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 Vaspect Study - An Open-Label Trial Of Donepezil in Vascular and Mixed Dementia (NCT00174382), a non-randomized phase 3 study. The primary outcome is Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00174382 |
| Phase | Phase 3 |
| Condition | Dementia, Vascular, Dementia, Mixed |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 149 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
People with vascular dementia or mixed Alzheimer’s disease and vascular dementia were the populations of interest. The registry record gives an enrollment of 149 and describes an efficacy population requiring at least one dose, baseline efficacy assessment, and at least one post-baseline efficacy assessment.
Intervention
The intervention was donepezil, described as a drug. The trial was open-label, so masking was not used. The registry record does not give further intervention details in the arm description.
Comparator
There was no concurrent comparison group in the single-group design. The allocation is recorded as non-randomized. Change from baseline therefore describes participants’ scores over time during the trial, rather than a randomized difference between treatment groups.
Primary question
The primary outcome was change from baseline in the total score on the standardized Mini-Mental State Examination (sMMSE), assessed at baseline, week 12, and week 24. The registry record describes the intended assessment, but does not report the observed sMMSE changes.
The brief study summary describes aims to document effectiveness, safety, and tolerability of donepezil in people with mixed Alzheimer’s disease and vascular dementia, and to further document these outcomes in vascular dementia. It also names executive functioning, behavior, general cognition, activities of daily living, and global functioning as areas of interest. These stated aims do not establish that the registry record contains results for each area.
The central statistical question is descriptive: how did the mean sMMSE score change from baseline among participants included in the stated Full Analysis Set? The record defines change as the mean total score at an observation minus the mean total score at baseline. Because there is no concurrent control group, this question is not equivalent to whether changes were caused by donepezil or how they compare with changes under another treatment or no treatment. The posted record does not report the estimates needed to describe the magnitude or precision of the primary outcome change.
3. Trial Design
This was a phase 3, open-label, non-randomized, single-group trial of donepezil. The registry lists the conditions as vascular dementia and mixed dementia. Enrollment is recorded as 149. The study start is listed as 2005-06, primary completion as 2008-04, and status as terminated. The record does not explain the reason for termination, so the status alone does not establish why the trial ended or how that affected the planned analyses.
A single-group design follows participants receiving the intervention without a concurrent control arm. In this trial, the primary endpoint was framed as change from baseline in sMMSE score. Such a design can describe the observed course of scores among participants assessed, but it cannot separate any treatment-associated change from other explanations, such as the natural course of illness, changes in care, learning or familiarity with assessments, or other influences over time. These are general limitations of uncontrolled before-and-after comparisons, not reported findings about what occurred in this study.
The open-label designation means the registry does not describe masking of participants or investigators. The allocation field is non-randomized, and the model is single-group; thus, no randomized treatment comparison is described. The arm description contains no additional detail. The registry record does not report a protocol-based rationale for choosing this design, the intended recruitment rate, or a sample-size justification.
The primary endpoint timeframe is baseline, week 12, and week 24. The listed Full Analysis Set includes subjects who received at least one dose and had baseline and at least one post-baseline efficacy assessment, with last observation carried forward (LOCF) used as stated in the population description. The record gives N=137 for this population and reports n=124 at week 12 and n=114 at week 24. These counts describe the stated analysis population and follow-up assessments; the record does not provide a full account of why participants lacked later assessments.
Although the registry labels the study phase 3, that label does not supply missing information about randomization, blinding, comparator choice, or statistical methods. Those features are described directly by the design fields and should not be inferred from the phase designation.
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 |
|---|---|
| STARTED | 149 |
| COMPLETED | 116 |
| NOT COMPLETED | 33 |
Reasons for not completing this period:
| Reason | Donepezil |
|---|---|
| Death | 2 |
| Adverse Event | 19 |
| Withdrawal by Subject | 6 |
| Protocol Violation | 3 |
| Arrived early for last visit in error | 1 |
| Subject felt pill not effective enough | 1 |
| Lost to Follow-up | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS):all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. N=137; Weeks 12, 24 n=124, 114
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 |
|---|---|---|
| Participants analysed | 149 | |
| Age, Customized: < 45 | Participants | 0 |
| Age, Customized: 45-64 | Participants | 20 |
| Age, Customized: >= 65 | Participants | 129 |
| Sex: Female, Male: Female | Participants | 82 |
| Sex: Female, Male: Male | Participants | 67 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set, measured over Baseline, week 12, week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in total sMMSE score from baseline. The registry describes the total score as the sum of its subscores, with a range from 0 to 30; a higher score indicates a better cognitive state. Change is defined as the mean total score at the assessment minus the mean total score at baseline. Assessments were specified at baseline, week 12, and week 24.
A cognitive score can provide a standardized way to describe performance on the measured aspects of cognition. Using change from baseline focuses the outcome on how scores differ over follow-up from participants’ starting scores. The mean summarizes the group’s average score change, while the standard deviation describes variation in individual scores around the mean. These are general interpretations of the stated summary measures; the registry record does not include the observed mean changes or standard deviations.
The endpoint is relevant to the study’s stated interest in general cognition. It is not a complete measure of every aim named in the brief summary, such as behavior, executive functioning, daily activities, or global functioning. The registry lists other outcomes related to daily functioning, drawing and fluency tasks, and neuropsychiatric symptoms. Those outcomes address distinct domains and should not be treated as interchangeable with sMMSE.
The registry record gives the endpoint definition and assessment schedule, but does not report the actual primary outcome results. It is therefore not possible from this record to describe the direction, magnitude, or precision of mean sMMSE change at either follow-up assessment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study intended to assess change in sMMSE score after participants received donepezil, but it does not report the primary endpoint estimates. No mean change, standard deviation, confidence interval, or hypothesis-test result for sMMSE appears in the record information. As a result, the magnitude and precision of the observed cognitive score change cannot be characterized from the registry record.
The stated analysis population was the Full Analysis Set: participants who received at least one dose and had a baseline and at least one post-baseline efficacy assessment, with LOCF specified. Its reported size is N=137, and the record gives n=124 at week 12 and n=114 at week 24. These figures indicate that the number with an assessment at the later listed time point was smaller than at the earlier one, but they do not identify the reasons for missing assessments or show how missingness may have affected the estimates.
The design is important when interpreting any within-group change. In general, a before-and-after change can reflect several influences in addition to the intervention. Without a concurrent comparator, the trial cannot estimate how outcomes would have changed over the same period without the intervention, nor can it support a randomized between-group treatment contrast. This is a design-based limitation, independent of whether the observed score change was positive, negative, or near zero; the registry record does not report which pattern occurred.
The record also does not contain uncertainty measures for the primary endpoint. In general, a confidence interval expresses a range of values compatible with the data and analysis assumptions, and helps readers assess how precisely an estimate has been measured. Without an estimate and its interval, neither the size of a possible change nor its statistical precision can be assessed. The absence of a reported p-value also means the registry record does not permit an inference about a formal statistical test.
Safety information is recorded separately. The Donepezil group has 24 participants reported as affected by serious adverse events and 53 reported as affected by other adverse events; the corresponding at-risk denominators are not reported in the registry record. Listed serious-event terms include hip fracture at 2.0%, myocardial infarction at 1.4%, chest pain at 1.4%, urosepsis at 1.4%, cerebrovascular accident at 1.4%, and cardiac failure congestive at 0.7%. These entries should be read as registry safety listings, not as comparative estimates: the design has no control group, and the record does not give the denominators needed to interpret these figures as event rates.
Overall, the registry record supports a description of the trial’s question, design, analysis population, outcome schedule, and selected safety entries. It does not support a conclusion about the size or precision of the primary outcome change, a causal treatment effect, or a comparison with another treatment.
9. Statistical Methods Explained
The registry describes a continuous primary measure summarized using a mean and standard deviation. It defines the sMMSE endpoint as change from baseline in total score. The record does not specify a primary statistical test, a model for repeated assessments, an adjustment strategy, or confidence intervals for the endpoint. Those details are not reported in the registry record and should not be assumed.
What does a mean change describe?
In general, a mean change is the average of participants’ score changes under the stated definition. Here, the record defines change using the mean score at an observation minus the mean score at baseline. This is a group-level summary. It does not show whether each participant changed by the same amount, and it can conceal variation in individual trajectories. The standard deviation is a descriptive measure of spread around the mean; it is not itself a measure of how precisely the mean has been estimated.
The sMMSE scale is recorded as ranging from 0 to 30, with higher scores indicating a better cognitive state. This gives direction to the score scale, but the record does not report observed score values or changes. A defined scale and direction are not a substitute for the estimated results.
How should repeated assessments be understood?
The stated assessment times are baseline, week 12, and week 24. Measurements from the same participant over time are generally related rather than independent. In general, an analysis of repeated assessments may account for that within-participant relationship, while a simple comparison of group means at separate times may not model it. The registry record does not report which approach was used, so no specific repeated-measures method can be attributed to this trial.
More generally, a model can describe patterns over time and may use available observations under specified assumptions. Its interpretation depends on the model form, the assumptions about the data, and the participants included. Since no model specification or primary results are reported in the registry record, readers cannot assess those choices for this endpoint.
What does the analysis population mean?
The record defines the Full Analysis Set as subjects who received at least one dose and had a baseline and at least one post-baseline efficacy assessment. It reports N=137, with n=124 at week 12 and n=114 at week 24. This definition excludes people without the required efficacy assessments, and thus is not automatically equivalent to analyzing everyone enrolled. The registry does not state whether other analysis populations were used for the primary endpoint or how the Full Analysis Set was chosen relative to a protocol-defined population.
The population description also names LOCF, or Last Observation Carried Forward. In general, this method fills a later missing measurement using a participant’s last observed value. It makes a dataset appear complete for the specified analysis, but it relies on an assumption about what the unobserved later score would have been. A carried-forward value is not a newly observed assessment. The registry record does not give the number of values imputed this way, the timing of those values, or sensitivity analyses evaluating the impact of the method.
Why does the lack of a comparator matter?
In general, a within-group change is a description of how scores differ over time in the observed group. A controlled comparison instead contrasts outcomes under different assigned conditions. Randomization can help make groups comparable with respect to measured and unmeasured factors on average, while masking can reduce some forms of influence on assessment or reporting. This trial is recorded as non-randomized, open-label, and single-group, so it does not provide a randomized contrast or a masked comparison. No causal effect estimate should be inferred from a change-from-baseline result alone.
What can uncertainty measures contribute?
In general, a confidence interval communicates uncertainty around an estimate under a particular analysis. A narrow interval indicates greater statistical precision than a wide interval, though precision does not by itself establish that an estimate is unbiased or clinically important. A p-value, when used, summarizes how compatible the data are with a specified null hypothesis under the test assumptions; it does not measure effect size or the probability that a treatment works. The registry record does not report the primary estimate, its interval, or a p-value, so these concepts cannot be applied to an observed sMMSE result.
What is the role of planning illustrations?
In general, a sample-size calculation describes how many participants might be needed under stated assumptions about an effect, variability, significance level, allocation, and analysis. A planning illustration based on an observed effect is not evidence that the original trial was designed around that effect, and it is not observed power. The record’s stated illustration assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a fraction of an observed effect. For non-time-to-event outcomes, the stated quantity is participants per arm for a specified power; for time-to-event outcomes, it is total events. Those assumptions describe a hypothetical planning framework, not this trial’s single-group design. The registry record does not report the trial’s own sample-size justification or a comparator-based planning target.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 14 outcome measures and 30 analyses. Its secondary outcomes include changes in the Disability Assessment for Dementia activities-of-daily-living and instrumental activities-of-daily-living domains, the total Disability Assessment for Dementia score, free-hand and copied clock drawing tests, a CLOX differential score, phonetic fluency, and the Neuropsychiatric Inventory Questionnaire. These outcomes cover multiple domains and do not all measure the same construct as the primary sMMSE endpoint.
When several outcomes, time points, or analyses are examined, the chance of obtaining at least one apparently unusual result can increase if results are interpreted without accounting for multiplicity. In general, a prespecified hierarchy or adjustment procedure can help control how multiple statistical tests are interpreted. The registry record does not report whether a multiplicity strategy was specified, whether the listed analyses were prespecified, or how primary and secondary results were prioritized. No adjusted or unadjusted outcome results are reported in the information.
Missing-data handling is also relevant. The Full Analysis Set requires baseline and at least one post-baseline efficacy assessment, and the population description specifies LOCF. The record gives N=137 for the set and n=124 at week 12 and n=114 at week 24. It does not report reasons for missing visits, the amount of imputation, assumptions about missingness, or sensitivity analyses. In general, missing-data methods depend on assumptions about why observations are absent and what unobserved values might have been. LOCF does not remove uncertainty about missing outcomes; it replaces them according to a particular rule.
The registry record does not report an interim-analysis plan, stopping boundaries, or a statistical analysis plan. The terminated status does not establish whether interim analyses occurred or why the study ended. These items are therefore not reported in the registry record, rather than evidence that such procedures were or were not used.
11. What the Result Does, and Does Not, Mean
The record establishes that a phase 3, open-label, non-randomized, single-group trial of donepezil enrolled 149 participants with vascular or mixed dementia conditions and planned to assess sMMSE change at baseline, week 12, and week 24. It also defines the Full Analysis Set and reports the sizes of that set and the follow-up assessments. These registry entries describe the study structure and the intended primary measure.
The record does not report the primary sMMSE results. It therefore does not show whether the mean score increased, decreased, or remained similar over follow-up, nor how variable individual scores were. Without an estimate and uncertainty measure, the magnitude and precision of any observed change cannot be assessed. The record also does not provide a reported statistical test for the primary endpoint.
Even if a within-group change were available, general interpretation would remain constrained by the lack of a concurrent control group and the open-label design. A before-and-after pattern cannot by itself distinguish the intervention’s contribution from other changes over time. This is a limitation of what the design can establish, not a statement about the direction or size of any unreported result.
The listed adverse-event entries provide safety information, but the registry record does not report at-risk denominators for the listed group. Consequently, the affected counts and event percentages should not be treated as comparative risks or used to compare safety with another intervention. The record does not describe a control group for such a comparison.
In short, the registry record documents the trial’s objective, design, endpoint definition, analysis population, assessment schedule, selected secondary outcomes, and adverse-event listings. It does not establish a treatment effect, comparative effectiveness, or the precision of the primary outcome. Nor does the absence of primary results in this record establish that the outcome was unchanged; the result is not reported in the registry record.
12. Why This Trial Matters Statistically
This trial illustrates why study design and outcome reporting need to be considered together. A clearly defined cognitive endpoint and assessment schedule make the intended measurement understandable, but they do not reveal the observed result. For the primary sMMSE outcome, the registry defines change and identifies the time points, yet the record does not report estimates or uncertainty. Statistical interpretation depends on both the analysis plan and the results needed to evaluate it.
The single-group, non-randomized, open-label design is also central to the scope of the evidence. Such a study can document scores and events among enrolled participants, but it does not create a randomized comparison. If a change over time is reported, it remains a within-group observation. The design cannot by itself establish what would have happened over the same period in a comparable group not receiving the intervention.
The analysis population and LOCF description highlight a separate issue: the meaning of the analyzed data depends on who is included and how unobserved measurements are handled. The registry reports fewer participants assessed at the later listed follow-up than at the earlier one, but does not explain the missing assessments or report sensitivity analyses. This limits assessment of how robust an estimate might be to missing-data assumptions.
Finally, the record names a range of outcomes and analyses, while leaving multiplicity procedures unreported. In general, a broad outcome set can be useful for describing distinct domains, but it also makes prespecification and transparent interpretation important. Since the statistical plan and primary results are not reported, readers should distinguish carefully between the trial’s stated aims and results that can actually be evaluated. The principal statistical lesson is not a conclusion about donepezil, but the need to interpret endpoint estimates in light of design, missingness, and reporting completeness.
13. 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 estimates. Without mean changes, standard deviations, confidence intervals, or a test result, the magnitude, direction, and precision of sMMSE change cannot be assessed. The record also does not provide enough information to evaluate whether the planned analysis was carried out as described.
The design offers no concurrent comparator and is recorded as non-randomized and open-label. These features limit causal interpretation of any within-group change and leave the result vulnerable, in general, to influences that change over time or affect assessment. The registry record does not report whether any steps beyond the stated design features were used to address these concerns.
The stated Full Analysis Set excludes participants who did not meet its efficacy-assessment requirements. It uses LOCF, but the record does not report how many observations were carried forward, why later assessments were absent, or whether conclusions were examined under alternative missing-data assumptions. The follow-up counts alone do not explain the missingness process.
Safety interpretation is constrained by absent at-risk denominators and the lack of a comparison group. The record lists affected counts and selected serious-event percentages, but does not provide the denominator details needed to assess the frequency of these events in context. The reason for the terminated status is also not reported in the registry record.
Other important information is not reported in the registry record: the sample-size justification, detailed statistical analysis plan, multiplicity approach, interim analyses, and results for the stated primary endpoint. These gaps prevent a full assessment of planned versus conducted analyses and of the precision or robustness of any efficacy result.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Vaspect Study - An Open-Label Trial Of Donepezil in Vascular and Mixed Dementia — NCT00174382.
- Registry record last updated 2015-03-24; status last verified 2015-03.
- Results first posted 2009-06-12.
- 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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17. Record Summary
The registry record describes NCT00174382, the Vaspect Study, as a phase 3 open-label trial of donepezil in vascular and mixed dementia. Allocation is non-randomized and the model is single-group; enrollment is 149. The study start is listed as 2005-06, primary completion as 2008-04, and status as terminated.
The primary endpoint is change from baseline in sMMSE total score at baseline, week 12, and week 24. The score ranges from 0 to 30, with higher scores indicating a better cognitive state. The Full Analysis Set is reported as N=137, with n=124 at week 12 and n=114 at week 24; its definition includes LOCF.
The registry lists 14 outcome measures and 30 analyses, as well as adverse-event entries for the Donepezil group. The primary endpoint results, statistical analysis plan, sample-size justification, reason for termination, and at-risk denominators for the listed adverse events are not reported in the registry record.