Smith-Lemli-Opitz Syndrome and Cholic Acid: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Smith-Lemli-Opitz Syndrome and Cholic Acid (NCT03720990), a na phase 1, phase 2 study. The primary outcome is Change in Plasma Cholesterol.

2. Clinical Question

These details define a within-group treatment question rather than a randomized treatment-effect comparison. A change from baseline can describe what happened among participants during the treatment period, but without a concurrent control group it cannot separate a treatment-associated change from changes that might have occurred over time for other reasons. The registry record does not report whether the study’s other stated interests in precursor metabolites were analyzed as outcomes.

3. Trial Design

The study, titled “Smith-Lemli-Opitz Syndrome: A Pilot Study of Cholic Acid Supplementation,” is identified as a phase 1 and phase 2 trial sponsored by the University of Nebraska. Its status is completed. The record gives a start date of 2021-03-27 and a primary completion date of 2022-08-30. Enrollment is reported as 12.

The design is single-group, with allocation listed as NA and masking listed as none. Participants received cholic acid at 10 mg/kg body weight, with treatment described as lasting 8 weeks. There is no concurrent control arm in the registry record, so the study does not support a randomized, between-group estimate of the effect of cholic acid. The listed design instead supports describing the participants’ measurements over the treatment period, if those measurements are reported.

The primary outcome is change in plasma cholesterol, expressed as change (%) compared to baseline and assessed at 8 weeks. The outcome is characterized as a continuous measure summarized by a mean and standard deviation. The description says plasma cholesterol will be measured and that response will consist of a change in plasma cholesterol.

The registry record does not report the protocol’s sample-size justification, details of participant selection, adherence, treatment discontinuation, or other operational aspects of the study. It also does not report a statistical analysis plan or the observed primary outcome result. The phase labels and pilot designation describe the study as registered; they do not substitute for information about those missing design and analysis details.

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.

Population: 12

6. Primary Endpoint

The registry lists the primary outcome as Change in Plasma Cholesterol, measured over 8 weeks.

The primary endpoint is change in plasma cholesterol, expressed as change (%) compared to baseline, with assessment at 8 weeks. The registry describes the endpoint as a continuous measure and specifies a mean and standard deviation as its summary statistics. The stated rationale is to measure plasma cholesterol and assess its change during cholic acid treatment.

In general, a baseline-referenced change expresses how a follow-up measurement differs from a participant’s starting measurement. A group mean can describe the average change, while a standard deviation describes how spread out individual measurements are around that average. These summaries address different features of the data: the mean represents the group’s average, and the standard deviation represents variability among measurements.

The unit is written as change (%) compared to baseline, but the registry record does not report the observed mean change, its standard deviation, the number of participants with evaluable endpoint data, or a confidence interval. It therefore does not provide a numerical estimate of the endpoint change or its precision. The record also does not give details about the measurement procedure, handling of repeated measurements, or the method used to calculate percentage change.

The brief summary mentions a possible increase in plasma cholesterol and reduction in harmful cholesterol precursors as aims of the study. Those statements describe the study’s purpose, not its findings. The listed primary endpoint is plasma cholesterol change, and the record does not report a result for that endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what the registry record specifies from what it leaves unknown. The registered primary endpoint is a continuous change measure, summarized by a mean and standard deviation. No observed values for that endpoint are reported, so the methods can be explained, but the trial’s numerical result cannot be interpreted from the record.

What does a mean change describe?

In general, a mean is the arithmetic average of the observations included in an analysis. For a change-from-baseline endpoint, the observations are changes rather than follow-up values alone. The mean can therefore describe the group’s average change over the stated assessment period. It does not show the range of individual responses, and a group average can conceal variation in the direction or size of individual changes.

The registry identifies the unit as change (%) compared to baseline. Percentage change is intended to express a change relative to a baseline measurement, rather than only as a raw difference. The record does not explain the exact calculation convention, measurement process, or handling of baseline values. Those details matter for reproducibility and for understanding precisely what a reported percentage represents.

Why report a standard deviation?

In general, a standard deviation describes how dispersed observations are around their mean. A relatively concentrated set of measurements has less spread around the average than a more dispersed set. The standard deviation is not itself a measure of uncertainty about the mean: it describes variability in the observed measurements. A confidence interval for a mean addresses uncertainty in the estimated average and depends on the analysis and data. The registry record does not report a confidence interval or enough endpoint data to assess one.

A mean and standard deviation are useful summaries for a continuous endpoint, but they are not a complete account of the distribution. They do not reveal whether observations are skewed, whether there are influential values, or whether changes differ across participant subgroups. Such features cannot be assessed from the registry record because it does not provide the endpoint data or distributional summaries beyond naming the planned statistics.

What can a single-group change establish?

In general, a before-and-after description can show how measurements in a group differ between baseline and follow-up. It does not, on its own, estimate what would have happened to the same participants without treatment. A concurrent control group helps address that question by providing a comparison over the same period. This trial is registered as single-group, with allocation NA and masking none, so a controlled treatment contrast is not available in the stated design.

This distinction concerns causal interpretation, not the validity of measuring change. A within-group change can be descriptively informative, but treatment attribution requires caution when other explanations for change are not ruled out by the design. The registry record does not report an alternative causal analysis or adjustment that would change this design description.

How should the planning illustrations be read?

The sample-size planning assumptions describe a hypothetical two-arm calculation using equal allocation, a normal approximation, and a two-sided significance level of 0.05. The effect to detect is framed as a stated fraction of the observed effect. These assumptions belong to planning illustrations; they are not a record of the design used to conduct this single-group trial. Any participant counts derived for such illustrations would be planning quantities, not observed study results or observed power.

In general, a power calculation estimates the sample size needed under specified assumptions about an effect, variability, allocation, and statistical test. Its output is conditional on those assumptions. If an effect is taken from a study’s observed result, the calculation is still a planning illustration rather than proof that the study had a particular probability of detecting an effect. The registry record does not report its own sample-size justification, and no trial-specific power claim can be made from the registered information.

What is not specified?

The registry record does not report the statistical test used for the primary endpoint, whether the analysis was adjusted, how missing measurements were handled, or which analysis population was used. It does not report a prespecified model, a confidence interval method, or any interim analysis. These are important choices because they influence how estimates and uncertainty are calculated and how the findings should be interpreted.

The stated endpoint and summary statistics indicate what the study intended to measure and how it planned to characterize a continuous result. They do not supply the result itself. Without observed endpoint values and the analysis details, it is not possible to reproduce the primary analysis, evaluate its assumptions, or determine how sensitive the findings are to alternative methods.

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("Cholic Acid")
n   <- c(12)
m   <- c(37.8)
sp  <- c(22.4)
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  Cholic Acid  12  37.800  22.400  23.568  52.032

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and one analysis. It identifies change in plasma cholesterol as the primary endpoint. The brief summary also describes interest in cholesterol precursor metabolites, but the record does not report whether those metabolites were measured or analyzed as additional outcomes. A formal multiplicity strategy is not reported in the registry record.

In general, multiplicity arises when several outcomes, comparisons, time points, or analyses are considered. The more opportunities there are to identify a result, the more important it is to know which analyses were planned and how their interpretation was controlled. The registry’s listed outcome and analysis counts do not establish whether other analyses occurred outside the registered information. No adjustment or hierarchy for multiple outcomes is reported.

The record does not report an analysis population or the number of participants with primary endpoint data. Enrollment is reported as 12, but that figure does not establish how many measurements were available at 8 weeks. Missing-data methods, reasons for missingness, and any sensitivity analyses are not reported in the registry record.

In general, missing measurements can affect an estimate if participants with observed data differ systematically from those without data. The consequences depend on the amount and pattern of missingness and on the analysis method. Because the record does not describe endpoint availability or missing-data handling, the impact cannot be assessed. The registry also does not report a statistical analysis plan, so it is not possible to determine from this record whether the listed endpoint and analysis capture every prespecified analysis.

12. 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.

The adverse-event figures list the cholic acid group with 12 participants at risk. The record reports 0 serious adverse events among those at risk, 0 other adverse events among those at risk, and 0 deaths. These are the posted counts; the record does not list serious adverse-event terms.

In general, an at-risk count is the group against which an event count is reported. A count of 0 means no events of that category were recorded in the listed group for the registry entry. It should not be read as proof that an event is impossible, nor does it describe risks beyond the study population and observation period. The record does not provide additional detail about adverse-event definitions, ascertainment, severity grading, relatedness assessment, or the period covered by safety monitoring.

The figures are descriptive and do not compare cholic acid with a control group. Because the study is single-group, they cannot estimate a comparative safety difference. They also do not establish how complete safety follow-up was or whether any events were captured outside the categories summarized in the registry. The reported counts should therefore be read as the safety information recorded in the registry, not as a comprehensive estimate of risk.

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

The registry describes a completed pilot study of dietary cholic acid in people with Smith-Lemli-Opitz syndrome. It specifies a single-group design, treatment at 10 mg/kg body weight for 8 weeks, and a primary endpoint of change in plasma cholesterol compared with baseline. It also reports the enrollment count and adverse-event counts.

Those details define what the study set out to examine. They do not establish what happened to plasma cholesterol. The measured primary endpoint result, including the mean change and standard deviation, is not reported in the registry record. The record therefore does not support a conclusion about the direction, size, or precision of the cholesterol change. The stated interest in cholesterol precursor metabolites is part of the study purpose, but results for those metabolites are not reported either.

Even if a before-and-after estimate were available, the absence of a concurrent control group would limit causal interpretation. In general, a change during treatment may coincide with treatment without proving that treatment caused it. A single-group study can describe observed changes, but it cannot provide the same controlled comparison as a trial with a concurrent control arm.

The adverse-event entry reports 0 serious events, 0 other events, and 0 deaths among the listed group at risk. These counts convey what the registry record reports; they do not establish that risk is absent, nor do they provide a comparative safety estimate. Details about event definitions and follow-up are not reported.

Overall, the registry record supports a description of the study’s purpose, design, endpoint definition, and recorded safety counts. It does not provide the outcome data needed to quantify the primary result or the analysis details needed to evaluate its precision and robustness.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between measuring change and estimating a treatment effect. Its primary endpoint is a continuous change in plasma cholesterol relative to baseline, which can describe what happened over the treatment period. Because the design is single-group, it does not include the concurrent comparison needed to separate a treatment-associated change from changes that could occur over time for other reasons.

The record also illustrates why endpoint definitions and results must be considered separately. It identifies the measurement, unit, summary statistics, and assessment time, but does not report the observed mean change or standard deviation. Naming a primary outcome is not equivalent to presenting its result. Without the estimate and its uncertainty, readers cannot assess magnitude or precision.

The pilot designation and phase labels provide context for the registered study, but they do not replace a statistical analysis plan or sample-size justification. The registry’s planning assumptions describe illustrations based on a hypothetical comparison, rather than the single-group design used in this trial. Keeping planning calculations separate from observed results prevents them from being mistaken for evidence about the study’s ability to detect an effect.

Finally, the safety counts show how registry entries should be interpreted at face value and within their limits. They report event counts for the listed group, but cannot establish comparative safety or address unreported details of follow-up and event ascertainment. Together, these features make the study statistically relevant as an example of the difference between a registered research question, a descriptive within-group analysis, and evidence that can support a controlled causal comparison.

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.

The most immediate limitation for interpretation is that the registry record does not report the observed primary endpoint result. Without the mean change, standard deviation, or an uncertainty interval, the size and precision of any cholesterol change cannot be assessed. The record also does not report results for the cholesterol precursor metabolites mentioned in the brief summary.

The single-group design has no concurrent control arm. A change from baseline, if reported, would be descriptive and would not by itself distinguish a treatment effect from other changes over time. Allocation is listed as NA and masking as none, so the registry does not describe a randomized or masked comparison.

Enrollment is reported as 12, but the registry does not report how many participants contributed measurements to the primary analysis, whether anyone discontinued treatment, or how missing endpoint data were handled. It also does not report participant characteristics beyond the condition, limiting assessment of how the enrolled group relates to the wider SLOS population.

Further methodological details are not reported in the registry record. These include the statistical analysis plan, sample-size justification, exact measurement and percentage-change procedures, analysis population, endpoint test, and any sensitivity analyses. Adverse-event definitions and ascertainment details are also not reported. The posted safety counts therefore cannot establish how events were collected or how complete follow-up was.

These limitations arise from the information recorded and the registered design. They do not imply that unreported methods were or were not used; they mean those details cannot be evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Smith-Lemli-Opitz Syndrome and Cholic Acid — NCT03720990.
• Registry record last updated 2024-04-30; status last verified 2024-04.
• Results first posted 2023-12-13.
• 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

NCT03720990 is a completed phase 1 and phase 2 pilot study titled “Smith-Lemli-Opitz Syndrome: A Pilot Study of Cholic Acid Supplementation,” sponsored by the University of Nebraska. The registry reports enrollment of 12 and dates of 2021-03-27 for study start and 2022-08-30 for primary completion.

The study used a single-group design with no masking and no control arm. Participants received cholic acid at 10 mg/kg body weight for 8 weeks. The primary endpoint was change in plasma cholesterol, expressed as change (%) compared to baseline and summarized by a mean and standard deviation.

The registry record does not report the observed primary endpoint result or its precision. The safety entry lists 0 serious adverse events, 0 other adverse events, and 0 deaths among 12 participants at risk. The record does not report the analysis population, missing-data methods, or the trial’s statistical analysis plan.