Cerebrotendinous Xanthomatosis (CTX) Prevalence Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cerebrotendinous Xanthomatosis (CTX) Prevalence Study (NCT02638220), a registered phase not stated study. The primary outcome is Number of Participants Who Had Positive Genetic Test Results.

2. Clinical Question

The study addresses a detection question in a specific clinical context, rather than a question about whether one treatment is better than another. Its official title identifies the target population as people diagnosed with early-onset idiopathic bilateral cataracts, and its stated rationale notes that idiopathic bilateral cataracts occur in many children with CTX. The aim was to use contact with health care providers during pediatric cataract evaluation and treatment as an opportunity for disease detection.

The enrollment was 442. That number describes the study enrollment; it does not establish how many participants had CTX, how many had a positive genetic result, or what proportion tested positive. Those outcome details are not reported in the registry record. Nor does the record describe a comparison with people without cataracts or with another clinical population. Consequently, the primary question can be identified, but its answer and the precision of any prevalence estimate cannot be assessed from the registered result.

3. Trial Design

This was an observational, multicenter study with a focus on the prevalence of CTX in patient populations diagnosed with early-onset idiopathic bilateral cataracts. The registry lists the study status as completed and records an enrollment of 442. It gives a start date of 2015-09 and a primary completion date of 2021-02-19. The sponsor is Travere Therapeutics, Inc.

Because the study is observational, the record does not describe random assignment to an intervention and comparator. Allocation is not stated, and the registry explicitly indicates that this is not a randomized comparison. The observational group therefore represents the study population being assessed, not a treatment arm that can be compared with a control arm to estimate a treatment effect.

The registered primary outcome is the number of participants who had positive genetic test results, measured at genetic testing. The record lists one outcome measure. Although the study title and rationale concern prevalence and detection, the registered endpoint is expressed as a participant count. A positive-result count alone does not specify a prevalence estimate unless the relevant tested denominator and result are also reported.

Details needed to reconstruct how the observational cohort was assembled are not reported in the registry record. These include recruitment procedures, the number and identity of participating centers, the duration of individual participation, and the handling of participants who did not complete testing. The genetic test method and any confirmation procedures are also not reported. The registry lists no analyses, so an analysis population, statistical model, or estimate of prevalence cannot be established from the 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.

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 Number of Participants Who Had Positive Genetic Test Results, measured over At genetic testing.

The primary endpoint is the number of participants who had positive genetic test results, with the measurement timeframe recorded as “At genetic testing.” It is a count of participants with a positive result, not a reported treatment response or a measure of change over time. The registry does not provide the number of positive results, so the endpoint's observed value is not reported in the registry record.

This outcome is relevant to the study's stated detection purpose: testing people in a clinical population with early-onset idiopathic bilateral cataracts could identify participants with genetic results consistent with CTX. As a general statistical point, a count can describe how many people in a defined group experienced an outcome. To interpret that count as prevalence, however, readers also need a clearly defined denominator and information about who was eligible, tested, and included in the analysis. The enrollment of 442 is recorded, but the result and the tested analysis denominator are not reported.

The record does not provide the genetic test's technical characteristics, the definition of a positive result, or whether positive findings were confirmed. Those details matter when interpreting what the endpoint represents: a count of positive tests is not automatically equivalent to a count of clinically confirmed cases. Without the outcome value and testing details, the endpoint's magnitude and its precision cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives limited information about the statistical methods. It identifies a participant count as the primary outcome and lists no analyses. The methods below explain general statistical considerations for interpreting this kind of study; they are not a description of methods confirmed to have been used by the investigators.

What does a participant count convey?

A count reports the number of people meeting an outcome definition. For this study, the outcome is a positive genetic test result at testing. A count is easiest to interpret when the population at risk and the number assessed are also clear. If some enrolled participants were not tested, or if some test results were unavailable, the enrolled total and the tested denominator would differ. The registry record does not report the tested denominator or how missing tests were handled.

Prevalence is generally expressed as the number of people with a condition in a defined population relative to the population assessed. A positive-test count can contribute to such an estimate, but it is not by itself a prevalence estimate. The outcome count, denominator, and case definition all matter. Here, the record does not report the positive-test count, the analysis denominator, or details of the genetic test and its interpretation. It is therefore not possible to derive or assess a prevalence estimate from the registered information.

Why does uncertainty matter?

General statistical context: an estimate based on a sample is subject to uncertainty because the observed participants may not perfectly represent the population of interest. A confidence interval is one way to express the precision of an estimate. It describes a range of values compatible with the data under the statistical procedure used; it does not remove bias from participant selection or measurement. No estimate or confidence interval is reported in the registry record, so readers cannot judge the statistical precision of the primary result.

Uncertainty is only one part of interpretation. The way participants were recruited, the proportion who completed testing, and the validity of the outcome measurement can affect how well a result applies beyond the enrolled group. These design and measurement details are not reported in the registry record. Even a precise estimate would need to be interpreted in the context of the specific cataract-defined population studied.

What does the observational design imply?

General statistical context: observational studies measure outcomes without randomly assigning participants to study interventions. They can describe the frequency of an outcome in an observed group, but comparisons across groups may be affected by differences in who enters each group. This record does not describe a comparator group, and it is not a randomized comparison. The primary question is therefore descriptive rather than a test of treatment efficacy.

For a prevalence study, representativeness is important. A group recruited through clinical evaluation may differ from people with the same diagnosis who do not reach participating providers or centers. That is a general consideration, not a documented finding about this study. Recruitment and center-level details are not reported in the registry record, so the direction or size of any selection effect cannot be assessed.

What can be inferred from the listed analyses?

The registry lists no analyses. This does not establish what analyses may have been conducted outside the registry record; it means that an analysis method, statistical model, adjustment strategy, or uncertainty calculation cannot be evaluated from the registered information. No p-value or effect estimate is reported for the primary outcome. Without those results, there is no statistical test to interpret and no basis for assessing whether a particular model or adjustment changed the findings.

The primary endpoint is a count. General methods for count outcomes depend on how the data are structured and on the question being asked. A simple count may be descriptive, while a rate or comparative analysis would require a denominator and additional modeling choices. Over-dispersion is a general issue in count modeling: it occurs when observed variability exceeds what a chosen model assumes, and it can make standard errors too small if ignored. The registry record does not report a count model or enough outcome data to determine whether such modeling was relevant.

Because no outcome estimate is reported, recalculation from summary statistics is not possible. A sample-size planning illustration based on an observed effect would also require an observed effect, and the registry record does not report one. Any planning assumptions or sample-size justification are not reported in the registry record. This absence should not be replaced by an assumed design rationale or by treating enrollment as evidence of statistical power.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Participants With CTX")
n      <- c(442)
events <- c(4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Participants With CTX  442  4  0.9  0.2  2.3  0.4  2.3  0.4  2.3

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome measure: the number of participants with positive genetic test results. It lists no analyses. A multiplicity strategy, including whether any additional outcomes or subgroup comparisons were considered, is not reported in the registry record. The single listed primary outcome does not establish that no other analyses were conducted; it only defines what is available in this record.

General statistical context: multiplicity arises when several hypotheses or outcomes are tested, because repeated testing can increase the chance of at least one apparently unusual result. Methods to address multiplicity depend on the planned analyses and the claims being made. Since no analysis plan or test results are reported, it is not possible to assess whether multiplicity was relevant or how it was handled.

Missing-data procedures are not reported in the registry record. The record does not state whether every enrolled participant underwent genetic testing, whether any test results were missing or indeterminate, or how such cases were treated. This matters because the number enrolled may not equal the number with an observed primary outcome. The positive-result count and the tested analysis denominator are not reported.

Analysis populations are also not reported in the registry record. It is not possible to determine whether the primary outcome was assessed in all enrolled participants, only those tested, or another defined group. For an observational study, a clear description of eligibility, testing completion, and exclusions would help readers understand the population represented by the result. Those details are not available, so the handling of incomplete observations and the representativeness of the analyzed group cannot be evaluated.

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 registry lists one observational group with 442 participants at risk in the serious adverse-event field and 0 affected. It also lists 442 at risk and 0 affected in the other adverse-event field, with 0 deaths. These are the recorded figures for the group; they are not a comparison between treatment and control groups.

General statistical context: a recorded count of zero means that no events were entered in that particular registry field for the stated group. It does not, on its own, establish that no events occurred under any definition or that the study could rule out uncommon events. Interpretation depends on what was monitored, how events were defined and collected, and how complete the reporting was. Those details are not reported in the registry record. No serious adverse-event terms are listed.

The safety fields should also be kept separate from the primary endpoint. They do not report the number of positive genetic test results and cannot be used to infer CTX prevalence. The record does not describe an assigned treatment, so these figures should not be read as a treatment safety comparison.

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

The registered information shows that a completed, observational, multicenter study enrolled 442 participants in a population diagnosed with early-onset idiopathic bilateral cataracts. Its primary question was how many participants had positive genetic test results at genetic testing. The registry does not report that count. Accordingly, the record does not establish the frequency of positive results or provide a measurable prevalence estimate.

The study's stated rationale links pediatric cataract evaluation and treatment with an opportunity for CTX detection. This makes the clinical setting relevant to the study question, but a rationale is not itself evidence of how often positive tests occurred. The record does not provide testing details, a result definition, the number tested, or the primary outcome value. It also does not report uncertainty around an estimate.

The design does not answer whether an intervention improves outcomes. It is observational, with no comparator group described and no randomized allocation. It also cannot establish the prevalence of CTX in all children, all people with cataracts, or the general population. The defined clinical population and the way participants were recruited would shape the scope of any valid inference, and recruitment details are not reported in the registry record.

The safety fields record 0 serious adverse events, 0 other adverse events, and 0 deaths in the observational group, but those records do not supply the missing primary outcome or establish comprehensive absence of events. Overall, the registry record identifies the study question and enrollment but does not report enough outcome information to determine the study's answer. No claim about the frequency of positive genetic results can be drawn from the registered data.

14. Why This Trial Matters Statistically

This study is statistically interesting because it frames a prevalence and detection question within a defined clinical population. Rather than testing a treatment, it asks whether genetic testing identifies positive results among people diagnosed with early-onset idiopathic bilateral cataracts. Such a question depends on more than the total number enrolled: readers need the outcome count, the number actually tested, and a clear definition of a positive result.

The record documents an enrollment of 442 and one primary outcome, but it does not report the outcome value or an analysis. That contrast illustrates an important distinction in clinical research reporting: a completed study and a recorded enrollment do not, by themselves, reveal the result. Without a numerator and an appropriate denominator, neither a prevalence estimate nor its precision can be interpreted.

The study also highlights the role of population definition. A frequency measured in a selected clinical group can be informative about that group without representing a broader population. General statistical reasoning therefore requires attention to eligibility and recruitment, as well as uncertainty. The record does not provide enough detail to evaluate these features or to assess how widely any result might apply.

Finally, the observational design is aligned with a descriptive detection question but does not create a randomized treatment comparison. Keeping that distinction clear prevents a prevalence study from being interpreted as evidence about treatment effects. The registry entry gives useful context about the intended question and study structure, while the absence of the primary result limits what can be concluded statistically.

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 direct limitation of the registered results is that the primary outcome value is not reported in the registry record. The number of participants with positive genetic test results is the endpoint needed to answer the study's stated question, but it cannot be quantified. The record also does not report the number tested or an analysis denominator, so enrollment cannot be used as a substitute.

Details of genetic testing are not reported in the registry record. The test method, criteria for a positive result, and any confirmation process are therefore not available for evaluating how the endpoint was measured. Recruitment procedures and eligibility details beyond the target population are also not reported. The number and identity of participating centers are not stated, despite the multicenter description.

The registry lists no analyses. Statistical methods, uncertainty estimates, analysis populations, missing-data handling, and any adjustments or subgroup analyses are not reported in the registry record. It is consequently not possible to determine how incomplete or indeterminate testing was handled, or how precisely a prevalence estimate was calculated.

As an observational study without a stated comparator, the record cannot support a randomized treatment comparison. Its target population is limited to people diagnosed with early-onset idiopathic bilateral cataracts, and the registry does not establish how representative enrolled participants were of a broader population. These limitations concern the information available in the registry record; they do not establish what may have been reported elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cerebrotendinous Xanthomatosis (CTX) Prevalence Study — NCT02638220.
• Registry record last updated 2024-09-19; status last verified 2023-06.
• Results first posted 2024-09-19.
• 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

NCT02638220 is a completed observational, multicenter study sponsored by Travere Therapeutics, Inc. It concerns the prevalence of CTX in patient populations diagnosed with early-onset idiopathic bilateral cataracts. The registry records enrollment of 442, a start date of 2015-09, and a primary completion date of 2021-02-19.

The primary outcome is the number of participants who had positive genetic test results, assessed at genetic testing. The registry record does not report the positive-result count, the tested denominator, or an analysis. It therefore does not provide a prevalence estimate or its precision. The record describes no randomized comparator; allocation is not stated.

The observational group has 442 at risk and 0 affected in both the serious and other adverse-event fields, with 0 deaths. No serious adverse-event terms are listed. Testing procedures, missing-data methods, analysis populations, and statistical plans are not reported in the registry record.