Neuromuscular Changes In Small For Gestational Age Children During Somatropin Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neuromuscular Changes In Small For Gestational Age Children During Somatropin Therapy (NCT00625872), a randomized phase 3 study. The primary outcome is Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6.

2. Clinical Question

The trial asked whether somatropin treatment was associated with a change in neuromuscular function among short children born small for gestational age (SGA). Its primary measure was change from baseline to Month 6 in the standard deviation score (SDS) for peak jump power during a two-leg jump. The registry also describes planned assessment of cognitive performance and other neuromuscular measures.

This question is narrower than the full set of study aims. The record also lists cognitive, behavioral, growth, and one-leg jumping outcomes, but the primary endpoint is specifically the two-leg jumping measure at Month 6.

3. Trial Design

The registry describes a Phase 3, randomized, controlled, open-label, multicenter trial with a parallel-group design. The study enrolled 23 participants and is listed as terminated. Its recorded start was 2008-07, and primary completion was 2011-03. The reason for termination is not reported in the registry record.

The treatment group is described as receiving somatropin for 12 months. The control group had no intervention for the first 6 months and then received somatropin for 12 months. The primary endpoint was assessed at Month 6, so the primary comparison concerns the initial treatment period against the no-intervention period. The summary describes planned somatropin doses of 0.035 mg/kg/d or 0.067 mg/kg/d, but the dose associated with each arm is not reported in the registry record.

Masking was listed as none. In an open-label study, participants and study personnel are not described as blinded to treatment assignment. General statistical context: awareness of assignment can affect outcomes that involve participant effort or assessment, although the registry record does not report whether or how this possibility was addressed.

The primary endpoint analysis used the FAS, defined as participants who received at least one dose and had at least one post-baseline efficacy assessment. The endpoint-specific counts were 4 in the somatropin group and 8 in the control group. These are the numbers evaluable for this measure, not the total enrollment. Other outcomes and safety summaries have different reported denominators, so those counts should not be treated as interchangeable.

The registry lists 53 outcome measures and 18 analyses. A full protocol, detailed recruitment information, and the reason for termination are not reported in the registry 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:

Analysis population for the primary outcome, as defined in the registry: FAS population included participants who received at least 1 dose of study medication and had at least one post baseline efficacy assessment. Number of participants analyzed (N) signifies participants evaluable for the measure.

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 From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6, measured over Baseline and Month 6.

The primary endpoint was change from baseline to Month 6 in peak jump power SDS during a two-leg jump. Peak jump power was defined as the peak of calculated power, with power based on force multiplied by velocity. Measurement used a Leonardo Jumping Platform. Participants performed 3 jumps, and the highest peak among the 3 recordings was selected for further calculation.

The SDS describes how similar a participant was to a reference population. General context: standardizing a measure against a reference can make a score easier to interpret in relation to that population, but it does not by itself establish why a score changed or whether a change matters to participants. The endpoint’s reported unit is Watt/kilogram (W/kg); the registry does not provide additional details about the reference population or the conversion from the measured jump to the reported SDS.

Jump power is used as a measure of neuromuscular performance: it captures the peak power reached during the selected jump. Requiring repeated jumps and selecting the highest peak is the stated measurement procedure, not evidence that repeated measurements were averaged. Because the primary comparison is a change from baseline at Month 6, it addresses change over that interval rather than long-term outcomes. The primary measure is distinct from the one-leg jump outcome listed among the secondary measures.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary comparison was reported as an ANCOVA least-squares mean difference. ANCOVA is a general method for comparing groups while accounting for one or more covariates; the specific covariates used in this trial are not reported in the registry record. A least-squares mean is a model-based group estimate, and the reported difference represents the model’s comparison rather than a raw difference between the displayed group summaries.

What does the confidence interval convey?

The reported 95% confidence interval runs from -3.93 to 3.08 around the estimated difference of -0.43. General explanation: a confidence interval expresses the uncertainty associated with an estimate under the assumptions of the analysis. An interval that includes zero does not establish that the groups are identical; it indicates that the analysis does not distinguish the observed estimate from zero at the corresponding conventional level. The interval also permits differences in either direction, and its width conveys limited precision.

The group-level primary summaries are reported with standard errors. General explanation: a standard error describes uncertainty in an estimated mean, rather than the spread of individual participant measurements. It should not be interpreted as a standard deviation. The registry record gives the primary measure’s dispersion as standard error and reports the adjusted comparison separately.

How should the reported p-value be read?

The reported primary-analysis p-value is 0.723. General explanation: a p-value is calculated under a null hypothesis and a statistical model; it is not the probability that the null hypothesis is true, nor does it quantify the probability that the result will replicate. It also does not convey the size or practical importance of an effect. The estimate and confidence interval are needed to understand direction and precision.

The primary endpoint is continuous, and the trial reports a change from baseline in a continuous score. General explanation: continuous measures retain information about the scale of observed values, but their interpretation depends on the measurement method, reference scale, and any meaningful-change threshold. Such a threshold is not reported in the registry record.

What do the recalculated secondary comparisons represent?

For several secondary outcomes, simple unadjusted comparisons were recalculated from posted group means, standard deviations, and sample sizes. These are not the registry’s reported ANCOVA or other adjusted analyses; no reported analyses are listed for those secondary outcomes. An unadjusted mean difference does not account for baseline values or other covariates. Its confidence interval and p-value therefore answer a more limited question than a prespecified adjusted model might answer.

General explanation: when variability is large relative to the group difference, estimates tend to be less precise. Conversely, a large estimated difference relative to variability may produce a more precise comparison, but the observed effect in a small trial can itself be unstable. A recalculation from summary statistics also cannot reproduce participant-level analyses, verify model assumptions, or account for details that are absent from the posted summaries.

What do the planning illustrations mean?

The sample-size illustrations are based on observed secondary effects and use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe participants per arm for 80% or 90% power under specified fractions of the observed effect. General explanation: such planning calculations ask how many participants a hypothetical future study might require under stated assumptions. They are not the trial’s original design justification, and they are not observed power. The trial’s own sample-size assumptions and justification are not reported in the registry record.

Planning from an observed effect is especially uncertain when the original study is small. General explanation: an effect selected from a small dataset may be larger or smaller than the effect that would be seen in another study. Illustrations using different fractions of that observed effect make the assumption explicit, but they do not turn the observed result into a reliable forecast. The planning values should therefore be read as conditional illustrations, not as evidence that the trial had adequate or inadequate power.

What analysis details remain unclear?

The registry defines the FAS and identifies the endpoint-specific numbers analyzed, but it does not report the covariates in the ANCOVA, the handling of missing measurements, or whether sensitivity analyses were conducted. The approach to multiplicity, the detailed statistical analysis plan, interim analyses, and the trial’s sample-size justification are not reported in the registry record. Those omissions constrain how fully the reported estimate can be assessed.

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("Somatropin", "Control Arm")
n   <- c(4, 8)
m   <- c(-0.15, 0.28)
sp  <- c(1.01, 0.51)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Somatropin  4  -0.150  2.020  -3.364  3.064
CARM  Control Arm  8  0.280  1.442  -0.926  1.486

11. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as an ANCOVA least-squares mean difference of -0.43, with a 95% confidence interval from -3.93 to 3.08 and a p-value of 0.723. This is the trial’s reported adjusted analysis of the Month 6 primary endpoint. It is the appropriate result to cite as the sponsor-reported analysis; the endpoint group means and their standard errors are descriptive summaries and do not substitute for that model-based comparison.

The secondary outcome comparisons described in the statistical material are simple unadjusted recalculations from posted summary statistics. They are not sponsor-reported analyses: the registry lists no reported analyses for those secondary outcomes. Such recalculations do not reproduce an adjusted model and cannot account for participant-level information or modeling choices that are not reported.

No discrepancy is flagged between the primary reported analysis and a recalculation. More generally, the primary sponsor analysis and secondary recalculations answer different statistical questions, so they should not be read as competing estimates of the same analysis. The registry record does not provide enough detail to independently recreate the primary ANCOVA.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 53 outcome measures and 18 analyses, alongside numerous secondary measures in cognitive performance, behavior, growth, and jumping. Multiple outcomes and time points raise a multiplicity issue: when many statistical comparisons are made, some may appear noteworthy by chance even if there is no underlying difference. General explanation: adjustments or a prespecified hierarchy can help control how multiple comparisons are interpreted, but the approach depends on the study’s objectives and analysis plan.

Whether a multiplicity adjustment was used, and which outcomes were treated as confirmatory, are not reported in the registry record. This matters especially for the secondary comparisons, which are unadjusted recalculations and have no sponsor-reported analyses listed. Their p-values should therefore be interpreted cautiously and should not be isolated from the broader set of outcomes.

The primary analysis population is defined as participants who received at least one dose and had at least one post-baseline efficacy assessment. That definition clarifies who could enter the FAS, but it does not explain how missing endpoint values were handled, whether every eligible participant contributed to the primary analysis, or whether missingness differed by group. Those details are not reported in the registry record.

The record gives endpoint-specific analyzed counts for the primary measure, but does not report a detailed flow of participants through every assessment or a missing-data sensitivity analysis. General explanation: if participants with unavailable outcomes differ systematically from those with observed outcomes, a complete-case comparison may not represent all randomized participants. The available record does not establish whether this concern affected the estimate.

The sample-size justification, interim analyses, detailed statistical plan, and methods for handling missing data are not reported in the registry record. Their absence limits assessment of the planned precision, analysis choices, and robustness of the findings. It does not by itself show that a particular method was or was not used.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 safety summary reports no serious adverse events in either listed group: 0 of 12 participants at risk in the somatropin group and 0 of 11 in the control group. No serious adverse-event terms are listed. The death counts are not reported in the registry record.

Other adverse events were reported for 10 of 12 participants in the somatropin group and 7 of 11 in the control group. These are participant counts with other adverse events, not counts of individual events. The registry summary does not provide event types or further detail in the information available for these figures.

General explanation: observing no serious events in a small group does not establish that serious events cannot occur or that the groups have equivalent safety. The at-risk denominators are distinct from the numbers analyzed for the primary endpoint, and safety counts should not be confused with efficacy counts. The registry record also does not provide enough detail in these figures to assess event timing, severity beyond the serious/non-serious distinction, or causal attribution.

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

The primary result is an imprecise estimate of the Month 6 difference in change in two-leg peak jump power SDS. The confidence interval includes both negative and positive values and extends across a broad range. The analysis therefore does not determine the direction or size of the group difference precisely. That is a statement about the information in this comparison, not proof that the groups are identical.

The estimate applies to the endpoint and analysis population described in the registry: participants in the FAS who were evaluable for the measure. It addresses the initial 6-month period, when the control group had no intervention according to the arm description. It does not answer questions about long-term effects, other populations, or outcomes beyond those assessed and reported.

The registry’s planned aims also include cognitive performance and other neuromuscular measures. The existence of those outcomes does not mean that the primary result establishes a broader effect on cognition, behavior, growth, or overall function. Each outcome has its own measurement properties, available data, and uncertainty. The secondary results are particularly limited by the small study, multiple outcomes, and lack of reported multiplicity details.

General explanation: statistical evidence and practical importance are related but distinct. A confidence interval describes uncertainty in an estimate, while a judgment about meaningfulness requires an appropriate context or threshold. The registry does not report a clinically important threshold for the primary score, so the result cannot be classified as meaningful or not meaningful on that basis.

The findings should therefore be read narrowly: the posted primary analysis reports a group comparison, but its estimate is not precise enough to establish a clear direction or magnitude. The record does not support claims beyond the specific population, endpoint, time point, and analysis reported.

15. Why This Trial Matters Statistically

This trial illustrates why a reported point estimate should not be read alone. The primary estimate is accompanied by a confidence interval that spans differences in either direction, and the endpoint-specific analyzed groups are small. Those features make precision central to interpretation: a single estimate cannot capture the range of values still compatible with the data.

It also shows the distinction between an adjusted primary analysis and unadjusted secondary recalculations. The primary result comes from an ANCOVA model, while the posted secondary comparisons were recalculated from summary statistics and do not incorporate reported covariate adjustment. These results are not interchangeable, even when both are expressed as differences between groups.

The outcome set combines measures of physical performance, growth, cognitive performance, and behavior. That breadth can be useful for describing the study’s scope, but it also makes transparent prioritization and multiplicity handling important. The registry does not report whether a multiplicity approach was used, so secondary findings require particular caution.

Finally, the record distinguishes the primary FAS counts from other denominators, including safety counts and secondary outcome counts. Keeping those populations separate prevents an apparent mismatch in sample sizes from being mistaken for a single analysis population. The trial is a useful statistical case in reading precision, analysis populations, and the limits of results from a small randomized study without extending the conclusions beyond the posted evidence.

16. 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 endpoint analysis included 4 participants in the somatropin group and 8 in the control group. These small endpoint-specific counts limit precision and make the estimate sensitive to the observations available. The total enrollment of 23 does not resolve this limitation, because not all enrolled participants were evaluable for the primary measure.

The study was open-label, with no masking listed. General explanation: for a performance measure requiring participant effort, awareness of assigned group can be relevant to measurement. The registry record does not describe procedures intended to reduce this potential influence, so its impact cannot be assessed from the record.

The trial is listed as terminated, but the reason is not reported in the registry record. The relationship between termination and the timing or completion of each outcome assessment is also not reported. The record describes planned treatment periods, but the dose assigned to each arm is not reported, and the details of treatment received by individual participants are unavailable in the posted summary.

Important analysis details are absent, including the ANCOVA covariates, handling of missing data, multiplicity methods, interim analyses, and sample-size justification. The registry does not report a clinically important threshold for the primary endpoint or the reference-population details underlying the SDS. These omissions limit assessment of clinical interpretation and analytic robustness.

The reported safety summary gives counts of participants with events but limited event detail. The secondary summaries do not include sponsor-reported analyses, and their recalculations are unadjusted. Together, these limitations mean the record supports a focused description of the posted estimates, but not a comprehensive evaluation of every protocol decision or outcome.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Neuromuscular Changes In Small For Gestational Age Children During Somatropin Therapy — NCT00625872.
• Registry record last updated 2012-02-29; status last verified 2012-01.
• Results first posted 2012-02-29.
• 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.

20. Record Summary

This Phase 3 randomized, open-label, controlled, multicenter trial studied somatropin in short children born SGA. The registry lists 23 enrolled participants and a terminated status. The primary endpoint was change from baseline to Month 6 in two-leg peak jump power SDS, analyzed in the FAS.

The reported ANCOVA least-squares mean difference was -0.43, with a 95% confidence interval from -3.93 to 3.08. The interval spans differences in either direction and reflects substantial uncertainty. The record also lists a broad set of cognitive, behavioral, growth, and neuromuscular outcomes, but important details about multiplicity, missing data, sample-size justification, and the reason for termination are not reported in the registry record.