First Year Growth Response Associated Genetic Markers Validation Phase IV Open-label Study in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children: the PREDICT Pharmacogenetics Validation Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for First Year Growth Response Associated Genetic Markers Validation Phase IV Open-label Study in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children: the PREDICT Pharmacogenetics Validation Study (NCT01419249), a non-randomized phase 4 study. The primary outcome is Change From Baseline in Height at Year 1.

2. Clinical Question

3. Trial Design

The registry record identifies this as a phase IV, open-label, non-randomized, single-group study. It describes a retrospective cohort and lists blood sampling as the intervention. Enrollment was 458. The study is marked completed; its recorded start was 2011-09 and its primary completion was 2012-10. These design details describe how the study was classified, but they do not establish how many enrolled participants contributed data to each outcome.

The study focused on children with idiopathic growth hormone deficiency and participants with Turner syndrome. Its stated purpose was to confirm whether some genes could be used to predict response to recombinant human growth hormone. The listed secondary outcomes concern the contribution of validated genetic markers to first-year growth response, evaluated separately with predictive models for IGHD children and TS girls. The names of the markers and the details of those models are not reported in the registry record.

The primary endpoint was change from baseline in height at year 1. The registry describes the primary population as participants who had provided informed consent, had non-missing height at treatment start and at 1 year, and had pharmacogenomics data available. The start measurement was defined as within one month before treatment start; the year-1 measurement allowed a window of plus or minus 120 days. This outcome population is therefore not necessarily identical to the enrollment total.

Because the study was non-randomized and single-group, it does not supply a randomized control comparison. The registry record does not report a protocol-level description of treatment dose, treatment duration beyond the endpoint timing, recruitment procedures, or a sample-size justification. Nor does it report an interim-analysis plan. Those omissions limit how completely the design can be reconstructed from the registry entry alone.

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: FAS population included all the participants who had provided informed consent and had non-missing height at start (defined as within one month prior to treatment start date) and at 1 year (+/- 120 days) of r-hGH treatment and had pharmacogenomics data available.

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: Full Analysis Set (FAS) population included all the participants who had provided informed consent and had non-missing height at start (defined as within one month prior to treatment start date) and at 1 year (+/- 120 days) of r-hGH treatment and had pharmacogenomics data available.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Height at Year 1, measured over Baseline and Year 1.

The primary endpoint, change from baseline in height at year 1, measures the difference in a participant’s height between the treatment-start assessment and the assessment around 1 year of r-hGH treatment. The measurement unit is centimeters, and the specified summary measure is the mean. The registry describes the measure as one of the growth parameters used to assess first-year response.

As a general statistical point, a change score focuses on how an outcome moves between two defined times rather than on the value at either time alone. Reporting a mean change can describe the average trajectory in the analyzed population. A standard deviation, if reported, would describe variability in individual changes around that average; it is not the same as uncertainty in the estimated mean. A confidence interval around the mean would express the estimate’s precision under the analysis assumptions.

The endpoint’s interpretation depends on the defined measurement windows and analysis population. Here, baseline height had to be measured within one month before treatment began, while the year-1 measurement could fall within plus or minus 120 days of the target time. Participants also needed non-missing measurements at both points and available pharmacogenomics data. The registry record does not report the resulting mean change, its standard deviation, a confidence interval, or a statistical test for this endpoint. It therefore describes what was intended to be measured, but does not provide the numerical primary result needed to characterize its magnitude or precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary measure as a mean of a continuous outcome: change in height from baseline to year 1, in centimeters. It names standard deviation as the dispersion measure. No numerical mean or standard deviation for the primary endpoint is reported in the registry record, and no analysis estimate or test is listed. The design and outcome definition can therefore be explained, but the numerical analysis cannot be independently assessed from this entry.

What does a mean change describe?

As a general statistical explanation, a mean change summarizes the average within-participant difference between two measurements for the participants included in an analysis. A mean is useful for describing the center of a continuous outcome, but it does not show whether individual participants had similar changes or widely varying changes. The standard deviation describes spread among observations; it does not, on its own, quantify the precision of the estimated mean. A confidence interval, when reported, describes a range of values compatible with the data and analysis assumptions and helps readers assess estimation uncertainty.

For this endpoint, the timing rules matter to the interpretation. Baseline was defined as a height measurement within one month before treatment start. The follow-up assessment was at 1 year, with a permitted window of plus or minus 120 days. Such windows define which observations qualify for the outcome; they do not mean every participant was measured on exactly the same day. The registry record does not report the actual measurement-time distribution.

What does the analysis population include?

The primary population was described as the FAS population. It included participants who had provided informed consent, had non-missing height at treatment start and at 1 year, and had pharmacogenomics data available. In general, defining an analysis population makes clear which participants contribute to an estimate. Requiring complete measurements and genetic data means that participants without those data do not meet this stated population definition. The number who met the definition, and any comparison of included and excluded participants, are not reported in the registry record.

The enrollment total is 458, but enrollment alone does not identify the number analyzed for the primary endpoint. A participant may be enrolled without meeting every outcome-specific data requirement. The record does not report a primary-outcome analysis count or explain how any missing observations were handled beyond describing the eligibility requirements for the FAS population.

How should the design shape interpretation?

As a general principle, a non-randomized, single-group design can describe outcomes in the observed cohort but does not provide the protection against confounding that random allocation can offer in a treatment comparison. The registry labels the study open-label, so masking is listed as none. The record does not report an inferential analysis plan that would clarify how the primary outcome or genetic-marker contributions were estimated.

The secondary outcomes refer to the contribution of genetic markers to first-year growth response using the GHD KIGS predictive model and the TS KIGS predictive model. Predictive modeling generally asks how well information helps estimate an outcome for individuals or groups. Evaluating prediction requires details such as the model specification, performance measures, validation procedure, and uncertainty. Those details and numerical model results are not reported in the registry record, so predictive accuracy cannot be judged from the outcome descriptions alone.

What do planning illustrations mean?

As a general statistical explanation, a sample-size planning illustration describes the number of participants that would be needed under stated assumptions to detect a specified effect with a chosen error rate and power. It is a design calculation, not evidence that the study had that probability of finding a result after completion. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect framed as a stated fraction of an observed effect. The record does not report the trial’s own sample-size justification. The study itself is listed as single-group and non-randomized, so an illustration based on two-arm allocation should not be mistaken for the actual design.

General statistical caution also applies to estimates derived from summaries: a recalculation from posted summary statistics would be an unadjusted recalculation, not a replacement for the sponsor’s analysis. No numerical primary endpoint summaries or recalculated results are reported in the registry record. It is therefore not possible to compare a recalculation with a sponsor analysis or to assess whether a discrepancy exists.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 5 outcome measures and 0 analyses. It identifies the primary endpoint as change from baseline in height at year 1 and describes secondary outcomes concerning genetic-marker contributions in the IGHD and TS populations. The record does not report how many statistical tests were conducted, which comparisons were prespecified, or whether any adjustment for multiple testing was used. Multiplicity handling is therefore not reported in the registry record.

As a general statistical point, when several outcomes, markers, subgroups, or model evaluations are tested, the chance of obtaining at least one apparently notable result can increase if each is assessed without accounting for the number of analyses. Adjustment strategies and their interpretation depend on the analysis plan. The registry entry does not provide enough detail to determine which strategy, if any, was used. The presence of multiple listed outcome measures alone does not establish that a particular multiplicity problem occurred, but readers cannot evaluate that issue without the analysis details and results.

The primary analysis population required informed consent, height measurements at treatment start and at 1 year, and pharmacogenomics data. The timing windows were within one month before treatment start for baseline and plus or minus 120 days around 1 year for follow-up. This definition excludes participants lacking any required component from the described FAS population. The number excluded for missing height or genetic data, and the reasons for missingness, are not reported in the registry record.

As a general matter, missing data can affect an estimate if participants with incomplete records differ from those with complete records. The registry does not report imputation, sensitivity analyses, or other missing-data methods. It also does not report the number analyzed for the primary endpoint. Thus, the relation between total enrollment and the outcome-specific analysis population cannot be determined from the record.

11. 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.

The registry lists two serious-adverse-event risk groups: the IGHD cohort, with 293 participants at risk, and the TS cohort, with 132 participants at risk. For each group, the number affected by serious adverse events is recorded as 0. No serious adverse-event terms are listed. The record also shows zero participants at risk and zero affected for the separate “other” event category in both cohorts.

These are descriptive counts within the groups and categories recorded in the registry. They do not supply event rates, follow-up-specific estimates, or a comparison with an untreated or randomized control group. The study design is non-randomized and single-group, so the safety entries do not support a comparative causal conclusion. The registry’s deaths entry is null rather than a reported numerical count; deaths are therefore not reported in the registry record as a value.

As a general statistical point, an observed count of zero is not proof that the underlying risk is zero. The meaning of a zero count depends on the number observed, the period of observation, event definitions, and how completely events were collected. The registry record does not report enough detail to assess those features or to infer that no unlisted events occurred. These figures should be read narrowly as the serious-event counts posted for the named cohorts.

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

The registry record establishes what the study set out to assess: whether genetic markers could help predict first-year response to r-hGH in participants with IGHD or TS. It specifies a primary outcome, mean change in height from baseline to year 1, and describes an outcome population requiring complete height measurements at the stated time points plus pharmacogenomics data. It also identifies secondary model-based evaluations for the two clinical populations.

What the entry does not establish is the size of the observed mean height change, how variable individual changes were, or how precise the estimated average was. The primary mean, standard deviation, confidence interval, and statistical test are not reported in the registry record. Marker-specific estimates and predictive model performance are also not reported. Without those results, the central pharmacogenetic validation question cannot be answered from this registry entry.

The design is non-randomized, open-label, and single-group. As a general interpretive point, an observed change over time in such a cohort is not by itself a randomized estimate of treatment effect. Nor does the design label alone tell whether a genetic marker predicts response well; that requires the model results and details of validation. The registry does not report the protocol, sample-size justification, interim analyses, or full statistical plan.

The safety entry records zero participants affected by serious adverse events in each listed cohort. That count is informative as a description of the posted data, but it is not a guarantee of zero risk and does not establish a comparison with another treatment or no treatment. The deaths field is not reported as a numerical value.

In short, the registry supports a description of the study’s objective, design, endpoint definition, analysis-population criteria, and posted serious-event counts. It does not provide the numerical primary outcome or genetic-prediction results needed to determine the magnitude, precision, or predictive contribution of the findings.

13. Why This Trial Matters Statistically

This study is statistically notable because it combines a continuous growth outcome with a pharmacogenetic prediction question. The primary endpoint is a mean change in height, while the stated secondary outcomes ask whether genetic markers contribute to predicted first-year response in two distinct populations. These are related but different questions: describing average growth change does not, on its own, establish how well a model predicts individual response.

The registry’s population definition also highlights an important analytic distinction. Enrollment was 458, but the primary population required complete height information at specified time points and available pharmacogenomics data. In general, estimates based on a restricted complete-data population may not describe every enrolled participant. Since the number meeting the criteria and the reasons for missing data are not reported, the extent and implications of that restriction cannot be assessed.

The non-randomized, single-group design matters because it does not create a randomized control comparison. A cohort’s change over time can describe what happened among those analyzed, but a causal treatment contrast requires a suitable comparison and appropriate analysis. Likewise, predictive claims require reported model performance and validation details, not merely a stated intention to evaluate genetic markers.

The entry therefore illustrates why registry outcomes and results must be distinguished. The outcome definition clarifies what investigators intended to measure, but the absence of numerical estimates prevents assessment of magnitude and precision. The safety counts provide a limited descriptive record, not a comparative safety analysis. These limitations are especially important when the study’s central aim concerns validation: readers need marker-level estimates, model assessment, and uncertainty to judge whether prediction was meaningfully evaluated.

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 registry record does not report the primary endpoint’s mean change, standard deviation, confidence interval, or test result. It also does not give the number of participants included in the primary analysis. Although enrollment was 458, the FAS definition required both height measurements and available pharmacogenomics data, and the number meeting those criteria is not reported.

The genetic markers themselves, their selection process, and their individual results are not reported in the registry record. The secondary outcomes name predictive models for IGHD and TS, but model specifications, validation methods, performance measures, and uncertainty estimates are absent. These omissions prevent assessment of whether the study validated prediction or how well the models performed.

The study is listed as non-randomized, open-label, and single-group. No randomized control comparison is described. Treatment details beyond the broad reference to r-hGH, as well as recruitment and cohort-selection procedures, are not reported in the registry record. The record also does not report a protocol, sample-size justification, interim-analysis plan, or complete statistical analysis plan.

Missing-data handling and multiplicity procedures are not reported. The registry defines which measurements were required for the primary population but does not state how many participants lacked measurements or genetic data, why data were missing, or whether sensitivity analyses were conducted. Five outcome measures are listed, but the record does not explain the testing strategy across outcomes.

The safety figures are limited to the recorded serious-event counts and risk groups. Follow-up detail for safety, event-collection methods, and a comparative safety group are not reported. The deaths field is null. These constraints mean the posted record supports a narrow description of design and recorded counts, rather than a complete evaluation of efficacy, prediction, or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: First Year Growth Response Associated Genetic Markers Validation Phase IV Open-label Study in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children: the PREDICT Pharmacogenetics Validation Study — NCT01419249.
• Registry record last updated 2014-01-16; status last verified 2013-11.
• Results first posted 2014-01-16.
• 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

NCT01419249 is a completed phase IV, open-label, non-randomized, single-group pharmacogenetic validation study with enrollment of 458. The recorded study start was 2011-09 and primary completion was 2012-10. Participants were drawn from IGHD and TS cohorts; blood sampling is listed as the intervention.

The primary outcome was mean change from baseline in height at year 1, in centimeters. The FAS population required consent, non-missing height at treatment start and at 1 year within the specified windows, and available pharmacogenomics data. Secondary outcomes concerned genetic-marker contributions evaluated with predictive models for IGHD and TS.

The registry record does not report the primary numerical result or the genetic-model results. It records zero participants affected by serious adverse events among 293 in the IGHD cohort and among 132 in the TS cohort; the deaths entry is null. Statistical-plan details, missing-data methods, and multiplicity handling are not reported in the registry record.