Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease (NCT01702246), a na phase 1, phase 2 study. The primary outcome is Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin.

2. Clinical Question

This question concerns change over time within the treated group, not a randomized comparison of simvastatin against another treatment or against no treatment. A before-and-after comparison can describe whether the measured outcome differed between the two time points. By itself, it cannot separate a treatment-associated change from other explanations, such as changes over time or differences in diary completion. The registry record does not report the numerical change, its uncertainty, or a statistical test for the primary endpoint, so the magnitude and precision of the observed change cannot be assessed from the posted results described in the record.

3. Trial Design

NCT01702246, titled “Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease,” is described as a Phase 2 study, with the phase listing also including Phase 1. The study is completed. Its recorded start is 2012-02, and its primary completion is 2015-05. The listed enrollment is 24 participants.

The design is single group, with no masking and allocation recorded as NA. Participants received simvastatin, described as a 40mg tablet taken orally once daily for 3 months. The primary endpoint compares baseline with the 3-month time point. There is no like-for-like control arm in the record, so the design does not estimate a randomized between-group treatment contrast. The skip note also identifies that the study is not a randomized comparison and that arms are not a like-for-like control comparison.

The registry record names two secondary outcomes: change in plasma high sensitivity C-reactive protein and change from baseline in total cholesterol level after treatment with simvastatin. It lists 3 outcome measures and 3 analyses, but their numerical results and analysis details are not reported in the registry record. The planned sample-size justification, any interim analyses, and a fuller statistical analysis plan are not reported in the registry record.

The distinction between enrollment and the number included in a particular analysis matters. The record lists enrollment of 24, while the serious adverse event group lists 19 participants at risk. It does not explain the difference, identify the primary analysis population, or report how many participants contributed complete baseline and follow-up pain diaries. Those details are important when interpreting both the endpoint and safety counts.

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:

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 in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin, measured over Baseline and 3 months.

The primary endpoint is change in the frequency of vaso-occlusive pain events before and after simvastatin treatment. Frequency is expressed as a proportion of pain days. The registry definition is the number of days with sickle cell disease-related pain divided by the number of daily pain diaries completed. The listed assessment times are baseline and 3 months.

This measure captures how often pain was reported over the days for which a participant completed a diary. Expressing pain days relative to completed diary days gives the endpoint a defined observation period, but the denominator depends on diary completion. If diary completion differs across participants or between assessment periods, the observed proportion may not represent the same amount of observed time for everyone. The record does not report diary completion summaries or methods for handling incomplete diaries.

The endpoint is used to quantify change in pain frequency in the study group over the treatment period. The endpoint description also mentions pain intensity, but the named primary outcome is the change in frequency; no numerical intensity result is reported in the registry record. The registry record does not report the numerical baseline value, the 3-month value, the estimated change, its standard deviation, or a confidence interval. Consequently, the direction, size, and precision of the primary endpoint change cannot be described from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

The primary endpoint is described as a mean continuous measure: change in the proportion of pain days from baseline to 3 months. A mean summarizes the average value in a group. For a before-and-after endpoint, the relevant quantity is the average within-person change when the same participants contribute measurements at both times. That summary does not imply that every participant changed in the same direction or by the same amount. The registry record does not report the numerical mean change or the analysis population used to estimate it.

What does the standard deviation describe?

The endpoint description identifies standard deviation as the measure of dispersion. In general, a standard deviation describes how spread out individual observations are around their mean. It is not the same as the uncertainty in the estimated mean: uncertainty also depends on the amount of information available and the analysis. The numerical standard deviation for the primary outcome is not reported in the registry record, so the variability among participant measurements cannot be assessed.

How should a confidence interval be read?

General explanation: a confidence interval gives a range of values compatible with the data under the statistical model and its assumptions. It communicates precision as well as the direction and size of an estimate. An interval that spans a range of possible changes may leave substantial uncertainty about the underlying effect. The primary endpoint’s confidence interval is not reported in the registry record. No statistical conclusion about its precision or compatibility with particular values can therefore be drawn.

Why does the design matter?

This is a single-group before-and-after study, not a randomized comparison. General explanation: repeated measurements can show how an outcome changes within the observed group, but they do not by themselves establish why it changed. A concurrent comparator can help distinguish a treatment contrast from changes that also occur over time, although the strength of inference depends on the design and conduct. No randomized comparator is described in this record, and no causal effect should be inferred from a within-group change alone.

What does the pain-day denominator mean?

The pain rate is defined as days with sickle cell disease-related pain divided by completed daily pain diaries. This makes diary completion part of the endpoint’s measurement. General explanation: if the number or pattern of observed diary days varies, the measured proportion can be affected by which days are recorded. Appropriate interpretation therefore depends on knowing how many diaries were completed and how incomplete records were handled. Those details are not reported in the registry record.

What are the planning illustrations?

The stated planning framework uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes an effect to detect as a stated fraction of the observed effect. For time-to-event settings, the framework would express the total number of events; for other settings, it would express participants per arm for 80% or 90% power when those planning values are displayed. These are planning illustrations based on an observed effect, not observed power and not the trial’s own design justification. The registry record does not report the protocol’s sample-size justification. Since the numerical primary effect is not reported in the registry record, a planning illustration cannot be interpreted as a result of this study or as evidence about its actual power.

What can be said about analyses and multiplicity?

The record lists 3 analyses and names the primary outcome and two secondary outcomes. It does not report the numerical estimates, test results, adjustment approach, prespecified testing hierarchy, or whether the outcomes were analyzed using the methods described in a full statistical plan. When several outcomes are tested, general explanation: the chance of obtaining at least one apparently unusual result can rise if no multiplicity strategy is used. Whether and how that issue was addressed is not reported in the registry record. The listed outcomes alone do not reveal the testing procedure.

How should missing information be treated?

The enrollment count is 24, while the serious adverse event listing identifies 19 participants at risk. The record does not explain the populations represented by these counts. It also does not state how many participants had usable pain diaries at both time points, whether missing measurements were imputed, or whether an analysis used all available observations. These are methodological details, not matters that can be inferred from the endpoint definition. Without them, the extent to which missing observations could affect the primary estimate is not assessable from the registry record.

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("Baseline", "Simvastatin")
n   <- c(19, 19)
m   <- c(0.2365, 0.1311)
sp  <- c(0.21, 0.15)
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  Baseline  19  0.236  0.210  0.135  0.338
CARM  Simvastatin  19  0.131  0.150  0.059  0.203

11. Multiplicity, Missing Data and Analysis Populations

The registry record names one primary outcome and two secondary outcomes: change in plasma high sensitivity C-reactive protein and change from baseline in total cholesterol level after simvastatin treatment. It lists 3 outcome measures and 3 analyses. The analysis methods, testing sequence, and any adjustment for multiple comparisons are not reported in the registry record. General explanation: when several outcomes are tested, interpreting each result as if it were the only test can make chance findings more likely across the set. The record does not establish whether that concern was addressed.

Missing-data methods are also not reported in the registry record. This is especially relevant to the primary outcome because pain frequency is calculated using the number of completed daily pain diaries. The registry record does not report diary completion by participant or time point, the number with paired observations, how missing diary days were treated, or whether any sensitivity analyses were conducted.

The recorded enrollment is 24, while the serious adverse event group lists 19 participants at risk. The record does not explain the difference or define the analysis populations. It also does not report whether the primary analysis followed an intention-to-treat approach, included only participants with measurements at both time points, or used another population definition. These omissions prevent assessment of how participant inclusion and missing observations may have affected the posted results.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sickle cell vaso-occlusive pain crisis (21.1%), hyperhemolysis (5.3%).

The serious adverse event listing identifies 19 participants at risk in the Simvastatin group and 5 participants with a serious adverse event. The listed serious-event terms include sickle cell vaso-occlusive pain crisis at 21.1% and hyperhemolysis at 5.3%. These are the terms and percentages reported in the registry record; the listing does not provide enough detail to infer the timing, duration, severity beyond the serious-event classification, or relationship of each event to treatment.

The listing also reports 19 participants at risk for other adverse events and 1 participant affected. No deaths are listed. The enrollment count for the study is 24, but the record does not explain why the safety group has 19 participants at risk or whether that group represents all participants who received treatment. The counts should therefore be read with the listed at-risk denominator, rather than assumed to describe every enrolled participant.

These safety figures are descriptive. They do not, on their own, establish that simvastatin caused or did not cause an event, and the record does not provide a comparison group for estimating relative risk. The listed serious-event terms should not be interpreted as a complete account of all clinical events without further information from the registry record.

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

The study addresses a specific measurement question: whether the mean proportion of pain days changed between baseline and 3 months among people receiving simvastatin. The registry record describes a single-group study with enrollment of 24 and a daily-diary definition of pain frequency. It also lists safety information and two secondary outcomes. These details establish what was studied and how the primary endpoint was defined.

The numerical primary result is not reported in the registry record. As a result, the direction and size of any change, its variability, and its precision cannot be evaluated. The record does not support a statement that pain frequency improved, worsened, or stayed the same. It also does not report numerical results for the named secondary outcomes.

Even if a before-and-after change were reported, the single-group design would describe change over time rather than provide a randomized comparison with another treatment or no treatment. General explanation: without a concurrent comparator, observed change cannot be attributed to the intervention with the same basis as a randomized treatment contrast. This does not negate the descriptive value of repeated measurements, but it limits the claims that can follow from them.

The endpoint also depends on completed pain diaries. The record does not report diary completion or missing-data methods, so it is not possible to assess how incomplete observations may have influenced the measure. The safety counts are likewise descriptive and use a listed at-risk group of 19, which the record does not reconcile with enrollment of 24.

The appropriate interpretation is therefore narrow: the registry describes the treatment regimen, study structure, endpoint definition, and certain safety counts, while leaving the numerical efficacy results and several key analysis details unreported. No treatment conclusion follows from the information recorded.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates the difference between defining an outcome and reporting its estimate. The registry record gives a clear operational definition of pain frequency: days with sickle cell disease-related pain divided by completed daily pain diaries. It also specifies baseline and 3-month assessment. Those details allow readers to understand the intended measure, but they do not reveal the observed change. Without the estimate and its uncertainty, neither magnitude nor precision can be evaluated.

The single-group structure is also important. A before-and-after design can describe change in a treated group, but it does not provide a randomized contrast against a concurrent control. This distinction is central to interpreting clinical evidence: a within-group pattern and a treatment effect relative to a comparator are different statistical quantities.

The diary-based denominator highlights how measurement and missingness are connected. The number of pain days is interpreted relative to the number of completed diaries, so incomplete reporting can affect what the proportion represents. The registry record does not give diary completion details or missing-data methods. Likewise, it lists 24 enrolled participants but identifies 19 at risk in the safety group without explaining the populations.

Finally, the record identifies primary and secondary outcomes and lists analyses, yet does not report numerical results or the multiplicity strategy. This limits the ability to evaluate both individual estimates and the overall pattern of testing. These features make the study useful for considering what information is needed for transparent statistical interpretation, while the absent numerical outcomes prevent assessment of the clinical endpoint itself.

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.

Several trial-specific limitations constrain interpretation. The design is single group, unmasked, and has no randomized comparator described. Consequently, the primary before-and-after assessment cannot estimate a randomized difference between simvastatin and a control condition. The registry record does not report how the absence of masking may have been considered in collecting or analyzing diary-based pain reports.

The endpoint depends on completed daily pain diaries, but the record does not report diary adherence, the number of observed diary days, or the approach to incomplete diaries. Because the denominator is completed diaries, variation in reporting could affect the measured proportion. The record also does not report the numerical primary outcome estimate, standard deviation, confidence interval, or test result, leaving the observed direction and precision unknown.

Enrollment is listed as 24, whereas the serious adverse event group lists 19 participants at risk. The registry record does not explain this difference or specify the analysis populations for the primary endpoint and safety summaries. Eligibility criteria and participant characteristics beyond the condition are not reported in the registry record.

The record lists two secondary outcomes and 3 analyses, but the numerical results, statistical methods, multiplicity approach, and missing-data procedures are not reported in the registry record. The protocol’s sample-size justification and any interim analyses are also not reported. These omissions limit assessment of the analysis choices and the strength of inference. The limitations describe what can be evaluated from the record, not proof that unreported procedures were or were not performed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease — NCT01702246.
• Registry record last updated 2016-12-19; status last verified 2016-01.
• Results first posted 2016-12-19.
• 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

NCT01702246 is a completed Phase 2 study, with Phase 1 also listed, of simvastatin for vaso-occlusive pain in sickle cell disease. It is recorded as a single-group, unmasked study with allocation NA and enrollment of 24. Participants received simvastatin 40mg orally once daily for 3 months. The primary endpoint is change in the mean proportion of pain days from baseline to 3 months, using completed daily pain diaries as the denominator.

The registry record names two secondary outcomes and lists 3 outcome measures and 3 analyses. It reports safety figures for 19 participants at risk, including 5 with a serious adverse event, and lists serious-event terms of sickle cell vaso-occlusive pain crisis and hyperhemolysis. The numerical primary and secondary outcome results, detailed analysis methods, missing-data procedures, and reconciliation of enrollment with the safety population are not reported in the registry record.