Effects of Statins on Lower Extremity Arterial Function Assessed by Magnetic Resonance Imaging: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Statins on Lower Extremity Arterial Function Assessed by Magnetic Resonance Imaging (NCT00770679), a na na study. The primary outcome is Mean Change in Low Density Lipoprotein (LDL).

2. Clinical Question

The clinical motivation in the registry summary is that the endothelium helps regulate whether blood vessels dilate or contract, affecting blood flow. Magnetic resonance imaging (MRI) is described as a noninvasive way to evaluate endothelial function in the arms and legs. That motivation is not the same as a reported result: the primary outcome listed in the record is LDL change, and no numerical LDL result or MRI outcome result is reported in the registry record.

Accordingly, the record defines a treatment exposure and a within-group change question, but it does not define a randomized treatment contrast. Without a concurrent comparator, a change between baseline and follow-up cannot by itself separate a treatment-associated change from other changes over time. Whether the investigators intended additional comparisons or analyses is not reported in the registry record.

3. Trial Design

The registry record describes a single-group study of atorvastatin in participants with diabetes. Its listed arm is High-Dose Statin, with 80 mg atorvastatin daily for 3 weeks. Enrollment is listed as 16. The study is not described as randomized: allocation is recorded as NA, and the record explicitly notes that it is not a randomized comparison. Masking is recorded as NONE.

The registry lists the study start as 2008-06 and primary completion as 2012-07. Its status is TERMINATED. The reason for termination, the date it was terminated, and whether all planned study procedures were completed are not reported in the registry record. The phase is recorded as NA. The sponsor is Johns Hopkins University.

The study title and summary refer to assessing lower-extremity arterial function with MRI and to endothelial function in the arms and legs. The listed intervention is a drug, and the only arm description is the atorvastatin regimen. A separate control arm, placebo, or alternative treatment is not listed. This matters for interpretation: a single-group baseline-to-follow-up assessment can describe change within the group, but it does not directly estimate how that change differs from what would have happened without the intervention.

The primary endpoint timeframe is described as change from baseline to follow-up, up to 5 weeks. The treatment duration is listed as 3 weeks; the record does not explain the timing of the follow-up visit in relation to the end of treatment. Additional visit schedules, eligibility criteria, recruitment details, adherence information, and the reason for choosing this treatment duration are not reported in the registry record.

The registry record lists 3 outcome measures and 0 analyses. It does not report an analysis plan, a sample-size justification for the original study, or interim analyses. Planning illustrations based on the observed effect are not the same as the study's original design or evidence of observed power. The registry record does not report enough outcome results to assess an observed effect in this account.

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: 3 participants were lost to follow-up, 3 participants did not have LDL values collected/reported at follow-up

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 Low Density Lipoprotein (LDL), measured over Change from baseline to follow-up, up to 5 weeks.

The registered primary endpoint is mean change in serum low density lipoprotein (LDL), measured in mg/dL. Its timeframe is change from baseline to follow-up, up to 5 weeks. The endpoint description defines the change as baseline LDL minus follow-up LDL. The population note states that 3 participants were lost to follow-up and that 3 participants did not have LDL values collected or reported at follow-up.

A continuous measure such as LDL can be summarized by a mean, which describes the average value or average change for the observations included in an analysis. A standard deviation describes how spread out individual measurements are around the mean. These are general statistical interpretations; the registry record does not report the actual mean change or standard deviation for this endpoint. Nor does it report a confidence interval or an endpoint-specific p-value.

Change in LDL is the outcome that the registry identifies as primary. The rationale for selecting LDL as the primary endpoint, and how it relates to the MRI assessment of arterial or endothelial function, are not reported in the registry record. The summary's interest in endothelial function should therefore not be mistaken for a reported MRI result or for the listed primary outcome. Numerical results for MRI measures are not reported in the registry record.

Without the observed endpoint estimate and its uncertainty, readers cannot determine the direction, size, or precision of the LDL change from this record. The endpoint definition alone specifies what the investigators intended to measure; it does not establish what the study found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a continuous endpoint, a common summary is the mean. It represents the arithmetic average of the observed measurements included in the analysis. The registry identifies the primary outcome as mean change in LDL, rather than a count or time-to-event outcome, and names standard deviation as the measure of dispersion. The actual mean and standard deviation are not reported in the registry record.

What does the change score represent?

The endpoint description defines change as baseline LDL minus follow-up LDL. In general, a change score compares a participant's measurement at one time with that participant's measurement at another time. Summarizing those scores can describe the average within-group change. The direction depends on the order of subtraction: for this endpoint definition, a positive value means baseline is higher than follow-up. This explains how to read the measure, not what the participants experienced; the result itself is not reported in the registry record.

When a study includes only one group, a baseline-to-follow-up change is not equivalent to a treatment-versus-control effect. The treated participants may change over time for reasons not caused by the intervention. A concurrent comparison group can help estimate how outcomes differ between treatment conditions, particularly when allocation supports a fair comparison. Here, the registry identifies a single-group study and does not list a control arm. Thus a within-group estimate, if reported, would not by itself establish a causal treatment effect.

What does standard deviation describe?

Standard deviation describes the spread of individual values around their mean. It is not the same as a confidence interval: the standard deviation concerns variation among observations, while a confidence interval describes uncertainty around an estimated quantity. Both may aid interpretation, but neither can be assessed for the primary endpoint because its numerical result and uncertainty are not reported in the registry record.

In general, confidence intervals make the precision of an estimate more visible than a point estimate alone. A point estimate gives one summary value; the interval conveys a range of values consistent with the data under the analysis assumptions. A confidence interval does not mean that every value inside the interval is equally plausible, and it does not repair design limitations such as the absence of a concurrent comparison. No confidence interval is reported for the primary endpoint.

Why does allocation matter?

Random allocation is used in comparative trials to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics. The registry records allocation as NA and explicitly says the study is not a randomized comparison. Because only a single group is listed, there is no randomized contrast to interpret. Masking is recorded as NONE, but the registry does not describe which study roles were unmasked or how outcome assessment was conducted. Those details are not reported in the registry record.

How should planning calculations be read?

General sample-size calculations estimate how many participants per arm might be needed under chosen assumptions to detect a specified effect with a chosen statistical procedure. They are planning illustrations, not observed power and not a substitute for an outcome estimate. The stated assumptions for the illustrations are 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 registry record does not report the study's own sample-size justification. Since the study is listed as single-group, illustrations premised on two arms should not be read as a description of the actual trial design.

In general, a normal approximation treats an estimate as having a distribution that can be approximated by a normal curve under the method's assumptions. Whether those assumptions fit a particular dataset depends on the data and analysis. The registry record does not provide the endpoint data or analysis details needed to evaluate that fit. No additional calculations or outcome estimates can be inferred from the design description alone.

Why can over-dispersion matter?

General statistical note: over-dispersion arises when observed variability is greater than a model assumes. If a model understates variability, its standard errors may be too small and intervals may be too narrow. This issue is most directly relevant to outcomes modeled as counts or rates; the registered primary endpoint is a continuous mean change, and the registry record does not report a count-model analysis. There is no basis in the registry record to claim that over-dispersion was present or that a particular adjustment was used.

The record lists 0 analyses. It does not report the statistical model, covariate adjustment, method for calculating uncertainty, handling of missing values, or a prespecified analysis plan. These details would be needed to reproduce or fully evaluate the primary analysis. General explanations of statistical methods clarify what such choices mean, but they cannot fill gaps in the record or establish the results of this study.

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("High-Dose Statin")
n   <- c(10)
m   <- c(75.54)
sp  <- c(12.98)
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  High-Dose Statin  10  75.540  12.980  66.255  84.825

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and identifies mean change in LDL as the primary outcome. The hierarchy or relationship among the other outcome measures is not reported in the registry record. The record lists 0 analyses and does not report a multiplicity adjustment, a testing sequence, or a plan for interpreting results across outcomes. Without those details and the results, the chance of false-positive findings across multiple tests cannot be assessed. This is a general concern when several outcomes or comparisons are examined, not evidence that a particular error occurred in this study.

Missingness is relevant to the primary endpoint. The registry states that 3 participants were lost to follow-up and that 3 participants did not have LDL values collected or reported at follow-up. It does not say whether those statements refer to the same people, so the counts should not be combined. Reasons for loss or missing measurement, baseline LDL values for those participants, and the timing of missingness are not reported in the registry record.

The record does not explain whether the analysis included only participants with observed baseline and follow-up LDL values, used an imputation procedure, or applied another approach. It also does not identify an intention-to-treat population, a per-protocol population, or another analysis population. These methods and populations are not reported in the registry record.

In general, missing-data methods rely on assumptions about why values are absent. If missingness is related to unobserved outcomes, an analysis restricted to available measurements can be biased. This general possibility does not establish that bias occurred. Because the analysis approach and outcome values are unavailable in the registry record, the effect of missing data on the primary estimate cannot be evaluated.

12. 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 reports the High-Dose Statin group as having 16 participants at risk for serious adverse events and 0 affected. For other adverse events, it reports 16 at risk and 0 affected. It reports 0 deaths. These are the safety counts recorded for the listed group; the record does not provide a separate comparator group.

Zero recorded events should be read as no events reported in these registry categories, not as proof that the intervention carries no risk. Safety estimates depend on how events were defined, collected, and followed. Definitions, ascertainment procedures, completeness of safety follow-up, and the time period used for these counts are not reported in the registry record. The record also does not identify specific non-serious adverse-event terms; no top serious terms are listed.

The number at risk is the denominator reported for each category, not an estimate of the probability of an event. No event rate, confidence interval, or comparison of safety between treatments is reported. With a single-group design and no listed control, the counts cannot establish how safety outcomes compare with another treatment or with no treatment.

These figures therefore describe the registry's recorded safety experience, while leaving uncertainty about event ascertainment and comparative risk. They should not be interpreted as a finding that adverse effects are impossible or that safety has been established.

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

The study's stated scientific motivation concerns statins, endothelial function, and MRI assessment of arterial function. The listed primary endpoint, however, is mean change in LDL from baseline to follow-up. Neither the numerical LDL result nor numerical MRI or endothelial-function results are reported in the registry record. The record therefore does not permit a conclusion about the size or direction of change in these measures.

The study is single-group, with no listed concurrent comparator, and allocation is recorded as NA. Even if an outcome change were available, a before-and-after difference would not alone show that the intervention caused the change. Other changes over time could contribute, and the study design does not provide a randomized control contrast to separate them.

The registry's summary describes the biological rationale and question; it is not evidence that the proposed effect was observed. Likewise, the treatment regimen is a description of what the study planned to administer, not evidence of benefit. No statement that atorvastatin improved or failed to improve LDL or arterial function is supported by the outcome information reported in the registry record.

For safety, the record reports zero affected for serious adverse events and other adverse events, and zero deaths. These counts are limited to what was recorded and do not demonstrate absence of risk. Safety event definitions and the completeness of follow-up are not reported in the registry record.

What can be said is limited to the design and registry entries: the listed group received 80 mg atorvastatin daily for 3 weeks; the study was recorded as terminated; and the primary outcome was specified as LDL change over a timeframe of up to 5 weeks. The reason for termination and the primary outcome values are not reported in the registry record. Any stronger inference about clinical efficacy, mechanism, or comparative safety would go beyond the reported information.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a research question, a design, and a result. The registry summary raises a question about whether endothelial function might change more in arteries with worse function at baseline. The listed primary endpoint is mean change in LDL. Knowing the motivation and endpoint helps define what was intended to be studied, but neither supplies an outcome estimate.

The single-group structure is important because it limits the kind of inference that can be made. A baseline-to-follow-up change can describe what happened within the enrolled group, but without a concurrent comparator it cannot directly estimate a treatment difference. The registry's allocation entry is NA, and it explicitly identifies the study as not a randomized comparison. This is a design limitation, not a judgment about the treatment itself.

The missing follow-up information also matters statistically. The record notes loss to follow-up and missing or unreported LDL values but does not explain their overlap or how they were handled. Readers need the analysis population and missing-data method to understand which observations inform an estimate and what assumptions support it. Those details are not reported in the registry record.

Finally, reporting uncertainty is essential. A mean alone would not show how precisely the change was estimated; a standard deviation and confidence interval answer different questions about variability and uncertainty. The registry record does not report the primary estimate or its uncertainty. Planning illustrations based on an observed effect are design aids, not evidence that the study had a particular observed power or that an effect was demonstrated. The record lists 0 analyses and does not report the original sample-size justification. These gaps make the entry useful for understanding the planned question and the limits of the design, but not for evaluating the magnitude or certainty of a treatment effect.

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 main limitation for interpretation is that the registry record does not report numerical results for the registered primary endpoint. The mean LDL change, its standard deviation, and its uncertainty are not reported. Numerical MRI outcomes and results addressing the stated endothelial-function question are also not reported. Without these, the direction, magnitude, and precision of any change cannot be evaluated.

The design is single-group and not described as a randomized comparison. No control arm is listed, and masking is recorded as NONE. A change from baseline to follow-up, if available, would not by itself isolate an intervention effect from other changes over time. The registry record does not report whether any additional comparisons were planned or conducted.

The status is TERMINATED, but the reason for termination and its consequences for study completion are not reported in the registry record. The record lists enrollment as 16, while also noting loss to follow-up and missing or unreported follow-up LDL values. It does not clarify whether these missingness notes overlap, why values were unavailable, or how they were handled in analysis.

Additional limitations arise from absent methods information. The analysis population, statistical model, covariate adjustment, missing-data approach, multiplicity strategy, and original sample-size justification are not reported in the registry record. Participant characteristics, eligibility details, adherence, and the timing of follow-up in relation to treatment completion are also not reported. These gaps constrain interpretation of the planned endpoint, the safety counts, and the study's broader MRI objective.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Statins on Lower Extremity Arterial Function Assessed by Magnetic Resonance Imaging — NCT00770679.
• Registry record last updated 2017-09-13; status last verified 2017-08.
• Results first posted 2017-09-13.
• 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 a single-group study in people with diabetes, sponsored by Johns Hopkins University. The listed intervention is 80 mg atorvastatin daily for 3 weeks. Enrollment is 16; allocation is recorded as NA, masking as NONE, and study status as TERMINATED. The listed start is 2008-06 and primary completion is 2012-07.

The primary endpoint is mean change in serum LDL, measured in mg/dL, from baseline to follow-up, up to 5 weeks. The record notes 3 participants lost to follow-up and 3 without LDL values collected or reported at follow-up. The observed primary result and the analysis method are not reported in the registry record.

The safety entries report 0 serious adverse events, 0 other adverse events, and 0 deaths. The record lists 3 outcome measures and 0 analyses. It does not report numerical MRI results, the reason for termination, or the original sample-size justification. The design and missing outcome information limit assessment of efficacy, precision, and comparative safety.