Pharmacological Treatment of Rett Syndrome With Statins: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacological Treatment of Rett Syndrome With Statins (NCT02563860), a na phase 2 study. The primary outcome is Gait Velocity as Measured by GAITRite System.

2. Clinical Question

3. Trial Design

This completed phase 2 study, NCT02563860, was sponsored by Montefiore Medical Center. The registry record gives a start date of 2015-07 and a primary completion date of 2016-07. It describes the study as an open-label, dose-escalating trial of lovastatin in Rett syndrome, with a single-group model and no masking.

The planned treatment schedule was 10 mg daily for 8 weeks, followed by 20 mg daily for 8 weeks and 40 mg daily for 16 weeks. The primary outcome was scheduled for measurement during the final week of treatment, week 32. The registry record lists an enrollment of 20. It does not report how many participants completed treatment or contributed a primary-outcome measurement, so enrollment should not be taken as the analysis population.

With no concurrent comparator, the design can describe outcomes observed in the treated group but cannot separate treatment-associated change from other explanations, such as changes over time or measurement variation. Open-label conduct also means participants and study personnel were not masked to treatment. The registry record does not report additional design features, a protocol rationale for the schedule, or a statistical analysis plan.

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

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 Gait Velocity as Measured by GAITRite System, measured over During final week of treatment, week 32.

The primary endpoint was gait velocity, measured in cm/sec with the GAITRite System during the final week of treatment, week 32. The outcome description refers to quantitative gait assessment using a computerized walkway with embedded pressure sensors. The registry record specifies that the result was to be summarized as a median and inter-quartile range.

In general, gait velocity gives a quantitative summary of walking speed. A computerized walkway can record movement across the measurement area, allowing a continuous measure rather than a purely descriptive account of gait. This general rationale explains why gait velocity can be selected as an outcome; the registry record does not state the trial investigators’ specific rationale for choosing it or define what size of change would be clinically important.

A median describes the middle of the observed values, while the inter-quartile range describes the spread of the central portion of those values. In general, these summaries can be useful when outcomes are skewed or include unusually high or low observations. They do not, by themselves, quantify a treatment effect or indicate uncertainty about that effect. The registry record gives no observed median, inter-quartile range, change from baseline, or inferential estimate for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median and inter-quartile range convey?

The primary outcome is specified as a median with an inter-quartile range. In general, the median is the central value after observations are ordered. The inter-quartile range describes the spread of the middle portion of the observations. These summaries focus on the center and spread of the measured data rather than relying on a mean and standard deviation. They can be informative when data are asymmetric or contain extreme values, though the registry record does not explain why this summary was selected for gait velocity.

A median and inter-quartile range are descriptive statistics. They do not directly provide the estimated change from baseline, a comparison with another group, or the uncertainty of an estimated treatment effect. Interpretation would require knowing which participants contributed measurements and how observations at different time points were handled. Those details and the primary endpoint values are not reported in the registry record.

What can a single-group study estimate?

In general, a single-group study can describe measurements made in participants receiving the intervention. If measurements are collected at more than one time, an analysis may describe within-participant change. A change over time is not equivalent to a controlled treatment effect: it lacks a concurrent group that indicates what might have happened over the same period without the intervention. Other changes during follow-up, natural variation, or measurement variability can contribute to a before-and-after pattern. The registry record does not describe a comparator or a primary analysis that estimates within-participant change.

The record identifies a single-group model, allocation as not applicable, and no masking. This makes the comparison structure important: there is no randomized treatment contrast to interpret. Randomization is generally used to balance factors between groups, while masking can reduce the influence of treatment knowledge on conduct and assessment. These general protections are not features of the design as recorded; their absence does not establish that bias occurred, but it limits what the study can rule out.

How should uncertainty be assessed?

In general, a confidence interval describes a range of values compatible with an estimate under the assumptions of the analysis. Its width conveys precision: a narrower interval indicates more precise estimation than a wider one. A point estimate alone gives no such indication. Here, the registry record reports no effect estimate or confidence interval for gait velocity, so the precision of any primary-outcome effect cannot be assessed from the posted results.

A statistical test addresses compatibility with a specified null hypothesis under an analysis model; it does not by itself establish clinical importance or causation. The registry record lists zero analysis records and does not report a test, significance level for the trial’s primary analysis, or a prespecified statistical plan. Any particular inferential result would therefore be unsupported by the registry information.

What do planning illustrations represent?

In general, sample-size planning illustrations ask how much information a future study might need to detect an assumed effect under stated statistical conditions. The planning assumptions described for this record refer to 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 record also distinguishes total events for time-to-event planning from participants per arm for other outcomes. These are planning assumptions, not a description of this trial’s single-group design.

Such planning values are illustrative rather than an observed feature of the completed study. They do not show that the study had a particular probability of detecting an effect, and they are not observed power. The registry record does not report a sample-size justification for the trial’s own design. A planned detectable effect is also dependent on the assumptions used; it cannot replace reporting the observed estimate and its uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: primary gait velocity and the secondary Visual Memory Novelty Score assessed by the TobiiTX 300 Eyetracking System. It does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment for testing multiple outcomes. Without that information and without outcome analyses, it is not possible to determine how the study handled the possibility of chance findings across multiple tests.

Missing-data handling is not reported in the registry record. The record does not state how incomplete outcome measurements were treated, whether any imputation was used, or what assumptions would support an analysis with missing observations. The population used for the primary outcome analysis is also not reported. Enrollment of 20 does not establish how many participants completed treatment or contributed data at week 32.

The record lists zero analysis records. It does not report analysis populations, exclusions, protocol deviations, or sensitivity analyses. These omissions matter because an outcome summary depends on which participants and measurements are included, and conclusions can be affected when data are incomplete. Without those details, the primary and secondary outcomes cannot be evaluated for either effect or robustness.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

For the Open Label group, the registry record lists 20 participants at risk for serious adverse events and 0 affected; it lists 20 at risk for other adverse events and 1 affected. The death count is 0. No serious adverse event terms are listed. These figures are the safety information recorded for the group and should be read as reported counts, not as a complete description of event types, timing, severity, or attribution.

In general, an adverse event recorded during a study is not necessarily caused by the intervention. The registry figures do not establish causation, and the record does not provide enough detail to assess event exposure over time or the completeness of adverse-event collection. The count of participants affected also does not describe the number or duration of events. The registry record does not report additional safety analyses or a comparison group, so these figures cannot establish a comparative safety profile.

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

The record establishes that a completed phase 2, open-label, single-group study of dose-escalating lovastatin in Rett syndrome was registered, and it identifies gait velocity as the primary outcome. It also describes the treatment schedule and the intended endpoint time. Those details define the research question and the design, but they are not evidence of an observed benefit or lack of benefit.

The registry record does not report the primary gait-velocity values, a change estimate, or a statistical analysis. It also does not report results for the secondary visual-memory outcome. Consequently, there is no posted estimate from which to judge the direction, magnitude, or precision of an outcome difference over time. The absence of a reported result is not evidence that there was no change.

Even with outcome results, a single-group, open-label design would need cautious interpretation. A change from an earlier measurement could not be cleanly separated from other influences over time, and there is no concurrent control group for comparison. The registry record does not supply a threshold for clinically meaningful change, so statistical differences alone could not be translated into clinical importance without additional context.

The safety counts report no participants affected by serious adverse events in the listed group, one affected by other adverse events, and no deaths. These are descriptive registry entries, not proof of the absence of unrecorded events or evidence that any event was or was not caused by treatment. Overall, the record supports a description of the study’s design and recorded safety counts, but it does not support a conclusion about efficacy or comparative safety.

13. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a defined endpoint and an interpretable treatment effect. The registry record gives a measurable primary outcome, gait velocity in cm/sec, and specifies a measurement system, summary form, and time point. Those details make the intended outcome clear. Yet without the observed values or an analysis, endpoint specification alone cannot answer whether participants’ gait velocity changed or how uncertain an estimate would be.

The single-group structure also illustrates why study design shapes the conclusions that statistics can support. A descriptive summary can characterize outcomes in the treated group, but causal interpretation ordinarily depends on a credible comparison. With no concurrent comparator and no masking, changes over time cannot be attributed to treatment from the design alone. This is a general limitation, not a finding that bias or a particular alternative explanation occurred.

The record also distinguishes planned sample-size illustrations from the trial’s own design. Illustrations based on an observed effect and assumptions about two-arm allocation do not demonstrate that a single-group trial had adequate power, nor do they replace reporting the observed endpoint estimate. The registry record does not report the trial’s sample-size justification or analysis results.

Finally, outcome reporting is essential to statistical interpretation. The listed measures and safety counts offer some information about what was planned and recorded, but the absence of efficacy analyses leaves the central outcome question unresolved in the registry record. This case therefore emphasizes that design, measurement, analysis, and transparent result reporting each contribute different parts of the evidence.

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.

Several limitations specific to this study follow from the information recorded. The trial was open label and single group, with no concurrent control. Thus, any change in gait velocity during treatment would not, by design alone, establish that lovastatin caused it. The registry record does not describe masking or a control condition beyond listing none and not applicable, respectively.

The primary outcome was scheduled for the final week of treatment, week 32, but no baseline measure or change analysis is reported. A single measurement time at the end of treatment, without reported outcome values, provides no basis for assessing the trajectory of gait velocity during the dose-escalation schedule. The record also does not report whether all enrolled participants completed that schedule or contributed endpoint data.

Eligibility criteria, participant characteristics, analysis population, handling of missing data, and the statistical plan are not reported in the registry record. The record lists zero analysis records, so it is not possible to assess endpoint results, precision, protocol deviations, or robustness. It does not report a clinical-importance threshold for gait-velocity change or a multiplicity approach for the primary and secondary outcomes.

Safety information is limited to group-level counts: the record lists affected participants and deaths but no serious adverse event terms or detailed event descriptions. These limits constrain interpretation of both the outcome question and safety experience. They do not establish that unreported information was absent from study conduct; they indicate that it is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacological Treatment of Rett Syndrome With Statins — NCT02563860.
• Registry record last updated 2019-07-12; status last verified 2019-07.
• Results first posted 2019-05-07.
• 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

NCT02563860 is a completed phase 2 study sponsored by Montefiore Medical Center, with a listed start date of 2015-07 and primary completion date of 2016-07. The registry describes an open-label, single-group, dose-escalating lovastatin study in Rett syndrome, with enrollment of 20. Treatment was scheduled as 10 mg daily for 8 weeks, 20 mg daily for 8 weeks, and 40 mg daily for 16 weeks.

The primary outcome was median gait velocity with an inter-quartile range, measured by the GAITRite System in cm/sec during the final week of treatment, week 32. Visual Memory Novelty Score assessed by the TobiiTX 300 Eyetracking System was listed as a secondary outcome. No outcome analysis is reported in the registry record. Safety entries list 0 participants affected by serious adverse events, 1 affected by other adverse events, and 0 deaths in the Open Label group.