Thyroid Function of Pediatric Subjects Following Isovue® Administration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Thyroid Function of Pediatric Subjects Following Isovue® Administration (NCT03779906), a na phase 4 study. The primary outcome is Abnormal Thyroid Function.

2. Clinical Question

The study addressed whether children from birth to 3 years who received intravascular Isovue as part of a standard-care radiologic procedure developed abnormal thyroid-stimulating hormone (TSH) values after exposure. It was designed to estimate the proportion of exposed children with abnormal thyroid function, using thyroid function tests before and after administration.

This question is descriptive: it concerns the frequency of an outcome among exposed participants. Without a comparison group, any observed post-exposure thyroid finding could not by itself establish whether exposure caused the finding. The registry record also does not report the criteria used to classify a TSH value as abnormal, so the outcome definition cannot be interpreted against a stated threshold.

3. Trial Design

NCT03779906 is a Phase IV, prospective, multicenter observational study of pediatric subjects exposed to Isovue. It began on 2019-03-26, had a primary completion date of 2021-11-15, and is listed as terminated. The registry record reports enrollment of 17 participants. It does not report why the study was terminated or whether enrollment and follow-up proceeded as originally intended.

The design is single-group, with no allocation to different treatments and no masking. Isovue was given to all participants in the course of a radiologic procedure that was part of standard clinical care. The study did not assign a dose in the way a randomized treatment trial might; the iodine concentration and volume depended on the procedure and the standards at the participating site. The registry record does not report the specific procedures, concentrations, or volumes used for individual participants.

The primary outcome was abnormal thyroid function, specifically abnormal TSH values after baseline. The stated measurement period began on Day 1, the day of Isovue administration, and extended to a 1-month follow-up or a 2-month follow-up. The registry record does not explain which participants had each follow-up interval or report how many completed follow-up.

Two secondary outcome topics are listed: hypothyroidism and thyroid hormone replacement therapy. The registry record lists three outcome measures in total, but does not report outcome analysis results. It also does not report a protocol-level sample-size justification, planned interim analyses, or a statistical analysis plan. Because the study has no comparison arm, it can describe outcomes among observed participants but cannot provide a randomized estimate of a treatment contrast.

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: Pediatric subjects (0-3 years of age) scheduled to undergo a routine radiologic procedure with intravascular administration of ISOVUE who had normal TFTs (serum TSH, T3, T4 \& fT4) at baseline were to be enrolled. TFTs were to be reassessed at 1 month and 2 months post-ISOVUE injection. If TSH values were abnormal at 1- or 2-months, follow-up (via pre-defined questionnaire) was required at 6 and 12 months to monitor subject's progress (if any). Efficacy of ISOVUE was not assessed.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Number of subjects evaluated for TFTs at baseline and post-baseline following intravascular administration of ISOVUE.

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: All participants enrolled and dosed in the study who provided demographic information.

6. Primary Endpoint

The registry lists the primary outcome as Abnormal Thyroid Function, measured over Day 1 (day dosed with intravascular administration of ISOVUE as part of their standard of care examination) to 1-month follow-up or 2-month follow-up.

The primary endpoint is the count of participants with abnormal thyroid function, defined in the outcome description as abnormal TSH values after baseline following intravascular Isovue administration. The population description specifies participants evaluated with thyroid function tests at baseline and after administration. The stated timeframe runs from Day 1, the day of dosing, to a 1-month follow-up or a 2-month follow-up.

A count is a binary-outcome summary: each participant is classified as having or not having the defined outcome, and the count records how many meet the criterion. To interpret a proportion, the count must be considered alongside the number of participants assessed. The registry record does not report the primary outcome count or the number evaluated for this endpoint, so the observed proportion cannot be read from the record.

In general, a post-baseline thyroid measure can be used to describe whether participants met an outcome criterion during follow-up. Interpretation depends on the criterion for an abnormal result, the timing of assessments, and the completeness of follow-up. The registry record does not report the TSH thresholds, the handling of repeated measurements, or the outcome result. It therefore supports a description of the intended endpoint, but not an estimate of its frequency or precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: whether a participant had abnormal TSH values after baseline. This type of endpoint is commonly summarized by counting participants with the event and relating that count to the number assessed. The registry record does not report either primary outcome count or the endpoint assessment denominator, so an observed proportion cannot be stated.

What does a proportion describe?

In general, a proportion summarizes the share of an assessed group meeting a specified condition. It is meaningful only when the event definition and denominator are clear. For this study, the event is described as an abnormal post-baseline TSH value, while the endpoint population is described as participants with thyroid function tests at baseline and after administration. The record does not provide the abnormality threshold or the number with these paired assessments. Enrollment alone does not determine the endpoint denominator.

How would precision be expressed?

In general, a confidence interval describes the statistical uncertainty around an estimated quantity, such as a proportion. It reflects the information in the observed data and the method used to calculate the interval; it is not a guarantee that the true value lies inside it. No primary outcome estimate or confidence interval is reported in the registry record. The precision of the primary endpoint therefore cannot be evaluated from the reported information.

What can a single-group design estimate?

A single-group observational study can describe outcomes among the participants who were observed and assessed. It does not include an assigned comparison group, and it does not randomly allocate participants to different exposures. In general, that means the observed frequency cannot distinguish an exposure-related effect from other explanations for an outcome. Here, all participants were to receive Isovue during a procedure as part of standard care. No like-for-like control comparison is described in the registry record.

Why do follow-up and missing observations matter?

For a post-baseline endpoint, the observed result depends on which participants have outcome assessments and when those assessments occur. In general, incomplete follow-up can change the composition of the analyzed group, particularly if the participants without assessments differ from those observed. The stated follow-up period extends to a 1-month or 2-month follow-up, but the record does not give completion counts, reasons for missing assessments, or a method for handling missing values. It is therefore not possible to assess the effect of missing endpoint data.

What statistical analysis is documented?

The registry record lists zero analyses. It does not report a test, model, confidence-interval method, covariate adjustment, or statistical analysis plan. This means the record does not provide a basis for describing how the primary outcome was analyzed. It does not establish whether analyses were or were not conducted outside the registry record.

The record includes a description of planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such assumptions describe hypothetical planning calculations, not the design of this single-group observational study. The registry record does not report a protocol sample-size justification. Any planning illustration should not be read as observed power, as an outcome result, or as evidence that the study had a particular probability of detecting an effect.

In general, over-dispersion is relevant when data vary more than a chosen statistical model expects, which can make model-based uncertainty estimates too narrow if ignored. The primary endpoint is described as a participant count for a binary outcome, but no fitted model or dispersion assessment is reported in the registry record. Over-dispersion should not be assumed to have been assessed or to affect an analysis that is not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures: the primary abnormal thyroid-function outcome and secondary outcomes concerning hypothyroidism and thyroid hormone replacement therapy. It does not report a statistical analysis plan or a method for controlling multiplicity across these outcomes. In general, evaluating multiple outcomes can increase the chance of at least one apparently noteworthy result when each is tested separately. Without reported analysis methods or results, it is not possible to determine whether multiplicity affected interpretation in this study.

The primary endpoint population is described as participants evaluated for thyroid function tests at baseline and after administration. The registry record does not report how many of the 17 enrolled participants met that definition. It also does not report the number completing each follow-up interval, reasons for missing data, or whether participants were excluded from any analysis. The registry record lists zero analyses, so there is no reported analysis population or account of how missing observations were handled.

In general, missing outcome data matter because the participants with observed assessments may not represent all enrolled participants. The direction and size of any resulting bias cannot be determined without information about missingness and the outcomes of those who were assessed. No imputation method, complete-case rule, or sensitivity analysis is reported in the registry record. The absence of these details should not be interpreted as evidence that a particular method was used or that there were no missing observations.

The record also does not report whether interim analyses were planned or conducted. The reason for the terminated status is not reported in the registry record. These omissions limit assessment of outcome selection, follow-up completeness, and the analytic population.

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 serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (5.9%).

The registry record lists 17 participants at risk for serious adverse events in the ISOVUE group, with 1 participant affected. It reports 0 deaths. Pyrexia is listed among the top serious-event terms at 5.9%. These are safety entries and should be read separately from the primary abnormal-TSH endpoint, whose result is not reported in the registry record.

A serious adverse event is a category of event in the registry record; the listed count does not, on its own, establish that the event was caused by Isovue. The record does not report the event-level clinical details, timing, seriousness criteria, or an assessment of relatedness. It also does not provide a comparator group for evaluating whether the listed events occurred more often than they would in another group.

In general, safety counts describe events recorded under the study’s reporting framework. A count of affected participants is not the same as a count of all events if a participant can experience more than one event. The available entries do not give enough detail to infer the full event history. The listed 5.9% should be retained as recorded; the registry record does not describe its calculation or provide further context for that percentage.

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

The record establishes that a prospective, multicenter, Phase IV observational study was intended to evaluate thyroid function in children from birth to 3 years after intravascular Isovue administration during standard-care radiologic procedures. It reports enrollment of 17 participants, a single-group design, a terminated status, and a primary endpoint based on abnormal post-baseline TSH values. It also reports limited serious adverse-event counts.

It does not report the primary endpoint result, the number of participants assessed for that endpoint, or an estimate of the proportion with abnormal thyroid function. Thus, the record cannot show the observed frequency of the primary outcome or how precisely that frequency was estimated. The absence of a reported primary result is not evidence that no participant had an abnormal value or that every participant had one.

The single-group observational design also does not provide a controlled estimate of the effect of Isovue. In general, an outcome observed after exposure does not by itself establish that exposure caused it. There was no separate comparator group, and participants received Isovue as part of standard care rather than through randomized allocation described in the record.

The safety entries indicate 1 participant affected by a serious adverse event among 17 at risk, 0 deaths, and a listed serious-event term of Pyrexia at 5.9%. These data do not establish causation or replace the missing primary thyroid-function result. The registry record does not report enough event detail to make a fuller safety interpretation.

Overall, the available record supports a description of the intended question, design, and selected safety information. It does not support a numerical conclusion about the primary thyroid outcome, a comparative treatment effect, or a causal claim.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a defined endpoint and a reported result. The registry describes an intended measure—abnormal TSH values after baseline—and identifies the population as participants with thyroid function tests before and after Isovue administration. But it does not report the endpoint count or the number assessed. Without both, a proportion cannot be interpreted, and without an estimate and uncertainty measure, the precision of the result cannot be assessed.

The design also matters to the question that can be answered. Prospective observation can describe outcomes over a defined follow-up period, but this study has one group and no like-for-like control comparison. The design can address what was observed among assessed participants, if those results are reported; it cannot by itself separate an exposure effect from other explanations.

Enrollment and analysis populations should not be treated as interchangeable. The record reports 17 enrolled participants, but does not say how many had the baseline and post-baseline tests required by the endpoint definition. That distinction is important when judging completeness and representativeness of the observed data.

Finally, registry entries can document study status and selected safety counts without providing a full statistical analysis. The terminated status, absence of reported outcome analyses, and missing endpoint results limit what can be learned from this record. These are not merely technical details: they determine whether the central study question can be answered quantitatively and how much confidence a reader can place in any estimate.

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.

Several trial-specific gaps limit interpretation. The primary endpoint is defined as abnormal post-baseline TSH values, but the threshold for abnormality is not reported in the registry record. The number of participants with the required baseline and post-baseline tests is also not reported, so the endpoint denominator is unknown. Although enrollment is reported as 17, the record does not establish that all enrolled participants contributed to the primary outcome assessment.

The registry record does not report the primary outcome count, an estimated proportion, or a confidence interval. It therefore does not permit evaluation of the endpoint’s observed frequency or precision. The record also does not report the number completing the 1-month or 2-month follow-up, the reasons for incomplete follow-up, or the method used to handle missing assessments.

Because the study is observational and single-group, it has no concurrent comparator. Any outcome frequency, if reported, would describe the assessed participants and would not by itself establish a causal relationship with Isovue. The specific procedure, iodine concentration, and volume varied according to clinical procedure and site standards; participant-level details are not reported in the registry record.

The study is listed as terminated, but the reason and its effects on recruitment or follow-up are not reported in the registry record. The record lists zero analyses and does not report an analysis plan, multiplicity approach, interim analyses, or protocol sample-size justification. These omissions prevent assessment of how the reported outcomes were selected and analyzed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Thyroid Function of Pediatric Subjects Following Isovue® Administration — NCT03779906.
• Registry record last updated 2025-07-30; status last verified 2025-07.
• Results first posted 2025-07-30.
• 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

NCT03779906 is a Phase IV, prospective, multicenter observational study titled “Thyroid Function of Pediatric Subjects Following Isovue® Administration.” It enrolled 17 participants and is listed as terminated. The study examined children from birth to 3 years who received intravascular Isovue during a radiologic procedure as part of standard care.

The primary outcome was abnormal thyroid function, described as abnormal post-baseline TSH values from Day 1 to a 1-month or 2-month follow-up. Hypothyroidism and thyroid hormone replacement therapy are listed as secondary outcome topics. The primary outcome result and the number assessed are not reported in the registry record.

The safety record lists 17 participants at risk for serious adverse events, 1 affected, 0 deaths, and Pyrexia at 5.9% among the top serious-event terms. No comparative treatment effect can be estimated from the single-group design.