Safety Profile of Insulin Like Growth Factor-1 (IGF-I) Administration in Adolescents: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Profile of Insulin Like Growth Factor-1 (IGF-I) Administration in Adolescents (NCT00516386), a na phase 1, phase 2 study. The primary outcome is Change in Levels of Insulin Like Growth Factor-1 (IGF-I) Following Recombinant Human (rh) IGF-1 Administration in Girls With Anorexia Nervosa.

2. Clinical Question

The registry describes a study intended to assess whether administering IGF-I to adolescent girls with low weight was safe and whether it increased bone formation markers. The registered primary outcome concerns change in IGF-I levels; a secondary outcome concerns change in P1NP, a bone formation marker. The primary outcome is therefore a laboratory measure of IGF-I, not a direct measure of bone health or a clinical outcome.

The single-group design means the question is about measurements before and after treatment in participants who received rhIGF-1. It does not compare treatment with placebo, usual care, or another intervention. A change over time in this group cannot by itself distinguish an effect of treatment from other changes that occurred during the same period. Numerical primary and secondary outcome results are not reported in the registry record, so the direction, size, and precision of any observed changes cannot be described.

3. Trial Design

This completed study is registered as phase I and phase II and as a single-group study. Its allocation is listed as NA, and masking is listed as none. Massachusetts General Hospital is the sponsor. The registry records a start date of 2007-03 and primary completion in 2008-05. The condition is anorexia nervosa.

Eligible adolescent girls with anorexia nervosa received recombinant human IGF-I by subcutaneous injection. The listed regimen was 35-40 mcg/k twice daily for a 7-10 day period. No separate comparator arm is recorded, so the design does not support a like-for-like comparison between treated participants and untreated participants. The primary outcome is change in IGF-I levels from baseline to 7-10 days. The listed secondary outcome is change in P1NP following rhIGF-1 administration.

The registry states that 16 subjects were screened, 10 completed the study, and 10 were analyzed. These statements describe screening, completion, and the primary analysis population as recorded; they do not explain why participants did not complete the study or how missing measurements were handled. The registry status is completed, but numerical outcome estimates and their uncertainty are not reported in the registry record.

The intervention period was brief, and the recorded outcomes focus on laboratory measures and safety observations. The registry record does not report details of a randomization procedure, a control condition, or masking beyond the entries stating allocation NA and masking none. It also does not report a detailed protocol description, reasons for the selected treatment duration, or whether the planned analysis differed from the analysis ultimately conducted.

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: Four subjects were not interested in the study after the screen, and two were lost to follow-up.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 16 subjects were screened for the study, and 10 completed the study. 10 were analyzed.

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 Levels of Insulin Like Growth Factor-1 (IGF-I) Following Recombinant Human (rh) IGF-1 Administration in Girls With Anorexia Nervosa, measured over Baseline and 7-10 days.

The primary endpoint is the change in levels of insulin-like growth factor-I following recombinant human IGF-I administration in girls with anorexia nervosa. The measure is continuous, its unit is ng/ml, and the registry identifies the summary parameter as a mean with standard error. The stated timeframe is baseline and 7-10 days. In practical terms, this endpoint concerns how the measured IGF-I level changed between those assessment times among participants included in the analysis.

IGF-I is the substance administered in this study, so measuring its levels is relevant to describing the biological response during the treatment period. The registry summary also states that the study aimed to determine whether giving IGF-I was safe and whether it increased levels of bone formation markers. Change in P1NP is listed as a secondary outcome related to the latter aim. The primary endpoint itself is not a direct measure of safety, bone formation, bone density, or a clinical benefit.

For a continuous endpoint, a mean describes the average measurement or average change for the analyzed group. A standard error describes the statistical precision of an estimated mean; it is not the spread of individual participants’ measurements. The registry identifies these summary conventions but does not report the numerical mean change, its standard error, the underlying measurements, or an interval estimate. The magnitude and precision of the primary result are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial results are easier to interpret when the outcome, analysis population, estimate, and uncertainty are considered together. The registry identifies the primary measure as change in IGF-I levels, a continuous outcome in ng/ml. It identifies the mean as the summary parameter and standard error as the measure of dispersion around that estimate. These labels describe the intended form of reporting, but the numerical result itself is not reported in the registry record.

What does a mean change describe?

In general, a mean change is the average of participant-level changes between the specified assessments. It summarizes the group’s average movement on the measured scale, while potentially concealing differences among individuals. A mean alone does not show whether all participants changed in a similar way, whether some changed in opposite directions, or how widely individual measurements varied. Those questions require participant-level distributions or additional summaries, which are not reported in the registry record.

The recorded timeframe is baseline and 7-10 days. For a pre-post outcome, interpretation depends on the values and timing of both assessments and on how a change is defined. The registry names the timeframe and outcome, but does not report the numerical baseline value, follow-up value, mean change, or a detailed calculation method. It is therefore not possible to reconstruct or verify the primary estimate from the registry record.

What does the standard error mean?

In general, the standard error describes how precisely a sample estimate such as a mean is estimated. It is distinct from the standard deviation, which describes variation among individual observations. A smaller standard error generally indicates a more precise estimate under the statistical model used, but does not by itself show that an effect is clinically important or that the model is appropriate. Here, the registry lists standard error as the dispersion measure but does not report its value.

A confidence interval is a general way to express uncertainty around an estimate by giving a range of values compatible with the data under specified assumptions. Its width depends on the estimate’s uncertainty and the method used. No confidence interval for the primary endpoint is reported in the registry record. Without an estimate and interval, readers cannot judge how tightly the data locate the average change or which values remain compatible with the analysis.

Why does the single-group design matter?

In general, repeated measurements in a treated group can describe change over time, but they do not supply the counterfactual comparison needed to establish what would have happened over the same period without treatment. A control group can help separate treatment-associated change from time trends, background variation, and measurement effects. This study is recorded as single group, with allocation NA and masking none; no concurrent control condition is described. Thus, even if a numerical pre-post change were reported, it would be a within-group observation rather than a randomized treatment-versus-control contrast.

Masking is a design feature that can reduce the influence of expectations on some aspects of a study, depending on who is masked and how outcomes are assessed. The registry lists masking as none. It does not describe outcome-assessor procedures or any additional safeguards. For a laboratory endpoint, the lack of masking should not be treated as proof that measurements were biased, but the record does not allow assessment of whether masking or other procedures influenced measurement and reporting.

How should planning calculations be read?

In general, a sample-size calculation estimates how many participants a future study might need under chosen assumptions about the effect to detect, variability, significance level, allocation, and statistical model. The registry’s planning assumptions describe an illustrative calculation based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not evidence that the original study was designed as a two-arm trial.

The planning note specifically distinguishes participants per arm for non-time-to-event outcomes from total events for time-to-event calculations. The present registered study is single group, and the stated planning approach assumes equal allocation between two arms. Such an illustration would concern a hypothetical future comparison, not the actual allocation in this study. The actual numerical planning results are not reported in the registry record.

Sample-size illustrations are not observed power. In general, observed power calculated after a study is complete is not a substitute for reading the effect estimate and its uncertainty. A planning calculation can show how assumptions affect a proposed future design; it cannot repair missing outcome results or establish whether the intervention changed the endpoint. Because the numerical observed effect is not reported in the registry record, readers cannot evaluate the effect-based planning illustration from the registry information alone.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. When relevant, failing to allow for extra variation can make uncertainty appear too small and can lead to misleading precision. The registered primary outcome is continuous and summarized as a mean with standard error; the registry does not report a model, residual assessment, or evidence of over-dispersion. It would therefore be inappropriate to claim that over-dispersion was assessed or affected this analysis. The broader lesson is that uncertainty estimates depend on both the data and the assumptions used to model them.

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("RhIGF-1")
n   <- c(10)
m   <- c(542.9)
sp  <- c(40.9)
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  RhIGF-1  10  542.900  129.337  450.378  635.422

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study assesses several outcomes, time points, subgroups, or statistical tests. In general, examining many results can increase the chance that at least one appears notable by chance, especially when interpretation focuses selectively on favorable findings. The registry lists a primary change in IGF-I levels and a secondary change in P1NP. It does not report a multiplicity adjustment, a hierarchy for interpreting secondary outcomes, or a detailed statistical analysis plan. Those details are not reported in the registry record, so it is not possible to determine how multiple outcomes were handled.

The registry describes 16 subjects as screened, 10 as completing the study, and 10 as analyzed. It does not explain why participants did not complete the study, whether all scheduled measurements were obtained, or how missing measurements were treated. The missing-data approach, if any, is not reported in the registry record. In general, missing measurements can affect a pre-post estimate when the participants with observed follow-up data differ from those without it. The record does not provide enough information to assess whether that concern applies or how it was addressed.

The analysis population is described as 10 analyzed, but further population definitions are not reported in the registry record. The record does not specify an intention-to-treat approach, a per-protocol approach, or a rule for including participants with partial data. It also does not report whether the analysis population was defined before results were examined. These omissions limit assessment of whether the analysis followed a prespecified approach and how the participant flow relates to the endpoint estimate.

Because the numerical endpoint results are not reported in the registry record, missing-data and multiplicity considerations cannot be evaluated alongside the estimates. This absence does not establish that a particular method was or was not used; it means the registry record does not document it.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization for weight gain (6.2%).

The registry lists one serious adverse event among 16 at risk in the rhIGF-1 group. It lists four other adverse events among 16 at risk. Hospitalization for weight gain appears among the serious adverse event terms, with a reported percentage of 6.2%. The registry also lists 16 at risk for the other adverse event category. These are recorded event counts and denominators; they should not be interpreted as a comparison with an untreated group, because no concurrent control group is recorded.

A serious adverse event is a classification of seriousness, not a statement that the event was caused by the study intervention. The registry entries do not establish causality. The listed term describes a hospitalization for weight gain, but further details about timing, clinical circumstances, relatedness assessment, or event resolution are not reported in the registry record. The other adverse event terms are not enumerated in the available record.

The death entry is null. This is not equivalent to a reported count of zero; death data are not reported in the registry record. The safety entries should therefore be read as a limited description of recorded events and the population listed as at risk, not as a complete characterization of safety or as evidence about comparative risk.

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

The registry supports a clear description of the study question and design: adolescent girls with anorexia nervosa received recombinant human IGF-I, and the primary outcome was change in IGF-I levels from baseline to 7-10 days. The regimen was 35-40 mcg/k twice daily by subcutaneous injection for a 7-10 day period. The registry also identifies P1NP change as a secondary outcome and records selected adverse event information.

What the record does not establish is the size or direction of the laboratory changes. Numerical results for the primary and secondary outcomes are not reported in the registry record. Without those estimates and their uncertainty, it is not possible to say how much IGF-I or P1NP changed, how precise the estimates were, or whether the observed results were compatible with a wide range of values. A stated study aim is not itself a reported result.

The design also does not permit a treatment-versus-control conclusion. Because the study is single group and has no concurrent comparison condition, a before-and-after change, if reported, would not isolate the effect of treatment from other explanations for change over time. This is a general interpretation limit of uncontrolled pre-post studies. It does not mean that no change occurred; the numerical outcome information needed to describe change is not reported in the registry record.

The safety entries indicate that the registry recorded serious and other adverse events in the rhIGF-1 group, including hospitalization for weight gain as a serious term. They do not establish that the intervention caused those events, and the absence of a concurrent control limits comparative interpretation. The death entry is null, so deaths are not reported in the registry record.

Accordingly, the record is informative about the study’s structure, intervention, outcomes of interest, and selected safety listings. It does not provide the outcome data needed to quantify biological changes or assess their precision, and it cannot support a causal or comparative conclusion about treatment effects.

14. Why This Trial Matters Statistically

This study is statistically instructive because its research question combines a safety aim with laboratory outcomes, while the design is a single-group pre-post study. Those features make it important to distinguish what a measured change can describe from what it can establish. A mean change can summarize the group’s trajectory over the observed period, but without a concurrent comparator it cannot by itself identify what would have happened without treatment.

The outcome definitions also show why precision matters. The primary outcome is continuous, reported in ng/ml, and intended to be summarized as a mean with standard error. A numerical estimate would describe the average change, while its uncertainty would indicate how precisely that average was estimated. The registry identifies the summary approach but does not report the outcome estimate or standard error. This prevents readers from evaluating magnitude and precision separately.

Participant flow is another important part of statistical interpretation. The registry records 16 subjects screened, 10 completing, and 10 analyzed. Knowing those stages helps readers see that screening, completion, and analysis are not interchangeable concepts. But the registry does not state why participants did not complete the study or how missing outcome measurements were handled. The flow figures therefore cannot answer whether missingness may have influenced the analysis.

The record also illustrates the distinction between a study’s actual design and a planning illustration. The study is single group, whereas the stated planning assumptions include equal allocation between two arms. A hypothetical two-arm sample-size calculation can inform future planning, but it does not change the design that produced the study’s data and should not be described as observed power.

Finally, adverse event counts should be interpreted on their own terms. They describe recorded events in a treatment group, not treatment-attributable risk or a comparison with another regimen. These distinctions are central to reading small early-phase studies carefully without overstating what the design or registry entries can establish.

15. 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 main limitation for interpretation is that numerical results for the primary and secondary outcomes are not reported in the registry record. The registry names the primary endpoint, unit, summary parameter, dispersion measure, and timeframe, but does not report the estimated change or its uncertainty. The direction and magnitude of the biological response therefore cannot be evaluated from the record.

The single-group design has no concurrent control, and masking is listed as none. Accordingly, any within-group change would not provide a direct treatment-versus-control contrast. The record does not describe details of measurement procedures that might clarify how laboratory assessments were conducted, nor does it report a detailed analysis plan.

The registry states that 16 subjects were screened, 10 completed the study, and 10 were analyzed, but does not report reasons for noncompletion or the handling of missing data. Further details about the analyzed population, eligibility deviations, and any exclusions from particular outcome analyses are not reported in the registry record. This limits assessment of possible selection effects and the relationship between participant flow and the analysis.

Safety interpretation is also limited. The registry lists serious and other adverse event counts and a serious term, but does not report detailed event narratives, relatedness assessments, timing, or resolution. The null death entry does not establish that there were no deaths; death information is not reported in the registry record.

The registry does not report a sample-size justification for the original study, a detailed statistical plan, or whether interim analyses were conducted. These matters are not reported in the registry record. The planning assumptions described for an illustrative calculation are not a substitute for documentation of the original design rationale, and they should not be read as proof of the study’s intended allocation or analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety Profile of Insulin Like Growth Factor-1 (IGF-I) Administration in Adolescents — NCT00516386.
• Registry record last updated 2021-11-18; status last verified 2021-10.
• Results first posted 2011-08-04.
• 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.

19. Record Summary

This completed phase I and phase II study examined recombinant human IGF-I administration in adolescent girls with anorexia nervosa. The listed regimen was 35-40 mcg/k twice daily by subcutaneous injection for a 7-10 day period. The study is recorded as single group, with allocation NA and masking none. Massachusetts General Hospital is the sponsor; the recorded start was 2007-03 and primary completion was 2008-05.

The primary outcome was change in IGF-I levels from baseline to 7-10 days, measured in ng/ml and summarized as a mean with standard error. Change in P1NP was listed as a secondary outcome. The registry reports 16 subjects screened, 10 completing, and 10 analyzed, but numerical outcome results are not reported in the registry record.

The safety entries list one serious adverse event and four other adverse events in the rhIGF-1 group, with hospitalization for weight gain listed as a serious term at 6.2%. The record does not establish causality or provide a concurrent control comparison. The death entry is null, so death information is not reported in the registry record.