This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Rapalogues for Autism Phenotype in TSC: A Feasibility Study (NCT01929642), a na phase 2 study. The primary outcome is Number of Participants With Compliance to the Treatment Protocol..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01929642 |
| Phase | Phase 2 |
| Condition | Tuberous Sclerosis Complex, Self-injury, Autism |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hugo W. Moser Research Institute at Kennedy Krieger, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned participants with tuberous sclerosis complex (TSC) and self-injury. Autism and self-injury are also listed among the conditions. The registry record does not report further eligibility details or describe the participants' characteristics.
Intervention
The study evaluated the rapalogues sirolimus or everolimus. Sirolimus was described as an oral solution or tablet, titrated to a therapeutic serum trough range; everolimus was described as an oral tablet, also titrated to a therapeutic serum trough range. The record does not explain how the choice between the drugs was made.
Comparator
There was no separate control group in the registered design: the study model is single group and allocation is listed as not applicable. The record therefore does not define a like-for-like comparison between treatment and control, or between sirolimus and everolimus.
Primary question
The primary outcome addressed feasibility by measuring family or participant compliance with the treatment protocol. Compliance was defined using completed study visits and assessments relative to those indicated by the protocol. The broader study aim also included safety and changes in cognition and behavior, including autistic symptoms, self-injury, and aggressive behavior. The record does not report the primary outcome value or results for those broader aims.
3. Trial Design
This was a Phase 2 feasibility study with a single-group design. The registry lists allocation as not applicable and masking as none. Those features mean the registered design does not describe random assignment or blinded treatment assessment. Enrollment is listed as 3, and the study status is completed. The recorded start was 2013-07, with primary completion in 2016-07.
The interventions were sirolimus and everolimus, grouped under the description “Sirolimus or Everolimus.” The record describes oral formulations and titration to therapeutic serum trough ranges. It does not report the number of participants who received each drug, how drug selection was determined, or whether treatment changed during the study. The adverse-event summary is specifically grouped under Everolimus; that does not establish how the treatment assignments or exposures were distributed across the entire study.
The primary outcome was a feasibility measure based on compliance with visits and assessments. Other planned outcomes included aggression or self-injury, cognitive function assessed by the Capute Scale, repetitive behavior, the Self-Injury Trauma Scale, and seizure frequency. The record lists 8 outcome measures, but the outcome descriptions do not supply numerical results.
A completed status indicates that the registry lists the study as completed; it does not by itself establish that results were posted or that the study met its feasibility aims. The registry record does not describe a control condition, a statistical analysis plan, an analysis population, or the rationale for the enrollment target. It also does not report whether participants completed treatment or how many contributed data to each outcome.
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
| Stage | Sirolimus or Everolimus |
|---|---|
| STARTED | 3 |
| COMPLETED | 1 |
| NOT COMPLETED | 2 |
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.
| Characteristic | Unit | Everolimus or Sirolimus |
|---|---|---|
| Participants analysed | 3 | |
| Age, Continuous | years | 7 (3 to 13) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Compliance to the Treatment Protocol., measured over Change from baseline to EOT visit 12 week 53.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of completed visits/measures |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of participants with compliance to the treatment protocol, expressed as a percentage of completed visits and measures. The description explains that compliance was assessed and documented at study visits and telephone follow-up calls by a physician or study team member. It was calculated from the study visits and assessments completed relative to the visits and assessments indicated by the protocol.
This kind of measure addresses whether a study procedure can be carried out, rather than whether a treatment changes a clinical condition. In a feasibility study, documenting attendance and completion can help characterize whether the protocol and its assessments are manageable for participants and families. As a general statistical point, a completion-based measure is most informative when its numerator, denominator, observation period, and handling of unavailable assessments are clear.
The registered timeframe is “Change from baseline to EOT visit 12 week 53.” The record does not report the resulting compliance percentage, the number of completed visits or assessments, or a separate result for telephone follow-up. It also does not describe how partial completion, missed visits, or assessments not attempted were handled. The endpoint definition is therefore available, but its observed value and the detail needed to independently interpret its calculation are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed feasibility study, not a randomized treatment comparison. Its single-group model and allocation listed as not applicable provide no separate control group against which to estimate a treatment effect. The record lists enrollment as 3, but does not report participant-level results or the number contributing data to the primary endpoint.
Most importantly, no numerical result for protocol compliance is reported in the registry record. Without that result, it is not possible to characterize the observed level of completion or how precisely it was estimated. The record also does not report a treatment-effect estimate, confidence interval, or inferential test for the primary outcome. A completed status should not be read as evidence that a particular compliance threshold was achieved.
The study description states an interest in safety and in cognitive and behavioral changes. The listed secondary outcomes cover aggression or self-injury, cognitive function on the Capute Scale, repetitive behavior, self-injury trauma, and seizure frequency. Outcome names identify what was intended for assessment, but they do not establish that data were collected or show the direction or magnitude of any change. Numerical findings for these measures are not reported in the registry record.
General statistical interpretation depends on both the estimate and its uncertainty. A confidence interval, when reported, describes a range of values compatible with the data under the analysis assumptions; it is not a guarantee that the true value lies in that range. No confidence interval is reported for the primary compliance outcome. With an enrollment of 3, any estimate based on the enrolled group would in general be vulnerable to substantial uncertainty and limited representativeness, but the record does not give an estimate from which to quantify that uncertainty.
The adverse-event summary lists Everolimus with 3 at risk, 0 affected for serious adverse events, and 3 at risk, 1 affected for other adverse events. These counts concern participants affected, not necessarily the total number of event occurrences. They do not establish that an event was or was not caused by treatment. The record does not provide event descriptions in the serious-event terms list, and the death count is not reported in the registry record.
Accordingly, the record supports a description of the study's aim, design, and registered outcome definitions. It does not support a conclusion about the success of the feasibility procedures, the size or direction of cognitive or behavioral changes, comparative efficacy, or treatment causality. Those conclusions require results and analysis details that are not reported in the registry record.
9. Statistical Methods Explained
What the design permits. The registered model is single group, with allocation listed as not applicable and masking listed as none. A single-group study can describe what was observed among participants who received the study intervention, but it does not provide a concurrent control group for separating treatment effects from other explanations for change. General examples of other explanations include natural variation over time, changes in care, and measurement variation; the registry record does not say whether any of these occurred in this study. No randomized or blinded comparison should be inferred from this design.
What the primary measure captures. The compliance endpoint is a process measure. It uses completed visits and assessments in relation to those specified by the protocol, with compliance documented at study visits and telephone follow-up. General considerations for interpreting such a measure include whether the denominator is defined consistently for every participant and how missed or unavailable assessments are classified. The registry record gives the broad calculation but does not report detailed rules for these situations or the observed percentage.
Precision and uncertainty. An estimate describes the observed data; a confidence interval communicates statistical uncertainty around an estimate under a specified method and assumptions. The narrower the interval, the more precise the estimate is often considered, although precision is not the same as freedom from bias. The registry record does not provide a compliance estimate or its confidence interval, nor does it describe an interval method. As a general point, a small enrolled group can yield imprecise estimates and limited ability to represent a broader population. No precision value can be reconstructed from the reported information.
Repeated observations and count outcomes. The registered outcomes include counts or frequencies, such as aggression or self-injury and seizures. General analysis of count data must account for the way events are recorded and the time over which each participant is observed. If counts vary more than a basic model expects, over-dispersion can make standard errors too small unless the analysis allows for that extra variation. Repeated observations from the same participant are also correlated rather than independent, and methods should account for that dependence when appropriate. The registry record does not report the models, observation denominators, or methods used for these outcomes, so it is not possible to determine how those issues were handled.
Multiple outcomes. The record lists 8 outcome measures, including the primary compliance measure and several cognitive, behavioral, and seizure outcomes. When many outcomes are tested, the chance of obtaining at least one apparently notable result by chance can increase. General approaches include designating a primary outcome in advance, adjusting for multiple testing, or treating additional analyses as exploratory. The registry record does not report a multiplicity strategy, the statistical tests, or results for the outcomes. The presence of several registered measures alone does not establish that all were analyzed or that any particular adjustment was used.
Planning calculations and observed power. The registry record describes sample-size assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as stated fractions of an observed effect. It also specifies that time-to-event planning uses total events and a Schoenfeld approach, while other planning outputs are expressed as participants per arm. These are planning assumptions, not the registered single-group study design. Any sample-size illustration based on an observed effect is a hypothetical design exercise and must not be interpreted as observed power or as evidence that the study was adequately powered. The registry record does not state that these assumptions were the trial's own design or sample-size justification.
Analysis plan and reproducibility. No analysis entries are reported, and the registry record does not identify statistical tests, model specifications, covariate adjustments, missing-data methods, analysis populations, or interim analyses. Those details are important because different choices can yield different estimates and uncertainty. Since no numerical primary result or analysis method is reported, a recalculation from summary statistics is not possible. The registry record does not report a sponsor analysis that could be compared with an unadjusted recalculation.
These are general principles for reading clinical-trial statistics. They do not assert that a particular model or test was used in this study. The available record identifies the feasibility aim and outcome definitions, but does not provide the analysis details needed to evaluate statistical assumptions or reproduce numerical findings.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 8 outcome measures, spanning feasibility, behavior, cognition, self-injury, and seizures. When several outcomes are assessed, general statistical practice distinguishes the primary question from additional outcomes and considers how multiple testing will be handled. No multiplicity adjustment, hierarchy of secondary outcomes, or exploratory analysis plan is reported in the registry record. The list of outcomes alone does not show which were analyzed or how their results should be interpreted together.
The registry record does not report missing-data counts, reasons for missingness, or a method for handling missing observations. It also does not define an intention-to-treat, per-protocol, or other analysis population. These details matter because the set of observations used in an analysis can affect the estimate and its interpretation. For the compliance endpoint, completed visits and assessments form part of the measure, but the record does not specify how missed or partly completed assessments were treated beyond its broad calculation description.
The record reports no statistical analysis entries. The tests, models, treatment of repeated measures, and any adjustment for baseline values are not reported in the registry record. It is therefore not possible to determine whether analyses were prespecified, whether all planned outcomes were analyzed, or how uncertainty was calculated. These omissions limit statistical interpretation; they do not establish that analyses were not conducted outside the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Everolimus | 0 | 3 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Everolimus | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Everolimus |
|---|---|---|
| aphthous ulcer | Skin and subcutaneous tissue disorders | 1 of 3 |
The registry adverse-event summary is for Everolimus. It lists 3 at risk and 0 affected for serious adverse events, and 3 at risk and 1 affected for other adverse events. These are counts of participants affected in the summary, not necessarily counts of individual event episodes. The record does not provide descriptions of the other adverse event or its timing, severity, or relationship to treatment.
No terms are listed in the serious adverse-event terms summary. The death count is not reported in the registry record. A zero in the serious-event affected count means that the registry summary records no affected participants in that category; it does not demonstrate that serious harms are impossible or that a treatment is safe. With a small study group, uncommon events may not be observed, and the record does not offer a comparison group for estimating excess risk.
These safety figures should be read as descriptive registry counts only. They do not establish causality, comparative safety between sirolimus and everolimus, or the frequency of adverse events in a wider population.
12. What the Result Does, and Does Not, Mean
This study addresses whether a treatment protocol involving sirolimus or everolimus could be implemented in participants with TSC and self-injury, while also assessing safety and possible cognitive or behavioral changes. The primary endpoint was designed to describe compliance with visits and assessments. In that sense, the principal question is about feasibility, not a controlled test of whether one treatment is better than another.
The registry record reports enrollment as 3 and describes a single-group design. It does not report the compliance result, numerical findings for the secondary outcomes, or an analysis of change from baseline. The registered outcome definitions and study aims therefore cannot be treated as observed evidence of improvement, worsening, or no change. Nor does study completion establish that the protocol was feasible according to a predefined criterion: no such criterion or result is reported.
The design does not include a like-for-like control comparison. As a general principle, changes observed over time in a single group cannot by themselves distinguish an intervention effect from other influences or ordinary variation. The record also does not report enough information to quantify uncertainty around outcomes or assess whether missing observations affected the findings.
The adverse-event summary records no participants affected by serious adverse events and one affected by other adverse events in the Everolimus group. Those descriptive counts do not establish whether an event was caused by treatment, and they cannot characterize uncommon risks with precision. The death count is not reported in the registry record.
The appropriate interpretation is limited to the registered study purpose, design, outcome definitions, and the safety counts that are listed. Conclusions about clinical benefit, treatment efficacy, comparative effects, or broad safety require results and analyses not reported in the registry record.
13. Why This Trial Matters Statistically
Feasibility questions can be important when a study requires ongoing treatment and repeated behavioral, cognitive, or safety assessments. In this study, the primary measure focused on completion of protocol visits and assessments, while the broader aims included self-injury, aggression, cognition, repetitive behavior, and seizures. Describing this distinction helps readers avoid treating a process measure as though it were a clinical treatment-effect outcome.
The study also illustrates why the design must shape interpretation. A single-group study can document experiences and outcomes within the group studied, but without a control group it cannot isolate the effect of an intervention from other influences. The registry record lists both sirolimus and everolimus but does not describe a randomized or controlled comparison between them. The adverse-event summary for Everolimus should not be mistaken for comparative safety evidence.
Statistically, the record makes clear that outcome definitions and numerical findings are different kinds of information. Naming an outcome, timeframe, and intended measurement does not supply an estimate or its uncertainty. The primary compliance result and the analysis details are not reported in the registry record, so readers cannot assess the achieved level of completion or the precision of an outcome estimate.
The study's listed enrollment is 3. In general, estimates from small groups may be unstable and may not represent the range of experience in a wider population. That context is especially relevant to safety: absence of a serious event in a small study summary is not proof that risk is absent. The registry record is useful for identifying what the study set out to assess, while its missing results limit what can be concluded statistically.
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 the primary compliance result. Although it describes how compliance was intended to be calculated, it does not provide the completed visits or assessments, the protocol-indicated denominator, or the resulting percentage. It is therefore not possible to evaluate the study's feasibility finding from the registered information.
The study is listed as single group, with allocation not applicable and masking none. It does not provide a control group for interpreting changes over time, nor does the record describe a randomized comparison between sirolimus and everolimus. It also does not report how participants were assigned to or selected for either drug, or the number exposed to each treatment. This limits treatment-specific interpretation, including of the Everolimus safety summary.
The enrollment is listed as 3, but participant characteristics and outcome-specific analysis counts are not reported in the registry record. The record does not provide numerical results for the secondary outcomes, confidence intervals, statistical tests, analysis populations, missing-data procedures, or a multiplicity strategy. No sample-size justification for the study is reported in the registry record. These omissions prevent assessment of precision, analytic choices, and the extent to which each planned outcome was evaluated.
The adverse-event summary provides affected-participant counts but does not describe event type, timing, severity beyond the serious-versus-other classification, or causal attribution. The death count is not reported. Taken together, these limitations mean the registered information supports a study-design description but not conclusions about clinical benefit, treatment effects, or comprehensive safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Rapalogues for Autism Phenotype in TSC: A Feasibility Study — NCT01929642.
- Registry record last updated 2021-03-29; status last verified 2021-03.
- Results first posted 2021-03-29.
- 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.
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18. Record Summary
The registry record describes NCT01929642, “Rapalogues for Autism Phenotype in TSC: A Feasibility Study,” as a completed Phase 2, single-group study. Enrollment is listed as 3. Allocation is not applicable and masking is none. The study concerned participants with TSC and self-injury and evaluated sirolimus or everolimus.
The primary outcome measured compliance with treatment-protocol visits and assessments. Registered secondary outcomes addressed aggression or self-injury, cognition, repetitive behavior, self-injury trauma, and seizure frequency. The record lists 8 outcome measures but reports no analysis entries and does not provide numerical efficacy or compliance results.
The adverse-event summary lists Everolimus with 0 affected for serious adverse events and 1 affected for other adverse events, among 3 at risk in each category. The death count is not reported in the registry record. The available information supports describing the study's aims and design, but not estimating treatment effects or drawing comparative conclusions.