Growth Hormone Treatment in Patients With Aggrecan (ACAN) Deficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Growth Hormone Treatment in Patients With Aggrecan (ACAN) Deficiency (NCT03288103), a na phase 1, phase 2 study. The primary outcome is Height Standard Deviation Score.

2. Clinical Question

The study therefore addresses a clinical growth-measurement question in a narrowly defined population, rather than estimating a randomized treatment effect against a comparable control group. The record also lists clinical features of Aggrecan deficiency involving osteochondritis dissecans and osteoarthritis as secondary outcomes. Their numerical results are not reported in the registry record. The study’s open-label, single-group structure is central to interpreting any observed change: a within-group trajectory can describe what happened among treated participants, but by itself it cannot separate treatment-associated change from other explanations.

3. Trial Design

This was an open-label, single-arm prospective pilot study listed as Phase 1 and Phase 2. Its intervention was daily Norditropin for pre-pubertal children with Aggrecan deficiency. The registry describes the treatment arm as a 3-year regimen. The brief summary says growth response would be tracked over a 12 month period and that a protocol extension was approved to continue treatment for an additional 2 years. The primary endpoint timeframe is stated as annually through three years of treatment.

The record lists enrollment as 22 and status as completed. The primary-outcome description, however, specifies results for 10 patients treated with recombinant human growth hormone. Safety information is presented separately for a Treatment Group and a Phenotype Group. The registry does not describe those groups as randomized or as a like-for-like control comparison; allocation is listed as NA. The group labels alone do not establish that the groups were exchangeable or that the Phenotype Group provides a causal counterfactual for the treated participants.

The study start is recorded as 2018-02-01, with primary completion on 2023-03-31. The sponsor is Children's Hospital Medical Center, Cincinnati. The record does not report the protocol’s detailed eligibility criteria, treatment dose, adherence procedures, or reasons for the difference between enrollment and the primary-outcome population. Those details should not be inferred from the single-arm description or the outcome counts.

A prospective pilot can characterize procedures and describe outcomes in a defined group. It is not, solely by virtue of being prospective, a randomized comparative trial. The registry does not report a formal sample-size justification or a detailed statistical analysis plan. Thus, the design supports descriptive interpretation of the available endpoint and safety information, while the strength of any causal conclusion is limited by the absence of a randomized, comparable control group and by the outcome information available in 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.

Before assignment: Total number of participants enrolled was 22, including 12 pediatric participants, and 10 adult participants. Only 10 of the pediatric patients were eligible to participate in the treatment arm of the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 10 pre-pubertal children with Aggrecan deficiency

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 Height Standard Deviation Score, measured over Annually through three years of treatment.

The primary endpoint is Height Standard Deviation Score, expressed in standard deviation score units. The registry defines it as the number of standard deviations that height lies above or below the mean for age and gender. Heights were plotted on Centers for Disease Control and Prevention growth charts. The description states that an increase in this score correlates with an increase in height.

Using an age- and gender-referenced score places a child’s height in context, rather than interpreting a raw height measurement without regard to expected growth patterns. Repeated measurements can describe how a participant’s relative position on the growth reference changes during follow-up. The stated assessment schedule is annually through three years of treatment.

The registry specifies a median and full range as the summary format. A median describes the middle of an ordered set of observations, while the full range describes the smallest and largest values. These summaries can be useful when a small group’s distribution may not be well represented by a mean and standard deviation. They do not, on their own, convey the precision of an estimated treatment effect or adjust for other influences on growth.

Although the endpoint definition and reporting format are recorded, numerical height standard deviation score results are not reported in the registry record. The size, direction, and variability of the observed outcome therefore cannot be evaluated from the information recorded.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summary describe?

The registry specifies the median and full range for height standard deviation score. A median is a measure of location: it identifies the middle observation after values are ordered. It is less influenced by unusually high or low values than the arithmetic mean. The full range describes the span from the lowest to the highest observation, so it can show whether measurements were tightly grouped or widely spread. General statistical principle: a range is sensitive to extreme observations and does not describe how the remaining values are distributed. A median and range are descriptive summaries, not a test of whether a treatment caused a change.

The endpoint is defined relative to age and gender norms, using Centers for Disease Control and Prevention growth charts. This makes the score a standardized measure of relative height rather than a direct measurement in units of length. The registry states that an increase in the score correlates with an increase in height. Interpretation still depends on knowing the actual score values and the relevant measurements at each assessment. Those numerical results are not reported in the registry record.

What can a single-group study estimate?

In a single-group study, the primary descriptive information concerns outcomes among people receiving the intervention. If measurements are repeated, their pattern can describe how the group changed over time. General statistical principle: a before-and-after change is not equivalent to a treatment-versus-control effect. Growth can change with time, and an observed trajectory can also reflect factors other than the intervention. Without an appropriate comparison, the study cannot directly show what would have happened to the same participants over the same period without treatment.

This distinction is particularly relevant because the record identifies the study as open-label and single-arm, and lists allocation as NA. The record’s Phenotype Group safety counts should not be treated as a randomized control comparison. The record explicitly cautions that the arms are not a like-for-like control comparison. The criteria used to form the groups, their role in the primary endpoint analysis, and any adjustment for differences between them are not reported in the registry record.

What do uncertainty and precision mean?

A confidence interval is a statistical range expressing uncertainty around an estimated quantity under a specified model and sampling procedure. A narrow interval generally indicates greater precision than a wide interval, while the interval’s location conveys which values are compatible with the data and method. General statistical principle: an interval is not a guarantee that the true value lies within it, and its interpretation depends on the analysis assumptions. The registry record does not report a confidence interval for the primary endpoint or an estimated treatment effect. With no numerical endpoint values or inferential analyses listed, precision cannot be assessed from the recorded primary outcome information.

A p-value, when reported, assesses how compatible data are with a specified null hypothesis under a statistical model. It does not measure the probability that a treatment is effective, nor does it describe the size or clinical importance of an effect. No p-values are reported in the registry record, and no analyses are listed. It would therefore be inappropriate to describe the primary outcome as statistically significant or not statistically significant based on this record.

How should planning calculations be read?

The registry includes a planning illustration computed from an observed effect. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Such calculations illustrate how a hypothetical future study might be planned under those assumptions. They are not evidence that the original study was designed with those assumptions, and they are not observed power.

The registry does not report a formal sample-size justification for this trial. A sample-size calculation based on an observed effect is also sensitive to the stability of that effect estimate. General statistical principle: estimates from small studies can be uncertain, so planning around a single observed estimate can give a misleading sense of certainty. The planning assumptions should not be mistaken for a protocol decision or a confirmed analysis method.

The record also states that time-to-event planning tables give total events using the Schoenfeld method, while other planning results are expressed as participants per arm. These are conventions for interpreting planning outputs, not observed trial outcomes. They do not change the fact that the trial is listed as single-group and that the record does not describe randomized allocation.

What role does over-dispersion play?

General statistical principle: over-dispersion arises when observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors may be too small and uncertainty may be understated. Models that account for extra variability can give more appropriate uncertainty estimates when their assumptions fit the data. The registry record does not identify an over-dispersion model or any other fitted model for the primary endpoint, and it does not report analyses from which such a choice could be evaluated.

For the listed median and full-range summaries, no distributional model is specified in the record. Describing the endpoint with robust summary statistics does not itself address missing observations, confounding, or the lack of a comparative design. Those questions require information about the analysis population and methods, which is not reported in the registry record.

Overall, the statistical information recorded for the primary outcome is descriptive in form, but its actual numerical summaries are absent. The record lists no analyses. It therefore does not support reconstruction of an effect estimate, uncertainty interval, model-based result, or significance test. Interpretation should remain with the design description, outcome definition, and counts that are explicitly recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and identifies height standard deviation score as the primary outcome. It also lists secondary outcomes concerning the number of participants with clinical features of Aggrecan deficiency: osteochondritis dissecans and osteoarthritis. Numerical results for these outcomes are not reported in the registry record.

Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are considered. General statistical principle: the more inferences made, the greater the chance that at least one result may appear noteworthy by chance, unless the analysis accounts for the planned family of tests. The record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or how repeated annual assessments were handled in an inferential analysis. No analyses are listed, so it is not possible to assess how many tests were performed or whether a multiplicity strategy was used.

The registry does not report the amount or pattern of missing primary-outcome data, reasons for missingness, or an approach to missing observations. It also does not specify which analysis population was used beyond stating that primary results are reported for 10 treated patients. The relationship between that population and the enrollment of 22 is not explained in the registry record. No imputation method, sensitivity analysis, or participant-flow detail is reported.

These omissions matter because missingness and analysis-population choices can affect both the interpretation and precision of a result. General statistical principle: analyses restricted to participants with observed measurements may differ from analyses that account for all enrolled participants, particularly when the reasons measurements are absent relate to outcomes. Without the relevant reporting, the direction or magnitude of any such influence cannot be determined. The record does not report whether interim analyses were planned or conducted.

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 reports serious adverse event counts separately for a Treatment Group and a Phenotype Group. In the Treatment Group, 10 participants were listed at risk for serious adverse events and 0 were affected; in the Phenotype Group, 12 were listed at risk and 0 were affected. No deaths are reported in either group, and the list of top serious-event terms is empty.

For other adverse events, the Treatment Group has 10 listed at risk and 10 affected, while the Phenotype Group has 12 listed at risk and 0 affected. These figures are counts recorded under the registry’s “other” category; the record does not identify the event types or provide further clinical descriptions. They should not be relabeled as specific symptoms or diagnoses.

General statistical principle: observing no serious events in a group does not establish that the risk is absent. Safety counts also do not demonstrate a causal difference between groups, especially when the groups are not randomized or described as like-for-like controls. The registry notes that the arms are not a like-for-like control comparison. The available counts describe what was recorded, but offer limited information about event severity, timing, duration, or relationship to treatment. Those details are not reported in the registry record.

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

The record describes a prospective pilot study of daily Norditropin in pre-pubertal children with Aggrecan deficiency. It defines height standard deviation score as the primary endpoint, gives its reference basis and summary format, and specifies an annual assessment timeframe through three years of treatment. It also records safety counts and lists secondary outcomes involving osteochondritis dissecans and osteoarthritis.

The primary endpoint’s numerical results are not reported in the registry record. Consequently, the record does not allow readers to determine the observed median, range, direction of change, or variability in height standard deviation score. No analyses are listed, so no inferential estimate or measure of statistical precision is available. The result cannot be characterized as evidence of a specific size or direction of effect from the information recorded.

The study’s design also limits what can be concluded. An open-label, single-arm study can describe the experience of treated participants, but it does not by itself establish that a change was caused by treatment. The registry lists a Phenotype Group in the safety information but cautions that the arms are not a like-for-like control comparison. The record does not describe randomized allocation.

The safety counts show that no serious adverse events or deaths were recorded in either group, alongside other-adverse-event counts as listed. These counts do not establish that serious events cannot occur or quantify a comparative treatment effect. The event details needed for a fuller safety characterization are not reported.

In short, the registry record establishes the study’s design, endpoint definition, planned timeframe, and certain counts. It does not provide the numerical primary outcome or analyses needed to estimate an effect or judge its precision. The distinction is between a study question and a result that can be quantitatively interpreted: the former is recorded, while the latter is not fully available in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the gap between a clearly defined endpoint and a fully interpretable result. The registry describes height standard deviation score, its age- and gender-referenced basis, its median-and-range summary, and its annual timeframe through three years of treatment. Yet the numerical outcome values are not reported in the registry record. Without them, readers cannot evaluate the observed trajectory or its variability.

The single-group, open-label design is equally important. It can provide descriptive information about participants receiving daily Norditropin, but it does not create a randomized counterfactual. The registry’s warning that the listed arms are not a like-for-like control comparison helps prevent an invalid treatment-versus-control interpretation. Statistical interpretation depends on both the measured outcome and the design that generated it.

The record also makes clear why enrollment and analysis populations need transparent explanation. Enrollment is listed as 22, while the primary endpoint description identifies 10 treated patients. The reason for this difference is not reported in the registry record. Participant flow, missing-data details, and the analysis population beyond that endpoint description would help readers understand how the reported results relate to enrollment.

Finally, safety counts are useful but incomplete without event descriptions and context. The counts show what was entered in the serious and other adverse-event categories, but they do not provide a comparative causal estimate. Taken together, the record illustrates a general statistical lesson: endpoint definitions, study design, analysis methods, and complete numerical reporting are all needed to assess what a clinical trial result can support.

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 primary limitation for interpreting efficacy is that numerical height standard deviation score results are not reported in the registry record. The endpoint definition and summary format are available, but not the median or full range values. No analyses are listed, and no confidence interval, p-value, or other inferential estimate is reported. The direction, size, and precision of any observed change therefore cannot be evaluated.

The study was open-label and single-group, with allocation recorded as NA. There is no randomized comparison described, and the registry cautions that the listed arms are not a like-for-like control comparison. This limits causal interpretation of any change during treatment. The Phenotype Group appears in the safety information, but its role in the primary endpoint analysis is not reported in the registry record.

Enrollment is listed as 22, while the primary outcome description reports results for 10 treated patients. The reason for the difference, participant flow, and the handling of missing measurements are not reported in the registry record. The record does not explain eligibility details, adherence, treatment dose, or whether all participants had the same follow-up schedule.

The registry lists four outcome measures, but numerical results for the secondary outcomes are not reported. It does not report how multiplicity across outcomes or annual assessments was addressed, whether interim analyses occurred, or the detailed statistical analysis plan. The absence of these details does not establish that a particular method was or was not used; it means the methods cannot be evaluated from the registry record.

Safety reporting is also limited: event descriptions, timing, severity details for other adverse events, and treatment attribution are not reported. The counts should therefore be read as registry entries rather than a complete characterization of safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Growth Hormone Treatment in Patients With Aggrecan (ACAN) Deficiency — NCT03288103.
• Registry record last updated 2024-07-30; status last verified 2024-07.
• Results first posted 2024-07-30.
• 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

NCT03288103 is a completed, open-label, single-arm prospective pilot study of daily Norditropin in pre-pubertal children with Aggrecan deficiency. It is listed as Phase 1 and Phase 2, with enrollment of 22. The primary endpoint is height standard deviation score, assessed annually through three years of treatment and summarized by median and full range. The primary outcome description reports results for 10 treated patients, but the numerical outcome values are not reported in the registry record.

The registry lists osteochondritis dissecans and osteoarthritis as secondary outcomes. It records no serious adverse events or deaths in either the Treatment Group or the Phenotype Group, while other-adverse-event counts differ as listed in the safety information. No analyses are listed. The record cautions that the arms are not a like-for-like control comparison. It does not report the detailed statistical plan, missing-data handling, or reasons for the difference between enrollment and the stated primary-outcome population.