Novel Cognitive Treatment Targets for Epidiolex in Sturge- Weber Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Novel Cognitive Treatment Targets for Epidiolex in Sturge- Weber Syndrome (NCT04447846), a na phase 2 study. The primary outcome is List Sorting Working Memory Test.

2. Clinical Question

The study addresses whether cognitive performance can be assessed during treatment with cannabidiol (Epidiolex) in people with Sturge-Weber syndrome (SWS). Its stated purpose is to better understand the utility of cannabidiol for improving cognitive impairments. The registry record identifies working memory as the primary cognitive target, measured at baseline and after 6 months on study drug. Because the design has one treatment group and no masking, it does not set up a randomized, blinded comparison with a control group.

This clinical question is therefore narrower than whether treatment caused a change. A before-and-after assessment can describe observed scores over time, but without a control group it cannot separate a possible treatment-associated change from other explanations for change.

3. Trial Design

This is a Phase II study recorded as completed, with a single-group model and no masking. The registry record lists an enrollment of 11 and identifies cannabidiol (Epidiolex) as the intervention. Allocation is listed as not applicable, consistent with the absence of a separate assigned comparison group. The sponsor is Anne Comi, MD.

The study start date is 2019-10-14, and the primary completion date is 2021-08-16. The registry status is completed. These registry milestones describe the study record; they do not by themselves establish that every enrolled participant completed every assessment or that all planned analyses were reported.

The intervention description says that participants would take the oral solution at home twice a day and be treated as outpatients. Treatment was described as lasting 24 weeks unless a participant chose to take part in an extension phase. The extension description is incomplete in the registry record, so its procedures and duration are not reported in the registry record.

The primary assessment schedule is baseline and follow-up at 6 months. The primary endpoint is continuous, expressed as a mean T-score with standard deviation as the stated dispersion. The design therefore supports description of scores at those assessment times, and potentially a within-person comparison when paired measurements are available. The registry record does not report a detailed analysis plan, the specific statistical test used, or a numerical primary-outcome estimate.

Other listed outcome domains include picture vocabulary, seizure frequency, migraine severity, motor and functional assessments, disability, hand function, and intelligence testing. The record lists 19 outcome measures overall. Their presence indicates that the study evaluated several domains, but the registry information does not establish which secondary findings were analyzed or how they were interpreted.

With no randomized or masked comparator, any change over time must be interpreted as an observation within the treated group rather than as a direct estimate of a treatment effect relative to an untreated or alternative-treatment group. The enrollment and design also mean the findings are specific to the participants who took part; generalizability beyond them is not established by 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.

Before assignment: After consent, subject 10 was not enrolled as they did not meet the inclusion criteria of remaining at a stable does of anti-epileptic drugs 4 weeks prior to enrollment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subject 1 was unable to complete this assessment due to lack of understanding of the instructions. Subject 10 was unable to complete this assessment due to a system error, where the fully adjusted score was not obtained. Subject 9 was withdrawn prior to the 6 month follow-up visit due to a persistent side effect and was not included in analysis.

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 List Sorting Working Memory Test, measured over Baseline, Follow-up (6 months).

The primary endpoint is the List Sorting Working Memory Test from the NIH Toolbox. It assesses working-memory performance, with results transformed to a T-score on a scale from 0 to 100. A higher score indicates better performance. A T-score of 50 represents the population mean, with a standard deviation of 10, according to the registry description.

Working memory is the specific cognitive function selected for the primary assessment. Measuring the same construct at baseline and at follow-up provides a way to describe participants’ scores over the study period. The record specifies baseline and follow-up at 6 months, after time on study drug. The endpoint is continuous, so its summary is described as a mean with standard deviation rather than as a count of events.

Using a standardized score can place an individual’s performance on a scale referenced to a population distribution. That context helps describe the score, but it does not establish why a score changes or whether a change is clinically important. The registry record does not report a threshold for a meaningful change, a primary-outcome estimate, or a confidence interval. It also notes that some participants could not provide a usable follow-up assessment, which affects how a group-level comparison should be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a continuous score, and the registry record identifies the mean and standard deviation as its summary measures. General statistical explanation: a mean describes the center of a set of scores, while a standard deviation describes how spread out individual scores are around that center. Neither measure alone shows the range of individual outcomes, and neither tells whether a difference is statistically compatible with no change. The record does not report the primary endpoint’s means or standard deviations at either assessment time.

What does a baseline-to-follow-up comparison represent?

For a continuous measure assessed at two times, a natural descriptive question is how each participant’s follow-up score relates to that participant’s baseline score. A paired comparison uses the link between the two observations from the same person. This can account for the fact that a participant’s own baseline score is relevant to interpreting their later score. This is a general explanation of repeated-measures data, not a claim about the analysis performed in this trial. The registry record does not report which test or model was used, or whether the analysis compared paired changes or separate group summaries.

In a single-group study, a baseline measurement is not equivalent to a control arm. It gives a pre-treatment reference for participants, but it does not show what would have happened to those same participants over the same period without the intervention. General statistical interpretation therefore distinguishes an observed change over time from a causal treatment effect. A concurrent randomized comparator can help address alternative explanations, whereas this record lists no such comparator.

How should uncertainty be understood?

General explanation: a confidence interval describes a range of estimates compatible with the data and the assumptions of the analysis at a stated confidence level. A narrow interval indicates greater precision than a wide interval, but precision is not the same as freedom from bias. In an uncontrolled study, a precise estimate of within-group change would still not, by itself, remove the design limitation when attributing change to treatment. No confidence interval for the primary endpoint is reported in the registry record.

A p-value, when reported, addresses how compatible the observed data are with a specified statistical model under a null hypothesis. It does not measure the size or clinical importance of an effect, and it does not establish causation. The record does not report a primary-outcome p-value or test. The absence of a reported test result should not be interpreted as evidence that a test was non-significant; the result is simply not reported in the registry record.

Why do incomplete assessments matter?

Repeated-measures analyses depend on what observations are available and on the assumptions used for participants with missing follow-up data. General explanation: if people with missing measurements differ systematically from those with observed measurements, a summary based only on observed cases may not represent the enrolled group. Some statistical methods can use incomplete longitudinal data under explicit assumptions, while other approaches may exclude participants without paired measurements. The registry record describes assessment difficulties for subjects 1 and 10 and withdrawal of subject 9 before the 6-month visit, but does not state the analysis population, missing-data method, or assumptions.

The reasons described are not interchangeable: one participant could not understand the instructions, one had a system error preventing a fully adjusted score, and one withdrew before follow-up. These details help identify practical and data-quality issues, but they do not establish whether missingness was related to cognitive performance or treatment response. That relationship and the handling of incomplete records are not reported in the registry record.

What do the planning illustrations mean?

The planning illustration is described as a hypothetical calculation based on an observed effect, not as the trial’s own design. Its stated assumptions include 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. For non-time-to-event outcomes, the illustration is expressed as participants per arm for a power target; time-to-event illustrations use a total event count. These assumptions describe a planning exercise and do not change the actual single-group design.

General explanation: sample-size planning asks how much information a future study might need to detect an effect under specified assumptions. Such an illustration is not observed power, does not show that the current study had a particular probability of detecting an effect, and does not establish that the assumed effect is reliable. The registry record does not report the trial’s own sample-size justification or the numerical values from any planning illustration.

Over-dispersion is a general concern when observed variability exceeds what a model assumes. If a model understates variability, its uncertainty estimates can be too small and its inferences too confident. The primary endpoint is continuous and summarized using a standard deviation, but no model diagnostics or over-dispersion assessment are reported in the registry record. There is therefore no basis to say that over-dispersion occurred or that a particular adjustment was used.

Finally, the registry lists 19 outcome measures and no analysis records. General statistical practice considers how multiple outcomes and repeated tests may affect the interpretation of isolated findings. The record does not report a multiplicity procedure, a prespecified hierarchy of secondary analyses, or an analysis plan. Those details cannot be inferred from the outcome list alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 19 outcome measures, including the primary working-memory assessment and secondary measures across cognitive, seizure, migraine, motor, functional, and intelligence domains. When a study evaluates multiple outcomes, general statistical interpretation considers the possibility that some results may appear notable by chance, especially when many hypotheses are tested. Methods such as prespecifying a primary outcome, organizing secondary outcomes hierarchically, or adjusting for multiple testing can address different aspects of this issue. The registry record does not report whether such a strategy was planned or applied.

The record lists no analysis records. It does not describe a statistical analysis plan, define analysis populations, or state whether any secondary outcome was treated as confirmatory or exploratory. Without those details, the outcome list should not be read as evidence that every measure was analyzed or that a specific multiplicity approach was used.

Missing primary assessments are explicitly noted for subject 1, subject 10, and subject 9. The record does not say how many participants contributed to the final primary analysis, whether incomplete records were excluded, or whether imputation or a repeated-measures method was used. It also does not report a sensitivity analysis examining alternative assumptions about missing observations. These omissions matter because conclusions from a repeated assessment can depend on who has usable measurements and how incomplete data are handled.

General explanation: missing-data methods rely on assumptions about why measurements are absent. When those assumptions are uncertain, sensitivity analyses can show whether conclusions change under different plausible scenarios. The registry record does not report such analyses, so the robustness of any primary-outcome estimate to missingness cannot be assessed. The record also does not provide a numerical endpoint result that could be evaluated under alternative methods.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports safety counts for the cannabidiol/Epidiolex group, with 10 participants at risk for serious adverse events and 10 at risk for other adverse events. Serious adverse events affected 0 participants, other adverse events affected 7 participants, and deaths were 0. No serious adverse-event terms are listed.

These are participant counts, not a comparison of event rates between treatment groups. The study has no separate control group, and the registry record does not provide a causal attribution for the events. The counts therefore describe what was recorded in the treated group; they do not establish whether the intervention caused or prevented an event. The record also does not provide details such as event timing, severity categories for other adverse events, or the number of events per participant.

A count of 0 serious adverse events in the participants at risk means that none were reported in this group in the registry record. It does not establish that serious events are impossible or that the intervention is risk-free. Similarly, the count of participants with other adverse events does not by itself describe the nature or clinical importance of those events. Interpretation is limited to the safety information recorded.

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

The registry record establishes that a completed Phase II, single-group study evaluated cannabidiol (Epidiolex) in people with Sturge-Weber syndrome, with working memory measured using the NIH Toolbox List Sorting Working Memory Test at baseline and 6-month follow-up. The score is a T-score on a 0-to-100 scale, with higher values indicating better performance. The record also reports safety counts and identifies some incomplete assessments.

It does not report a numerical primary-outcome result. There is no reported baseline or follow-up mean, change estimate, confidence interval, or primary-outcome test result in the record. As a result, the size and direction of any observed change, and the precision of that estimate, are not reported in the registry record. The scale’s reference values explain how scores are interpreted, but they do not reveal the study participants’ results.

Even if a before-and-after change were available, the single-group design would limit causal interpretation. A baseline score is useful context, but it is not a concurrent counterfactual. Without a comparator, the study cannot separate changes associated with treatment from other changes over time using the design alone. The absence of masking also means participants and study personnel were not blinded, according to the registry record.

The safety data are similarly descriptive: 0 serious adverse events, 7 participants with other adverse events, and 0 deaths among the 10 participants listed at risk in each adverse-event category. These counts should not be generalized as a comparative safety estimate or as proof of absence of risk.

The appropriate conclusion is bounded by what is recorded: the study’s purpose, design, measure, assessment schedule, incomplete assessments, and safety counts are described, but the primary cognitive result is not reported in the registry record. Claims about cognitive benefit, lack of benefit, or treatment causation would go beyond the available information.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clearly defined cognitive measure can be used in a small, single-group study while also illustrating the limits of inference when no concurrent comparator is present. The endpoint is specific: working-memory performance on the List Sorting Working Memory Test, expressed on a standardized T-score scale. The record states the score direction and reference mean, which supports an understanding of the measure’s scale.

The design creates an important distinction between describing change and attributing change. Baseline and follow-up assessments can characterize participants’ scores over time, but a single-group comparison does not isolate the intervention’s contribution. This distinction remains important even if a result is statistically precise. Statistical precision and causal identification are separate issues.

The registry record also makes assessment feasibility and data completeness visible. It describes different reasons that three subjects did not contribute a usable primary follow-up observation: difficulty understanding instructions, a system error, and withdrawal before the follow-up visit. These details matter because missing observations can affect both the analysis population and the interpretation of group summaries. The record does not explain how these cases were handled, so the analysis cannot be reproduced or evaluated from the available information.

Finally, the record lists multiple outcome measures but no analysis records and no numerical primary result. That combination underscores why prespecified analysis methods, transparent reporting of outcomes, and clear accounting of missing data are important for interpreting clinical research. The safety counts add descriptive information, but without a control group they cannot establish comparative risks. The trial therefore matters statistically as a case in which endpoint definition is available, while outcome reporting and design constraints limit what can be concluded.

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 trial-specific limitation is the absence of a reported numerical result for the primary endpoint. Although the measure, scoring, and assessment times are described, the registry record does not report the observed means, change estimate, uncertainty interval, or test result. A reader therefore cannot assess the magnitude, direction, or precision of the working-memory outcome.

The study is single group, with no masking and no comparator. This restricts causal interpretation of any change between baseline and follow-up. The registry record does not report a randomized comparison, and baseline is not a substitute for a concurrent control group. The enrollment is 11, while the primary-outcome description identifies participants who could not provide a usable assessment or were withdrawn before the planned follow-up. The final analysis population and data-handling approach are not reported in the registry record.

The reason for subject 9’s withdrawal is not fully specified in the registry record. The account for subject 1 refers to difficulty understanding instructions, and the account for subject 10 refers to a system error that prevented the fully adjusted score. The record does not state whether alternative scoring, repeat testing, imputation, or sensitivity analysis was considered.

The registry lists multiple outcome measures but does not report a statistical analysis plan or multiplicity approach. It also does not report the trial’s sample-size justification, analysis model, or detailed interpretation criteria for a meaningful change in the primary score. The planning illustration is not the trial’s own design and does not fill those gaps.

For safety, the record gives participant counts but no serious-event terms and no control-group comparison. It does not provide enough detail to assess event timing, severity beyond the serious/other distinction, or causal attribution. These limitations are specific to the available registry record and constrain interpretation of both efficacy and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Novel Cognitive Treatment Targets for Epidiolex in Sturge- Weber Syndrome — NCT04447846.
• Registry record last updated 2023-05-25; status last verified 2023-05.
• Results first posted 2023-05-25.
• 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

NCT04447846 is a completed Phase II, single-group study titled “Novel Cognitive Treatment Targets for Epidiolex in Sturge-Weber Syndrome.” The registry record lists enrollment of 11, no masking, and cannabidiol (Epidiolex) as the intervention. The study began on 2019-10-14, with primary completion on 2021-08-16.

The primary outcome is the NIH Toolbox List Sorting Working Memory Test, reported as a T-score at baseline and 6-month follow-up. Higher scores indicate better performance; 50 is the population mean with a standard deviation of 10. The registry record describes incomplete assessments but does not report a numerical primary-outcome result or analysis method.

For the cannabidiol group, 0 of 10 participants at risk had a serious adverse event, 7 of 10 had other adverse events, and deaths were 0. The record does not list serious-event terms. With no comparator group, these counts are descriptive rather than comparative. The primary cognitive finding and its precision are not reported in the registry record.