Trial of Sertraline to Treat Children With Fragile X Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of Sertraline to Treat Children With Fragile X Syndrome (NCT01474746), a randomized phase 2 study. The primary outcome is Change in Mullen Scales of Early Learning - Expressive Language Raw Score.

2. Clinical Question

The trial summary describes a controlled study intended to investigate language and autistic symptoms in young children with Fragile X syndrome. The primary endpoint identified in the registry is narrower: change in expressive-language raw score on the Mullen Scales of Early Learning (MSEL). Other listed outcomes cover autism-related assessments, language, sensory processing, visual reception, eye tracking, and adaptive behavior.

The clinical question is therefore about a particular measured domain and interval, not about every developmental or behavioral outcome in the trial. The registry record identifies the treatment groups and intended comparison, but it does not provide a single primary-outcome estimate with which to quantify the difference in change. That absence limits what can be concluded statistically from this record about the primary question.

3. Trial Design

The registry identifies this as a phase 2 randomized, triple-masked, parallel-group trial. It was marked completed and lists an enrollment of 57. The recorded start was 2012-01 and primary completion was 2015-08. The study summary describes a six-month trial in children aged 2 years to 5 years 8 months with Fragile X syndrome.

Participants were assigned to sertraline or placebo. The arm descriptions say that treatment and assessments were otherwise identical, with the active group receiving sertraline and the comparison group receiving placebo. The masking field is recorded as triple; the registry record does not specify which roles were masked or give further operational details about maintaining masking.

The primary endpoint was change in MSEL expressive-language raw score from baseline to the six-month visit. The measure was administered at both visits, according to the outcome description. The record also lists secondary outcomes, including the Autism Diagnostic Observation Schedule, Visual Analog Scale, Eye Tracking, Preschool Language Scale-fifth Edition, sensory measures, Vineland-II adaptive behavior, and Mullen visual reception.

The registry lists 29 outcome measures and zero analyses. Those entries do not explain how outcomes were prioritized, how the analysis population was defined, or which statistical model was used. The allocation procedure, concealment details, stratification factors, and study-specific sample-size justification are not reported in the registry record. The stated planning illustration is explicitly not the trial's own design justification, so it should not be treated as evidence about how the enrollment target was selected.

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:

Analysis population for the primary outcome, as defined in the registry: Two subjects from the sertraline arm discontinued - 1 lost to follow up, 1 withdrew consent Three subjects from the placebo arm discontinued - 1 lost to follow up, 2 withdrew consent

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 Change in Mullen Scales of Early Learning - Expressive Language Raw Score, measured over From baseline visit to six-month visit..

The primary endpoint is change in the Mullen Scales of Early Learning expressive-language raw score from the baseline visit to the six-month visit. The MSEL is described as a cognitive test measuring cognitive ability and language development, with scales covering gross motor, visual reception, fine motor, receptive language, and expressive language. The endpoint uses the expressive-language scale, which focuses on that one aspect of development rather than the full range of MSEL domains.

The recorded outcome is a mean, with standard deviation as the dispersion measure, and the score is expressed in units on a scale. The expressive-language raw-score range is 0 to 50; higher scores represent greater ability and lower scores weaker ability, as stated in the outcome description. A change endpoint compares a participant's follow-up score with their baseline score, making the measured interval explicit.

This type of measure is used to represent performance on a defined developmental assessment. Its interpretation depends on the instrument, the assessment schedule, and the analysis of scores across participants. A group mean can describe the central tendency, while a standard deviation describes variability among scores; neither alone conveys the precision of a treatment-group comparison. The registry record does not include a numerical estimate of mean change by group or a between-group estimate, so the size and precision of the primary comparison cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary measure summarized by a mean and standard deviation. General statistical explanations below describe what those quantities and common inferential tools mean; they do not imply that a particular unreported method was used in this trial.

What does a mean change represent?

For a participant, change is the follow-up score compared with the baseline score. A group mean change describes the average of those participant-level changes. A comparison between groups asks whether the average change differs between the sertraline and placebo arms. That comparison is the relevant treatment contrast for the stated endpoint; separate within-group changes do not, by themselves, answer whether the groups differ.

A mean gives a concise description of the center of a set of scores, but it can conceal variation between participants. The standard deviation describes the spread of individual scores around the group mean. It is not the same as the uncertainty in the estimated mean or the uncertainty in a between-group contrast. Those questions require an inferential estimate and its precision, neither of which is reported for the primary comparison in the registry record.

How should a confidence interval be understood?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. Its width conveys precision: a narrower interval indicates a more precise estimate under that method, while a wider interval indicates greater uncertainty. A confidence interval would help readers judge both the plausible size and direction of a group difference. No primary-outcome confidence interval is reported in the registry record, so the precision of the treatment contrast cannot be evaluated.

A p-value, in general, describes how unusual data at least as inconsistent with a specified null hypothesis would be under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A p-value should be read alongside an effect estimate and its interval, rather than as a stand-alone verdict. No primary-outcome p-value is reported in the registry record.

Why do the analysis details matter?

The outcome is measured at baseline and follow-up, so an analysis needs to address the relationship between repeated measurements from the same participant. Possible general approaches include comparing participant-level changes or modeling follow-up while accounting for baseline scores. These approaches can answer related questions, but their estimates and assumptions are not identical. The registry record does not identify the model or the exact primary comparison procedure.

Randomization is intended to make the treatment groups comparable on average at assignment, but an analysis still needs to describe which participants were included and how unavailable outcomes were addressed. The record reports discontinuations and reasons, but does not state whether analyses followed assignment regardless of treatment received, were limited to participants with observed endpoint scores, or used another population definition. Those details are not reported in the registry record.

What is over-dispersion, and does it apply?

In general, over-dispersion arises when observed variability in data is greater than a statistical model expects. It is particularly relevant to count or binary outcomes when a model assumes a specific variance structure. If ignored where present, standard errors and confidence intervals can be too optimistic. The primary endpoint is continuous and summarized by a mean and standard deviation, so the registry record does not establish that over-dispersion was an issue for this analysis. No model diagnostics or variance assessment are reported.

How should planning illustrations be read?

The registry's sample-size assumptions describe a planning illustration based on the observed effect, not the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. Such calculations illustrate how a planning target can depend on the assumed effect and statistical choices. They are not evidence of the study's original sample-size justification, and they are not observed power. The registry record does not report that justification. No planning sample-size values are reported in the registry record in the registry record for this analysis.

In general, power is a design-stage probability of detecting a specified effect under stated assumptions. It is not a measure of whether a completed trial has demonstrated an effect. Planning illustrations based on an observed effect are especially dependent on that effect estimate and should not be recast as observed power. The enrollment of 57 is the trial's recorded enrollment, not itself a statistical power calculation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures, while the primary outcome description states that it has several categories or time points and was not reduced to one comparison. The record lists zero analyses. It does not report how the primary endpoint was selected from the measurements, whether a hierarchy of outcomes was specified, or whether any method was used to account for multiple comparisons.

In general, evaluating many outcomes or comparisons increases the opportunities for apparently notable findings to arise by chance. Multiplicity methods can define which comparisons are confirmatory, adjust inferential thresholds, or organize outcomes in a prespecified sequence. The registry record does not describe such a plan. Without analysis results and a stated approach, readers cannot assess how multiplicity was handled or distinguish any designated confirmatory result from exploratory comparisons.

Missing-data reporting is also limited. The primary-outcome description records two discontinuations in the sertraline arm and three in the placebo arm, with loss to follow up and withdrawal of consent listed as reasons. The registry does not state the number with an observed six-month expressive-language score, the assumptions used for unavailable measurements, or whether imputation or another method was used. A discontinuation count alone cannot establish how missing outcomes affected the estimate.

The analysis population is not reported in the registry record. In general, an analysis population defines which assigned participants contribute to a particular estimate and under what rules. Different population definitions can answer different questions. Because neither the population nor the missing-data procedure is stated, the completeness and interpretation of any primary analysis cannot be evaluated from the registry record.

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 safety entries list 30 participants at risk in the placebo group and 27 in the active group for the serious-adverse-event field. Zero affected participants are recorded in each group, and deaths are recorded as zero in both groups. The entry for other adverse events lists 26 affected participants among 30 at risk in the placebo group and 25 among 27 at risk in the active group.

These are counts associated with the registry's group labels and safety fields. They should be read as descriptive entries, not as a statistical comparison or an estimate of a causal effect. No serious adverse-event terms are listed. The record also does not provide the types of other adverse events, their severity, timing, duration, or whether participants had more than one event.

Counts of participants affected do not give the full event history. Without event definitions and fuller detail, readers cannot determine which events contributed to the totals or how they were assessed. Zero recorded serious adverse events and zero deaths are statements about the entries in this record; they do not establish the absence of all possible harms. The safety figures also do not answer the primary question about change in expressive-language score.

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

The record establishes that a randomized, triple-masked, parallel phase 2 trial compared sertraline with placebo in young children with Fragile X syndrome. It identifies change in MSEL expressive-language raw score from baseline to six months as the primary endpoint and describes the score's direction and range. It also lists discontinuations, secondary outcome measures, and safety counts.

What the record does not establish is the size or direction of the primary treatment-group difference. A single numerical comparison, its uncertainty, and a test result are not reported in the registry record. It is therefore not possible from these entries to say how much the groups changed, whether their changes differed, or how precisely a difference was estimated. A completed status does not fill that information gap.

The outcome measure itself is one component of a broader developmental assessment context. The registry lists additional outcomes relating to autism-related observations, language, sensory processing, visual reception, eye tracking, and adaptive behavior. Those measures may address different domains, but their inclusion does not substitute for the primary comparison or show what any of those outcomes found. The registry record does not report their numerical results in the registry record for this analysis.

Similarly, the discontinuation reasons provide context about follow-up but do not reveal the effect of missing scores on any estimate. The safety counts are descriptive and do not determine the developmental outcome. Statistical interpretation depends on the analysis, its target comparison, and the uncertainty around the estimate; those primary-analysis details are not reported in the registry record.

Accordingly, the defensible conclusion is limited to the trial's recorded design and outcome definitions, plus the reported discontinuation and safety entries. No conclusion about whether sertraline changed expressive-language scores relative to placebo can be drawn from the registry information described in this record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a registered endpoint and a reported result are different kinds of information. The record defines a specific question: compare change in expressive-language raw score from baseline to the six-month visit between randomized groups. Yet the record does not give one numerical estimate for that contrast. Without the estimate and its precision, readers cannot judge the magnitude, direction, or uncertainty of the primary result.

The record also illustrates how a clinical study can measure multiple domains while identifying one primary endpoint. The listed 29 outcome measures span several areas of development and behavior. Such breadth can be useful for describing a multidimensional research question, but it makes transparent outcome prioritization and analysis reporting important. The registry does not describe a multiplicity plan or provide a single primary comparison.

Discontinuation information matters because a longitudinal endpoint requires follow-up measurements. The record lists reasons for discontinuation in each arm, but does not explain which participants were included in analysis or how unavailable scores were handled. Reporting these methods alongside outcome estimates would help readers evaluate the connection between the enrolled group and the analyzed group.

Finally, the registry's planning illustration is distinct from the original design rationale. It states assumptions for an illustrative calculation, but is explicitly not the trial's own design. Keeping that distinction clear prevents a retrospective illustration from being mistaken for the trial's prespecified sample-size basis or for observed power. The central statistical lesson is that design labels, endpoint definitions, and safety counts are valuable context, but they cannot replace a transparent comparative estimate with an account of its uncertainty and analysis assumptions.

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 most important limitation of the registry information is that it does not report a single primary-outcome comparison. Although the endpoint, scale, assessment interval, mean summary, and standard-deviation summary are identified, there are no group-specific primary outcome results or between-group estimate in the record. Consequently, the treatment contrast's direction, size, and precision cannot be assessed.

The outcome description says the primary outcome has several categories or time points and was not reduced to one comparison. That leaves the exact analysis target unclear. The registry does not state which categories or time points were included in the reported analysis, whether the primary comparison used change scores or another approach, or how repeated measurements were modeled.

The record reports discontinuations and reasons, but does not describe the analysis population or missing-data handling. It is therefore unclear how many participants contributed an endpoint score or what assumptions would apply to unavailable scores. This is particularly relevant to an endpoint defined across baseline and follow-up visits.

Although 29 outcome measures are listed, the registry does not explain outcome prioritization or a multiplicity strategy. It also lists zero analyses, so the statistical methods and results cannot be assessed in detail. The record does not report the original sample-size justification, allocation procedure details, concealment procedures, or which roles were masked. The planning illustration is not the trial's own design justification.

Safety reporting is also limited to counts: event terms, severity, timing, and fuller event histories are not reported. These limitations describe what the registry record lacks; they do not establish that the underlying study did not collect or analyze such information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial of Sertraline to Treat Children With Fragile X Syndrome — NCT01474746.
• Registry record last updated 2017-09-25; status last verified 2017-08.
• Results first posted 2017-09-25.
• 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

The record describes a completed, randomized, triple-masked, parallel phase 2 trial of sertraline versus placebo in young children with Fragile X syndrome. Enrollment was 57. The study summary describes a six-month trial and ages 2 years to 5 years 8 months. The primary endpoint is change in Mullen Scales of Early Learning expressive-language raw score from baseline to the six-month visit.

The registry lists 29 outcome measures and zero analyses. It records two discontinuations in the sertraline arm and three in the placebo arm. Safety entries list zero serious adverse events and zero deaths in both groups, with other adverse events recorded for 26 participants in the placebo group and 25 in the active group.

A single numerical primary-outcome comparison, its confidence interval, and its p-value are not reported in the registry record. The analysis population, missing-data approach, multiplicity plan, and original sample-size justification are also not reported.