Effect of Niacin on Transport of HDL and Relationship to Atherogenic Lipoproteins and Lipolysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Niacin on Transport of HDL and Relationship to Atherogenic Lipoproteins and Lipolysis (NCT01250990), a randomized na study. The primary outcome is Rate of Appearance of 3H Cholesterol in the Total HDL Fraction Before and After 12 Weeks of Treatment With Niacin.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group study with quadruple masking. The official title calls it randomized, double-blind, and placebo controlled; the record does not explain how the double-blind wording relates to its quadruple-masking classification or identify which roles were masked. The study is listed as phase NA and completed. The sponsor was the University of Pennsylvania.

Enrollment was 22. The intervention arms were niacin and placebo. The niacin regimen was oral treatment for 12 weeks, starting with Niaspan and advancing to Niacor as tolerated, up to the stated dose limits. The placebo arm used a tablet with 50 mg niacin for the first 4 weeks and pure placebo thereafter, according to the registry description. The record does not report participant-level exposure, adherence, treatment discontinuation, or reasons for withdrawal.

The study began in 2010-11 and had primary completion in 2011-05. Its principal measurement was made at baseline and after 12 weeks: participants received an intravenous bolus of labelled cholesterol mixed with human serum albumin, and tracer appearance in plasma total HDL cholesterol was assessed over the stated sampling interval. The record says the final outcome analysis included only participants who completed both the baseline and 12-week studies. It does not report the number included, the handling of missing measurements, or the exact analysis population by treatment arm.

The record does not report a sample-size justification, a detailed statistical analysis plan, interim analyses, or the method used to compare treatment groups. Randomization and masking describe design features, but do not by themselves establish how the outcome data were analyzed or how uncertainty in the treatment comparison was quantified.

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: Of the 22 subjects enrolled, only subjects who completed the baseline and 12 week reverse cholesterol transport studies were included in the final outcome analysis.

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 Rate of Appearance of 3H Cholesterol in the Total HDL Fraction Before and After 12 Weeks of Treatment With Niacin, measured over Baseline and 12 weeks.

The primary endpoint is titled as the rate of appearance of 3H cholesterol in the total HDL fraction before and after 12 weeks of niacin treatment. It is expressed in %/mol/h, with a mean as the stated summary measure and a 95% confidence interval as the stated dispersion. The time points are baseline and 12 weeks.

Participants received an intravenous bolus of labelled cholesterol mixed with human serum albumin. The record explains that the injected tracer is taken up by macrophages. The endpoint assesses HDL cholesterol enrichment: the percentage of injected tritiated tracer appearing in plasma total HDL cholesterol between 60 and 240 minutes after injection, expressed per mole of HDL cholesterol per hour. The registry describes this rate as a measure of reverse cholesterol transport.

As a general statistical point, a tracer-based rate can represent a biological process that is not directly captured by a single concentration measurement. Its interpretation depends on the stated measurement procedure and the assumptions connecting tracer appearance to the process of interest. The endpoint is not itself a direct measure of a clinical event or health outcome. The registry record does not report the observed mean, confidence interval, or treatment-group comparison, so it does not establish what the endpoint values were or how precisely any difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is a design method intended to make treatment assignment independent of participant characteristics, on average. In a randomized comparison, this can help limit confounding when comparing groups. It does not guarantee that the groups are identical, particularly in a small study, and it does not remove the need to report the analysis population, outcome data, and statistical method. The registry identifies the study as randomized, but does not report the sequence-generation method, allocation concealment details, or baseline characteristics by arm.

What does the endpoint summary mean?

The primary endpoint is described as a continuous measure summarized by a mean. A mean represents the arithmetic average of the measured values in the analysis group. A 95% confidence interval is a measure of statistical uncertainty around an estimate under the method used to construct it. In general, a narrower interval indicates greater precision and a wider interval indicates less precision, conditional on the analysis assumptions. The record states that a 95% confidence interval was the dispersion measure, but gives no interval limits or method of calculation. The label alone cannot show the estimate's precision.

The endpoint is measured at baseline and after 12 weeks. A treatment comparison might be based on follow-up values, changes from baseline, or a model that uses both time points. These approaches answer related but not identical statistical questions and may handle baseline values and within-participant correlation differently. The registry record does not state which approach was used. It is therefore not possible to infer whether the reported analysis, if any, compared follow-up means, changes, or another modeled quantity.

Why does the tracer procedure matter?

The tracer measure is based on labelled cholesterol appearing in plasma total HDL cholesterol over a specified post-injection interval. As a general measurement principle, interpreting a tracer-derived rate requires attention to the tracer, sampling schedule, biological compartment, and calculation method. The record describes the bolus, the HDL fraction, and the 60 to 240 minute interval. It does not describe the detailed kinetic model, laboratory measurement procedures, or assumptions used to derive the rate. Those details are not reported in the registry record.

Repeated measurements from the same participant are generally correlated: a participant's baseline and follow-up values are not independent observations. Statistical methods for repeated measures account for that dependence in different ways. The record establishes that measurements were intended at baseline and 12 weeks, but does not report whether the analysis modeled the repeated observations jointly or reduced them to a single participant-level value. No claim about the implemented method is warranted from the endpoint description alone.

What can be said about power and planning?

Sample-size planning concerns the number of participants needed to detect a prespecified effect under assumptions about variability, allocation, and the statistical test. It is different from the observed treatment estimate and does not show how likely a result was to be statistically significant after data collection. The registry record does not report the trial's sample-size justification, target effect, variability assumptions, or planned power. The stated enrollment is not itself evidence that the study had adequate or inadequate power.

Planning illustrations based on an observed effect, when available, are hypothetical design calculations rather than observed power. Such calculations depend on assumptions and should not be presented as a property of the completed trial. The record details do not include a numerical observed effect or values for planning illustrations, so no sample-size calculation can be interpreted from them.

What is missing from the analysis description?

The registry record does not report the statistical test or model, whether estimates were adjusted for covariates, how the confidence interval was calculated, or whether analyses followed a prespecified plan. It also does not report an estimate and uncertainty measure for a treatment contrast. These omissions mean that the statistical method and result cannot be independently appraised from the record description alone.

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors and confidence intervals unreliable if not addressed. The listed primary measure is continuous, and no information in the registry record indicates that over-dispersion was assessed or that a particular variance model was used. It would be inappropriate to assert that over-dispersion was present or relevant to the investigators' analysis.

Likewise, a p-value, when reported, measures how incompatible data are with a specified null model under its assumptions; it does not quantify the size or clinical importance of an effect. No p-value is reported in the record details. In this study, interpretation would require the outcome estimate, its interval, and the analysis details, not just a test result. Since these numerical results and methods are not reported, the trial's statistical evidence for a treatment contrast cannot be characterized from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is recorded as one outcome measure and one analysis, but it includes baseline and 12-week measurements and is not reduced to one comparison because it has several categories or time points. The record does not state which contrast was designated as primary for statistical testing, how the repeated measurements were handled, or whether there were additional endpoints or analyses outside the listed outcome. It also does not report a multiplicity-adjustment method or explain whether any adjustment was considered.

Multiplicity is a general concern when several outcomes, time points, or statistical comparisons are examined. The more opportunities there are to identify an apparently notable result, the more important it is to understand which analyses were planned and how inference across them was handled. This general principle does not establish that the investigators conducted unreported comparisons or that any particular adjustment was necessary. The registry record does not report enough detail to evaluate those questions.

For the primary outcome, the record says that only participants who completed both the baseline and 12-week reverse cholesterol transport studies were included in the final outcome analysis. It does not report the number of completers in either arm, reasons for missing measurements, or whether participants were excluded for other reasons. It does not describe imputation, a model-based approach to incomplete data, sensitivity analyses, or an intention-to-treat analysis population. The registry record therefore does not allow assessment of whether missingness could have affected the results.

The actual analysis population and the statistical plan are not reported in enough detail to determine how the randomized groups were represented in the outcome analysis. These are material gaps: without them, readers cannot fully assess potential selection from restricting analysis to completers or evaluate whether the reported analysis followed a prespecified plan.

11. 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 event counts for the niacin and placebo groups. For each group, the number at risk for serious adverse events is 11 and the number affected is 0. The record also lists 11 at risk for other adverse events in each group and 0 affected in each group. No serious adverse event terms are listed. Death counts are not reported in the registry record.

These entries describe what was recorded in the registry fields; they do not establish that every possible safety event was sought or captured in the same way, nor do they describe event severity beyond the serious-versus-other categories. The record does not specify the safety observation period, adverse-event collection procedures, definitions used, or whether any participants discontinued treatment because of an event. The entries should not be expanded into claims about safety outside the recorded counts.

Zero affected participants in the listed fields is not proof that an event is impossible or that a treatment has no risk. Event counts are descriptive, and their interpretation depends on the study size, follow-up, ascertainment, and reporting. The registry record does not provide enough detail to evaluate those aspects. The safety figures should therefore be read narrowly as the recorded counts for the listed groups, alongside the explicit absence of reported death counts.

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

This trial addresses a mechanistic question: whether niacin changes a tracer-based measure of cholesterol appearance in total HDL over the stated treatment period. The endpoint is intended to reflect reverse cholesterol transport, and the record describes how tracer enrichment was measured. That design focus differs from a direct assessment of clinical events. A change in this biomarker would not by itself establish a change in symptoms, disease outcomes, or overall health.

The registry record does not report the numerical primary outcome results. It therefore does not establish whether the mean measure differed between niacin and placebo, whether it changed from baseline in either group, or how uncertain any estimate was. It is not possible to conclude from these record details that the treatment increased, decreased, or had no effect on the endpoint.

Even if numerical biomarker results were available, their interpretation would depend on the precise comparison, statistical analysis, missing-data handling, and uncertainty. The registry does not report these details sufficiently to assess them. Nor does it report a sample-size justification or the actual number included in the final outcome analysis. The enrollment count alone cannot establish the precision of the outcome estimate.

The record describes healthy volunteers and a 12-week intervention. Its findings, if fully reported elsewhere, would need to be interpreted in the context of that population and study duration. The registry information does not support generalizing the study design to populations not described in the record or drawing conclusions about long-term clinical outcomes.

The sound conclusion is limited: this completed randomized study was designed to assess a tracer-based HDL measure under niacin and placebo, but the numerical outcome results and important analysis details are not reported in the registry record. The absence of those results is not evidence for either a benefit or a lack of effect; it is a limit on what can be inferred from this record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the gap between a clearly described endpoint and an interpretable treatment estimate. The registry specifies a continuous tracer-based measure, a mean summary, a confidence-interval format, and the measurement times. Those details establish what investigators intended to measure. They do not show the observed values or the uncertainty around a treatment contrast.

The distinction matters because readers need more than an endpoint definition to evaluate evidence. A useful statistical report would identify the analysis population, the contrast being estimated, the model or test used, and the estimate with an uncertainty interval. Here, the registry says that completion of both tracer studies determined inclusion in the final outcome analysis, but it does not report the number analyzed or the handling of incomplete data. That leaves uncertainty about both the data contributing to the estimate and the scope of the result.

The study also illustrates why measurement timing and analysis choices matter. Baseline and follow-up values from the same participant are related, and a comparison of follow-up levels is not necessarily the same estimand as a comparison of change. The record identifies both time points but does not report how they were incorporated statistically. Without that information, a reader cannot reconstruct the intended treatment contrast.

Finally, the safety fields and the primary outcome serve different purposes. The recorded adverse-event counts are descriptive safety information, while the tracer endpoint addresses a biological process. Neither substitutes for the other. Careful reporting of effect estimates, confidence intervals, analysis populations, and missing-data methods would be needed to connect the study design to an assessable statistical conclusion.

14. 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 central limitation for interpretation is that the registry record does not report numerical results for the primary endpoint. The outcome title, unit, mean summary, and confidence-interval label do not supply an estimate or its precision. No treatment contrast, group-specific mean, change, confidence-interval limits, or p-value is stated in the record details.

The endpoint is described at baseline and 12 weeks, but the registry does not explain which comparison was intended for inference or how the repeated observations were analyzed. It does not report the statistical model, any adjustment, or the assumptions used to estimate uncertainty. As a result, the analytical estimand and method cannot be evaluated.

The record states that only participants completing both tracer studies were included in the final outcome analysis. It does not report how many completed the studies, how many were excluded from that analysis, reasons for noncompletion, or the handling of missing values. This prevents assessment of the analysis population and the possible effect of incomplete outcome data.

Other details are also not reported in the registry record: the sample-size justification, statistical analysis plan, interim analyses, allocation-concealment procedures, actual niacin doses received, adherence, and detailed measurement procedures. The record's descriptions of randomization and masking are useful design information but do not resolve these omissions. The title's double-blind wording and the quadruple-masking classification are both recorded, without further explanation of the masking roles.

These limitations do not establish that the study was conducted improperly or that analyses were not performed. They define what cannot be independently assessed using the registry record alone. In particular, the available information does not support a conclusion about the direction, magnitude, or precision of the primary treatment comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Niacin on Transport of HDL and Relationship to Atherogenic Lipoproteins and Lipolysis — NCT01250990.
• Registry record last updated 2016-07-28; status last verified 2016-06.
• Results first posted 2016-06-24.
• 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.

18. Record Summary

NCT01250990 is a completed, randomized, parallel-group, placebo-controlled study sponsored by the University of Pennsylvania. The record lists enrollment of 22 and describes the population as healthy volunteers. The intervention was oral niacin for 12 weeks, compared with a placebo regimen. The study began in 2010-11, with primary completion in 2011-05.

The primary endpoint concerns the rate of labelled cholesterol appearance in total HDL at baseline and after 12 weeks, expressed as %/mol/h. The registry describes a mean and 95% confidence interval as the intended summary. It says the final outcome analysis included participants completing both tracer studies, but does not report the analysis count or numerical outcome results.

The registry lists 0 affected participants for serious and other adverse events in each arm; death counts are not reported in the registry record. The statistical analysis plan, sample-size justification, missing-data methods, and numerical treatment estimate are also not reported.