To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects (NCT01420328), a randomized na study. The primary outcome is Change in CD68 mRNA Expression in MNC.

2. Clinical Question

The study also posted results for three secondary measures: cream-induced expression of CD16, IL-1b mRNA expression, and plasma endotoxin concentrations. These outcomes extend the focus beyond the primary CD68 measure to other inflammatory markers. The registry record identifies the study condition as inflammation and describes the broader focus as examining inflammatory markers.

The posted primary means are 10.0 for placebo and -68.0 for Vytorin, in percentage of change. The recalculated unadjusted mean difference is -78.0, with a 95% confidence interval from -109.0 to -47.01. These values describe the recorded group summaries and their estimated contrast. They do not by themselves establish how the outcome was measured in detail, whether the observed difference reflects a biological mechanism, or how it relates to clinical outcomes. Those matters are not reported in the registry record.

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group study. The arms were placebo and Vytorin, with 10 participants in each arm and an enrollment of 20. Both arm descriptions specify treatment for 6 weeks. The record lists the study as completed, with a start date of 2011-05-01 and a primary completion date of 2015-07-01. The phase is listed as NA, and the sponsor is University at Buffalo.

Randomization indicates that participants were assigned to study arms by a random process, but the method used to generate or conceal that assignment is not reported in the registry record. Triple masking indicates masking at three levels, but which groups of people were masked and how masking was maintained are not reported in the registry record. The parallel design means the two arms are described separately rather than as a crossover comparison; details such as whether participants could switch treatments are not reported in the registry record.

The primary outcome population is described as all patients entered into the study. The posted arm summaries each include 10 participants. Further details about participant flow, withdrawals, adherence, and the number contributing data to each endpoint are not reported in the registry record. The record describes a placebo comparison but does not provide enough detail to characterize other aspects of trial conduct, such as sites, eligibility criteria, or the allocation ratio planned before enrollment.

This is a small study of short duration, with outcomes recorded at baseline and 6 weeks for the primary measure. The registry record does not state the original design assumptions, sample-size justification, or planned analysis strategy. The posted comparisons can therefore be read as descriptions of the recorded summaries, rather than as a full account of the trial's prespecified statistical analysis.

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

Analysis population for the primary outcome, as defined in the registry: All patients entered into study were analyzed

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 Change in CD68 mRNA Expression in MNC, measured over 0 weeks and 6 weeks.

The primary endpoint is the percent change from baseline in cream-challenge-induced CD68 mRNA expression in MNC after 6 weeks of treatment with Vytorin or placebo. The record describes the measure at 0 weeks and 6 weeks and specifies that the outcome is calculated from the change at 6 weeks relative to the change at 0 weeks, expressed as a percentage. The measure is reported as a mean with a standard error.

This endpoint was used to assess change in a marker of inflammation following a cream challenge. In general, measuring a response after a challenge can provide information about how a biological marker changes under that condition; it does not, by itself, show whether a change leads to a patient-important benefit. The registry record does not describe the laboratory procedures, the reason CD68 was selected as the primary marker, or what magnitude of change would be considered important.

The posted means are 10.0 in the placebo arm and -68.0 in the Vytorin arm. The recalculated unadjusted mean difference is -78.0 percentage of change. This is a comparison of group averages, not a description of each participant's response. The endpoint's formula, interpretation of negative values, and any handling of missing or non-measurable results beyond the stated calculation are not reported in the registry record.

7. Results Posted in the Registry

• Vytorin Arm: mean -68.00 versus 10.00 on control; difference -78.00 (95% CI -108.99 to -47.01), standardized effect d = -2.21; z-test p = <0.001.

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.

Change in Cream-induced Expression of CD16

• 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:
  • Vytorin Arm: mean -57.00 versus -10.00 on control; difference -47.00 (95% CI -81.68 to -12.32), standardized effect d = -1.19; z-test p = 0.008.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Vytorin Arm than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change IL-1b mRNA Expression

• 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:
  • Vytorin Arm: mean -74.00 versus -13.00 on control; difference -61.00 (95% CI -94.32 to -27.68), standardized effect d = -1.60; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Vytorin Arm than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Plasma Endotoxin (LPS) Concentrations

• 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:
  • Vytorin Arm: mean -0.23 versus 0.11 on control; difference -0.34 (95% CI -0.58 to -0.10), standardized effect d = -1.26; z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Vytorin Arm than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The three posted secondary outcomes cover cream-induced CD16 expression, IL-1b mRNA expression, and plasma endotoxin concentrations. Across these measures, the recalculated Vytorin-versus-placebo mean differences are negative, and the confidence intervals are below zero. Taken as a pattern, the direction is consistent with the primary comparison: the Vytorin group means are lower than the placebo group means on the posted scales.

This directional agreement can add context to the primary result because the secondary outcomes concern other inflammatory markers. It does not make the outcomes interchangeable with the primary measure, and it does not demonstrate that they share a mechanism or clinical interpretation. The registry record does not explain whether these outcomes were prespecified as confirmatory, exploratory, or part of a hierarchy. Their place in the study's inferential plan is not reported in the registry record.

Unadjusted secondary results carry less weight because several outcomes were examined and the record does not describe an adjustment for multiple comparisons. In general, when many hypotheses are assessed, a notable result can occur by chance more often across the set than for a single planned test. Without a reported multiplicity plan, the separate p-values do not establish a controlled overall error rate. The secondary outcomes should therefore be treated as supportive descriptive evidence, not as independent confirmation of the primary finding.

The record lists no reported analyses for these secondary outcomes. Their comparisons are recalculated from the posted group summaries and are unadjusted. The data do not show whether these results were emphasized in the original study analysis or how they were interpreted by the investigators. No additional clinical outcomes or longer-term measures are listed among the secondary outcomes described in the record.

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

• Change in Cream-induced Expression of CD16
• Change IL-1b mRNA Expression
• Change in Plasma Endotoxin (LPS) Concentrations

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference describe?

A mean difference compares the average value in one group with the average value in another. In these comparisons, the Vytorin mean is contrasted with the placebo mean. A negative estimate means the posted mean for Vytorin is lower than the posted mean for placebo, using the outcome's stated scale. It does not describe how every participant changed, nor does it establish why the groups differed.

The registry record reports continuous outcomes as means with standard errors. A mean condenses the observations into a group average. A standard error describes the uncertainty of that estimated average, with smaller standard errors generally indicating a more precise estimate of the mean. It is not the same as a standard deviation, which describes variation among individual observations. The record does not post individual values or standard deviations for these outcomes.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the observed data under the assumptions of the calculation. It communicates precision as well as direction: a narrower interval indicates a more precise estimate than a wider one. A confidence interval is not a guarantee that the true effect lies in the interval, and it does not indicate whether an effect is important to patients. The primary interval is -109.0 to -47.01 for the recalculated unadjusted mean difference of -78.0.

How should the p-value be read?

A p-value describes how unusual data at least as incompatible with a specified no-difference model would be, if that model and the analysis assumptions were appropriate. It is not the probability that there is no difference, nor the probability that the finding happened by chance. The primary unadjusted p-value is <0.001. A small p-value does not measure effect importance or remove uncertainty about study design, measurement, missing observations, or multiplicity.

The record does not report the trial's original statistical analysis plan or the inferential procedure used by the investigators. The displayed comparisons are simple, unadjusted recalculations from the posted summary statistics. They are not substitutes for an investigator-reported analysis that might account for design features or prespecified decisions not available in the registry record. The record lists no reported analyses.

Why does multiplicity matter?

When several outcomes are tested, the chance of obtaining at least one apparently notable result can increase, even if each test is considered individually. An adjustment or a prespecified hierarchy can help control that issue, but the registry record does not report a multiplicity strategy. The primary outcome has a distinct role in interpretation; secondary outcomes can add context, but unadjusted results across several measures are less definitive than results interpreted under a stated multiplicity plan.

The record lists four outcome measures in total, including the primary measure and three secondary outcomes. The secondary comparisons are unadjusted. Without a reported plan specifying how the outcomes were prioritized or whether adjustment was intended, the p-values should be read as outcome-specific summaries rather than as a family-wise conclusion.

What can be said about the analysis population?

The primary outcome description says all patients entered into the study were analyzed. The registry record does not report participant-level missingness, imputation, exclusions, or sensitivity analyses. It is therefore not possible to determine from the record whether all enrolled participants contributed usable measurements at both time points or how incomplete measurements were handled. The posted arm summaries contain 10 participants each, but those summaries alone do not document the flow of observations through the analysis.

In general, missing data can affect a comparison if the availability of measurements differs between groups or is related to the outcome. Different assumptions about missing values can lead to different estimates. No missing-data method is reported in the registry record, so no particular approach should be attributed to this study.

The record's listed design is randomized, triple-masked, and parallel. These features describe the intended comparison framework but do not, on their own, establish that allocation concealment, masking, adherence, or follow-up were successful. Further operational details are not reported in the registry record. A full assessment of the analysis would require details of the prespecified model, treatment of baseline values, handling of missing observations, and any planned interim analyses; these are not reported in the registry record.

11. Confidence Intervals and Precision

The primary recalculated unadjusted mean difference is -78.0, with a 95% confidence interval from -109.0 to -47.01. The interval is entirely below zero, which is consistent with a lower posted mean in the Vytorin arm than in the placebo arm for this outcome. The width of the interval also matters: it shows that the estimate is not pinned to a single value, and a range of differences remains compatible with the calculation.

In general, a confidence interval expresses precision by showing the range of estimates that fit the observed data under the calculation's assumptions. It does not express the probability that a particular value is true, and it does not establish whether the estimated difference is clinically meaningful. The registry record does not report a threshold for an important change in CD68 mRNA expression, so the interval cannot be classified against such a threshold.

The arm means are based on 10 participants each, and the standard errors are 9.0 for placebo and 13.0 for Vytorin. The limited number of participants is relevant to precision, although the interval itself is the direct summary of uncertainty for this recalculated comparison. Individual participant values are not reported, so the degree of within-arm variation and the influence of individual observations cannot be assessed from the registry record.

The interval is a recalculation from posted summary statistics, not a confidence interval attributed to a reported investigator analysis. The registry record lists no reported analyses, and the calculated comparison is unadjusted. The interval also does not account for questions that cannot be evaluated from the record, such as missing-data handling or multiplicity. It should be interpreted as precision for this specific summary-statistic comparison, not as a complete measure of uncertainty about all aspects of the study.

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, not total events. They are illustrative calculations based on the observed effect, rather than the trial's original design assumptions. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a planning scenario with an 80% chance of detecting the specified effect under those assumptions, if that effect and the model assumptions were correct. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. These are planning probabilities, not guarantees about a future study's result. The figures are not observed power.

Rows for 100% of the observed effect use the full estimated effect from this small study as the planning target. Rows for 75% and 50% use smaller target effects. Smaller effects are harder to distinguish from random variation under the same assumptions, so the planning figures call for more participants per arm as the target effect becomes smaller. This relationship is a general feature of power planning, not evidence that the smaller effect is the true effect.

The illustrations are based on the observed estimates, which can be uncertain, particularly with 10 participants per arm. They do not account for an original protocol or analysis strategy that is not reported in the registry record. The figures should therefore be read as conditional planning examples for the stated assumptions, rather than as a reconstruction of how the study's enrollment was chosen or as a recommendation for another study.

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 = -78.000; pooled standard deviation σ = 35.355.
2. n = 2 × (1.96 + 0.842)² × 35.355² / -78.000² = 3.2, rounded up to 4 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 <- -78                      # observed difference in means
sigma <- 35.3553390593274                     # 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(1420328)
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 = 4 (80% power), 5 (90% power)
 75% of observed effect: n per arm = 6 (80% power), 8 (90% power)
 50% of observed effect: n per arm = 13 (80% power), 18 (90% power)
power.t.test: 4.4 
Simulated power at n = 4 per arm: 0.743 (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. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and three secondary outcomes, but a multiplicity strategy is not reported in the registry record. It does not state whether the secondary measures were tested within a hierarchy, whether any adjustment was planned, or whether the family of hypotheses was defined in advance. This matters because interpreting several unadjusted tests as though they were one isolated test can overstate the strength of evidence across the group of outcomes. The secondary p-values are therefore best read as separate, unadjusted summaries.

The primary analysis population is described as all patients entered into the study. The posted arm summaries include 10 participants per arm. However, participant flow and endpoint-specific missingness are not reported in the registry record. It is not possible to establish from the posted summaries whether every enrolled participant had complete measurements at both time points, whether any measurements were excluded, or how missing values were handled.

In general, missing-data methods matter because an analysis based only on observed measurements may be affected if the reasons measurements are absent are related to treatment or outcome. Imputation, complete-case analysis, and other approaches rely on different assumptions. The registry record does not report which, if any, method was used. It also does not report sensitivity analyses evaluating the effect of missing data.

The analysis plan, including any interim analyses or stopping rules, is not reported in the registry record. Nor are details of the model, adjustment for baseline measurements, or prespecified handling of unusual observations. These omissions do not show that a particular practice was or was not followed; they limit what can be concluded about the analysis process from the registry record. The posted results support description of the recorded group summaries, while fuller assessment of confirmatory inference would require the missing methodological details.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The registry record lists 0 serious adverse events among 10 participants at risk in the placebo arm and 0 among 10 at risk in the Vytorin arm. It also lists 0 other adverse events in each arm, with 10 at risk in each. Deaths are recorded as 0 in both arms. No serious adverse event terms are listed.

These figures describe the reported counts for the categories recorded in the registry. They do not mean that no symptoms or health events of any kind occurred, because the record reports zero in the listed categories rather than a complete narrative of every event. The record does not provide further details about how adverse events were collected, defined, graded, or attributed to treatment.

With 10 participants per arm, zero recorded events should not be read as proof that an event cannot occur or that the treatments have equivalent safety. The counts are descriptive and cover the study as recorded; they cannot characterize uncommon events or safety over periods beyond the study's 6-week treatment descriptions. No medical conclusion follows from the absence of events in these posted categories alone.

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

The posted primary result describes a lower mean percent change in cream-challenge-induced CD68 mRNA expression in the Vytorin arm than in the placebo arm. The recalculated mean difference is -78.0, with a 95% confidence interval from -109.0 to -47.01 and an unadjusted p-value of <0.001. This is evidence about the recorded group summaries for this marker at the stated timeframe.

It does not show that every participant had a lower measurement, because individual results are not posted. It does not establish the biological explanation for the group difference, the amount of change that would matter to patients, or whether a marker change translates into a clinical benefit. The registry record does not report a threshold for meaningful change or clinical outcome results that would answer those questions.

The results also do not establish how the comparison would look in a broader population or over a longer period. The trial enrolled 20 participants, with 10 per arm, and the treatment descriptions specify 6 weeks. Further eligibility details and longer-term outcomes are not reported in the registry record. Generalizability and persistence therefore cannot be determined from these results.

The secondary results point in the same direction across the posted markers, but they are unadjusted and the record does not report a multiplicity plan. That pattern may be informative as context, but it does not replace a prespecified analysis or independently establish a clinical effect. The trial record supports a statistical description of several biomarker comparisons; it does not support medical advice or a conclusion about treatment decisions.

17. Why This Trial Matters Statistically

This study is statistically notable because it combines a randomized, masked comparison with a small sample and several continuous biomarker outcomes. The primary estimate is large relative to its reported uncertainty, and its recalculated confidence interval lies below zero. At the same time, the modest number of participants means the summary is based on a limited set of observations, and participant-level data are unavailable for examining distribution, outliers, or the consistency of responses.

The record also illustrates why a statistically clear contrast and a clinically interpretable result are different questions. A mean difference and confidence interval quantify a comparison on the stated scale, but the record does not give a threshold for a meaningful change or link the marker to a clinical outcome. Those gaps prevent a direct judgment of practical importance based on the numerical result alone.

Several secondary endpoints provide a consistent directional pattern, while the absence of a reported multiplicity plan limits how strongly that pattern can be treated as confirmatory. The study therefore offers a useful example of reading primary and secondary results with different weights: the primary comparison anchors interpretation, while secondary comparisons can add context without necessarily establishing a separate conclusion.

Finally, the planning illustrations show how sample-size calculations depend on the chosen target effect and stated assumptions. They are not the original study rationale. Distinguishing a retrospective planning illustration from a prospective design calculation is important when reading small-study results and considering what information the registry record does, and does not, document.

18. 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 enrollment was 20, with 10 participants in each arm. This limits the amount of information available about the distribution of participant responses and the precision of group comparisons. The registry record does not post individual observations, so the influence of unusual values and the consistency of changes across participants cannot be assessed.

The outcome is a biomarker measure following a cream challenge, and the record does not report a threshold for clinically meaningful change or clinical outcomes linked to the marker. The findings therefore have a narrow interpretation as changes in the posted measures. The study's duration is described as 6 weeks of treatment; longer-term outcomes are not reported in the registry record.

Important design and analysis details are not reported in the registry record, including the randomization and concealment procedures, which parties were masked, the original statistical plan, handling of missing data, and any multiplicity strategy. The record says all patients entered were analyzed for the primary outcome, but it does not provide a participant flow account or endpoint-specific missingness. These gaps limit assessment of the analysis population and robustness of the comparisons.

The secondary comparisons are unadjusted, and their role in a prespecified testing hierarchy is not reported in the registry record. The sample-size figures are planning illustrations based on observed effects rather than the original enrollment rationale. Finally, eligibility details beyond the description of obese subjects and the brief summary's reference to normal cholesterol are not reported in the registry record, limiting assessment of how broadly the results may apply.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects — NCT01420328.
• Registry record last updated 2024-04-17; status last verified 2024-03.
• Results first posted 2024-04-17.
• 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.

22. Record Summary

NCT01420328 is a completed, randomized, triple-masked, parallel-group study sponsored by University at Buffalo. It enrolled 20 participants and compared placebo with Vytorin for 6 weeks, with 10 participants in each arm. The study condition is listed as inflammation, and the brief summary describes a focus on inflammatory markers in subjects with normal cholesterol.

The primary outcome was percent change from baseline in cream-challenge-induced CD68 mRNA expression in MNC. The recalculated unadjusted mean difference was -78.0, with a 95% confidence interval from -109.0 to -47.01 and p < 0.001. Three secondary outcomes were also posted, with a directionally consistent pattern of negative recalculated contrasts.

The record lists zero serious adverse events, zero other adverse events, and zero deaths in both arms. It does not report a multiplicity strategy, missing-data methods, or the trial's original statistical plan. The numerical comparisons are recalculated from posted summary statistics and should be interpreted as biomarker findings rather than evidence about clinical outcomes.