Systemic Immunomodulatory Effects and Pharmacogenetics of Atorvastatin in Early Atherosclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Systemic Immunomodulatory Effects and Pharmacogenetics of Atorvastatin in Early Atherosclerosis (NCT00361283), a na phase 4 study. The primary outcome is Mean Change in Level: Week 16-baseline in Ena-78.

2. Clinical Question

3. Trial Design

This is a Phase 4, single-group study sponsored by the University of Florida. The registry record lists enrollment of 108 and describes atorvastatin as the sole intervention. The planned regimen was 80mg once daily for 16 weeks. Allocation is listed as NA, masking as none, and the model as single group. These design features mean the study does not provide a randomized control group for separating change during treatment from change that might have occurred over time for other reasons.

The record lists the study as completed, with a start date of 2004-06 and a primary completion date of 2008-12. Those dates describe the registered study timeline; they do not establish when each participant was enrolled or completed follow-up. Individual follow-up information is not reported in the registry record.

The primary outcome is a continuous measure: mean change in ENA-78 from baseline to week 16, in pg/ml. The outcome description says the change is calculated as week 16 minus week 0 and analyzed with a one-sample t comparison. The record lists one outcome measure and one analysis, but does not give the observed estimate, standard deviation, confidence interval, or test result.

The study summary also describes an interest in genetic differences and drug response. The specific genetic measures, analyses, and findings are not reported in the registry record. The listed population for the primary outcome is “Power calculation,” which does not identify an analysis population of participants. Details such as eligibility criteria, recruitment, adherence, withdrawals, and the number contributing outcome data are not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Power calculation

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 Mean Change in Level: Week 16-baseline in Ena-78, measured over 16 weeks after baseline.

The primary endpoint is mean change in ENA-78 from baseline to week 16, measured in pg/ml. The registry record defines the change as the week 16 value minus the week 0 value. A positive change under that definition would indicate a higher measured level at week 16 than at baseline; a negative change would indicate a lower level. The record does not report the observed mean change, so its direction cannot be determined from the registered results.

As a general statistical explanation, a continuous endpoint retains the size of each measured value rather than sorting participants only into categories. A mean change provides a group-level summary of how the measured levels shifted over time. It can be useful for describing a biomarker response, but the average alone does not show whether every participant changed in the same direction or how widely individual changes varied.

The registry identifies ENA-78 as the primary measure in a study focused on immunomodulatory effects. That identifies the question the endpoint was intended to address; it does not establish that ENA-78 is a validated surrogate for clinical outcomes or that a change has a particular clinical meaning. Such validation and interpretation are not reported in the registry record. The assay procedures, timing details beyond baseline and week 16, and handling of measurements below any assay limit are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary analysis as a one-sample t comparison of the week 16 minus week 0 ENA-78 change. In a general one-sample t method, the analysis uses a sample mean and its estimated variability to compare the mean with a reference value. The registry record does not identify the reference value, state the formal null and alternative hypotheses, or report the test statistic or p-value. It is therefore possible to describe the type of analysis but not reconstruct or interpret its specific test.

What does a mean change represent?

For each participant with measurements at both time points, a change score is the later measurement minus the baseline measurement. The mean change summarizes those individual differences. This is not the same as comparing the mean at week 16 with a separate group of untreated participants. In a single-group study, the contrast concerns change within the treated group; without a control group, it does not directly estimate a between-group treatment effect.

As a general statistical explanation, the mean is sensitive to the values of all included observations and can be affected by unusually large or small changes. The standard deviation describes variation among individual values around the mean. The registry identifies standard deviation as the dispersion measure for the outcome, but does not report its value. Without that dispersion estimate and the number of participants with complete endpoint data, readers cannot assess how variable the changes were or how precisely the mean was estimated.

What assumptions matter for a t comparison?

General t-based inference for a mean relies on a suitable model for the observations, including how the individual change values vary and whether the sample provides a reasonable basis for approximating the mean's sampling distribution. The actual distribution of changes, possible outliers, diagnostic checks, and any transformations are not reported in the registry record. No claim can therefore be made about whether the assumptions were checked or how well they fit the observed data. Over-dispersion is a concern in settings where observed variability exceeds a model's assumed variability; for a continuous change outcome, the relevant practical issue is whether the analysis adequately represents the spread of individual changes. The registry does not report enough detail to assess that issue.

A confidence interval for a mean change would communicate the uncertainty around the estimated mean under the analysis model. A p-value would summarize evidence against a specified null value under that model. These are related but different summaries: a p-value is not an effect size, and a confidence interval conveys more directly which mean changes are compatible with the data and assumptions. Neither is reported for the primary outcome in the registry record. The record also does not report a prespecified clinically meaningful threshold, so statistical evidence could not, by itself, establish clinical importance.

How should planning calculations be understood?

General sample-size calculations use assumptions about the effect to detect, variability, significance level, power target, allocation, and statistical model. The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The record's general note says non-time-to-event illustrations are expressed as participants per arm. These are planning assumptions, not a description of the trial's actual single-group design. The illustration is explicitly not the trial's own design calculation, and its numerical outputs are not reported in the registry record.

Planning values derived from an observed effect are conditional on that effect estimate and the other assumptions. They are not observed power, and they do not show the probability that the completed study detected a real effect. The registry does not report the observed endpoint effect needed to evaluate such an illustration. The protocol's sample-size justification and any prospectively chosen target effect are not reported in the registry record.

Finally, the registry labels the primary outcome population as “Power calculation.” That wording does not tell readers which participants were included in the analysis, whether all enrolled participants were analyzed, or how missing measurements were handled. Those details, along with the exact statistical software, any covariate adjustment, and the analysis plan's timing, are not reported in the registry record. The method can thus be understood at a broad level, but the analysis cannot be independently reproduced from the registered information.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Atorvastatin 80 MG/Day")
n   <- c(81)
m   <- c(-111.2)
sp  <- c(690.5)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Atorvastatin 80 MG/Day  81  -111.200  690.500  -263.882  41.482

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and one analysis for the reported primary outcome. It does not report a multiplicity strategy, such as whether any adjustment was planned for testing multiple outcomes, time points, subgroups, or genetic associations. The study summary mentions investigating whether genetic differences relate to drug response, but the number and nature of those analyses are not reported in the registry record. A single listed primary outcome does not establish that no other analyses were conducted.

Missing-data methods are not reported in the registry record. The record does not state how many of the 108 enrolled participants had both baseline and week 16 ENA-78 measurements, whether any participants withdrew, or how incomplete measurements were addressed. It also does not describe imputation, exclusion rules, sensitivity analyses, or any assumptions about why data might be missing. These omissions matter because a mean change based only on participants with two measurements may not represent all enrolled participants if data availability is related to their outcomes.

The population field for the primary outcome is listed as “Power calculation,” rather than an analysis population definition. The registry does not specify an intention-to-treat, per-protocol, or other participant set. The analysis population and its relationship to enrollment are therefore not reported in the registry record. Without these details, the extent to which the reported endpoint, if available, would represent all enrolled participants cannot be assessed.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero participants with serious adverse events among 108 at risk in the atorvastatin group. It also reports 14 participants affected by other adverse events among 108 at risk. These are participant counts in the recorded categories, not counts of individual event episodes; the registry record does not provide further event-level detail in these figures.

The record does not list serious adverse-event terms, so the types of serious events assessed or reported cannot be described. Specific terms for the other adverse events are also not reported in the registry record. Death information is not reported in the registry record; a null entry should not be read as a reported zero.

As a general explanation, adverse-event counts describe events recorded during the study and should be interpreted alongside the observation period, collection procedures, and definitions used. Those details are not reported in the registry record. Since this study has no comparator group, these counts alone do not establish whether an event was caused by the intervention or how the counts compare with another treatment. The available figures should be read as the registered safety counts, not as a complete account of all possible harms.

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

The registry record documents a completed Phase 4, single-group study of atorvastatin at 80mg once daily for 16 weeks, with a primary outcome defined as mean ENA-78 change from baseline to week 16. It also records the use of a one-sample t comparison. These details establish what outcome and analysis were registered, but the observed endpoint result is not reported in the registry record.

That absence means readers cannot determine the average direction or size of the ENA-78 change, the range of plausible values around the estimate, or the statistical evidence relative to the analysis's reference value. It also prevents assessment of whether a change was clinically meaningful. No conclusion that the treatment increased or decreased ENA-78, or that it had or did not have an anti-inflammatory effect, can be drawn from the outcome information recorded.

The study's single-group structure is important to interpretation. As a general principle, observing change from baseline does not provide the same evidence as comparing concurrent randomized groups. A before-and-after change can reflect multiple influences, and the design does not supply a like-for-like control comparison to separate them. This is a limitation of what the design can establish, not a claim about the direction or cause of any unreported change.

The summary says the study also investigated whether genetic differences played a role in drug response. Specific genetic findings are not reported in the registry record. The safety entries report zero participants with serious adverse events and 14 affected by other adverse events, but provide limited detail on event types and no death information. Overall, the registry supports a description of the study's intent, regimen, design, and recorded safety counts; it does not provide the primary outcome estimates needed to judge the measured response.

14. Why This Trial Matters Statistically

This study illustrates why the analysis question and the design must be read together. A one-sample t comparison of change addresses whether the average within-person change differs from a reference value under the statistical model. It does not estimate a randomized difference between atorvastatin and a control treatment. Since the registry describes a single group and no comparator, the analysis type should not be mistaken for a controlled treatment-effect estimate.

It also illustrates the distinction between specifying an endpoint and reporting its result. The registry identifies a continuous biomarker, units, measurement interval, dispersion type, and a broad analysis method. Those details make the intended outcome understandable. But without the actual mean change, its variability, and an uncertainty measure, readers cannot evaluate either the magnitude or precision of the finding. A well-described outcome definition does not substitute for an outcome estimate.

The record's planning note provides another useful statistical distinction. Calculations based on fractions of an observed effect are planning illustrations, while the study itself is described as single group. A planning calculation is not evidence that an effect occurred, and it is not observed power. Treating illustrative assumptions as though they were the completed study's design or results would conflate planning with inference.

Finally, the record shows why analysis-population and data-handling details are essential. It lists enrollment and labels the endpoint population as “Power calculation,” but does not identify who contributed measurements or how missing data were handled. Such information is needed to understand what the estimated mean would represent. The registry's incomplete endpoint reporting leaves these statistical questions open rather than answering them.

15. 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 most direct limitation is that the registry record does not report the primary outcome estimate or its statistical uncertainty. The mean change in ENA-78, standard deviation, confidence interval, and test result are not reported in the registry record. As a result, readers cannot assess the direction, size, variability, or precision of the primary outcome.

The single-group design has no like-for-like control comparison. It can describe change over time among participants who received atorvastatin, but it does not by itself separate a treatment-associated change from other explanations for change. Masking is listed as none, and allocation is listed as NA. Details about measurement procedures and whether outcome assessment could have been influenced by knowledge of treatment are not reported in the registry record.

The entry does not report detailed eligibility criteria or participant characteristics, adherence, withdrawals, or the number with evaluable measurements at week 16. Missing-data handling and the analysis population are also not reported. The primary outcome population is labeled “Power calculation,” which does not clarify who contributed to the analysis. These omissions limit assessment of representativeness and of how the endpoint estimate would relate to all 108 enrolled participants.

The statistical plan is only partly described. The record names a one-sample t comparison and standard deviation, but does not identify the reference value, formal hypothesis, diagnostic checks, or confidence-interval method. Multiplicity procedures and any prespecified sample-size justification are not reported in the registry record. The study summary mentions genetic response differences, but genetic methods and results are not reported. Safety details are similarly limited: event terms and death information are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Systemic Immunomodulatory Effects and Pharmacogenetics of Atorvastatin in Early Atherosclerosis — NCT00361283.
• Registry record last updated 2012-05-15; status last verified 2012-04.
• Results first posted 2012-05-15.
• 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.

19. Record Summary

The registry record describes NCT00361283, a completed Phase 4, single-group study sponsored by the University of Florida. Enrollment was 108. Participants received atorvastatin at 80mg once daily for 16 weeks. The stated study purpose was to examine anti-inflammatory effects in people with no known heart disease or high cholesterol and to investigate whether genetic differences relate to drug response.

The primary outcome was mean change in ENA-78 from baseline to week 16, in pg/ml, with change defined as week 16 minus week 0. The planned analysis was a one-sample t comparison, with standard deviation listed as the dispersion measure. The observed outcome estimate and its statistical results are not reported in the registry record.

The safety record reports zero participants with serious adverse events among 108 at risk and 14 affected by other adverse events among 108 at risk. Event terms and death information are not reported in the registry record. The record does not describe a control group, missing-data methods, or a defined analysis population.