Histrelin Subcutaneous Implant in Children With Central Precocious Puberty: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Histrelin Subcutaneous Implant in Children With Central Precocious Puberty (NCT00779103), a na phase 3 study. The primary outcome is Luteinizing Hormone (LH).

2. Clinical Question

The record describes the primary outcome as mean LH, with standard deviation as the measure of dispersion. It defines LH suppression as a peak LH < 4 mIU/mL following stimulation with a GnRH analog. The timeframe is baseline to 6 months post last implant. However, the numerical LH results, the number of observations contributing to them, and any statistical comparison are not reported in the registry record.

The study summary says its purpose is to follow children and collect additional medical and developmental information after histrelin subcutaneous implant therapy is discontinued. That follow-up purpose is relevant when interpreting the stated timeframe: it does not, by itself, provide a numerical account of each child’s LH trajectory or establish how the outcome was analyzed. The record does not report a separate control condition or a randomized treatment comparison. Consequently, the clinical question described by this record is a follow-up and outcome-description question, rather than an estimate of a treatment difference against a concurrent control.

3. Trial Design

This is a Phase III, open-label study with a single-group model. The record lists allocation as NA and masking as none. These design details mean that the registry does not describe random assignment to competing treatment groups or blinded assessment. The intervention listed is the histrelin subcutaneous implant (50 mg), described as designed to deliver histrelin continuously for 12 months. The record does not describe a concurrent control intervention.

The listed condition is central precocious puberty, and the primary outcome population is named the Extension Safety Population. The registry records enrollment of 36. It does not report additional details in the information about eligibility criteria, participant flow, reasons for discontinuation, or the number contributing to the primary outcome. Those details should not be inferred from the enrollment figure.

The study is marked completed. Its recorded start is 2004-09, and its primary completion is 2011-08. The sponsor is Endo USA Inc., a Keenova Therapeutics Company. The study summary describes follow-up and collection of additional medical and developmental information after implant therapy is discontinued. The record also lists secondary outcomes including FSH, testosterone, DHEA sulfate, estradiol by MS and RIA, average number of implants received, average mean implant duration by subject, and a summary of EN3326 implantation and explantations.

The registry lists nine outcome measures and zero analyses. The absence of analyses in the record means that detailed statistical methods and numerical outcome results cannot be assessed from this entry. In particular, it does not establish how repeated measurements were handled, how missing observations were treated, or whether analyses adjusted for any covariates. The single-group design also means that any interpretation concerns the observed participants and measurements, not a randomized contrast with a control group.

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

Analysis population for the primary outcome, as defined in the registry: Extension Safety Population

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: Initial Extension Phase/Extended Access Phase (Second and Third Implant)

6. Primary Endpoint

The registry lists the primary outcome as Luteinizing Hormone (LH), measured over Baseline - 6 Months Post Last Implant.

The primary endpoint is mean luteinizing hormone (LH), with standard deviation identified as its dispersion measure. Its stated timeframe runs from baseline to 6 months after the last implant. LH is a gonadotropin, and the endpoint description places it within the broader question of suppressing gonadotropins and gonadal sex steroids during treatment. The record defines LH suppression as a peak LH < 4 mIU/mL following stimulation with a GnRH analog.

As a continuous measure, mean LH describes the average level across the observations included in an analysis. Standard deviation describes how spread out those measurements are around their mean; it is not a measure of uncertainty in the mean itself. A mean can communicate the overall level, while the spread helps readers understand how much measurements vary among observations. Neither statistic alone gives the proportion of participants meeting the stated suppression definition.

LH is used in the registry’s stated assessment because the study concerns suppression of gonadotropins. The endpoint description also mentions follicle stimulating hormone and gonadal sex steroids, with estrogen in girls and testosterone in boys, but the primary outcome listed is LH. The numerical mean, standard deviation, observation counts, and any result relative to the suppression definition are not reported in the registry record. Therefore, the endpoint definition can be described, but its observed magnitude and precision cannot be evaluated from this entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

For a continuous outcome such as LH, the mean is the arithmetic average of the measurements included in the analysis. It describes the center of those observed values, but it does not show their full distribution. The standard deviation describes the spread of measurements around that mean. A small spread indicates that observations are relatively close to the average; a larger spread indicates greater variation. Standard deviation is descriptive and should not be confused with a standard error or confidence interval, which concern uncertainty in an estimate.

The registry names mean and standard deviation for the primary outcome, but does not report their numerical values. It also does not report the number of measurements used to calculate them or whether all participants had measurements at each time point. Consequently, readers cannot judge the observed LH level, its variability, or how precisely the mean is estimated from this record.

How does the suppression threshold relate to a mean?

The endpoint description defines LH suppression as a peak LH < 4 mIU/mL after stimulation with a GnRH analog. This is a threshold definition applied to a peak measurement. A group mean is a different kind of summary: it averages values and can conceal variation between participants. General statistical interpretation therefore distinguishes the average level from the proportion of observations meeting a criterion. The registry does not report that proportion or enough detail to derive it, and it would not be appropriate to infer it from a mean even if a mean were reported.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and a specified statistical procedure, expressing uncertainty around an estimate. A narrow interval indicates greater precision under the method’s assumptions; a wide interval indicates less precision. It is not a guarantee that a particular individual’s measurement lies in that range, and it does not by itself establish clinical importance. No confidence interval for the primary LH outcome is reported in the registry record, so its precision cannot be evaluated using this measure.

Why does the study structure matter?

This is an open-label, single-group study, with allocation recorded as NA and masking recorded as none. General statistical interpretation of a single-group study differs from interpretation of a randomized comparison. Measurements over time can describe patterns in the observed group, but without a concurrent control group they do not separate treatment-related changes from changes that might have occurred for other reasons. Open-label conduct also means the record does not describe masking of participants or investigators. The registry does not report whether outcome assessors or analysts were masked by other means.

The primary outcome’s timeframe spans baseline to 6 months after the last implant, but the record does not say which repeated-measure model, if any, was used. In general, repeated observations from the same participant are related rather than independent. An analysis that treats them as independent can misrepresent uncertainty; methods for repeated measures account for that relationship. The registry does not report an analysis method or numerical analysis results, so it is not possible to determine how within-participant correlation was handled.

What do the planning illustrations represent?

Planning illustrations based on an observed effect are not observed power and are not evidence that the study was designed with those assumptions. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations are hypothetical planning scenarios. This trial is recorded as single-group, so a two-arm planning framework does not describe its actual allocation. The registry does not report the trial’s own sample-size justification, and the listed analyses count is zero. Any planning illustration should therefore be kept separate from the trial’s design and results.

For continuous outcomes, general sample-size planning depends on the target effect, variability, significance level, desired power, and allocation assumptions. If variability is uncertain or differs from planning assumptions, a resulting planning estimate can be misleading. The record does not report a trial-specific calculation or the information needed to evaluate one. No sample-size illustration should be interpreted as a retrospective claim about the probability that this completed study detected an effect.

Why can over-dispersion matter?

General count-data methods often rely on a model for how event counts vary. Over-dispersion means the observed variability is greater than the model assumes; ignoring it can make standard errors too small and confidence intervals too narrow. This issue is relevant in principle to event-count analyses, but the registry does not report a count model or analyses for the safety events listed. It therefore cannot be said whether over-dispersion was assessed or whether it affected any analysis.

These statistical concepts explain what different summaries and assumptions mean. They do not fill in missing results: the registry record gives no numerical primary LH estimate, confidence interval, detailed analysis method, or trial-specific sample-size rationale.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, including the primary LH outcome and secondary measures of FSH, testosterone, DHEA sulfate, estradiol by MS and RIA, implant use and duration, and implantation and explantation summaries. When a study examines multiple outcomes or multiple time points, the chance of at least one apparently notable result can increase. General statistical approaches may address multiplicity by specifying a primary outcome, adjusting inference, or treating secondary analyses as exploratory. The registry does not report a multiplicity strategy, so it is not possible to determine whether or how the listed outcomes were handled together.

The record lists zero analyses. It does not report a statistical analysis plan, the number of participants with outcome data at each assessment, reasons for missing measurements, or an approach to missing data. Missingness can affect interpretation when participants with observed outcomes differ systematically from those without them. General methods may use assumptions about missingness, but the assumptions and method must be stated to assess their implications. No such method is reported in the registry record.

The primary population is named the Extension Safety Population, but the record does not provide a definition of that population or explain its relation to all enrolled participants. Enrollment is recorded as 36, whereas the safety fields list 31 at risk. The record does not report a participant flow accounting for this difference or the primary outcome denominator. It would therefore be inappropriate to assume that all enrolled participants contributed to every outcome, or to infer why the listed populations differ.

Because the analysis methods and missing-data details are not reported, the robustness of any primary or secondary estimate cannot be assessed. The absence of a reported multiplicity approach also limits interpretation across the set of outcome measures. These are reporting limitations; they do not establish that a particular method was or was not used outside what the registry records.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: aggression (6.5%), depression (3.2%), bronchopneumonia (3.2%), apnoea (3.2%).

The overall histrelin subcutaneous implant group lists 31 at risk for serious adverse events and 3 affected. The other adverse-event fields list 31 at risk and 31 affected. The record separately lists 1 death. These are registry counts, and the entry does not provide detailed event-level descriptions or a causal assessment. The death count should not be interpreted as evidence that the implant caused a death.

The listed serious adverse-event terms are Aggression (6.5%), Depression (3.2%), Bronchopneumonia (3.2%), and Apnoea (3.2%). These percentages are reported as given; the record does not provide event counts alongside each term in the information. A term listing does not by itself describe severity beyond its placement among serious terms, timing, duration, recurrence, or relationship to treatment.

Safety counts describe reported events in the recorded group, not comparative risk against a control group. This study has a single-group design and no concurrent comparator. The record also does not report a detailed safety analysis method, follow-up time for each participant, or adjudication procedures. The figures should therefore be read as descriptive registry entries, with the limits of the available population and event detail in mind.

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

The record establishes that a Phase III, open-label, single-group study evaluated a histrelin subcutaneous implant in children with central precocious puberty. It identifies mean LH as the primary outcome, standard deviation as its dispersion measure, and baseline to 6 months after the last implant as the timeframe. It defines suppression using a stimulated peak LH threshold. These details clarify the intended measurement, but the numerical LH result is not reported in the registry record.

Without the observed mean, standard deviation, participant count for the endpoint, or confidence interval, the magnitude and precision of the primary result cannot be evaluated. The endpoint definition also does not reveal how many participants met the suppression criterion. The available record therefore does not support a numerical conclusion about the primary outcome.

The single-group design permits descriptive reporting of the group’s recorded outcomes, but it does not provide a randomized comparison with a control group. Even if a change from baseline were reported, a change over time alone would not identify what would have happened without the intervention. The registry does not report an adjusted treatment effect or a causal comparison.

The adverse-event counts and serious-event terms are descriptive entries. They do not establish that an event was caused by the implant, and no control group is available for comparison. The record does not report detailed event timing, clinical narratives, or a causal assessment that could further contextualize the listings.

Thus, the record supports a description of study design, intervention, outcome definitions, and selected safety information. It does not support a conclusion about the size or precision of the primary LH result, comparative effectiveness, or causal attribution of adverse events. Those questions require numerical outcome and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a registry entry’s endpoint definition and numerical result are distinct pieces of evidence. The record specifies mean LH, standard deviation, a timeframe extending from baseline to 6 months after the last implant, and a stimulated peak threshold for defining suppression. Yet the numerical result and its uncertainty are not reported. A clearly described endpoint is useful, but without its estimate and supporting analysis, readers cannot judge magnitude, variability, or precision.

The single-group, open-label design is also statistically important. It can describe outcomes within the recorded group, but it does not estimate a randomized contrast with a concurrent control. This distinction helps prevent within-group observations from being mistaken for comparative evidence. The record’s allocation and masking entries make the design limits explicit.

The entry also distinguishes enrollment from safety reporting: enrollment is recorded as 36, while safety fields list 31 at risk. Without participant flow or endpoint denominators, readers cannot assume that every enrolled participant contributed to each measure. This is a practical reminder that denominators and analysis populations are integral to interpreting a result, not administrative details.

Finally, the registry lists multiple outcomes but no analyses. That combination makes it impossible to assess how multiplicity, repeated measurements, missing observations, or uncertainty were handled. These gaps do not show that an analysis was necessarily inappropriate; they show that the record does not contain enough detail to evaluate it. The trial is statistically instructive because its design and measurement definitions can be described while its main numerical finding and analytical precision remain unreported.

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 interpreting this specific record is that the primary LH estimate is not reported. Although mean and standard deviation are specified, their values, the number of observations contributing to them, and an uncertainty interval are absent. The registry also does not report the number meeting the stated suppression threshold. As a result, neither the average outcome nor the frequency of threshold attainment can be evaluated.

The trial is recorded as single-group and open-label, with no concurrent control comparison. This limits what can be inferred about changes over time and precludes a randomized between-group estimate in the registry record. Allocation is listed as NA and masking as none. The record does not explain whether any other procedures were used to reduce assessment or analysis bias.

Enrollment is recorded as 36, while the safety fields use 31 at risk. The registry does not report participant flow, reasons for any difference, or the denominator used for the primary outcome. It also does not give outcome-specific missingness, follow-up completeness, or a missing-data method. Those omissions constrain assessment of how representative the reported safety entries or any unreported outcome analysis would be.

The record lists nine outcome measures and zero analyses, but does not report a statistical analysis plan, multiplicity handling, repeated-measure methods, covariate adjustment, or the trial’s sample-size justification. It also provides no detailed event-level safety narratives or causal assessments. These are limits of the information recorded; they should not be treated as proof about procedures or results that are not described.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Histrelin Subcutaneous Implant in Children With Central Precocious Puberty — NCT00779103.
• Registry record last updated 2021-01-08; status last verified 2020-10.
• Results first posted 2021-01-08.
• 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 registry describes NCT00779103, a completed Phase III, open-label, single-group study of a histrelin subcutaneous implant (50 mg) in children with central precocious puberty. The implant is described as designed to deliver histrelin continuously for 12 months. The study summary states that it follows children and collects additional medical and developmental information after therapy is discontinued.

The primary outcome is mean LH, with standard deviation, from baseline to 6 months after the last implant. LH suppression is defined as a stimulated peak LH < 4 mIU/mL. The numerical primary outcome and detailed analyses are not reported in the registry record. The entry lists nine outcome measures and zero analyses.

Enrollment is recorded as 36. The overall safety group lists 31 at risk and 3 affected for serious adverse events; the other adverse-event fields list 31 at risk and 31 affected. The record lists 1 death and several serious-event terms with percentages. These entries are descriptive and do not establish causation or a comparison with a control group.