Observational Study on Hypothyroidism in Young Children Following Iodine Contrast Exposure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Observational Study on Hypothyroidism in Young Children Following Iodine Contrast Exposure (NCT02766283), a registered phase not stated study. The primary outcome is Number of Pediatric Patients With Detected Hypothyroidism After Iodinated Contrast Exposure in a Routine Clinical Practice Setting.

2. Clinical Question

The study’s stated aim was to investigate detected hypothyroidism after iodinated contrast exposure in routine clinical practice. Its focus is therefore on the number of children with a detected outcome following exposure, rather than on a randomized comparison of exposure against a control condition. The record describes children age 0-3 years, inclusive, who underwent an iodine contrast-enhanced radiological examination, and specifies that the primary endpoint concerns the final cohort.

This question is clinically framed around an event being detected after exposure. That framing does not, by itself, establish that exposure caused an event. Without a reported comparator and details of outcome ascertainment, the registry record cannot establish how the observed occurrence compares with what would have happened without exposure. The primary outcome count and a measure of uncertainty around that count are not reported in the registry record.

3. Trial Design

Despite the word “study” in its title, this registry entry describes an observational investigation. Children were included after undergoing an iodine contrast-enhanced radiological examination in routine clinical practice; random assignment is not reported. The registry record lists iodinated contrast agents as the intervention and describes a cohort of children age 0-3 years, inclusive. It does not identify a like-for-like control group, so the record does not support a randomized treatment comparison.

The registry record lists enrollment of 843 and identifies the primary outcome population as the final cohort. The relationship between enrollment and the final cohort, including any exclusions or reasons for exclusion, is not reported in the registry record. The study status is COMPLETED. Its start date is 2016-06-30 and its primary completion date is 2016-08-30. The sponsor is Bayer.

The primary outcome timeframe is up to one year after iodinated contrast material exposure, with 828 person years stated. The record does not describe the follow-up schedule, the methods used to identify hypothyroidism, or how variation in observation time was handled. It also does not report the study protocol, a sample-size justification, or whether interim analyses were planned.

The registry lists 13 outcome measures and 2 analyses. Secondary outcomes concern characteristics such as sex, age, weight, comorbidity, examination counts and types, and time between examinations, compared between cases with an indication of hypothyroidism and cases without. Detailed results and analysis methods for these outcomes are not reported in the registry record. The available design description therefore supports an account of the study’s broad observational question, but not a full reconstruction of its conduct or analysis.

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: Between 1.1.1998 and 31.12.2015, 877 participants were identified. After applying exclusion criteria, 34 participants were excluded from the initial cohort and the final cohort consisted of 843 participants.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Final Cohort

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: Final Cohort

6. Primary Endpoint

The registry lists the primary outcome as Number of Pediatric Patients With Detected Hypothyroidism After Iodinated Contrast Exposure in a Routine Clinical Practice Setting, measured over Up to one year after iodinated contrast material (ICM) exposure (828 person years).

The primary endpoint is the number of pediatric participants in the final cohort with detected hypothyroidism after iodinated contrast exposure. The registry record gives the unit as participants and sets the timeframe as up to one year after iodinated contrast material exposure, with 828 person years. The endpoint is a count of participants with an event, not a reported comparison of event rates between randomized groups.

A count is useful for describing how many people in a defined population had the outcome detected. To interpret that count as a frequency, readers also need to know the relevant population denominator and how completely outcomes were ascertained. A rate additionally requires a clearly defined person-time denominator and an analysis appropriate to follow-up duration. Although the registry record states 828 person years, it does not report the number of participants with detected hypothyroidism or a rate calculated from the observation time.

The endpoint reflects detected hypothyroidism, which makes the ascertainment process important: the record does not specify diagnostic criteria, testing schedules, or how an outcome was confirmed. Those details are not reported in the registry record, so the meaning of “detected” cannot be evaluated in greater depth. The endpoint can describe occurrence after exposure, but by itself it cannot determine whether exposure caused the outcome or how occurrence compares with an unexposed group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a binary primary outcome expressed as a participant count: children with detected hypothyroidism after iodinated contrast exposure. It names the population as the final cohort and gives a follow-up timeframe of up to one year after exposure, with 828 person years. The primary count, denominator details, and statistical estimates are not reported in the registry record. The methods therefore need to be interpreted cautiously: the endpoint is identifiable, but the analysis used to summarize it is not.

What does a participant count convey?

A count describes the number of people in a population who meet an outcome definition. A count alone does not convey how common the outcome was unless the size of the population at risk is also clear. A proportion uses an eligible population denominator, while an incidence rate uses accumulated person-time. These quantities answer related but different descriptive questions. General statistical explanation: choosing a denominator that matches the question is essential, and the definition of the population at risk should be explicit.

Here, the registry record gives enrollment of 843 and identifies the primary population as the final cohort, but does not report the final cohort size or explain exclusions. It gives 828 person years, but does not report a rate or explain how person-time was accumulated. It is therefore not appropriate to infer a proportion or rate from the available record. No new estimate can be reconstructed from the stated information.

Why does follow-up matter?

In a cohort followed over time, participants may contribute different amounts of observation. A person-time measure can account for that variation when the underlying analysis is designed to use it. General statistical explanation: an event count and person-time together can support a rate, but only when the event definition, risk period, and handling of incomplete follow-up are specified. The registry record does not describe these analysis details, so it is unclear whether or how the stated person years informed the primary analysis.

Follow-up also affects outcome ascertainment. A child must be observed and assessed for the event to be detected. If assessment opportunities differ, detected outcome counts may reflect differences in observation as well as differences in underlying occurrence. The record does not report a testing schedule, diagnostic criteria, or the completeness of follow-up. Those omissions prevent assessment of whether outcome detection was consistent across participants.

What can a confidence interval add?

General statistical explanation: a confidence interval provides a range of values compatible with an estimate under a specified statistical model and its assumptions. It helps readers judge the precision of a point estimate; it does not correct for selection bias, outcome misclassification, confounding, or an unsuitable comparison. No confidence interval or primary point estimate is reported in the registry record. The precision of the primary result therefore cannot be evaluated.

How should the planning illustration be read?

The record’s planning assumptions describe an illustration based on the observed effect, not the study’s original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event settings, the illustration uses a total number of events, while other settings use participants per arm. These assumptions describe a planning calculation, not an observed study result or an account of the actual observational cohort.

General statistical explanation: planning estimates depend on the target effect, variability, allocation, significance level, and chosen power. When a target is based on an observed effect, it is an illustration of the sample size that might be needed to detect an effect of that scale under the stated assumptions. It is not “observed power,” and it cannot establish that a study was adequately powered. No numerical planning outputs or original sample-size justification are reported in the registry record.

What analysis details remain unknown?

The registry record lists 2 analyses but does not report their statistical methods, model specifications, handling of covariates, or whether estimates were adjusted. It also does not specify how baseline characteristics were analyzed. Since the study is observational, a comparison of cases with and without an indication of hypothyroidism would need clear definitions and appropriate consideration of differences between groups before supporting adjusted interpretation. The record does not provide those details or the corresponding results.

General statistical explanation: model choice should reflect the outcome and design. For binary outcomes, analyses may estimate counts, proportions, odds, or risks; for time-to-event outcomes, methods may incorporate timing and censoring. These are general possibilities, not claims about methods used in this study. The registry record does not identify which, if any, of these approaches was used. No recalculated estimate is available from the stated summary information.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Iodine Contrast Agent")
n      <- c(843)
events <- c(11)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Iodine Contrast Agent  843  11  1.3  0.7  2.3  0.7  2.3  0.7  2.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures and 2 analyses. It identifies a primary outcome and several secondary outcomes concerning participant characteristics and examination history, but the full statistical analysis plan is not reported in the registry record. The record does not state whether the outcomes were prespecified in a protocol, how analyses were assigned to outcomes, or whether any adjustment for multiple testing was planned.

General statistical explanation: when many outcomes or subgroup comparisons are examined, the chance of finding at least one apparently unusual result can increase. Multiplicity methods can address that issue, but their relevance depends on which tests were planned and how results are interpreted. Because the record does not report the testing strategy or secondary results, the impact of multiplicity cannot be assessed. The number of listed outcomes alone does not establish that all were tested or that any particular adjustment was needed.

Missing-data procedures are not reported in the registry record. The record does not explain whether missing baseline characteristics, incomplete follow-up, or unavailable outcome assessments occurred, nor how any such data were handled. It also does not report a flow from enrollment to the final cohort. Enrollment is listed as 843, but the number included in the primary analysis is not given.

The primary population is described as the final cohort, but eligibility details and analysis-population rules are not reported. It is therefore unclear whether the primary analysis included all participants with exposure, only those with complete follow-up, or another defined set. Interim analyses and stopping rules are not reported in the registry record. Without these details, readers cannot evaluate the effects of missingness, analysis-population selection, or repeated testing on the reported findings.

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

The registry record describes an observational study intended to investigate detected hypothyroidism after iodinated contrast exposure among children from birth to 3 years of age. It defines the primary outcome as a participant count in the final cohort within up to one year after exposure, and states 828 person years. The primary outcome count itself is not reported in the registry record. As a result, the available record does not establish how many children had the outcome or how precisely its frequency was estimated.

The study’s stated question concerns occurrence after exposure in routine clinical practice. A finding that an outcome occurred after exposure would establish sequence in time, but would not by itself prove that exposure caused the outcome. This is an observational study, and a like-for-like control comparison is not reported. Other characteristics or clinical circumstances could be related to both exposure and outcome detection; the registry record does not report adjusted analyses that might address such differences.

The absence of a reported outcome count is not evidence that no events occurred. Nor does it show that events were common. It means that the registry record, as described, does not provide the result needed to distinguish between those possibilities. The completion status does not substitute for numerical outcome reporting.

General statistical explanation: statistical uncertainty and causal uncertainty are distinct. A narrow confidence interval can indicate precision under an analysis model, but it cannot resolve confounding or incomplete outcome ascertainment. Conversely, a descriptive count can be informative about a cohort without establishing a causal effect. Neither a point estimate nor a confidence interval is reported for the primary outcome in the registry record.

The results should therefore be understood as unavailable for quantitative interpretation in the registry record, not as positive or negative evidence about an effect. The record identifies a question, population, exposure context, and timeframe; it does not provide enough result or methods detail to determine the magnitude, precision, or causal significance of detected hypothyroidism after exposure.

13. Why This Trial Matters Statistically

This study is statistically interesting because its question concerns an outcome detected after exposure in routine clinical practice, while its design is observational. That combination makes the distinction between describing occurrence and estimating a causal effect especially important. A count within an exposed cohort can describe what was detected among those participants, but a causal comparison requires a suitable reference and a defensible approach to differences between groups. The registry record does not report a like-for-like control comparison.

The primary endpoint is framed as a participant count, and the timeframe includes 828 person years. Interpreting such information requires clarity about who entered the analysis, how outcomes were ascertained, how long participants were observed, and how incomplete observation was handled. The record identifies the final cohort as the primary population but does not give its size or explain its relationship to enrollment of 843. These gaps illustrate why endpoint definitions and analysis-population details matter alongside a headline count.

The entry also lists 13 outcome measures and 2 analyses. This makes transparent reporting of the analysis plan relevant: readers need to know which comparisons were prespecified, how multiple outcomes were handled, and whether analyses were adjusted. Those details are not reported in the registry record. General statistical explanation: a clearly documented plan helps readers distinguish confirmatory questions from exploratory analyses and evaluate how uncertainty should be interpreted.

Most importantly, the primary outcome count is not reported in the registry record. Statistical interpretation depends not only on the study question and design, but also on accessible outcome estimates and their precision. This record provides a useful example of the limits of design information when the numerical results and key analytical details are unavailable.

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 principal limitation for interpreting this specific registry entry is that the primary outcome count is not reported in the registry record. No primary estimate, confidence interval, or rate is given, so neither the observed frequency nor its precision can be assessed. Although 828 person years are stated, the record does not describe how that person-time was accumulated or used in analysis.

The relationship between enrollment of 843 and the final cohort is not explained. The record does not report a participant flow, exclusions, the final analysis population size, or reasons for any exclusions. It also does not report the completeness of follow-up, outcome ascertainment procedures, diagnostic criteria, or handling of missing data. These omissions limit assessment of selection and measurement processes.

The design is observational, and a like-for-like control comparison is not reported. The record does not describe an allocation method, adjustment strategy, or model specification. It therefore does not support a causal interpretation or an assessment of how potential differences between participants were handled. The secondary outcome results and analysis details are also not reported.

The registry record does not provide a statistical analysis plan, multiplicity strategy, sample-size justification, or information about interim analyses. These details cannot be inferred from the completed status, enrollment figure, or listed analyses. Together, the missing outcome results and methods information prevent a quantitative appraisal of the study’s findings and their robustness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Observational Study on Hypothyroidism in Young Children Following Iodine Contrast Exposure — NCT02766283.
• Registry record last updated 2018-03-26; status last verified 2018-03.
• Results first posted 2018-03-26.
• 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

NCT02766283 is an observational study titled “Observational Study on Hypothyroidism in Young Children Following Iodine Contrast Exposure,” sponsored by Bayer. The registry record lists a start date of 2016-06-30, a primary completion date of 2016-08-30, and a COMPLETED status. Enrollment is listed as 843.

The study concerns children age 0-3 years, inclusive, who underwent an iodine contrast-enhanced radiological examination. Its primary outcome is the number of participants with detected hypothyroidism after iodinated contrast exposure, in the final cohort, up to one year after exposure. The record states 828 person years. It lists 13 outcome measures and 2 analyses.

The primary outcome count, final cohort size, and detailed statistical methods are not reported in the registry record. A like-for-like control comparison is not reported, so the entry describes an observational question rather than a randomized treatment comparison.