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 Acute Effects Of Donepezil On Brain Perfusion And Memory In Subjects With Cognitive Impairment And Mild Alzheimer's Disease (NCT01082965), a randomized na study. The primary outcome is Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01082965 |
| Phase | NA |
| Condition | Alzheimer's Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with amnestic mild cognitive impairment (MCI) and mild Alzheimer’s disease, described in the official title, and people with memory deficits and/or mild dementia, described in the study summary. Alzheimer’s disease is the condition listed in the registry. The full analysis set was defined as randomized participants who received at least 1 dose of study drug; for each measure, the reported N refers to participants evaluable for that measure.
Intervention
The active intervention was donepezil. The study summary describes the aim as evaluating acute effects, including change in brain blood flow and memory. The dose and detailed dosing instructions are not reported in the registry record.
Comparator
The comparator was placebo. The registry lists randomized assignment and a parallel-group model. It does not report the planned allocation ratio or further details about the treatment and placebo arms.
Primary question
The primary endpoint was change from baseline in posterior cingulate cortex perfusion at Hour 4 on Day 1, measured using arterial spin labeling (ASL). The study hypothesis was that donepezil would positively affect brain blood-flow deficits and that improved blood flow would accompany improved memory. The registry record does not report numerical results for this primary endpoint, so the stated hypothesis cannot be assessed from the recorded results.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group study comparing donepezil with placebo. The registry lists the phase as NA and enrollment as 18. It records a start date of 2010-07 and primary completion in 2012-07. The study status is terminated; the reason for termination is not reported in the registry record.
The official title describes a methodology study of acute effects on regional cerebral perfusion and cognition in people with amnestic MCI and mild Alzheimer’s disease. The study summary frames the hypothesis around brain blood flow and memory. No dose, administration schedule, allocation ratio, or detailed arm descriptions are reported. The registry identifies the interventions as donepezil and placebo, but it does not describe further treatment procedures.
Quadruple masking indicates that the record classifies the study as masked at four levels, but which people or roles those levels refer to is not reported in the registry record. Randomization can help balance participant characteristics between groups on average, while masking is intended to limit influences on care, measurement, and assessment. Those are general design principles; the record does not provide details that would establish how either feature was implemented.
The full analysis set included all randomized participants who received at least 1 dose of study drug. For an outcome measure, N means the number of participants evaluable for that measure, rather than necessarily every member of the full analysis set. The registry does not report a detailed account of exclusions or the numbers contributing to each outcome in the available record.
The outcome listing includes seven outcome measures and 62 analyses. Secondary measures cover ASL perfusion, CogState tasks and test battery results, and Rey Auditory Verbal Learning Test recall. They are assessed at several specified time points on Day 1 and Day 8. Numerical results for the primary endpoint are not reported in the registry record, so the design and outcome descriptions alone do not establish the direction or size of any observed effect.
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 | Donepezil | Placebo |
|---|---|---|
| STARTED | 10 | 8 |
| COMPLETED | 9 | 6 |
| NOT COMPLETED | 1 | 2 |
Reasons for not completing this period:
| Reason | Donepezil | Placebo |
|---|---|---|
| Protocol Violation | 0 | 1 |
| Other | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all randomized participants who received at least 1 dose of the study drug (donepezil or placebo). Here, 'N' (Number of participants analyzed) signifies those participants who were evaluable for this measure.
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 | Donepezil | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 8 | 18 | |
| Age Continuous | years | 74.7 (SD 9.6) | 70.6 (SD 6.9) | 72.9 (SD 8.5) |
| Sex: Female, Male: Female | Participants | 5 | 6 | 11 |
| Sex: Female, Male: Male | Participants | 5 | 2 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1, measured over Baseline, 4 hours post-dose on Day 1.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ratio |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in posterior cingulate cortex perfusion at Hour 4 on Day 1. Perfusion is a measure of blood flow through tissue. The registry says it was assessed using arterial spin labeling (ASL), a noninvasive magnetic resonance method for measuring regional cerebral perfusion.
The reported measure is average relative perfusion rate. It is defined as average absolute perfusion rate divided by whole-brain absolute perfusion rate at the same time point. Average absolute perfusion rate is the average of left and right absolute perfusion rates at that time point. Thus, the endpoint is a relative measure: it expresses perfusion in the posterior cingulate cortex in relation to whole-brain perfusion, rather than reporting only an absolute regional blood-flow value.
Baseline provides the reference for describing change after dosing. A regional perfusion measure is relevant to the study’s stated question because the study hypothesized that donepezil could affect brain blood-flow deficits. The endpoint is a physiological measurement, not itself a direct measure of memory or day-to-day functioning. The study separately listed cognitive outcomes, including CogState measures and verbal-learning recall.
The registry specifies a mean and standard deviation as the endpoint summary approach, but does not report the primary endpoint’s group means, variability, or between-group comparison in the available record. It also does not provide a numerical estimate or confidence interval for the endpoint. Consequently, the measurement definition can be described, but the magnitude and precision of the recorded treatment contrast cannot be evaluated from the registry results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and design, but it does not provide numerical results for the primary perfusion endpoint. It is therefore not possible to describe whether the posted primary results favored donepezil or placebo, to quantify the difference between groups, or to judge its precision. The hypothesis in the study summary is a proposed relationship, not a finding.
The listed primary outcome concerns change from baseline in posterior cingulate cortex perfusion at Hour 4 on Day 1. The endpoint uses relative perfusion, defined in relation to whole-brain perfusion at the same time point. That definition matters for interpretation: the measure is not simply an absolute blood-flow reading in the posterior cingulate cortex. The registry does not provide values needed to determine the observed regional change or the contrast between assigned groups.
Memory and cognition were also part of the study’s stated aims. The listed secondary outcomes include ASL perfusion at additional time points, CogState measures, and immediate and delayed recall on the Rey Auditory Verbal Learning Test. A list of outcomes is not evidence that any one of them changed. Numerical results for those measures are not included in the registry record for this analysis, so no direction or size of cognitive effects can be reported.
The registry lists enrollment as 18, while the analysis population definition distinguishes the full analysis set from the participants evaluable for each measure. The actual evaluable Ns for individual outcomes are not reported in the registry record. Without those Ns and outcome summaries, it is not possible to assess how much information contributed to a particular estimate or whether the contributing participants differed across outcomes.
For a continuous endpoint, an estimate of a group difference describes the observed contrast, while a confidence interval describes the range of values compatible with the data under the analysis assumptions. This is general statistical interpretation; the registry record does not report an estimate or interval for the primary endpoint. In their absence, neither the size of any possible effect nor its statistical precision can be assessed. The record also does not state a primary comparison result or a p-value for that endpoint.
The study is marked terminated, but the reason is not reported in the registry record. Termination status alone does not explain why the study ended or indicate what the unreported outcome values were. The posted information supports a description of the research question, design, endpoint definitions, and some safety counts, but not a conclusion about the primary treatment contrast.
9. Statistical Methods Explained
The registry describes a randomized, quadruple-masked, parallel-group study and reports continuous outcomes summarized by means and standard deviations. The primary endpoint is a change-from-baseline measure of relative ASL perfusion. The record does not include the numerical group summaries or a statistical comparison for that endpoint. The concepts below explain how such methods are generally interpreted; they do not fill in analyses or results that are absent from the registry record.
What does a mean describe?
For a continuous outcome, the mean is the arithmetic average of the observed measurements in a group. A change-from-baseline mean describes the average difference between follow-up and baseline for the participants included in that analysis. Comparing group means can summarize how the observed average changes differ between randomized groups. A mean alone does not show how widely individual observations vary or how precisely the group contrast has been estimated.
The registry identifies the primary endpoint’s dispersion measure as standard deviation. A standard deviation describes spread among participant measurements around the group mean. It is different from a standard error, which describes uncertainty in an estimated mean. The record does not report the primary outcome means, standard deviations, or standard errors, so those quantities cannot be interpreted for this trial.
Why does the endpoint use a relative measure?
ASL is described in the record as a noninvasive magnetic resonance method for measuring regional cerebral perfusion. The primary measure is average relative perfusion rate: average absolute perfusion in the posterior cingulate cortex divided by whole-brain absolute perfusion at the same time point. The regional absolute value is itself defined as the average of left and right absolute perfusion rates. This construction places the regional reading in relation to a whole-brain reading. As a general point, a relative measure can vary with its numerator and its reference denominator; interpretation therefore depends on the exact definition and on the observed values. The registry does not report those values.
What does randomization contribute?
In general, random assignment is used to make treatment groups comparable in expectation with respect to measured and unmeasured characteristics. It does not guarantee that groups are identical, especially when enrollment is limited. The registry reports randomization but does not provide the allocation ratio, sequence-generation method, concealment procedure, or baseline characteristics in the registry record. Those details cannot be inferred from the design label alone.
Masking is also identified as quadruple. In general, masking can reduce the influence of treatment knowledge on participant expectations, care, measurement, and assessment. The registry does not identify which roles were masked or describe how masking was maintained. It is therefore possible to report the masking classification but not to assess its practical implementation from this record.
How should a confidence interval be understood?
In general, a confidence interval expresses uncertainty around an estimated quantity under a specified statistical procedure and its assumptions. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its limits, and its interpretation depends on the method and study design. No numerical confidence interval for the primary endpoint is reported in the registry record, so precision cannot be judged for its treatment comparison.
What do the analysis counts tell the reader?
The record lists seven outcome measures and 62 analyses. These counts indicate that the registry contains multiple outcome and analysis entries, but they do not reveal the full analytic plan, the hierarchy among outcomes, or which results were emphasized. The primary outcome is identified by name and timeframe, yet the record’s outcome entry is not reduced to one comparison because it has several categories or time points. Numerical estimates for the primary comparison are not reported in the registry record for this analysis.
When many outcomes or comparisons are examined, the chance of at least one apparently notable finding can increase. As a general statistical principle, multiplicity procedures or a prespecified hierarchy may address this concern. The registry record does not report whether such procedures were planned or used. The number of analyses alone is not evidence that a particular adjustment was or was not performed.
What can the planning illustrations establish?
The planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrated effect is expressed as a fraction of the observed effect. These are planning assumptions, not a report of observed power. Sample-size planning illustrations are hypothetical: they show the number of participants per arm that would be needed under stated assumptions, rather than the amount of power actually achieved in the completed trial.
The numerical observed effect and the resulting planning values are not reported in the registry record available for this analysis. Consequently, no particular required sample size or precision can be stated. In general, a planning calculation based on an observed effect is sensitive to uncertainty in that effect estimate; it should not be read as independent confirmation of the effect. The registry does not report the trial’s original sample-size justification or statistical analysis plan.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures and 62 analyses, including several secondary cognitive and perfusion measures assessed at different time points. These counts indicate that the record encompasses multiple outcome and analysis entries. They do not establish which comparisons were designated as confirmatory, whether outcomes were ranked in a hierarchy, or whether any multiplicity adjustment was applied. The multiplicity strategy is not reported in the registry record.
When many outcomes or comparisons are examined, the possibility of obtaining at least one seemingly notable result by chance can rise. This is a general statistical concern, not a claim about what happened in this study. Prespecified outcome hierarchies, adjusted significance thresholds, or other procedures can be used to address multiplicity, but the registry does not report whether any such approach was planned or used. The listing of 62 analyses alone does not establish the statistical plan.
The analysis population is described as the full analysis set: all randomized participants who received at least 1 dose of study drug. The record clarifies that N for a particular measure refers to participants evaluable for that measure. This distinction matters because the number analyzed can differ by outcome. The evaluable Ns and reasons for any missing outcome data are not reported in the registry record.
Missing-data methods can affect estimates when some outcome measurements are unavailable. In general, interpretation depends on how much data are missing, why they are missing, and how the analysis handles them. The registry record does not report the extent or pattern of missing data, imputation methods, sensitivity analyses, or the statistical analysis population used for each particular outcome. It also does not report the original sample-size justification or the complete analysis plan. Those omissions limit assessment of the outcome analyses, independent of the reported design labels.
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 |
|---|---|---|---|
| Donepezil | 0 | 10 | 0.0% |
| Placebo | 0 | 8 | 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 |
|---|---|
| Donepezil | 3 of 10 |
| Placebo | 2 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Donepezil | Placebo |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 10 | 1 of 8 |
| Abdominal discomfort | Gastrointestinal disorders | 1 of 10 | 0 of 8 |
| Asthenia | General disorders | 1 of 10 | 0 of 8 |
| Fatigue | General disorders | 0 of 10 | 1 of 8 |
| Excoriation | Injury, poisoning and procedural complications | 0 of 10 | 1 of 8 |
| Sensory disturbance | Nervous system disorders | 0 of 10 | 1 of 8 |
The registry lists serious adverse events for the donepezil and placebo groups. It reports 0 serious adverse events among 10 participants at risk in the donepezil group and 0 among 8 participants at risk in the placebo group. These are counts within the groups recorded for safety; they are not estimates of a between-group treatment effect.
The record also lists other adverse events: 3 affected participants among 10 at risk in the donepezil group and 2 among 8 at risk in the placebo group. These counts should be read as recorded group counts, not as proof that the study drug caused an event. The registry does not provide event-term details for these other events in the registry record.
The serious-adverse-event listing contains no serious event terms. Death counts are not reported in the registry record. The safety counts do not establish that no events occurred beyond those recorded, and they do not establish comparative safety. The enrollment is limited, and the record does not provide event timing, severity detail beyond the serious/other categorization, or an account of how events were assessed. A zero count in a group is a description of the recorded observations, not evidence by itself that the underlying risk is zero.
12. What the Result Does, and Does Not, Mean
The study was designed to examine acute effects of donepezil on regional cerebral perfusion and cognition in people with amnestic MCI and mild Alzheimer’s disease. The primary endpoint focused on change from baseline in posterior cingulate cortex perfusion at Hour 4 on Day 1. The study summary states a hypothesis linking an effect on brain blood-flow deficits with improvement in memory.
The registry record does not report numerical results for the primary endpoint. It therefore does not establish the observed direction, magnitude, or precision of a donepezil-versus-placebo contrast in posterior cingulate cortex perfusion. Nor can the record establish from the listed outcome names whether cognitive measures changed, or whether any perfusion change was accompanied by a memory change. A hypothesis and an outcome definition are not results.
The primary outcome is a relative perfusion measure, calculated in relation to whole-brain perfusion at the same time point. It is a physiological endpoint, distinct from the listed measures of learning, recall, and cognition. Even if a numerical difference were available, its statistical interpretation would need to be kept separate from any clinical interpretation. The registry record does not give a threshold for a clinically important change or report evidence relating this measure to participant-level functioning.
Enrollment is listed as 18, and the record is marked terminated. It does not state why the study was terminated. The record also does not report the primary outcome estimate, its uncertainty, or the analysis details needed to assess robustness. These omissions prevent conclusions about whether the observed data support the study hypothesis.
The safety listing reports no serious adverse events in either group and records other adverse events in both groups. Those descriptive counts do not demonstrate a treatment effect or establish that one intervention is safer. Overall, the record supports an account of the research question, design, endpoint definitions, and recorded safety counts. It does not support a conclusion about efficacy, the size of a physiological effect, or a clinical benefit.
13. Why This Trial Matters Statistically
This trial illustrates why a clear endpoint definition is not a substitute for a reported result. The registry identifies a specific regional perfusion measure, its baseline comparison, its measurement method, and its timing. Those details help clarify what investigators intended to assess. But without numerical outcome values and a treatment contrast, readers cannot determine the observed effect or its precision.
The endpoint also illustrates how measurement definitions shape interpretation. Average relative perfusion rate compares a regional absolute perfusion measure with whole-brain absolute perfusion at the same time point. This is not interchangeable with an absolute regional blood-flow value. Understanding the numerator, denominator, and timing is essential when assessing what a reported change would mean.
The record combines a physiological primary outcome with cognitive secondary outcomes. The study summary proposed that improved blood flow would accompany improved memory. Assessing that proposed relationship would require results for the relevant perfusion and memory measures, with clear information about timing, analysis populations, and uncertainty. Outcome names alone cannot show whether the measures moved together.
The listing of seven outcome measures and 62 analyses also makes transparency about multiplicity relevant. Multiple outcomes and time points can complicate interpretation, particularly when the analysis plan and adjustment methods are not reported. The record does not establish whether multiplicity was addressed; that uncertainty is itself important for readers interpreting a broad outcome listing.
Finally, the distinction between the full analysis set and participants evaluable for each measure highlights the importance of reporting analysis-specific Ns and missing-data handling. The registry defines these populations but does not provide the relevant detail for the primary endpoint. Together, these features show how design descriptions, outcome definitions, analytic transparency, and numerical results all contribute to statistical interpretation.
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 most consequential limitation of the available registry information is the absence of numerical results for the primary endpoint. The record identifies the measure and timeframe but does not report group summaries, the between-group estimate, a confidence interval, or a p-value. The treatment contrast therefore cannot be evaluated for direction, size, or precision.
The study is marked terminated, but the reason for termination is not reported in the registry record. That status does not explain whether termination was related to recruitment, operations, safety, or another reason; no such explanation can be inferred. Enrollment is listed as 18, but the record does not state the number evaluable for each outcome in the information.
Although the full analysis set is defined, the registry does not report how missing measurements were handled, the amount or pattern of missing data, or sensitivity analyses. It also does not report the allocation ratio, detailed arm procedures, dose, masking roles, original sample-size justification, or full statistical analysis plan. These omissions restrict assessment of the implementation and analysis without implying that a particular practice was or was not used.
The outcome listing includes multiple measures and analyses, but multiplicity procedures and the hierarchy of comparisons are not reported. The primary outcome entry is not reduced to one comparison because it has several categories or time points. No unadjusted recalculation can be made without posted summary statistics, and the sponsor’s own analysis cannot be compared with an independent recalculation from the available information.
Safety information is also limited to group counts for serious and other adverse events. Death counts are not reported, and the record does not give detailed event terms for the other adverse events. These limitations mean that the safety listing is descriptive and does not support a broad comparative safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Acute Effects Of Donepezil On Brain Perfusion And Memory In Subjects With Cognitive Impairment And Mild Alzheimer's Disease — NCT01082965.
- Registry record last updated 2013-09-12; status last verified 2013-07.
- Results first posted 2013-09-12.
- 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 a randomized, quadruple-masked, parallel-group study of donepezil and placebo in people with amnestic MCI and mild Alzheimer’s disease. Enrollment is listed as 18, the phase as NA, and status as terminated. The recorded start is 2010-07, with primary completion in 2012-07.
The primary endpoint was change from baseline in posterior cingulate cortex relative perfusion at Hour 4 on Day 1, measured by ASL. The record defines the analysis population and the relative perfusion measure, but does not report numerical primary endpoint results. It lists seven outcome measures and 62 analyses, while the statistical plan, multiplicity approach, missing-data handling, and reason for termination are not reported in the registry record.
The safety listing records 0 serious adverse events among 10 at risk in the donepezil group and 0 among 8 at risk in the placebo group. Other adverse events are recorded for 3 among 10 and 2 among 8, respectively. Death counts are not reported. The available information supports describing the study design and recorded counts, but not estimating the primary treatment effect.