An Study to Evaluate Rosuvastatin in Children and Adolescents With Familial Hypercholesterolaemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Study to Evaluate Rosuvastatin in Children and Adolescents With Familial Hypercholesterolaemia (NCT01078675), a non-randomized phase 3 study. The primary outcome is Percent Change From Baseline in LDL-C.

2. Clinical Question

The question is therefore framed around change over time in a treated group, rather than a randomized estimate of how outcomes differ between rosuvastatin and a concurrent control. The brief summary also describes pharmacokinetic assessment, including a single-dose phase over 24 hours for a small number of patients at baseline. These activities are part of the study description, but the registry record does not report their numerical findings.

3. Trial Design

This completed phase 3 study is registered as non-randomized, unmasked and single-group. Its official title describes an open-label study of rosuvastatin in children and adolescents aged from 6 to less than 18 years with familial hypercholesterolaemia. Enrollment is listed as 315. The record reports that 198 patients were treated, and that one patient received 1 dose of study drug but was not included in the efficacy and safety analyses because follow-up data were lacking. The relationship between the enrollment total and the treated group is not reported in the registry record.

The primary outcome is percent change from baseline in LDL-C, with assessments at Month 3, Month 12 and Month 24. The registry names both an intent-to-treat analysis set and a per-protocol analysis set. It does not report the numerical primary outcome results, or explain how participants were assigned to those analysis sets. The arm description is blank in the registry record, and detailed dosing information is not reported in the registry record.

The brief summary says healthy siblings would help researchers compare certain results. However, the registered design is single-group and non-randomized, and the record does not specify which outcomes were compared with siblings or how those comparisons were conducted. The registry record therefore does not establish a randomized comparison for the primary outcome.

The record lists secondary outcomes covering changes in several lipid measures, carotid intima and media wall thickness, adverse events, total exposure duration and treatment adherence. It also describes measuring drug levels in blood. The study began in 2010-02, reached primary completion in 2013-02, and has a completed status. Further details of the protocol, including the rationale for the enrollment target and the statistical analysis plan, 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: Intent-to-treat analysis set and Per-protocol analysis set

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.

Population: Rosuvastatin; All treated patients. Healthy siblings; All patient who started this study

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in LDL-C, measured over At Month 3, Month 12 and Month 24.

The primary endpoint is percent change from baseline in LDL-C, summarized as a mean, with standard deviation as the stated measure of dispersion. It is assessed at Month 3, Month 12 and Month 24. The registry clarifies the direction of the measure: negative values represent a decrease from baseline, while positive values represent an increase. The numerical values themselves are not reported in the registry record.

As a general statistical explanation, change from baseline describes how a measurement at follow-up differs from the starting measurement, expressed as a percentage. This can make changes easier to interpret when participants begin at different levels than an endpoint measured only on the original scale. A mean describes the average change in the analysis group, while a standard deviation describes variation among the individual measurements around that mean. Neither summary alone describes the full distribution or the precision of the estimated mean.

Repeated assessments at three stated follow-up times can describe the course of the mean change across the study period. They do not, by themselves, establish that any change was caused by treatment: in a single-group design, changes can also reflect factors unrelated to treatment. The registry record does not report confidence intervals, hypothesis tests, or a model used to estimate this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change summarize?

The registry says that the primary endpoint is the mean percent change from baseline in LDL-C. As a general statistical explanation, the mean is a summary of the values in a group: it gives an average, not a description of every participant’s response. Participants can have changes in different directions or of different sizes while contributing to the same group mean. For that reason, the mean is best read alongside a measure of spread, which the registry identifies as the standard deviation. The numerical mean and standard deviation are not reported in the registry record.

A standard deviation describes how dispersed individual values are around the mean. It is not the same as the uncertainty of the mean estimate. In general, a confidence interval or standard error is used to communicate the precision of an estimate. The registry does not report either for the primary endpoint. It also does not report a statistical model, a test statistic, or a p-value for the primary outcome. Those omissions mean the registered description is insufficient to reconstruct an inferential analysis.

How should the repeated assessments be understood?

The primary endpoint is assessed at Month 3, Month 12 and Month 24. Each time point can describe the mean change at that point in follow-up. Repeated observations can also be analyzed as a trajectory, but that requires choices about how to account for within-participant dependence, missing follow-up values and the shape of change over time. Those choices are not reported in the registry record. It is therefore not appropriate to assume that the study used a repeated-measures model, or any particular method of handling correlation between measurements.

In general, observations from the same participant tend to be related rather than independent. An analysis that treats them as unrelated may misstate uncertainty. A model for repeated measures can account for that relationship, but the model and its assumptions must be specified. The registry’s listing of three assessment times does not, on its own, establish which analysis was used or whether all three time points were analyzed together.

What can the design say about treatment effects?

General statistical reasoning distinguishes a change observed within one group from a contrast between groups. A single-group before-and-after analysis can describe how measurements changed during follow-up. Without a suitable concurrent comparator, it cannot separate a treatment-related change from changes that might have occurred over time for other reasons. This study is listed as non-randomized, unmasked and single-group. Accordingly, a primary outcome estimate, if reported, would need to be interpreted in light of those design features.

The brief summary mentions healthy siblings as helping compare certain results. The record does not identify the outcomes involved, the comparison procedure, or whether siblings contributed to the primary endpoint analysis. It would be unwarranted to infer the details of that comparison from the brief description. The statistical plan, including any adjustment for baseline values or other covariates, is not reported in the registry record.

What does a planning calculation represent?

General sample-size calculations estimate how many observations may be needed to detect a specified effect under stated assumptions. The planning illustration associated with this study is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It uses fractions of an observed effect as planning targets. Those assumptions are not a description of the registered trial design: the trial is listed as a single-group study, not a two-arm randomized study.

Such planning figures should be treated as illustrations, not as evidence about how many participants were actually needed or the probability that this completed study detected an effect. They are not observed power. In general, power is a design-stage probability calculated under assumptions about an effect and variability; it cannot be read as a retrospective measure of whether a result is true. The registry’s own sample-size justification and any prospective calculation are not reported in the registry record. Numerical planning outputs are not reported in the registry record.

For continuous outcomes, a sample-size illustration expressed as participants per arm presumes an allocation structure and statistical model. Here, the stated equal allocation assumption does not match the registered single-group design. Thus it should not be used as a description of the study’s enrollment or analysis. The enrollment listed in the record is 315; the treated group is reported as 198 patients. The record does not explain the difference between those counts.

What remains unknown about the statistical analysis?

The registry identifies intent-to-treat and per-protocol analysis sets, but it does not define the populations or report the number analyzed in each. It does not describe how missing outcome values were handled, whether any sensitivity analyses were conducted, or whether results were adjusted for multiple outcomes or time points. The named analysis populations should not be taken to establish a specific statistical procedure.

As a general concept, a protocol-defined statistical plan can specify the estimand, analysis population, model, handling of missingness, and multiplicity strategy before results are examined. These details are important because different reasonable choices can yield different estimates or uncertainty. The statistical analysis plan, interim analyses and sample-size rationale are not reported in the registry record. The available description supports an account of what endpoint was registered and when it was assessed, but not a reconstruction of how the results were analyzed.

10. Multiplicity, Missing Data and Analysis Populations

The registry names a primary outcome at three follow-up times and several secondary outcome families. These include percent changes in HDL-C, TC, TG, non-HDL-C, lipid ratios, ApoB and ApoA-1; change in maximum and mean carotid intima and media wall thickness; adverse events; total exposure duration; and treatment adherence. The record lists 13 outcome measures. Numerical results for the primary endpoint are not reported in the registry record.

As a general statistical point, testing many outcomes or time points can increase the chance of obtaining at least one apparently unusual result by chance. A multiplicity strategy may prioritize a primary endpoint, adjust tests, or otherwise define how evidence across outcomes is interpreted. The registry record does not report whether any adjustment or hierarchical testing plan was used. The order of outcome priority beyond the stated primary endpoint, and any prespecified approach to secondary analyses, are not reported in the registry record.

The primary outcome description names intent-to-treat and per-protocol analysis sets, but does not define either set or provide their sizes. In general, an intent-to-treat approach aims to retain participants according to an assigned treatment strategy, while a per-protocol approach focuses on participants meeting specified study requirements. The interpretation of these labels depends on the protocol and analysis rules, which are not reported in the registry record. Because the study is listed as single-group and non-randomized, the labels do not imply a randomized assignment.

One patient received 1 dose but was excluded from efficacy and safety analyses because follow-up data were lacking. Other missing-data patterns, reasons for missingness, and methods used to address missing outcomes are not reported in the registry record. The record also does not state whether sensitivity analyses assessed the impact of missing data. These gaps limit assessment of how well the analyzed populations represent the treated group and how robust any estimate might be to missing observations.

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 0.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (0.5%), urinary retention postoperative (0.5%), forearm fracture (0.5%), streptococcal toxic shock syndrome (0.5%), femur fracture (0.5%).

The adverse-event record lists 197 patients at risk for serious adverse events and 9 affected. For other adverse events, it lists 197 at risk and 172 affected. These are counts in the registry’s safety record; the registry does not provide a comparative safety estimate against a randomized control group. The study is listed as single-group and non-randomized, so these counts describe reported events among treated patients rather than a controlled difference in risk.

The serious-event terms listed are appendicitis, urinary retention postoperative, forearm fracture, streptococcal toxic shock syndrome, femur fracture and viral pericarditis. Each term is accompanied by 0.5%. The registry does not report further detail about event timing, duration, severity beyond the serious-event classification, relatedness to treatment, or whether an individual could contribute more than one term. Deaths are not reported in the registry record.

As a general statistical point, counts and percentages describe observed events in the recorded group; they do not establish causation. The at-risk denominator, duration of follow-up and event definitions are important context when interpreting safety data. The record lists total duration of exposure as a secondary outcome but does not provide its numerical result. No conclusion about comparative safety can be drawn from these single-group figures alone.

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

The registered question is whether LDL-C changed from baseline over follow-up in children and adolescents treated with open-label rosuvastatin. The record specifies a mean percent change at Month 3, Month 12 and Month 24 and explains how to interpret positive and negative values. It does not report the numerical estimates or their variability. As a result, the direction, size and precision of the observed primary outcome cannot be judged from the registry record.

This lack of numerical results should not be mistaken for evidence that there was no change, nor for evidence that there was a change. It means the registry record does not report the outcome values needed to assess either possibility. The record also does not report inferential statistics such as confidence intervals or p-values, so statistical uncertainty cannot be characterized from the registered information.

Even if a within-group change were available, the design would matter to its interpretation. The trial is listed as non-randomized, unmasked and single-group. A change during follow-up can describe the experience of the treated group but cannot, by itself, establish what would have happened without treatment. The mention of healthy siblings for comparisons of certain results does not establish that the primary endpoint used a randomized or otherwise comparable control group.

The safety counts likewise describe events recorded in the treated group. They do not establish whether event rates were higher or lower than they would have been under another treatment or no treatment. The registry reports 9 affected among 197 at risk for serious adverse events, and 172 affected among 197 at risk for other adverse events, but comparative interpretation is limited by the design and the absence of further detail in the record.

These findings must also be interpreted in light of the reported analysis populations and incomplete information about follow-up. One patient who received 1 dose was excluded from efficacy and safety analyses for lack of follow-up data. Rules for other missing outcomes and the sizes of the intent-to-treat and per-protocol sets are not reported in the registry record. The appropriate conclusion is therefore narrow: the record describes a completed study and its intended outcomes, but does not include the numerical primary results needed to determine the observed LDL-C change.

13. Why This Trial Matters Statistically

This study is statistically notable for the contrast between its long-term repeated outcome schedule and its single-group design. LDL-C percent change was to be assessed at Month 3, Month 12 and Month 24, allowing the registry to define a question about change across follow-up. Yet the listed design is non-randomized, unmasked and single-group. These features shape the kinds of conclusions that an analysis could support, regardless of the statistical method used.

The record also illustrates why a clearly named endpoint is not enough to evaluate a result. It gives the primary measure, its direction, its summary as a mean with standard deviation, and the planned time points. But the numerical estimates and measures of precision are not reported in the registry record. Without them, readers cannot assess the scale of the observed change or its uncertainty. Without details of the analysis plan, they also cannot establish how repeated assessments, multiple outcomes or missing data were handled.

Enrollment and analysis populations require separate attention. The registry lists enrollment of 315 and reports 198 treated patients, while also noting one treated patient excluded from efficacy and safety analyses because follow-up data were lacking. The record does not explain how participants progressed from enrollment to treatment or define the analysis sets. This makes participant flow and the relationship between enrollment, treatment and analysis difficult to evaluate from the registry alone.

Finally, the safety counts demonstrate the value of reporting denominators and event terms, while also showing the limits of descriptive single-group data. Counts can communicate what was recorded, but they cannot provide a randomized comparison. A careful statistical reading therefore separates the study’s stated objectives and outcome definitions from evidence about treatment effects. In this record, the former are described more fully than the numerical results needed for the latter.

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 main limitation for interpreting the primary outcome is that numerical results are not reported in the registry record. Although the endpoint, time points and summary measures are specified, the mean percent changes and standard deviations are absent. The record also does not report confidence intervals, p-values, or the statistical model used. Consequently, neither the observed magnitude nor the statistical precision of the primary outcome can be assessed from the registry record.

The registered design is non-randomized, unmasked and single-group. A within-group change over time cannot, by itself, separate treatment-associated change from other changes over follow-up. The brief summary mentions healthy siblings as helping compare certain results, but the record does not specify which outcomes they informed or how those comparisons were conducted. Their mention does not establish a randomized comparator for the primary outcome.

There is limited information about participant flow and analysis populations. Enrollment is listed as 315, while 198 patients are reported as treated. The registry does not explain the route between those counts. It notes that one patient received 1 dose and was excluded from efficacy and safety analyses because of missing follow-up, but does not report the sizes or definitions of the intent-to-treat and per-protocol sets. Other missing-data patterns and their handling are not reported in the registry record.

The statistical plan, sample-size justification, interim analyses, multiplicity approach and any sensitivity analyses are not reported in the registry record. The posted planning assumptions describe an illustrative two-arm calculation, whereas the registered trial is single-group; they should not be taken as the trial’s design rationale. For safety, the record gives counts and several serious-event terms but not detailed timing, treatment relatedness or comparative estimates. These limitations restrict both causal interpretation and assessment of uncertainty.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Study to Evaluate Rosuvastatin in Children and Adolescents With Familial Hypercholesterolaemia — NCT01078675.
• Registry record last updated 2015-04-07; status last verified 2015-03.
• Results first posted 2015-02-02.
• 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

NCT01078675 is a completed phase 3, open-label, non-randomized, single-group study of rosuvastatin in children and adolescents aged from 6 to less than 18 years with familial hypercholesterolaemia. The registry lists enrollment of 315 and reports that 198 patients were treated. The study began in 2010-02 and reached primary completion in 2013-02.

The primary outcome is mean percent change from baseline in LDL-C at Month 3, Month 12 and Month 24, with standard deviation specified as the measure of dispersion. Negative values indicate a decrease and positive values an increase. Numerical primary outcome results are not reported in the registry record. The record names intent-to-treat and per-protocol analysis sets but does not define them or provide their sizes.

Secondary outcomes include lipid measures, carotid intima and media wall thickness, adverse events, exposure duration and treatment adherence. The record reports serious and other adverse-event counts, but no randomized comparator. Statistical analysis details, missing-data methods and the sample-size justification are not reported in the registry record.