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 Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for Alzheimer's Disease (NCT00939822), a randomized phase 2 study. The primary outcome is Changes in Cerebrospinal Fluid (CSF) Beta-amyloid-42 Levels Compared to Baseline as Measured by xMAP.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00939822 |
| Phase | Phase 2 |
| Condition | Alzheimer's Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 88 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Wisconsin, Madison |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns adults described as healthy and at risk for Alzheimer's disease. Alzheimer's disease is listed as the condition. The registry record does not provide a more detailed eligibility description in the primary outcome population field, so the precise characteristics used to define risk are not reported in the registry record.
Intervention
The intervention was simvastatin, with the arm description specifying 40 mg. Simvastatin/day. The research question focused on whether treatment was associated with a change in cerebrospinal fluid beta-amyloid-42 from baseline to 18 months. The study summary also describes interest in memory and thinking, cerebral blood flow, and blood vessel function.
Comparator
The comparison group received matching placebo. The study is listed as randomized, triple-masked, and parallel. The registry record does not describe the masking roles or the detailed procedures used to maintain masking.
Primary question
The primary endpoint was the ratio of cerebrospinal fluid beta-amyloid-42 levels at 18 months to baseline, measured by xMAP. The clinical question is whether the endpoint's reported mean differs between the simvastatin and placebo arms. The registry reports arm-specific means and 95% confidence intervals; it does not report a comparative effect estimate or p-value for this endpoint.
3. Trial Design
This was a randomized, triple-masked, parallel phase 2 trial sponsored by the University of Wisconsin, Madison. The registry record lists an enrollment of 88 and a completed status. The study started in 2009-03, and primary completion was recorded in 2013-09. These dates describe the registry record and do not establish when every participant began or completed follow-up.
The intervention arms were simvastatin and matching placebo. The simvastatin arm description specifies 40 mg. Simvastatin/day. The primary outcome timeframe was baseline and 18 months. The registry lists 39 participants for the simvastatin primary outcome and 40 for the placebo primary outcome. These are the group counts attached to the posted endpoint results; the record does not explain why they differ from the enrollment figure.
Random allocation means assignment was intended to occur by chance, which can help balance measured and unmeasured participant characteristics across groups on average. A parallel design assigns participants to a treatment group for comparison rather than describing a crossover. Triple masking indicates that the registry classifies the trial as masked at three levels, but which people or roles were masked and how masking was implemented are not reported in the registry record. The record also does not report the randomization method, allocation concealment procedures, eligibility criteria in detail, or the planned sample-size justification.
The trial's stated broader purpose included evaluating beta-amyloid in spinal fluid, memory and thinking, brain blood flow, and blood vessel function. The posted primary endpoint is specifically the change in cerebrospinal fluid beta-amyloid-42 expressed as a ratio to baseline. Three secondary outcomes are listed, covering beta-amyloid-40, soluble alpha and beta precursor proteins, and total and phosphorylated tau. Outcome results for those secondary measures are not included in the record summarized by the posted primary result.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Screened individuals were not randomized to drug or placebo if they withdrew consent, were unable to complete baseline procedures or no longer met inclusion criteria.
Overall Study
| Stage | Simvastatin | Placebo |
|---|---|---|
| STARTED | 44 | 44 |
| COMPLETED | 42 | 41 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | Simvastatin | Placebo |
|---|---|---|
| Lost to Follow-up | 1 | 0 |
| withdrew from study due to busy schedule | 1 | 1 |
| Mental health issues | 0 | 2 |
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 | Simvastatin | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 44 | 44 | 88 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 41 | 38 | 79 |
| Age, Categorical: >=65 years | Participants | 3 | 6 | 9 |
| Age, Continuous | years | 55.95 (SD 6.2) | 54.4 (SD 7.8) | 55.21 (SD 6.99) |
| Sex: Female, Male: Female | Participants | 31 | 32 | 63 |
| Sex: Female, Male: Male | Participants | 13 | 12 | 25 |
| Region of Enrollment: United States | participants | 44 | 44 | 88 |
6. Primary Endpoint
The registry lists the primary outcome as Changes in Cerebrospinal Fluid (CSF) Beta-amyloid-42 Levels Compared to Baseline as Measured by xMAP, measured over Baseline and 18 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | ratio |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the change in cerebrospinal fluid beta-amyloid-42 from baseline to 18 months. It is defined as the ratio of the 18-month level to the baseline level and measured by xMAP. A ratio expresses a follow-up measurement in relation to its baseline measurement; a value close to 1 indicates that the follow-up and baseline levels are close on that ratio scale. This description explains the measure, not a clinical threshold.
Beta-amyloid-42 is described in the registry as a substance found in plaques in the brains of people with Alzheimer's disease and detectable in cerebrospinal fluid. The registry also states that a defined normal range for middle-aged adults is not yet available. The biomarker was selected to address the study's question about whether simvastatin affects beta-amyloid in spinal fluid. A biomarker outcome can characterize a biological measurement, but by itself it does not establish a change in memory, thinking, disease risk, or clinical health.
The registry reports a mean ratio and 95% confidence interval for each arm. It does not report the comparative mean difference, an adjusted estimate, a p-value, or a threshold defining a meaningful change. Accordingly, the endpoint results describe the observed arm-specific ratios and their uncertainty; they do not alone answer whether any difference is clinically important.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The mean ratio reported for simvastatin is 1.01, with a 95% confidence interval from 0.96 to 1.07. For placebo, the reported mean ratio is 0.98, with a 95% confidence interval from 0.95 to 1.02. Both intervals include 1, the value corresponding to equal follow-up and baseline levels on the ratio scale. The reported values therefore describe means close to the baseline reference, while the intervals indicate uncertainty around each arm's mean.
These are arm-specific estimates, not a direct estimate of the treatment contrast. The registry does not report a difference between the arm means, a confidence interval for that contrast, or a p-value. The arm-level intervals should not be used as a substitute for an interval around the between-arm comparison: the precision of a contrast depends on the uncertainty and relationship of the group estimates, and the necessary comparative analysis is not posted. It is therefore not possible from these results to quantify the difference between simvastatin and placebo or to assess that difference using a reported comparative test.
A confidence interval describes the statistical uncertainty associated with an estimate under the analysis assumptions. It is not a range guaranteed to contain the true value, and it does not show the spread of individual participant measurements. The reported intervals are for the arm means. Individual responses could vary more or less than the uncertainty around those means, but that variation is not described by the posted summary statistics.
The endpoint is a cerebrospinal fluid biomarker measured as a ratio, and the registry says that no defined normal range is available for middle-aged adults. The results should therefore be read as biomarker estimates on the stated ratio scale, not as classifications of normal or abnormal levels. Nor do they establish effects on cognition, brain perfusion, blood vessel function, or the chance of developing Alzheimer's disease. Although the study summary identifies those broader interests, the primary result displayed is specifically the beta-amyloid-42 ratio.
The registry records 39 participants in the simvastatin arm and 40 in the placebo arm for this outcome. The record does not explain the relationship between these endpoint counts and the enrollment figure, or whether participants were excluded from this analysis and why. An analysis population, missing-data handling, and any adjustment for baseline variables are not reported in the registry record. These omissions limit interpretation of how the estimates were produced and whether the analyzed groups fully reflect randomized assignment.
The record lists three secondary outcomes in addition to the primary endpoint, but does not include their results in the posted outcome information. It also lists zero analyses. No multiplicity adjustment, prespecified hierarchy, or other approach to interpreting several outcomes is reported in the registry record. The primary endpoint can be described on its own, but the available record does not establish how it fits into a complete analysis plan across outcomes.
Overall, the posted data give a mean ratio and confidence interval for each arm, with both intervals including the baseline-reference value. They do not provide the direct comparison needed to estimate a treatment contrast. The evidence available in the registry record is consequently limited to descriptive arm-level biomarker results and cannot support a conclusion about clinical benefit or harm.
9. Statistical Methods Explained
The primary measure is continuous: it is a numerical biomarker ratio rather than an event count or a category. The registry identifies the summary parameter as a mean. A mean gives a central summary of the measurements in a group, but it does not reveal their full distribution. Without individual-level data or a reported measure of spread, the range of participant values and the extent of variation within each arm are not available from these results.
What does the ratio represent?
The endpoint is defined as the 18-month cerebrospinal fluid beta-amyloid-42 level divided by its baseline level. The ratio puts follow-up in relation to baseline for the measure. A ratio of 1 represents equality between those two measurements; values above or below 1 represent a follow-up level above or below baseline on the ratio scale. This is a general explanation of ratio measures. The arm means reported by the registry are 1.01 for simvastatin and 0.98 for placebo.
Using a ratio is not the same as reporting an absolute concentration change. The registry's unit is ratio, and it does not provide absolute beta-amyloid-42 concentrations in the primary result. Interpretation also depends on the baseline measurements and the way the ratio behaves across participants. The registry does not report individual values, distributions, or a transformation used in analysis.
How should the confidence intervals be read?
The registry reports 95% confidence intervals around each arm's mean. In general, a confidence interval communicates the precision of an estimate under the statistical model and assumptions used to construct it. A narrower interval indicates greater precision than a wider interval on the same scale; neither interval is a display of the spread of individual measurements. Repeated use of the same interval procedure would capture the target parameter at the stated rate under its assumptions. That general interpretation does not mean that a particular interval is guaranteed to contain the true mean.
The simvastatin mean is 1.01, with an interval from 0.96 to 1.07. The placebo mean is 0.98, with an interval from 0.95 to 1.02. Each interval includes 1, the ratio-scale reference for no change from baseline. This observation concerns the uncertainty around each arm's mean. It does not test whether the two arms differ. A treatment comparison requires a contrast between groups and its own uncertainty estimate; that contrast is not reported in the registry record.
What can randomization and masking contribute?
Randomized allocation is intended to reduce systematic differences in treatment assignment. In general, randomization supports a fair comparison because assignment does not depend on a participant's prognosis as known at enrollment. It does not guarantee that all baseline characteristics will be identical between arms, especially in a trial, and the record does not provide baseline characteristics or the randomization procedure. Triple masking is recorded, but the specific masked roles and methods are not described. Masking can reduce the influence of expectations on care, measurement, and assessment when it is successfully maintained; the record does not report whether masking was assessed or maintained.
The parallel design indicates that the two arms are compared as separate groups. The registry does not report an intention-to-treat designation, a per-protocol population, or another formal analysis population. It also does not report whether the primary analysis was adjusted for baseline biomarker level or other variables. Thus, the design labels alone do not specify the statistical model or the exact population used to estimate the posted means.
Why is the group comparison important?
Within-arm change and between-arm contrast answer different questions. The reported ratios describe average follow-up relative to baseline within each arm. The causal treatment question concerns how outcomes compare under randomized assignment to simvastatin versus placebo. In general, the direct comparison is the relevant estimate for that question, with its confidence interval and test reflecting the uncertainty of the contrast. The registry record does not post that estimate or test, so the arm summaries cannot be treated as a complete inferential comparison.
The sample-size assumptions recorded for planning describe illustrations based on the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. The planning description says that the effect to detect is a stated fraction of the observed effect. Such illustrations are prospective planning scenarios, not observed power and not evidence that the trial was designed around a particular effect. No numerical planning results are reported in the registry record, and the trial's own sample-size justification is not reported in the registry record.
The registry reports 39 participants for the simvastatin endpoint estimate and 40 for placebo, while its enrollment entry is 88. Counts attached to an outcome do not establish why other enrolled participants are not represented in the endpoint estimate. The record does not describe missing-data mechanisms, imputation, exclusions, or sensitivity analyses. These details matter because a mean estimated from available observations can be affected if outcome availability is related to the outcome or treatment assignment.
Finally, the record lists a primary endpoint and three secondary outcomes, but no analysis entries. In general, examining multiple outcomes can increase the chance of a chance finding if each is tested without accounting for the family of tests. A prespecified hierarchy, adjustment procedure, or rationale for treating outcomes separately could help interpret that issue; none is reported in the registry record. Without the comparative model, analysis population, missing-data procedures, or multiplicity approach, the posted arm means and intervals can be described, but the analysis cannot be fully reconstructed.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary outcome and lists three secondary outcomes. The primary measure is the cerebrospinal fluid beta-amyloid-42 ratio; the secondary outcomes concern beta-amyloid-40, soluble alpha and beta precursor proteins, and total and phosphorylated tau. Considering several outcomes raises a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that possibility. The registry record does not report a multiplicity adjustment, testing hierarchy, or other strategy for interpreting the outcome family.
The record lists zero analyses, and results for the three secondary outcomes are not included in the posted outcome information. It is not possible to determine whether those outcomes were analyzed but not posted, were not analyzed, or were handled in another way. The statistical analysis plan, prespecified contrasts, and any interim analyses are not reported in the registry record.
The endpoint summaries include 39 participants for simvastatin and 40 for placebo, while the registry enrollment entry is 88. Missing-data procedures and the analysis population are not reported in the registry record. In particular, there is no description of exclusions, the reasons outcome measurements may be unavailable, imputation, or sensitivity analyses. These details are important because missing measurements can affect the interpretation of group means if their availability is related to treatment or outcomes. The record also does not state whether the analysis followed randomized assignment or used another population definition.
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 |
|---|---|---|---|
| Simvastatin | 0 | 44 | 0.0% |
| Placebo | 0 | 44 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Simvastatin | 0 of 44 |
| Placebo | 0 of 44 |
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 |
|---|---|
| Simvastatin | 0 of 44 |
| Placebo | 0 of 44 |
For both simvastatin and placebo, the registry lists 44 participants at risk for serious adverse events and 0 affected by serious adverse events. It also lists 44 at risk for other adverse events and 0 affected by other adverse events in each arm. Deaths are listed as 0 in both groups. These are the posted counts for the safety categories, not estimates of comparative risk.
Zero reported events means no events were recorded in those categories in the registry results. It does not establish that no symptoms or other harms occurred, that every possible event was captured, or that the treatments have identical safety profiles. The registry record does not give the event-collection methods, observation period for these counts, definitions used for the categories, or details about adverse events not included in these summaries. With no reported events in these categories, the listed counts do not provide a basis for estimating a between-arm difference in event rates. They should be interpreted as registry-reported event counts rather than proof of absence of risk.
12. What the Result Does, and Does Not, Mean
The posted primary results show arm-specific mean ratios of cerebrospinal fluid beta-amyloid-42 at 18 months relative to baseline. The simvastatin mean is 1.01, with a 95% confidence interval from 0.96 to 1.07; the placebo mean is 0.98, with a 95% confidence interval from 0.95 to 1.02. Both intervals include 1, the ratio reference for equal follow-up and baseline levels. These summaries describe biomarker measurements and their uncertainty within each arm.
The registry does not report a direct treatment contrast, confidence interval for the contrast, or p-value. The available results therefore do not quantify how the arms compare statistically. They also do not establish that a difference is absent: an arm-specific interval that includes the ratio reference is not a test of the difference between arms. The comparative estimate and its precision are needed to assess that question directly.
The endpoint is a biomarker, and the registry notes that a defined normal range for middle-aged adults is not available. The result cannot be interpreted as a normal-versus-abnormal classification or as evidence of a clinically meaningful threshold. It also does not establish changes in memory, thinking, blood flow, or blood vessel function, nor does it demonstrate prevention of memory loss or reduced likelihood of Alzheimer's disease. Those broader aims appear in the study summary, but the posted primary endpoint is the cerebrospinal fluid beta-amyloid-42 ratio.
The outcome counts, missing-data procedures, analysis population, and statistical model are not fully described. The secondary outcome results are not posted in the available registry results, and the record does not state how multiplicity was handled. The findings should therefore be understood as limited arm-level summaries, not a complete account of the trial's inferential results or a basis for clinical advice.
13. Why This Trial Matters Statistically
This trial illustrates why an outcome's scale and its comparison matter. The primary endpoint is a ratio of a follow-up biomarker level to baseline, so the reference value has a direct interpretation: 1 represents equality on that scale. The posted means and confidence intervals can be read against that reference, but the treatment question is comparative. Arm-specific summaries do not replace an estimate of the difference between randomized groups.
The registry reports uncertainty around each arm's mean, which is useful descriptive information. Yet the direct contrast and its uncertainty are not reported. This distinction is important in biostatistics: a conclusion about treatment assignment depends on the between-group comparison, not only on whether each group's interval includes a reference value. A complete interpretation also depends on knowing the analysis population, model, and handling of missing measurements.
The trial also makes clear that a biomarker result and a clinical outcome are not interchangeable. Cerebrospinal fluid beta-amyloid-42 was the primary measure, while the study summary describes broader interests such as memory, thinking, perfusion, and vessel function. The registry notes that no defined normal range exists for middle-aged adults, so biological interpretation requires care, and the biomarker alone cannot establish a clinical effect.
Finally, multiple listed outcomes make the analysis plan relevant. The registry record gives no multiplicity approach and no secondary outcome results. These gaps do not change the reported arm summaries, but they limit how comprehensively the evidence can be interpreted. The trial is statistically informative as an example of the difference between a registered design, posted descriptive results, and the full analysis needed to make a comparative inference.
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 registry provides limited detail about who qualified as an adult at risk for Alzheimer's disease. The primary outcome population field is empty, and detailed inclusion and exclusion criteria are not reported in the registry record. This restricts assessment of how broadly the findings might apply. The record's description of beta-amyloid-42 also notes that a defined normal range for middle-aged adults is not available, which limits clinical interpretation of the ratio values.
The primary result includes arm-specific means and confidence intervals, but no direct comparative estimate, p-value, baseline adjustment, or statistical model. The outcome counts are 39 for simvastatin and 40 for placebo, while enrollment is listed as 88; the reasons for this difference are not reported in the registry record. The analysis population and handling of missing data are also not reported, limiting assessment of possible selection or attrition effects.
The registry lists three secondary outcomes, but does not post their results in the outcome information summarized by the primary result. It lists zero analyses, and does not report a multiplicity strategy, analysis hierarchy, or interim analysis plan. Sample-size justification for the trial is not reported in the registry record; the recorded planning description is an illustration based on the observed effect and is not the trial's own design justification.
Masking is classified as triple, but the masked roles and procedures are not described. The registry also does not provide detailed methods for outcome measurement beyond identifying xMAP, or explain the adverse-event collection period and definitions. These record-level limitations constrain interpretation of the results and do not establish that the underlying study lacked these procedures or analyses.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for Alzheimer's Disease — NCT00939822.
- Registry record last updated 2019-08-09; status last verified 2019-08.
- Results first posted 2019-08-09.
- 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 completed phase 2 trial was randomized, triple-masked, and parallel, with simvastatin compared with matching placebo. Enrollment is listed as 88. The study started in 2009-03, with primary completion in 2013-09. The simvastatin arm description specifies 40 mg. Simvastatin/day.
The primary endpoint was the mean ratio of cerebrospinal fluid beta-amyloid-42 at 18 months to baseline, measured by xMAP. The reported mean was 1.01 for simvastatin, with a 95% confidence interval from 0.96 to 1.07, and 0.98 for placebo, with a 95% confidence interval from 0.95 to 1.02. The registry does not report a direct between-arm estimate or p-value.
Three secondary outcomes are listed, but their results are not included in the posted outcome information. The record also lists zero analyses. The serious adverse event, other adverse event, and death counts are listed as 0 in both arms. Details of the analysis population, missing-data handling, and multiplicity procedures are not reported in the registry record.