The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial (NCT00605072), a randomized phase 2 study. The primary outcome is Cognitive Assessment: Trail Making Test Part B.

2. Clinical Question

3. Trial Design

The AVEC Trial was a completed Phase 2, randomized, quadruple-masked, parallel-group study sponsored by the University of Southern California. The registry record lists enrollment of 53 and a start of 2008-01, with primary completion in 2011-12. It lists three groups for the posted primary outcome: ACEI (Lisinopril), ARB (Candesartan), and HCTZ. The registry record does not report the sequence-generation method, allocation concealment procedures, or the meaning of quadruple masking in operational terms.

The registry lists candesartan, lisinopril, hydrochlorothiazide, nifedipine, long acting, and metoprolol, long-acting, as drug interventions. It describes candesartan as an angiotensin receptor blocker, lisinopril as an angiotensin-converting enzyme inhibitor, and HCTZ as a diuretic. It does not report in the registry record how the additional listed drugs fit into the three posted outcome groups or the treatment regimen.

The primary outcome is a continuous measure reported as a least-squares mean with standard error. Its timeframe is Baseline-12 months. Posted outcome counts are 18 for lisinopril, 20 for candesartan, and 15 for HCTZ. These outcome-specific counts need not be interpreted as the complete randomized population or as evidence of the reason for missing observations; those details are not reported in the registry record.

The sponsor reports a Mixed Models Analysis across the three groups, with p = 0.008 for the primary outcome. Numerical model estimates, confidence limits, and detail about the model specification are not reported in the registry record. Two secondary outcomes are also posted: systolic blood pressure and sitting blood flow velocity, each over Baseline-12 months. The record does not report the original sample-size justification or the planned statistical analysis in sufficient detail to reconstruct them.

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

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Cognitive Assessment: Trail Making Test Part B, measured over Baseline-12 months.

The primary endpoint is change in Trail Making Test Part B from baseline to 12 months, expressed in seconds. The test asks a participant to connect sequentially numbered circles and then connect circles marked by numbers and letters in alternating sequence. The registry describes the test as a benchmark of executive function. The score is the time required to complete the task, so the measure reflects task completion time rather than a count of correct answers.

A continuous endpoint retains information about the measured score across participants and groups. The posted group summaries are least-squares means, accompanied by standard errors. These are model-based summaries, but the registry record does not report the model specification or the adjustments used to produce them. The direction of a change should be interpreted in light of the endpoint's scale: the recorded quantity is seconds required for completion. The data alone do not establish why a score changed, nor do they identify the clinical importance of a particular difference.

The endpoint is relevant to the trial's stated interest in cognition because the registry describes Trail Making Test Part B as a measure of executive function. It is nevertheless a specific test score, not a complete assessment of cognition or physical function. The posted primary outcome does not directly measure cerebral blood flow, blood flow regulation, or physical function. Those parts of the study hypothesis cannot be inferred from this endpoint alone.

7. Results Posted in the Registry

• ARB (Candesartan): mean 17.00 versus -14.00 on control; difference 31.00 (95% CI 4.63 to 57.37), standardized effect d = 0.74; z-test p = 0.021.
• HCTZ: mean 4.00 versus -14.00 on control; difference 18.00 (95% CI -6.95 to 42.95), standardized effect d = 0.49; z-test p = 0.157.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Blood Pressure Outcome: Systolic BP

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • ARB (Candesartan): mean 27.00 versus 28.00 on control; difference -1.00 (95% CI -14.86 to 12.86), standardized effect d = -0.05; z-test p = 0.888.
  • HCTZ: mean 21.00 versus 28.00 on control; difference -7.00 (95% CI -20.86 to 6.86), standardized effect d = -0.36; z-test p = 0.322.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ARB (Candesartan) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between HCTZ and the control. The interval gives the range of effects that remain compatible with the data.

Blood Flow Velocity, Sitting

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • ARB (Candesartan): mean -2.85 versus -0.30 on control; difference -2.55 (95% CI -7.01 to 1.91), standardized effect d = -0.38; z-test p = 0.262.
  • HCTZ: mean 0.35 versus -0.30 on control; difference 0.65 (95% CI -3.76 to 5.06), standardized effect d = 0.11; z-test p = 0.773.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ARB (Candesartan) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between HCTZ and the control. The interval gives the range of effects that remain compatible with the data.

The two posted secondary outcomes concern systolic blood pressure and sitting blood flow velocity, each measured over Baseline-12 months. Across those outcomes, the sponsor's reported mixed-model p-values are 0.74 for systolic blood pressure and 0.81 for sitting blood flow velocity. The unadjusted recalculations likewise do not provide clear evidence of a pairwise difference: their intervals span zero for both secondary measures. Together, the posted secondary results do not establish a group difference in these outcomes.

This pattern does not directly confirm or refute the primary result. The primary endpoint measures time to complete a cognitive task, while the secondary endpoints measure blood pressure and blood flow velocity. A group result for the primary test does not demonstrate a corresponding change in either secondary measure, nor does the absence of a clear secondary group difference settle the mechanism proposed in the trial hypothesis. The registry record does not report a complete analysis of blood flow regulation or all aspects of cognition and physical function described in the hypothesis.

Secondary outcomes generally carry less confirmatory weight when many outcomes or contrasts are examined, particularly if they were not assigned a prespecified place in a testing hierarchy. Multiple statistical tests increase the opportunity for chance findings. The registry record lists five outcome measures and five analyses, but does not report a multiplicity adjustment, a hierarchy of hypotheses, or which analyses were prespecified. Therefore, secondary p-values should be considered exploratory in the absence of further analysis-plan detail. This is a general caution about interpretation, not a claim that a particular adjustment was required or performed.

The secondary estimates also have uncertainty, and their reported sample counts are smaller than enrollment. The registry does not explain the difference in counts or report whether missingness could have influenced the results. As with the primary analysis, these limitations prevent a strong conclusion from the secondary pattern alone.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Blood Pressure Outcome: Systolic BP
• Blood Flow Velocity, Sitting

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a Mixed Models Analysis for the primary outcome and an overall p-value of 0.008 across three groups. A mixed model is a statistical approach that can represent relationships among repeated or otherwise structured measurements while accounting for dependence in the data. That is a general description of the method; the record does not specify the exact model used, the repeated-measure structure, the covariates, or the method for handling incomplete observations. Those details should not be inferred from the method label alone.

What does the reported overall test address?

An overall group test evaluates whether the modeled outcome pattern is compatible with a common result across the groups or whether the data provide evidence of some group difference. It is distinct from a single pairwise contrast. The reported p = 0.008 belongs to the Mixed Models Analysis across the three groups. The registry record does not provide the model's parameter estimates, confidence limits, or a complete description of the null hypothesis, so the p-value cannot identify which pair of groups accounts for the reported overall result.

How do the recalculated contrasts differ?

The recalculated contrasts use the posted summary statistics to compare each non-reference group with ACEI (Lisinopril). They are described as unadjusted because they do not reproduce the sponsor's mixed model or account for unreported covariates and model structure. Their standard deviations are approximate, derived from the posted standard errors, as indicated in the calculation record. These recalculations are useful as a transparent comparison of the posted summaries, but they are not a substitute for the sponsor's own analysis. Given the flagged discrepancy, the sponsor's own analysis takes precedence.

A mean difference describes the difference between group means on the outcome's original scale. Here, that scale is seconds. The comparison estimate of 31.0 for ARB (Candesartan) versus ACEI (Lisinopril) is accompanied by an interval from 4.631 to 57.37; the estimate of 18.0 for HCTZ versus ACEI (Lisinopril) is accompanied by an interval from -6.946 to 42.95. The direction of each contrast follows the displayed group order: the non-reference group relative to the ACEI group. These pairwise results and the overall mixed-model result answer related but not identical statistical questions.

What does a p-value tell the reader?

As a general statistical concept, a p-value measures how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not quantify the size or clinical importance of a difference. A smaller p-value does not resolve possible bias, missing observations, model limitations, or multiplicity. Interpretation requires the estimate, its uncertainty, the analysis plan, and the study context. The registry does not report enough detail to assess all of those elements for the sponsor's model.

Why can over-dispersion matter?

Over-dispersion is a general issue for outcomes whose variability exceeds what a model assumes. It can make standard errors too small if the analysis does not accommodate the extra variability, which in turn can make intervals appear narrower and p-values more persuasive than warranted. The primary endpoint is continuous, and the registry record does not report an over-dispersion assessment or identify over-dispersion as a concern. This general concept is not evidence that over-dispersion affected this trial's analysis.

The posted group summaries are least-squares means with standard errors, while the sponsor's analysis is labeled mixed models. A standard error describes the estimated uncertainty of a mean or model estimate, not the spread of individual participant scores. The record does not give sufficient model details to determine exactly how the least-squares means were estimated, how missing measurements were treated, or whether the same observations contributed to each analysis.

11. Confidence Intervals and Precision

A confidence interval expresses a range of estimates that are reasonably compatible with the data and the assumptions used to calculate it. It conveys uncertainty around an estimate more directly than a p-value alone. A wide interval indicates that the data are consistent with a broad range of possible differences; an interval near zero may include both little difference and potentially meaningful differences in either direction.

For the recalculated primary comparison of ARB (Candesartan) with ACEI (Lisinopril), the estimate is 31.0 seconds and the interval runs from 4.631 to 57.37. The interval is on the seconds scale and does not include zero. For HCTZ compared with ACEI (Lisinopril), the estimate is 18.0 seconds and the interval runs from -6.946 to 42.95, including zero. These intervals are attached to unadjusted recalculations from posted summaries, not to the sponsor's mixed-model estimates.

The registry reports a 95% confidence level for the mixed-model analysis, but numerical model-based confidence limits are not reported. The comparison intervals do not have a confidence level stated alongside their posted values in the registry record, so they should not be described as the sponsor's 95% intervals. The record also does not report a threshold for a clinically important difference on Trail Making Test Part B. Statistical uncertainty and clinical importance are related but distinct questions.

Precision is limited by the outcome-specific group counts of 18, 20, and 15, as well as by the observed variability reflected in the summaries. A result can be compatible with a range of effects even when its point estimate appears substantial. Precision also depends on the analysis model and missing-data handling, neither of which is fully described for the sponsor analysis. Accordingly, the reported overall p-value should not be read as providing precise knowledge of the pairwise differences or their practical importance.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total events: these are continuous outcomes, and the planning illustration uses participants per arm. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row considers a stated fraction of the observed effect: 100%, 75%, or 50% of the observed effect.

The 80% power column gives the per-arm sample size that the planning calculation associates with an 80% chance of detecting the assumed effect under those assumptions. The 90% power column gives the per-arm size associated with a 90% chance under the same assumptions. These are design targets for a hypothetical comparison, not descriptions of the number of participants analyzed in this trial. The trial's original design assumptions and sample-size justification are not reported in the registry record.

The rows illustrate how the required sample size changes when the assumed effect is smaller: planning for 75% or 50% of the observed effect requires more participants per arm than planning for the full observed effect. Because observed effects can be unstable, especially in a small study, these calculations should not be treated as a reliable forecast of the effect in a future study. This is not observed power.

The listed calculations are based on a two-arm comparison, whereas the sponsor's posted primary analysis concerns three groups. Their assumptions therefore do not reproduce the sponsor's mixed model, and the figures should not be read as an account of how enrollment of 53 was chosen. The original protocol rationale is not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 31.000; pooled standard deviation σ = 41.762.
2. n = 2 × (1.96 + 0.842)² × 41.762² / 31.000² = 28.5, rounded up to 29 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 31                      # observed difference in means
sigma <- 41.7618911874876                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(605072)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 29 (80% power), 39 (90% power)
 75% of observed effect: n per arm = 51 (80% power), 68 (90% power)
 50% of observed effect: n per arm = 114 (80% power), 153 (90% power)
power.t.test: 29.5 
Simulated power at n = 29 per arm: 0.793 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor's Mixed Models Analysis for all three primary-outcome groups, with p = 0.008. It does not report the corresponding model estimate or confidence limits, and it does not give enough specification to recreate the model from the posted summaries. That reported analysis is the sponsor's own result for the primary endpoint.

The recalculated comparisons use the posted least-squares mean changes and standard errors to create simple, unadjusted pairwise estimates. They yield p = 0.021 for ARB (Candesartan) versus ACEI (Lisinopril) and p = 0.157 for HCTZ versus ACEI (Lisinopril). Those pairwise comparisons differ in scope from an overall three-group mixed-model test. They also do not incorporate any modeling or adjustment not represented in the summaries.

The registry record flags a discrepancy between the sponsor's analysis and the recalculations. For that reason, the sponsor's own analysis takes precedence. The recalculations are best treated as a descriptive check on the reported summaries, not as a correction to or replacement for the sponsor analysis. Without model estimates, confidence limits, and analysis details, the source of the difference cannot be established from the registry record.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several hypotheses, outcomes, time points, or pairwise contrasts are tested. As a general statistical matter, testing more hypotheses creates more opportunities for a chance finding, so confirmatory interpretation depends on a prespecified strategy for prioritizing tests or controlling the overall error rate. The registry record lists five outcome measures and five analyses, and reports a primary endpoint plus two secondary outcomes. It does not report a multiplicity adjustment, a testing hierarchy, or the details of a prespecified analysis plan.

The sponsor reports an overall primary-outcome analysis across three groups. The registry record does not state whether that test was the sole confirmatory test, whether pairwise tests were planned, or how secondary outcomes were treated in the original analysis plan. The pairwise recalculations are unadjusted. They should not be interpreted as multiplicity-controlled results. The sponsor's model-based p-value and the recalculated pairwise p-values answer different questions, and the registry's discrepancy flag means the sponsor's own analysis takes precedence.

Missing-data handling is another unresolved issue. The registry reports primary-outcome counts of 18 for lisinopril, 20 for candesartan, and 15 for HCTZ, and smaller counts for the secondary outcomes. It does not report reasons for missing measurements, the number of participants randomized to each group, the analysis population, or a missing-data method. The mixed-model label alone does not establish how incomplete data were handled. It also does not show whether the analysis followed an intention-to-treat principle or another population definition.

These omissions limit assessment of bias and reproducibility. If outcome availability is related to treatment assignment or participants' results, analyses of observed measurements can differ from the results that would have been obtained with complete follow-up. That is a general concern, not a finding that missingness caused bias in this trial. The registry record does not report sensitivity analyses or enough information to judge the impact of missing data.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event figures are zero affected participants in each of the three outcome groups: ACEI (Lisinopril) had 0 of 18 at risk, ARB (Candesartan) had 0 of 20, and HCTZ had 0 of 15. These are the registry's reported serious adverse event counts for the listed groups. No serious adverse event terms are listed among the top serious terms.

Other adverse events are reported for 5 of 18 participants in the ACEI group, 6 of 20 in the ARB group, and 6 of 15 in the HCTZ group. The registry record does not provide event-level descriptions for these other events in the information, so their nature, severity, timing, and relationship to treatment cannot be assessed from these counts. Death counts are not reported in the registry record.

These figures describe the recorded event counts in the stated groups; they do not establish that no unreported events occurred or that the groups have equivalent safety. Small group counts also limit how much can be inferred about uncommon events. The registry record does not report further safety-analysis methods or a comparison of adverse-event rates.

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

The main statistical result in the registry is an overall mixed-model group analysis for Trail Making Test Part B, with p = 0.008. It supports the conclusion that the sponsor's reported analysis found evidence of a difference among the three groups for this endpoint over Baseline-12 months. It does not, on its own, identify the size of the difference, which groups account for it, or whether the difference is clinically important.

The simple recalculated pairwise comparisons offer estimates in seconds but do not reproduce the sponsor's analysis. The ARB comparison interval is above zero, while the HCTZ comparison interval spans zero. Because the registry record flags a discrepancy, the sponsor's own analysis takes precedence. The absence of numerical estimates and confidence limits from that model makes it difficult to describe its group-specific pattern and precision.

The endpoint is a task completion time used as a benchmark of executive function. A result on this test is not equivalent to a broad claim about cognition, daily functioning, cerebral blood flow, or physical function. Although those broader topics appear in the trial's stated hypothesis, the registry's posted primary and secondary measures do not establish every component of that hypothesis. The secondary outcomes do not show clear group differences in the reported mixed-model analyses.

The statistical results do not establish a causal explanation beyond the reported trial comparison, and they do not show whether observed changes are attributable to a particular biological pathway. The record does not report enough information about the allocation process, adherence, missing data, or model specification to fully assess the analysis. Nor does it report a threshold for a meaningful difference on the test. The results should therefore be interpreted as limited evidence about a specific measured outcome in this completed trial, rather than as a comprehensive conclusion about treatment effects.

18. Why This Trial Matters Statistically

This trial is statistically notable because it reports an overall group result for a continuous cognitive test while also providing group-level summaries that can be used for transparent, unadjusted comparisons. Putting those forms of evidence side by side illustrates how an overall model test and pairwise estimates can address different questions. The significant overall p-value does not supply the missing group-specific effect estimates, and the pairwise recalculations do not replace the sponsor's model.

The record also illustrates why estimates and uncertainty matter alongside statistical significance. A p-value alone does not show the size of a difference or how precisely it is known. The recalculated intervals span different ranges for the two comparisons, while the registry does not provide confidence limits for the sponsor's primary mixed-model result. That gap restricts interpretation even though the reported overall p-value is small.

The study's enrollment and outcome-specific group counts also make precision and analysis transparency important. The registry does not report the original sample-size justification, complete model specification, missing-data handling, or multiplicity strategy. Each omission limits the ability to determine how robustly the posted results address the trial hypothesis.

Finally, the trial connects a cognitive test with proposed vascular and functional outcomes, but the posted secondary measures do not show clear group differences. The contrast between a primary overall result and less conclusive secondary findings is a reminder that related outcomes are not interchangeable. Each measure supports conclusions only about the specific construct and analysis it represents.

19. 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.

Several limitations are specific to what the registry reports for this trial. Although it lists randomized allocation and quadruple masking, it does not describe the randomization procedure, concealment, or masking implementation. It lists five drug interventions but reports outcome groups for three treatments; the role of nifedipine, long acting, and metoprolol, long-acting, in the posted outcome groups is not reported in the registry record.

The primary outcome counts are 18, 20, and 15 across groups, while the registry enrollment is 53. Counts are lower for the posted secondary outcomes. Reasons for the differences, participant flow, and the analysis population are not reported in the registry record. The record also does not describe adherence, treatment changes, or how missing measurements were handled.

The sponsor's primary analysis is reported only as a Mixed Models Analysis with p = 0.008. Its estimates, confidence limits, model specification, and covariate adjustments are not reported. The registry flags a discrepancy with unadjusted recalculations, so the sponsor's own analysis takes precedence; the information available does not establish why the results differ. The recalculated standard deviations are approximate, and those comparisons are not adjusted for the model or multiplicity.

Other limitations include the absence of a reported original sample-size justification, an explicit multiplicity strategy, and a threshold for a clinically important Trail Making Test Part B difference. The record describes the endpoint and time frame but does not provide broader cognitive, physical-function, or blood-flow-regulation results sufficient to evaluate all elements of the stated hypothesis. These are limitations in the registry record and do not demonstrate that the trial did not collect additional information.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial — NCT00605072.
• Registry record last updated 2013-02-15; status last verified 2013-01.
• Results first posted 2013-02-15.
• 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.

23. Record Summary

The AVEC Trial is a completed Phase 2 randomized parallel-group study sponsored by the University of Southern California. The registry record lists quadruple masking, enrollment of 53, a start of 2008-01, and primary completion in 2011-12. The primary outcome is change in Trail Making Test Part B completion time, in seconds, from baseline to 12 months.

The sponsor reports a three-group Mixed Models Analysis with p = 0.008. Unadjusted recalculations give pairwise estimates, but the registry flags a discrepancy; the sponsor's own analysis takes precedence. The posted secondary analyses do not show clear group differences. Key details about model specification, sample-size rationale, multiplicity, and missing-data handling are not reported in the registry record.