summaries describe 15 AD Subjects, 15 MCI Subjects, and 18 Healthy Controls at risk for the reported event categories. These groups represent clinical-status categories, not groups assigned at random.
Intervention
Participants received florbetapir (18F) for positron emission tomography (PET) imaging. The registry describes the intervention as a drug and the study as open label. The primary endpoint concerns the qualitative interpretation of the resulting images, rather than a clinical treatment outcome.
Comparator
The imaging findings were considered across AD, MCI, and healthy-control groups. Because allocation was non-randomized, the groups are not like-for-like control arms created by random assignment. Their clinical characteristics define the categories being distinguished; the record does not describe a randomized comparison of different treatments.
Primary question
Can blinded readers classify florbetapir PET images as positive or negative for amyloid, with the majority read serving as the primary qualitative endpoint? The endpoint was assessed 50-60 min after injection. The registry record does not report the group-specific primary outcome counts or diagnostic-performance estimates, so the magnitude or precision of any separation among the clinical groups cannot be determined from the recorded outcome information.
3. Trial Design
The record describes an open-label, parallel-group, multicenter study of florbetapir (18F) PET imaging in Japan. It lists the study phases as Phase II and Phase III, allocation as non-randomized, masking as none, and the model as single group. The enrollment is 48. The record lists AD Subjects, MCI, and Healthy Controls as the participant groups; the safety summaries report 15, 15, and 18 participants at risk, respectively, for the event categories recorded.
The study began in 2012-10, reached primary completion in 2013-02, and has completed status in the registry record. Its stated aim was to evaluate imaging for distinguishing Japanese healthy control subjects from Japanese subjects with AD or MCI. This is a question about the characterization and classification of images across clinical groups, not a randomized treatment-effect comparison.
Non-randomized allocation means clinical status determined the group category; the record does not describe random assignment to those categories. As a result, observed differences between groups, if reported, would not by themselves establish that florbetapir caused differences in clinical status or outcomes. The study is open label at the study level, while the primary image-reading description specifies that five readers were blinded to all clinical information. These describe different aspects of the design: readers were kept unaware of clinical information for the image assessment, even though the record does not list masking for the study overall.
The registry identifies the sponsor as Avid Radiopharmaceuticals. It does not report further details of the site structure, eligibility criteria, participant flow, or a protocol-based sample-size justification. The enrollment figure describes the study record; it should not be interpreted as the number contributing to the primary endpoint, because the primary analysis population and endpoint denominators are not reported in the registry record.
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
| Stage | AD Subjects | Healthy Controls | MCI Subjects |
|---|---|---|---|
| STARTED | 15 | 18 | 15 |
| COMPLETED | 15 | 18 | 15 |
| NOT COMPLETED | 0 | 0 | 0 |
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.
| Characteristic | Unit | AD Subjects | Healthy Controls | MCI Subjects | Total |
|---|---|---|---|---|---|
| Participants analysed | 15 | 18 | 15 | 48 | |
| Age Continuous | participants | 73.3 (SD 7.80) | 70.0 (SD 11.15) | 73.3 (SD 5.09) | 72.1 (SD 8.57) |
| Sex: Female, Male: Female | Participants | 14 | 10 | 6 | 30 |
| Sex: Female, Male: Male | Participants | 1 | 8 | 9 | 18 |
| Region of Enrollment: Japan | participants | 15 | 18 | 15 | 48 |
6. Primary Endpoint
The registry lists the primary outcome as Qualitative Amyloid Image Assessment, measured over 50-60 min after injection.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled “Qualitative Amyloid Image Assessment.” It measures the number of participants whose florbetapir PET image was classified as positive or negative for amyloid. Five readers, blinded to all clinical information, assessed the images. The majority read was designated as the primary efficacy endpoint for the qualitative evaluation. The timeframe is 50-60 min after injection.
A binary classification reduces an image-reading judgment to two categories. The majority-read approach uses the collective direction of the reader assessments to define the primary classification, rather than treating each reader as a separate participant-level outcome. Blinding readers to clinical information is relevant because knowledge of a participant’s diagnosis could influence subjective interpretation. This is a general reason for blinding in image assessment; the record does not report additional procedures used to maintain it.
Qualitative classification is used to address whether images can be distinguished by an image feature of interest—in this case, amyloid positivity—across the clinical groups under study. It is not, by itself, a measure of diagnostic accuracy. Interpreting accuracy would require outcome information such as the classifications in each clinical group and a clearly specified reference standard. The registry record gives the endpoint definition but does not report its participant counts, group-specific results, or estimates of sensitivity, specificity, or other diagnostic performance. Thus, the endpoint’s intended meaning is clear, while its observed result cannot be evaluated from the outcome information recorded.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the study question and the primary image-assessment procedure, but it does not report the primary endpoint’s outcome values. In particular, the number of participants classified as amyloid positive or negative in the AD, MCI, and healthy-control groups is not reported in the registry record. Without those counts, there is no basis in the recorded results for describing how often the majority read was positive, comparing groups, or assessing the precision of a group contrast.
The study’s objective was to evaluate whether florbetapir PET imaging could distinguish healthy control subjects from subjects with AD or MCI. That objective should not be mistaken for a reported finding. The record’s description of an endpoint and its intended use does not establish that the groups were separated, nor does it show how consistently readers classified images. Diagnostic-performance measures and their uncertainty are also not reported in the registry record.
The five readers were blinded to clinical information for the qualitative image assessment. That feature limits one potential source of reader influence, but it does not remove other sources of uncertainty. The record does not give reader-level classifications, agreement measures, or the procedure for resolving any reading differences beyond specifying that the majority read was primary. It is therefore not possible to assess the level of agreement among readers or the stability of the majority classification.
For safety, the record reports no serious adverse events in the listed AD, MCI, or healthy-control groups. It reports one event in the “other” category for MCI and five for Healthy Controls, with none for AD Subjects. These are event counts, not estimates of a causal effect or a formal comparison between groups. The record does not provide event descriptions in this summary, and deaths are not reported in the registry record. The safety counts should therefore be read separately from the missing primary imaging results.
Because allocation was non-randomized, the clinical groups are not treatment arms balanced by random assignment. Even if group-specific imaging results were available, differences would describe comparisons among clinical-status groups and would not constitute randomized evidence about an intervention’s effect. The registry record does not report the primary analysis population, missing-data handling, statistical model, confidence intervals, or multiplicity procedures. Consequently, the available record supports a description of the design and endpoint, but not a quantitative conclusion about imaging performance or the precision of group differences.
9. Statistical Methods Explained
The primary outcome is a participant-level binary classification: positive or negative for amyloid on florbetapir PET. The endpoint is based on the majority read from five readers, who were blinded to all clinical information. The timeframe is 50-60 min after injection. The registry record does not report the positive and negative counts or the analysis denominators. This distinction matters because an endpoint definition explains what would be counted, but does not supply the observed distribution of those counts.
What does a binary endpoint describe?
In general, a binary endpoint places each assessed participant into one of two categories. A count in one category is interpretable only alongside its denominator and the rule used to assign the category. For this study, the rule is the majority read; the clinical question concerns classifications across AD, MCI, and healthy-control groups. The recorded information does not give the group-specific classifications, so proportions, differences, or uncertainty intervals cannot be interpreted from the registry record.
In general, a confidence interval expresses the range of effect estimates compatible with the data under a specified statistical procedure. Its width reflects precision as well as the amount and variability of information in the data. No confidence interval for the primary endpoint is reported in the registry record. It would be inappropriate to infer precision from the overall enrollment figure alone, because the endpoint denominators and outcome counts are not reported.
Why is blinding relevant to image reading?
As a general statistical and measurement principle, blinding can reduce the risk that a reader’s expectations about a participant’s diagnosis influence a subjective classification. The record states that five readers were blinded to all clinical information and that the majority read was the primary efficacy endpoint. It does not report individual reader results, agreement statistics, or additional details about image-reading procedures. The presence of blinding therefore describes a design safeguard, but does not quantify reader consistency.
A majority rule converts multiple readings into one classification for the endpoint. In general, this can make a prespecified decision rule easier to apply consistently, but it can also conceal variation among readers if reader-level results are not presented. The registry record does not report how many readers classified each image in either direction, so reader agreement and disagreement cannot be assessed from the recorded outcome information.
How should the group comparison be understood?
The groups represent clinical categories rather than randomized assignments. In general, non-randomized group comparisons can be influenced by differences between the people in each group, in addition to the characteristic being studied. The recorded design is intended to examine imaging across Japanese healthy volunteers, participants with MCI, and participants with AD. It does not create a randomized treatment contrast, and any reported group contrast would need to be interpreted as an association between clinical category and image classification.
Measures such as sensitivity and specificity require a specified classification rule, a reference status, and the relevant counts. Although the endpoint specifies positive or negative amyloid image assessments and the study objective concerns distinguishing clinical groups, the registry record does not provide diagnostic-performance results or enough outcome information to derive them. No such measures should be inferred from the endpoint description alone.
What do the planning assumptions mean?
The record describes planning illustrations based on a stated fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It specifies that the illustrations use participants per arm for non-time-to-event outcomes; time-to-event calculations, when applicable, use total events. These are planning assumptions, not evidence that the study was designed using those calculations. The record does not report the study’s own sample-size justification.
In general, sample-size planning estimates how much information may be needed to detect a specified effect under chosen assumptions. A planning illustration based on an observed effect is conditional on that effect and the calculation assumptions; it is not observed power and does not establish the probability that the study’s result is true. No numerical planning outputs are reported in the registry record, and the primary endpoint results needed to evaluate the observed effect are not reported there.
What inferential details are missing?
The record lists eight analyses and two outcome measures, but it does not report the primary endpoint’s analysis method, a statistical model, adjustment variables, confidence intervals, or a multiplicity strategy. These omissions limit the ability to reconstruct how uncertainty was quantified or how multiple outcomes and analyses were handled. General statistical principles can explain why these details matter, but they cannot substitute for the unreported analysis plan or results.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures and eight analyses. It does not report whether the primary endpoint was tested alongside other endpoints under a prespecified hierarchy, whether any multiplicity adjustment was used, or how the analyses relate to one another. When multiple outcomes or comparisons are examined, multiplicity is a general concern because repeated testing can increase the chance of at least one apparently notable result. Whether that issue affected this study cannot be determined from the registry record.
The record identifies the majority read as the primary efficacy endpoint for the qualitative evaluation, but does not report the inferential procedure used for it. The analysis population is not reported in the registry record. It is therefore unclear from the recorded information which participants contributed to the endpoint analysis, how missing images or unreadable scans were handled, or whether any participants were excluded from the analysis.
Missing-data handling is also not reported in the registry record. In general, the consequences of missing observations depend on how many are missing, why they are missing, and how the analysis handles them. Those details are necessary for assessing possible bias and for understanding the denominator behind a result. Since the primary outcome counts and denominators are absent, the effect of missing data cannot be evaluated.
The registry’s safety summaries have at-risk counts for the listed categories, but those do not establish the analysis population for the imaging endpoint. The record also does not report an interim-analysis plan, a statistical analysis plan, or whether any estimates were adjusted. These are unreported details, not evidence that a particular procedure was or was not used.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| AD Subjects | 0 | 15 | 0.0% |
| MCI Subjects | 0 | 15 | 0.0% |
| Healthy Controls | 0 | 18 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| AD Subjects | 0 of 15 |
| MCI Subjects | 1 of 15 |
| Healthy Controls | 5 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AD Subjects | MCI Subjects | Healthy Controls |
|---|---|---|---|---|
| Blood pressure increased | Investigations | 0 of 15 | 1 of 15 | 1 of 18 |
| Fatigue | General disorders | 0 of 15 | 0 of 15 | 1 of 18 |
| Malaise | General disorders | 0 of 15 | 0 of 15 | 1 of 18 |
| Vessel puncture site pain | General disorders | 0 of 15 | 0 of 15 | 1 of 18 |
| Vision blurred | Eye disorders | 0 of 15 | 0 of 15 | 1 of 18 |
| Nausea | Gastrointestinal disorders | 0 of 15 | 0 of 15 | 1 of 18 |
| Back pain | Musculoskeletal and connective tissue disorders | 0 of 15 | 1 of 15 | 0 of 18 |
| Headache | Nervous system disorders | 0 of 15 | 0 of 15 | 1 of 18 |
| Dermatitis diaper | Skin and subcutaneous tissue disorders | 0 of 15 | 0 of 15 | 1 of 18 |
The registry reports serious adverse event counts of 0 among 15 AD Subjects, 0 among 15 MCI Subjects, and 0 among 18 Healthy Controls. For the separate “other” event category, the record reports 0 among 15 AD Subjects, 1 among 15 MCI Subjects, and 5 among 18 Healthy Controls. These counts describe the listed groups in the registry safety summary; they should not be read as randomized comparisons.
The serious-event counts are not a complete account of safety unless the event definitions, observation period, collection procedures, and analysis population are also understood. The record does not give those details in the safety summary. It also does not provide event descriptions for the “other” category. The counts alone do not establish whether an event was related to florbetapir or to the imaging procedure, and they do not support a causal comparison across clinical groups.
Deaths are not reported in the registry record. That is different from a reported count of zero deaths. The absence of a reported death value should not be interpreted as confirmation that no deaths occurred. These safety entries should be considered alongside the limits of the registry information, rather than as a comprehensive assessment of risks.
12. What the Result Does, and Does Not, Mean
This record describes a study designed to evaluate florbetapir (18F) PET imaging across Japanese healthy volunteers and participants with MCI or AD. It specifies a qualitative image endpoint in which five readers, blinded to clinical information, classified images as positive or negative for amyloid, with the majority read designated as primary. Those details explain the question and measurement approach.
The record does not report the primary endpoint’s observed counts, group-specific results, or diagnostic-performance estimates. It therefore cannot establish from the recorded outcome information how well the imaging classifications distinguished the clinical groups, how precise any comparison was, or how consistent the reader assessments were. A stated study aim is not itself evidence that the aim was achieved.
The non-randomized design also limits what a group comparison could mean. The clinical groups were not created by random assignment, so differences in image classification would be descriptive comparisons among groups with different clinical status. They would not show that the imaging agent caused a change in disease status or that an intervention produced a treatment benefit.
The safety summary reports no serious adverse events in the three listed groups and reports “other” event counts for MCI and healthy controls, but the record does not provide event descriptions or report deaths. These entries do not establish causality or provide a complete characterization of safety.
In general, evaluating an imaging test requires both a clearly defined classification rule and outcome data that allow its performance and uncertainty to be assessed. The registry provides the classification rule but not the primary outcome values needed for that evaluation. The most defensible interpretation is therefore limited: the design and endpoint are described, while the main imaging result and its precision are not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically relevant because it illustrates the difference between defining an imaging endpoint and reporting evidence about its performance. The endpoint is clearly framed as a binary image classification, with a majority read from five readers and blinding to clinical information. Those design details help explain what the study intended to measure. Without the group-specific classifications and denominators, however, the endpoint cannot be translated into an estimate of separation among clinical groups.
The design also highlights the distinction between diagnostic-group comparisons and randomized treatment comparisons. AD, MCI, and healthy-control status define the groups of interest, but non-randomized allocation does not create exchangeable groups through random assignment. Any observed differences would need to be interpreted in light of that design rather than as causal effects of an intervention.
Reader blinding is another important statistical feature. Subjective assessments may be influenced by knowledge of clinical information, so masking readers to that information is a relevant safeguard. At the same time, the majority rule does not reveal the degree of agreement among readers. Reader-level results or agreement measures would help characterize the reliability of the classification, but they are not reported in the registry record.
Finally, the record demonstrates why interpretation depends on more than an endpoint label or an enrollment figure. Outcome counts, denominators, analysis populations, uncertainty estimates, missing-data procedures, and multiplicity methods all contribute to a complete statistical reading. Several of these details are not reported. The available information supports a careful description of the design and the limits of the recorded results, not a quantitative conclusion about imaging performance.
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 main limitation for interpreting efficacy is that the registry record does not report the primary endpoint results. It gives the endpoint definition, reader procedure, and timeframe, but not the positive or negative counts, group-specific denominators, or diagnostic-performance estimates. Consequently, the principal imaging question cannot be answered quantitatively from the recorded outcome information.
The non-randomized design means comparisons among AD, MCI, and healthy-control groups are not randomized comparisons. Differences between groups could reflect characteristics associated with clinical status as well as differences in image classification. The record does not provide details sufficient to assess the extent of such differences.
The record states that five readers were blinded to clinical information and that the majority read was primary, but it does not report reader-level results or agreement. The analysis population, missing-image handling, statistical model, uncertainty estimates, and multiplicity procedures are also not reported in the registry record. These omissions prevent assessment of the reproducibility and precision of the primary result.
Safety interpretation is limited by the lack of event descriptions in the summary and the absence of a reported death value. The serious and “other” event counts do not establish causality, and the record does not give further details on event ascertainment or observation. The registry lists Phase II and Phase III, but does not report a sample-size justification or enough protocol detail to explain that designation. These limitations concern what can be concluded from the registry information; they do not establish that unreported procedures were not conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase II Trial of Florbetapir (18F) Positron Emission Tomography (PET) Imaging in Japan of Healthy Volunteers, Patients With Mild Cognitive Impairment (MCI) and Patients With Alzheimer's Disease (AD) — NCT01662882.
- Registry record last updated 2013-09-19; status last verified 2013-07.
- Results first posted 2013-09-19.
- 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.
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18. Record Summary
The registry record describes NCT01662882, an open-label, parallel-group, multicenter study of florbetapir (18F) PET imaging in Japanese healthy volunteers and participants with MCI or AD. The record lists Phase II and Phase III, non-randomized allocation, no masking, and a single-group model. Enrollment is 48; the study started in 2012-10, reached primary completion in 2013-02, and is listed as completed.
The primary endpoint was a qualitative amyloid image assessment at 50-60 min after injection. Five readers blinded to clinical information classified images as positive or negative, with the majority read designated as primary. The primary outcome values are not reported in the registry record. Safety summaries report no serious adverse events in the listed groups; deaths are not reported in the registry record. The record does not report the analysis population, missing-data procedures, statistical model, or multiplicity strategy.