Effect of Aged Garlic Extract on Atherosclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Aged Garlic Extract on Atherosclerosis (NCT01534910), a randomized phase 4 study. The primary outcome is CT Angiography Plaque.

2. Clinical Question

The trial addressed whether assignment to aged garlic extract was associated with a different average one-year change in low attenuation plaque than assignment to placebo. This is a question about a continuous imaging measure, not a direct comparison of whether individual participants did or did not experience a change. The registry also describes interest in coronary and neck artery plaque and markers of inflammation, but the primary endpoint identified in the results is CT angiography plaque. The registry lists coronary calcium as a secondary outcome; a result for that outcome is not reported in the registry record.

3. Trial Design

This was a phase 4 randomized, parallel-group trial comparing aged garlic extract with placebo. The registry records enrollment of 65 and status as completed. The start is listed as 2012-05 and primary completion as 2014-12. The reported primary outcome timeframe is baseline to 1 year. These dates describe the registry record; they do not establish how long each participant took to enroll or complete follow-up.

The structured trial information identifies masking as quadruple. The brief summary describes the study as double blind. The registry does not explain which groups of people were masked or how the two masking descriptions relate to each other. Allocation is listed as randomized, but the method used to generate or conceal the assignment sequence is not reported in the registry record. The model is parallel, meaning participants were assigned to one of the two study groups rather than receiving both interventions in sequence.

The arm descriptions identify a sugar pill comparator and 2400 mg of aged garlic extract. The primary outcome summaries report 28 participants for the sugar pill arm and 27 for the aged garlic extract arm. The registry enrollment field is 65; the reason that the outcome summaries include those group counts is not reported in the registry record. It is also not reported whether these counts refer to all randomized participants, participants with evaluable scans, or another analysis population.

The registry summary describes CT scans of the heart, carotid ultrasound, and blood work, with tests repeated after one year. The primary results concern low attenuation plaque measured by CT angiography. Details of scan acquisition, central reading, treatment adherence, follow-up procedures, and protocol deviations are not reported in the registry record. The sponsor is the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center.

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 CT Angiography Plaque, measured over baseline to 1 year.

The primary endpoint is the mean percent change in low attenuation plaque from baseline to one year. Plaque volume is measured at baseline and again at the one-year follow-up. The registry defines percent change as follow-up volume minus baseline volume, divided by baseline volume, then multiplied by 100%. Under that definition, a negative value represents a lower measured volume at follow-up than at baseline, while a positive value represents a higher measured volume. The endpoint therefore expresses change relative to each participant’s baseline value rather than as an absolute volume change.

The results list a mean and standard deviation for each group. The posted mean is 0.17 for the sugar pill group and -1.53 for the aged garlic extract group. The comparison is expressed as the mean difference, with the aged garlic extract group contrasted against the sugar pill group. This type of continuous endpoint uses the observed values across participants to compare average change between groups; it does not indicate that every participant had a change matching the group mean.

Imaging measures can quantify features of plaque that are not captured by a simple event count, which is one general reason a trial may use them as endpoints. However, the registry record does not explain why low attenuation plaque was selected as the primary endpoint, how it relates to other measures of plaque, or what magnitude of change would be considered clinically important. The registry lists coronary calcium as a secondary outcome, but its result is not reported in the registry record.

7. Results Posted in the Registry

• Aged Garlic Extract: mean -1.53 versus 0.17 on control; difference -1.70 (95% CI -2.84 to -0.56), standardized effect d = -0.79; z-test p = 0.003.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s plaque measure is represented by a numeric percent change, and the group result is summarized by a mean. A mean is the arithmetic average of observed values. The standard deviation describes how dispersed those values are around the mean. These summaries are useful for understanding a group’s average and variability, but they do not show the full distribution, identify outliers, or indicate how many participants had increases versus decreases.

What does the mean difference express?

The reported comparison is a mean difference, with aged garlic extract contrasted against sugar pill. It is the difference between the group averages on the endpoint scale. The estimate of -1.7 means that the average percent change was lower in the aged garlic extract group by 1.7 percentage points on this scale, as represented by the posted means. The unit is percent change of low attenuation plaque, so the contrast is not an absolute plaque volume difference. The confidence interval describes uncertainty around this estimated contrast.

A group mean is not the same as a typical individual response. For example, a mean can arise from many participants with similar changes or from a mix of increases and decreases. Without participant-level observations or distribution summaries, the registry results do not show which pattern occurred. Nor do the group means reveal whether the observed contrast was driven by baseline differences, particular participants, or other features of the data. Random assignment is intended to make groups comparable on average, but the record does not give baseline results for the primary measure or enough information to assess balance.

How should the p-value be read?

The reported unadjusted p-value is 0.003. In general, a p-value measures how incompatible the observed data, or data more extreme under a specified test, are with a null model of no group difference. It is calculated under assumptions about the analysis and does not measure the probability that the treatment is effective, the size of a difference, or the chance that the result will repeat. The registry record does not identify the exact test used, the sidedness of the trial’s original test, or the complete statistical analysis plan. The p-value should therefore be interpreted as the posted unadjusted result, not as evidence that all possible sources of bias or uncertainty have been addressed.

When several outcomes or analyses are examined, the chance of at least one small p-value can increase. Statistical procedures for multiplicity can address that issue, but whether the trial specified or used such procedures is not reported in the registry record. The comparison is explicitly described as unadjusted. The registry lists two outcome measures and one posted secondary outcome, but that information alone does not reveal how many outcomes, time points, subgroups, or analysis choices were considered during the study.

Why does variability matter?

The standard deviations are 1.97 for sugar pill and 2.32 for aged garlic extract. In general, greater variation makes it harder to estimate a group average precisely when sample size is held constant. Variability also matters for planning future studies because it helps determine how many participants may be needed to distinguish a target difference from random noise. The two reported standard deviations are not identical, and the record does not explain whether the original analysis used a method that allowed for unequal variances or checked distributional assumptions.

For outcomes with skewed or heavy-tailed distributions, a mean-based analysis can be affected by extreme values. General statistical practice includes checking the outcome distribution and assessing whether the selected model is suitable. Those checks and any transformations or robust methods are not reported in the registry record. The registry identifies the outcome as a continuous measure summarized by means and standard deviations, but that alone does not establish that a particular model was used.

What does randomization contribute?

Randomization assigns participants to groups by chance and, when properly implemented, helps reduce systematic differences between groups at the start of a trial. Masking can reduce the influence of expectations on care, assessment, or reporting. The registry lists randomized allocation and quadruple masking, while the brief summary calls the trial double blind. The sequence generation, allocation concealment, and specific masked roles are not reported in the registry record. Consequently, the design labels indicate intended safeguards, but the record does not supply enough detail to evaluate their implementation.

Randomization does not resolve every analytical issue. Missing outcomes can compromise the comparison if the probability of missingness is related to participant characteristics or outcomes. Analysis populations also matter: an analysis of all randomized participants answers a different operational question from an analysis restricted to those with completed scans. The registry does not report the primary analysis population, the number of missing primary outcomes, or the method used to address missing data.

What is not established by the posted analysis?

The primary comparison gives an estimate, a confidence interval and an unadjusted p-value. These quantities summarize the observed evidence under an analysis framework, but they do not determine whether the difference is meaningful to patients or predicts clinical outcomes. No threshold for an important change is reported in the registry record. The stated endpoint is an imaging measure, and results for other outcomes are not reported. The registry also does not report an original statistical analysis plan, interim analyses, or a sample-size justification. Those omissions limit assessment of how the posted analysis relates to the trial’s prespecified design.

10. Confidence Intervals and Precision

The posted mean difference is -1.7, with a 95% confidence interval from -2.839 to -0.561. This interval describes a range of values compatible with the observed comparison under the statistical model used to construct it. In general, a 95% confidence interval is produced by a procedure that would cover the underlying parameter in 95% of repeated samples when its assumptions hold. It is not a statement that there is a 95% probability that this particular interval contains the true value.

The interval is on the negative side of zero, which aligns with the posted unadjusted p-value of 0.003. The estimate is more precise than a point estimate alone because the interval conveys uncertainty, but it still permits a range of possible mean differences. The distance between the interval limits should be considered on the endpoint’s scale: percent change of low attenuation plaque. The registry does not state what range would be clinically important, so statistical precision cannot by itself establish practical importance.

Precision depends on the amount of information in the data and the variability of the outcome. The primary summaries report 28 participants in the sugar pill group and 27 in the aged garlic extract group, with standard deviations of 1.97 and 2.32, respectively. These counts are the ones attached to the outcome summaries, not necessarily the number randomized or the number with complete follow-up; the analysis population is not reported in the registry record. The registry also does not provide a separate interval for each group mean or information about missing scans, so precision cannot be evaluated for those features from the posted record.

The confidence interval addresses sampling uncertainty under the calculation’s assumptions. It does not account automatically for possible outcome measurement error, selective reporting, protocol deviations, or unreported analytic choices. The interval also pertains only to the mean difference in the specified one-year endpoint. It should not be generalized to other outcomes, timeframes, or participant groups without evidence for those settings.

11. 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, not total event counts. They illustrate the approximate group size for a future two-arm study under the stated assumptions, using the observed mean difference as a reference. For planning to detect 100% of the observed effect, the illustration gives 26 participants per arm for 80% power and 34 participants per arm for 90% power. For planning to detect 75% of the observed effect, it gives 45 participants per arm for 80% power and 60 participants per arm for 90% power. For planning to detect 50% of the observed effect, it gives 101 participants per arm for 80% power and 135 participants per arm for 90% power.

Power is the probability, under a specified model and effect assumption, that a study will reject the null hypothesis when the assumed effect is present. The 80% column uses a design with an 80% chance of detecting the specified effect under those assumptions; the 90% column uses a design with a 90% chance. Higher power generally calls for more participants. The assumptions listed for this illustration are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect equal to the stated fraction of the observed effect. These are planning assumptions for the illustration; the original trial’s own design assumptions are not reported in the registry record.

Smaller target effects require more participants because they are harder to distinguish from random variation. The figures are a planning illustration based on the observed effect, not observed power. The original study’s sample-size justification is not reported in the registry record, so the illustration should not be treated as the rationale for its enrollment target or as proof that the study was adequately or inadequately sized.

12. 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 = -1.700; pooled standard deviation σ = 2.149.
2. n = 2 × (1.96 + 0.842)² × 2.149² / -1.700² = 25.1, rounded up to 26 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 <- -1.7                      # observed difference in means
sigma <- 2.14883338247999                     # 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(1534910)
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 = 26 (80% power), 34 (90% power)
 75% of observed effect: n per arm = 45 (80% power), 60 (90% power)
 50% of observed effect: n per arm = 101 (80% power), 135 (90% power)
power.t.test: 26.1 
Simulated power at n = 26 per arm: 0.796 (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.

13. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified as CT angiography plaque, and the registry lists coronary calcium as a secondary outcome. It records two outcome measures and one posted secondary outcome. A secondary result is not reported in the registry record. The primary comparison has an unadjusted p-value of 0.003. Whether the original protocol designated a single primary analysis, whether there were additional outcomes or time points, and whether any multiplicity adjustment was planned or applied are not reported in the registry record.

Multiplicity is the statistical issue that arises when several hypotheses are tested. In general, each additional test can create another opportunity for a chance finding; adjustments can control the overall error rate across a defined family of tests. The unadjusted p-value is interpreted without such a correction. Because the registry record does not describe the full set of planned or performed analyses, it is not possible to determine whether the posted p-value reflects the trial’s complete testing strategy or how it would compare with an adjusted result.

The analysis population for the primary outcome is not reported in the registry record. The enrollment field gives 65, and the outcome summaries list 28 participants for sugar pill and 27 for aged garlic extract. The registry does not explain why those figures differ or whether all randomized participants were included in the analysis. It also does not report the number of missing one-year scans, reasons for missing measurements, withdrawals, or exclusions.

Methods for handling missing data are not reported in the registry record. In general, excluding participants with missing outcomes can affect a group comparison if missingness is related to the outcome or differs between groups. Alternatives may require assumptions about unobserved values; those assumptions and any sensitivity analyses are also not reported. The record does not identify an intention-to-treat, per-protocol, or other named analysis population. It therefore cannot establish whether participants were analyzed according to random assignment or under another rule.

The statistical analysis plan, interim analyses, and protocol deviations are not reported in the registry record. Their absence does not establish that none occurred; it means the posted record does not permit an assessment of their role. These gaps matter when interpreting the p-value and confidence interval because both depend on the chosen analysis and the data included.

14. 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.

The registry lists serious adverse events for 33 participants at risk in the sugar pill group and 32 at risk in the aged garlic extract group. It records zero participants affected by serious adverse events in each group. The same at-risk counts are listed for other adverse events, with zero affected in each group. These are counts of participants affected, not counts of separate event episodes. The registry does not provide serious adverse event terms, and the list of top serious terms is empty.

Deaths are not reported in the registry record. The adverse event counts should be read in relation to the stated at-risk denominators and the study’s observation period, which is not specified for these safety summaries. Zero recorded participants affected does not prove that no adverse events occurred outside the registry’s reporting definitions or observation window. The record does not provide event severity details beyond the serious-versus-other categories, causality assessments, exposure duration, or the method of safety monitoring.

The safety counts are not the same as the primary outcome counts: the adverse event groups list 33 and 32 participants at risk, while the primary outcome summaries list 28 and 27. The reason for these different denominators is not reported in the registry record. These safety figures describe what was posted for this trial and do not establish a broader safety profile.

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

The posted result supports a statistical comparison of the average one-year percent change in low attenuation plaque between the two randomized groups. The estimated mean difference is -1.7 for aged garlic extract versus sugar pill, with a 95% confidence interval from -2.839 to -0.561 and an unadjusted p-value of 0.003. The interval is compatible with a negative difference under the model used for the reported comparison. The data indicate that the observed group average was lower in the aged garlic extract arm on this endpoint scale.

That statistical result does not establish how important the difference is for health. The registry record does not state a threshold for a clinically meaningful change or report whether the imaging difference corresponded to fewer clinical events. The primary measure is a plaque imaging endpoint over the stated timeframe, not a direct measure of how participants felt, functioned, or experienced cardiovascular events. Results for the listed secondary outcome of coronary calcium and other measures mentioned in the trial summary are not reported in the registry record.

The result also does not mean that each person in the aged garlic extract group had a reduction, or that each person in the comparator group had an increase. Group means do not describe individual responses. The record does not provide the distribution of changes, missing-outcome details, or the precise analysis population. The enrollment field and the outcome-summary counts differ, and the registry does not explain why. These limitations make it difficult to assess how completely the primary comparison represents all randomized participants.

Randomization and masking are features of the recorded design, but the registry does not report enough operational detail to evaluate how assignment and masking were implemented. The structured information identifies quadruple masking; the brief summary describes double blinding. The record does not clarify the terminology or identify masked roles. The statistical analysis plan and multiplicity approach are also not reported, while the p-value is unadjusted.

Accordingly, the posted evidence is best understood as an estimate for a specific mean imaging outcome in this trial, accompanied by a confidence interval and unadjusted test result. It does not settle the clinical meaning, establish effects on unreported outcomes, or provide a complete basis for conclusions beyond the measured comparison.

16. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation requires more than reading a p-value. The mean difference provides a direction and scale for the comparison, while its confidence interval communicates uncertainty. Here, the estimate is -1.7 on a percent-change scale, and the interval extends from -2.839 to -0.561. Those quantities describe the observed comparison more fully than a significance label alone, but they do not say whether the size of the contrast matters clinically.

The endpoint is a continuous imaging measure. Such measures can capture changes that are not expressed as event counts, but their interpretation depends on how they are measured, how variable they are, and how well they relate to outcomes that matter to participants. The registry identifies the measurement and timeframe but does not report a clinically meaningful threshold, the imaging reading procedures, or the relationship between the endpoint and clinical events. This makes the distinction between statistical evidence and clinical relevance especially important.

The record also highlights the importance of understanding denominators. Enrollment is listed as 65, while the primary outcome summaries include 28 and 27 participants. Safety at-risk counts are 33 and 32. Without an explanation of analysis populations and missing outcomes, readers cannot tell why these counts differ or how representative the primary comparison is of everyone assigned to the trial. Reporting the number assessed, excluded, and missing at each outcome would clarify the flow of information into the analysis.

Finally, the posted p-value is unadjusted, and the analysis plan and multiplicity procedures are not reported. A p-value can be read in context only when the testing strategy and analysis choices are understood. The registry result is informative as a reported comparison, while the missing methodological details limit assessment of prespecification and robustness. These are general lessons for clinical trial interpretation: examine the effect estimate, its uncertainty, the endpoint’s meaning, the population analyzed, and the analysis context together.

17. 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 trial-specific details needed to assess the primary result are not reported in the registry record. These include eligibility criteria beyond the listed metabolic syndrome condition, baseline participant characteristics, the randomization sequence method, allocation concealment, and the specific people masked. The structured record identifies quadruple masking, while the brief summary says double blind; it does not explain that difference.

The registry does not explain why the outcome summaries include 28 participants in the sugar pill group and 27 in the aged garlic extract group when enrollment is listed as 65. It also does not reconcile those outcome counts with safety at-risk counts of 33 and 32. The primary analysis population, missing scan counts, withdrawals, reasons for missingness, and missing-data methods are not reported. Without them, the completeness of the analyzed outcome and the handling of participants without follow-up measurements cannot be assessed.

Measurement and analysis details are also limited. The registry describes low attenuation plaque volume at baseline and one year, but the scan acquisition and interpretation procedures, reader masking, quality control, and measurement reliability are not reported. The precise statistical test or model, analysis plan, assumption checks, subgroup analyses, interim analyses, and protocol deviations are not reported in the registry record. Nor is an original sample-size justification available.

The posted primary estimate does not provide results for coronary calcium or the other outcomes described in the summary, and those results are not reported in the registry record. No clinically meaningful threshold is given for the percent-change measure. These limits do not negate the reported comparison, but they restrict assessment of its robustness, clinical relevance, and relation to outcomes beyond the primary imaging endpoint.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Effect of Aged Garlic Extract on Atherosclerosis — NCT01534910.
• Registry record last updated 2017-04-20; status last verified 2017-03.
• Results first posted 2015-04-03.
• 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.

21. Record Summary

The registry record describes a completed phase 4 randomized, parallel-group trial of aged garlic extract versus placebo for participants with metabolic syndrome. Enrollment is listed as 65. The primary endpoint is mean percent change in low attenuation plaque on CT angiography from baseline to one year. The arm descriptions specify 2400 mg of aged garlic extract and a sugar pill comparator.

The primary outcome summaries list 28 participants in the sugar pill group and 27 in the aged garlic extract group. Their means are 0.17 and -1.53, respectively. The posted mean difference is -1.7, with a 95% confidence interval from -2.839 to -0.561 and an unadjusted p-value of 0.003. The registry lists coronary calcium as a secondary outcome, but its result is not reported in the registry record.

Serious and other adverse event counts are zero in both groups among the listed at-risk participants; deaths are not reported in the registry record. Details about the analysis population, missing data, the statistical analysis plan, and the original sample-size justification are not reported in the registry record.