Statin Therapy in Young Adult Survivors of Childhood Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Statin Therapy in Young Adult Survivors of Childhood Cancer (NCT01733953), a randomized phase 2 study. The primary outcome is Change From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, phase 2 pilot study comparing atorvastatin with sugar-pill placebo. The registry records quadruple masking. The study summary describes a double-blind design involving participants and investigators; the record does not further explain how masking was implemented or reconcile the two descriptions. The trial status is completed.

The registry reports enrollment of 27. The study summary describes a planned enrollment of 24 young adult survivors and a six-month treatment period. The record does not explain the difference between planned enrollment in the summary and the enrollment figure in the registry. The listed treatment was atorvastatin 40mg by mouth once daily, compared with oral placebo once daily.

The recorded study start was 2012-11, and primary completion was 2015-11. The primary outcome was change from baseline in brachial artery flow-mediated dilation at six months. The record also lists changes in carotid artery compliance, carotid artery distensibility, pulse wave velocity, augmentation index and carotid intima-media thickness as secondary outcomes.

These design features describe a controlled pilot comparison, but they do not establish the details of the trial's statistical plan. A sample-size justification, planned interim analyses, and detailed analysis procedures are not reported in the registry record. The posted primary analysis includes 8 participants in the atorvastatin arm and 3 in the placebo arm. Those analysis counts are distinct from the registry's enrollment figure and the safety populations, and the record does not give a complete accounting of the differences.

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: Physician withdrawals, loss to follow-up, drug compliance \<70%, unrelated injury, and self-withdrawal reduced number analyzed. Also, participant movement during FMD assessment and/or poor ultrasound image quality due to difficult brachial artery anatomy or poor circulation led to some unusable data and thus lowered the analyzable sample size.

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 From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months, measured over Baseline and 6-Months.

The primary endpoint was change from baseline in brachial artery flow-mediated dilation at six months, expressed as percentage change. FMD assesses how a conduit artery responds to a temporary increase in blood flow. It is used as a measure of endothelial function, the function of the inner lining of blood vessels. In this study, that measure was selected to assess vascular health in young adult survivors of childhood cancer.

The endpoint is a continuous measure. The registry reports a mean change for each arm and a 95% confidence interval around each mean. A mean describes the center of the observed values, while the confidence interval conveys uncertainty in the estimated mean. The arm-specific intervals do not, by themselves, give the uncertainty for a direct difference between treatment groups. The posted results do not provide an estimable two-arm comparison for this endpoint.

The stated measurement window was baseline and six months. The record notes that some data could not be analyzed because of physician withdrawals, loss to follow-up, drug compliance below 70%, unrelated injury, self-withdrawal, participant movement during FMD assessment, or poor ultrasound image quality related to difficult brachial artery anatomy or poor circulation. The registry does not report how these reasons were distributed between arms.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary summary estimate?

The outcome is continuous, and the registry identifies the reported statistic as a mean. For each treatment arm, the posted estimate is the average change from baseline in brachial artery FMD at six months among participants included in that arm's analysis. The values are reported as percentage change. A mean summarizes the center of the observed measurements; it does not describe the spread of all individual values or imply that every participant changed by the mean amount.

The arm-level estimates are -0.5 in the atorvastatin group and -3.4 in the placebo group. Their confidence intervals are reported separately. These summaries answer a within-arm descriptive question about the average observed change. They do not directly answer the comparative question of how much the average change differed between randomized groups.

How should confidence intervals be read?

General explanation: a confidence interval communicates uncertainty in an estimate under the method used to calculate it. A narrower interval indicates greater precision, while a wider interval indicates less precision. The posted intervals are 95% confidence intervals: -2.9 to 1.9 for atorvastatin and -7.3 to 0.6 for placebo. Both intervals include zero. That fact describes the reported intervals for each arm's mean change; it is not a test of the difference between arms.

The registry does not identify the confidence-interval construction method or provide an interval for the treatment contrast. Separate arm intervals cannot be substituted for an interval on the difference. A formal comparison would require a specified analysis of the two groups and a corresponding estimate of uncertainty. The registry reports that a two-arm comparison was not estimable for this continuous endpoint, and no comparative p-value or confidence interval is posted.

Why does the analysis count matter?

The primary analysis includes 8 participants in the atorvastatin arm and 3 in the placebo arm. With small analysis groups, individual measurements can have substantial influence on the group mean, and estimates may be imprecise. The confidence intervals reflect uncertainty as calculated for the reported arm means, but the registry does not provide enough methodological detail to assess the assumptions behind those intervals.

Randomization is intended to make treatment groups comparable on average, but a small trial can still have imbalances by chance. The registry does not report baseline characteristics for the analyzed groups or an adjusted analysis. It is therefore not possible to assess whether any observed baseline differences were accounted for in the posted estimates.

What does a missing comparison mean?

The registry identifies the two-arm comparison as unavailable because values were missing or not estimable for a continuous endpoint. This is different from a reported comparison with a non-significant result. No numerical treatment contrast or inferential test is posted, so the data record does not establish whether an estimated contrast would be compatible with no difference or with a range of other effects. The arm means alone should not be treated as a substitute for that missing analysis.

General explanation: comparative analyses can be affected by assumptions about the outcome distribution, participant inclusion, missing observations and any adjustment for baseline values. The registry record does not report the analysis model, whether an adjustment was planned or used, or how the reported means and intervals were calculated. Those details should not be inferred from the form of the outcome summary.

How should planning calculations be distinguished from results?

General explanation: sample-size planning illustrations ask how many participants might be needed under stated assumptions to detect a specified effect with a chosen statistical procedure. They are planning tools, not observed trial outcomes. The record describes an illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. It does not report these assumptions as the trial's original design justification. The registry does not report the trial's sample-size justification or indicate that the trial was powered for a particular treatment effect.

Any planning illustration should therefore be interpreted as conditional on its assumptions, not as evidence that this completed pilot had a particular probability of finding an effect. Such calculations do not replace an analysis of the observed groups, and they do not resolve the absence of an estimable two-arm comparison in the posted primary results.

10. Multiplicity, Missing Data and Analysis Populations

The record lists the primary FMD outcome and five secondary vascular outcomes: carotid artery compliance, carotid artery distensibility, pulse wave velocity, augmentation index and carotid intima-media thickness. Considering multiple outcomes raises a multiplicity issue: when many statistical questions are examined, the chance of at least one apparently notable result can increase. General explanation: methods such as prespecifying a primary outcome or adjusting significance thresholds can address aspects of multiplicity. Whether such procedures were planned or used is not reported in the registry record. The posted results do not include analyses for the secondary outcomes.

The primary outcome description identifies several reasons for fewer usable measurements or participants: physician withdrawals, loss to follow-up, drug compliance below 70%, unrelated injury, self-withdrawal, movement during FMD assessment, and poor ultrasound image quality due to difficult brachial artery anatomy or poor circulation. The record does not report counts for each reason, their distribution by arm, or the statistical handling of missing outcomes. It also does not report whether the analysis followed an intention-to-treat principle or used another analysis population.

The arm-specific primary analysis counts are 8 for atorvastatin and 3 for placebo, whereas the registry enrollment is 27. The record does not give a full participant flow explaining this difference. Safety populations are reported separately as 14 participants per arm, but the registry does not explain the relationship between those populations and the primary analysis groups. These distinctions matter because results based on available outcome measurements may differ from results based on all randomized participants. The effect of missing measurements or exclusions on the primary estimates cannot be determined from the registry record.

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 reports 0 serious adverse events among 14 participants at risk in the atorvastatin group and 0 among 13 at risk in the placebo group. It also reports 0 other adverse events among 14 at risk in the atorvastatin group and 0 among 13 at risk in the placebo group. These are the posted event counts and group sizes for the safety summaries.

A count of zero in a registry summary means that no events of that category were recorded for the stated group in that summary. It does not prove that an event could not occur, and it does not establish that the treatments have identical safety profiles. General explanation: when a study is small, estimates of uncommon outcomes are especially uncertain, and a lack of recorded events is not equivalent to evidence that risk is absent.

The registry does not report death counts; those values are not reported in the registry record. No serious adverse event terms are listed. The record does not provide further detail about event definitions, surveillance procedures, timing, or a formal comparison of adverse event rates. Safety counts should therefore be read as descriptive registry summaries rather than as a comparative safety analysis.

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

This pilot trial addresses a relevant statistical question: whether vascular measures change during six months of atorvastatin treatment compared with placebo among young adult survivors of childhood cancer. The posted primary outcome is a mean change in brachial artery FMD for each arm. The estimates are -0.5 for atorvastatin and -3.4 for placebo, with 95% confidence intervals of -2.9 to 1.9 and -7.3 to 0.6, respectively.

Those results describe the observed arm-specific changes, but the registry does not report an estimable comparison between the arms. The results therefore do not show the magnitude or precision of a treatment contrast. They also do not demonstrate that the groups were equivalent. A failure to report a comparative estimate is not the same as a finding of no difference.

The study is described as a pilot, and the primary analysis includes small groups. The posted data can be read as an initial description of the measured outcome in the analyzed participants, not as a definitive answer about vascular effects in all survivors of childhood cancer. The record also notes exclusions and unusable measurements, without fully accounting for their distribution or their potential influence on the results.

The trial does not, by itself, establish a clinical outcome such as prevention of cardiovascular disease. Its primary endpoint is a measure of endothelial function, and the record does not provide a reported two-arm result for that measure. No medical conclusion or treatment recommendation follows from these registry summaries. The most defensible interpretation is limited to the reported means, their arm-specific uncertainty intervals, the small analysis counts, and the absence of a posted comparative estimate.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a randomized design and an analyzable comparative result. Randomization describes how treatment assignment was intended to occur; it does not guarantee that every outcome will be available or that a treatment contrast will be estimable in the final posted analysis. Here, the registry records a randomized, placebo-controlled pilot, but the primary results consist of arm-specific mean changes and confidence intervals, with no estimable two-arm comparison.

The small analysis groups and the reported reasons for unusable data make participant accounting especially important. Readers need to distinguish enrollment, the number included in the primary endpoint analysis, and the safety populations. The registry reports these counts, but does not provide a complete flow that reconciles them. That gap limits assessment of how exclusions and missing measurements could influence the estimates.

The trial also illustrates why outcome-specific interpretation matters. FMD is a vascular measure, while the study summary's broader motivation concerns vascular health and cardiovascular disease. A measure of endothelial function is not itself a reported clinical event outcome. The registry lists additional vascular measures, but results for those secondary outcomes are not posted.

Finally, pilot results and planning calculations serve different purposes. A sample-size illustration based on an observed effect is conditional on its assumptions and is not a statement of observed power or evidence that the trial was designed to detect a particular effect. The record's lack of a reported sample-size justification and detailed statistical plan makes it important to separate what the registry reports from what cannot be established from the record.

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 primary result is based on 8 participants in the atorvastatin arm and 3 in the placebo arm, and the registry reports no estimable two-arm comparison. The small analysis groups limit precision and make the arm means potentially sensitive to individual observations. The confidence intervals are wide, and the registry does not provide a comparative estimate with which to quantify the treatment difference.

Participant and measurement exclusions are described, but not fully accounted for. The registry lists withdrawals, loss to follow-up, compliance below 70%, unrelated injury, self-withdrawal, movement during FMD assessment and poor image quality. It does not state how many participants or measurements were affected by each reason, whether these reasons differed between arms, or how missing data were handled. The enrollment figure and the primary analysis counts are not reconciled in a participant flow.

The registry records quadruple masking, while the study summary describes double-blinding of participants and investigators. The record does not clarify that difference. It does not report baseline characteristics for the analyzed groups, the analysis model, the confidence-interval method, a sample-size justification, interim analyses or a detailed statistical plan. It also lists five secondary outcomes without posted results or a reported multiplicity procedure. These omissions restrict evaluation of analysis choices and broader interpretation.

The primary endpoint is a vascular function measure, not a reported clinical cardiovascular outcome. The registry's posted primary results therefore do not establish effects on cardiovascular disease or other clinical outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Statin Therapy in Young Adult Survivors of Childhood Cancer — NCT01733953.
• Registry record last updated 2016-12-14; status last verified 2016-10.
• Results first posted 2016-10-14.
• 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

The registry describes a completed, randomized, parallel-group, phase 2 pilot study of atorvastatin versus sugar-pill placebo in young adult survivors of childhood ALL or NHL. The study summary describes an age range of 18-39 years and six months of once-daily treatment; atorvastatin was listed at 40mg. Registry enrollment was 27.

The primary endpoint was change from baseline in brachial artery FMD at six months. The posted mean changes were -0.5 for atorvastatin, based on 8 participants, and -3.4 for placebo, based on 3 participants. Their 95% confidence intervals were -2.9 to 1.9 and -7.3 to 0.6. A two-arm comparison was not estimable. The record lists five secondary vascular outcomes but no posted analyses for them.

The safety summaries report no serious or other adverse events in the stated groups. The registry does not report a complete accounting of missing primary outcome data, a sample-size justification, or a detailed statistical plan.