Pediatric Reporting of Adult-Onset Genomic Results: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pediatric Reporting of Adult-Onset Genomic Results (NCT03832985), a non-randomized early/phase 1 study. The primary outcome is The Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale.

2. Clinical Question

The study also describes qualitative interviews with adolescents and parents and legal research concerning the loss of chance doctrine and its applicability to genomic research. Those objectives broaden the project beyond a single quantitative comparison. The registry record does not report findings from the interviews or legal research, so the clinical question should be read as the study’s stated focus rather than as evidence of a particular effect.

3. Trial Design

The registry record describes a longitudinal, mixed-methods cohort study with parallel groups. Its allocation is non-randomized and its masking is listed as none. The groups distinguish parents and adolescents according to whether a child or adolescent received an adult-onset result, a pediatric-onset result, or tested negative for a familial variant. Because participants were not randomly allocated to these categories, group comparisons are observational rather than randomized treatment contrasts.

The study’s stated enrollment is 162. The record lists the study status as completed, with a start date of 2020-11-25 and a primary completion date of 2024-10-31. These administrative details describe the registered study; they do not establish that every planned outcome was analyzed or reported.

The described quantitative component uses surveys covering distress, family functioning, quality of life, body image, perceived cancer or heart disease risk, satisfaction with genetic counseling, genomics knowledge, and adjustment to genetic information. Qualitative interviews with adolescents and parents are also described. Electronic health records are to be reviewed for children’s initiation of risk-reduction behaviors. The registry record does not report the timing or completion rates for each survey, interview, or record review.

The primary outcome entry is the HADS anxiety subscale, measured at baseline and summarized as a mean with standard deviation. The registry lists 35 outcome measures and zero analyses. It does not report a detailed statistical analysis plan, the number of participants contributing to each measure, or outcome estimates. Consequently, the study’s registered structure and aims can be described, but its outcome findings and the intended inferential comparisons cannot be reconstructed from 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.

Before assignment: Parents were assigned to a group once their child(ren) received genetic test results. Group 1 comprised parents whose child (or all tested children) had an adult-onset genetic result. Group 2 comprised parents whose child (or all tested children) had a pediatric-onset genetic result. Group 3 comprised parents who child (or all tested children) tested negative for the familial genetic variant. Groups 4-6 are adolescents who corresponded to the parent groups.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants who have completed the survey at each follow-up time.

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: Explain the gap between those who consented vs. who completed the survey.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as The Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale, measured over Baseline.

The primary endpoint is the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), reported as a mean in units on the scale with a standard deviation. The registry identifies the timeframe as baseline. HADS contains 14 items, split into seven anxiety questions and seven depression questions; the two subscales are scored separately. Each item is scored from 0-3, and the anxiety score ranges from 0 (lowest anxiety) to 21 (most severe anxiety).

The registry description gives score bands of 8-10 for mild, 11-14 for moderate, and 15-21 for severe symptoms. A total score of less than 7 indicates non-cases. These categories provide context for interpreting the scale, but the endpoint’s stated summary is a mean and standard deviation, not the proportion of participants in each category. A group mean alone would not show how individual participants’ scores are distributed or how many cross a category threshold.

HADS is used to measure symptoms of anxiety and depression through a structured questionnaire. In this study, the anxiety subscale gives a quantitative psychosocial measure relevant to the study’s focus on adjustment to genomic information. The registry record describes the participants as those who completed the survey at each follow-up, while the primary outcome timeframe is specified as baseline. It does not report a baseline mean, standard deviation, sample count for the endpoint, or follow-up change estimate. The endpoint therefore defines what was intended to be measured, but the registry record does not establish the observed anxiety level or its course over time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the non-randomized design imply?

In a randomized trial, chance allocation is used to make comparison groups more alike, on average, with respect to measured and unmeasured characteristics. This study is registered as non-randomized. Its groups are formed according to genomic result categories rather than random assignment. Consequently, comparisons between groups are observational. Differences could be associated with the result category, but they could also be associated with other differences between the families or adolescents in those categories. Statistical adjustment can address measured differences when appropriate data and a prespecified method are available; it cannot guarantee removal of unmeasured confounding.

The parallel model means that the record describes groups observed alongside one another rather than a crossover design in which each participant receives multiple conditions in sequence. The record does not describe participants switching between result categories. The groups should therefore be interpreted as distinct observational categories, not as stages of a randomized intervention.

How should a mean and standard deviation be read?

A mean summarizes the average score in a group. The standard deviation describes the spread of individual scores around that average. They answer different questions: the mean locates the group’s average score, while the standard deviation conveys variability among participants. Neither summary alone describes the full shape of the score distribution. For a bounded scale such as HADS, distributions can also be constrained by the scale’s minimum and maximum values.

A comparison of means would need an estimate of the difference, an uncertainty measure such as a confidence interval, and an analysis that matches the study design and data structure. A confidence interval expresses the range of estimates reasonably compatible with the data and analysis assumptions. A narrow interval indicates greater precision than a wide interval, but precision does not remove bias from non-random group formation. The registry record does not report group means or a comparison interval for the primary endpoint.

What do HADS score ranges contribute?

The registry describes the HADS anxiety subscale as ranging from 0 (lowest anxiety) to 21 (most severe anxiety), with score bands of 8-10 for mild, 11-14 for moderate, and 15-21 for severe symptoms; a total score of less than 7 indicates non-cases. These cut points help give a score context, but a group average does not reveal how many people fall into a given band. To assess categories, participant counts or proportions within each band would be needed, and none are reported in the primary endpoint entry.

Why does over-dispersion matter in general?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. The appropriate response depends on the outcome type and model. The primary endpoint is continuous and summarized by a mean and standard deviation; the registry record does not identify a model or report a diagnostic assessment of dispersion. Over-dispersion should therefore be understood as a general statistical concern, not as a reported feature of this study.

What are the sample-size illustrations for?

The registry’s planning assumptions describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. Such calculations are planning illustrations rather than evidence of the study’s original design or its statistical power after completion. They do not establish that the registered study was designed around those assumptions. The registry record does not report the trial’s own sample-size justification, and any calculated sample size should not be described as observed power.

For a continuous outcome, a planning calculation depends on assumptions about the effect to detect, variability, allocation, and analysis method. If the effect used for planning is estimated from the same study’s results, that estimate may itself be uncertain. A planning scenario is not a substitute for reporting the observed estimate and its uncertainty. The record does not provide numerical endpoint results with which to assess such uncertainty.

What can be said about statistical significance?

Statistical significance is an assessment made under a specified statistical model and testing procedure. A p-value, if reported, would describe how compatible the data are with a null hypothesis under those assumptions; it would not measure the probability that a hypothesis is true or establish clinical importance. An interval estimate would help describe plausible effect sizes and their precision. Neither is reported for the primary endpoint. With no analyses listed, the registry record does not support a claim of statistical significance or non-significance.

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("Group 1 (Parents of Child(Ren) With Adult-onset Re", "Group 2 (Parents of Child(Ren) With Pediatric-onse", "Group 3 (Parents of Child(Ren) Who Tested Negative")
n   <- c(21, 36, 35)
m   <- c(10.32, 8.26, 8.96)
sp  <- c(3.68, 3.33, 3.1)
sd  <- sp      # posted standard deviations
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  Group 1 (Parents of Child(Ren) With Adult-onset Re  21  10.320  3.680  8.645  11.995
CARM  Group 2 (Parents of Child(Ren) With Pediatric-onse  36  8.260  3.330  7.133  9.387
CARM  Group 3 (Parents of Child(Ren) Who Tested Negative  35  8.960  3.100  7.895  10.025

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 35 outcome measures and zero analyses. It also lists the Decision Regret Scale twice among secondary outcomes. The record does not explain whether the repeated listing represents separate assessments, different timepoints, or a duplicate entry, so it should not be interpreted as evidence of two distinct analyses.

When many outcomes or comparisons are examined, the chance of finding at least one apparently unusual result can increase. In general, statistical plans may address multiplicity by identifying a limited set of primary comparisons, adjusting testing thresholds, or emphasizing estimation and uncertainty rather than isolated p-values. The registry record does not report a multiplicity strategy, a hierarchy of outcomes beyond identifying the HADS anxiety subscale as primary, or which analyses were ultimately conducted. It is therefore not possible to evaluate the effect of multiple testing on any findings.

Missing-data methods are also not reported. The primary outcome description refers to participants who completed the survey at each follow-up, but the registry does not give completion counts, reasons for non-completion, or methods for handling missing scores. If survey completion is related to participants’ experiences or characteristics, analyses limited to completed surveys could differ from results for all eligible participants. This is a general concern; the registry does not establish that such a pattern occurred.

The analysis populations are not defined beyond the survey-completion description. The record does not specify whether analyses included all enrolled participants, only those with a particular result category, or a subset with complete outcome data. It also does not report how repeated measurements were handled. These omissions prevent a detailed assessment of the analysis denominator, missingness, and the relationship between the registered outcome measures and the analyses performed.

12. 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.

The registry lists zero serious adverse events, zero other adverse events, and zero deaths in each of the six groups. For the serious and other adverse event entries, the listed numbers at risk are 21 for parents of children with adult-onset results, 36 for parents of children with pediatric-onset results, 35 for parents of children who tested negative for the familial variant, 15 for adolescents with adult-onset results, 20 for adolescents with pediatric-onset results, and 35 for adolescents who tested negative for the familial variant. The numbers at risk are the same for the serious and other adverse event entries within each group.

These figures describe what the registry reports for adverse events; they do not prove that no adverse experiences occurred outside the recorded definitions, collection period, or reporting process. The record does not provide event-monitoring procedures, the duration of safety observation, or explanations of how adverse events were ascertained. No serious adverse event terms are listed. The zero counts should therefore be read as registry-reported counts, not as a guarantee of absence of risk or as a comparison demonstrating that one group was safer than another.

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

The registry record describes a completed, non-randomized cohort study about psychosocial outcomes, health behaviors, and genomic results among adolescents and parents. It identifies the HADS anxiety subscale at baseline as the primary endpoint and provides the scale’s scoring description. It also describes surveys, interviews, and electronic health record review, alongside legal research on the loss of chance doctrine.

What the record does not provide is equally important for interpretation. It gives no numerical primary outcome results, no group-specific means or standard deviations, no estimates of change, no confidence intervals, and no reported analysis results. The registry lists zero analyses. Readers therefore cannot determine from this record whether anxiety scores differed among groups, changed over time, or were estimated precisely. The study’s completed status is not a substitute for outcome reporting.

The observational group structure also limits causal interpretation. Adult-onset, pediatric-onset, and negative familial-variant categories were not randomly assigned. Any differences in measured outcomes could be associated with factors other than the result category. The registry does not report an adjustment strategy that would permit a more detailed appraisal of those comparisons.

The adverse event entries show zero reported serious adverse events, other adverse events, and deaths in each listed group. Those registry entries describe recorded counts; they do not establish that an event was impossible or that the groups had equivalent safety profiles. Details about safety ascertainment and observation are not reported.

Overall, this record is informative about the study’s aims, design, endpoint definition, and broad measurement approach. It does not provide the numerical findings needed to judge the magnitude, direction, or precision of psychosocial or behavioral outcomes. No conclusion about benefit, harm, or lack of effect should be drawn from the absence of posted results.

14. Why This Trial Matters Statistically

This study addresses a statistical problem that is not captured by a simple comparison of two treatments: how to describe outcomes in families facing different types of genomic results when result categories are not randomly assigned. The registered groups include adolescents and parents associated with adult-onset results, pediatric-onset results, and negative familial-variant results. Such a design makes careful description of group composition and uncertainty important, because observed differences cannot automatically be attributed to the result category.

The study also has multiple kinds of evidence. Surveys provide quantitative scores, interviews can capture participants’ accounts, and electronic health record review can document health behaviors. These sources answer related but different questions. A scale score does not replace interview findings, and a reported behavior does not by itself describe psychosocial adjustment. Combining methods can broaden a study’s scope, but clear reporting is needed to show how each source was analyzed and how conclusions were drawn.

The HADS anxiety subscale offers a defined quantitative endpoint, with a specified score range and interpretation bands. Reporting its group summaries, uncertainty, timing, and analysis population would help readers distinguish average score levels from individual symptom categories and distinguish baseline description from change over time. The registry record identifies the endpoint but does not report those results.

The record’s listing of 35 outcome measures also illustrates why prespecified analysis choices and transparent multiplicity handling matter. Without reported analyses, outcome hierarchy, and missing-data methods, readers cannot assess how results across many measures were selected or interpreted. These are general statistical reporting concerns, not evidence that the study’s analyses were conducted improperly.

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.

Several limitations specific to this record constrain interpretation. First, the primary endpoint is listed as a baseline HADS anxiety score, but the registry does not report the score’s mean, standard deviation, or analysis sample. Although the study is described as longitudinal, no numeric follow-up values or change estimates are given. The record therefore cannot support a description of anxiety trajectories.

Second, the six groups are non-randomized categories based on genomic result status. The record does not report group characteristics, matching, covariate adjustment, or sensitivity analyses. Differences between groups could be influenced by characteristics associated with result status, and the available information does not permit an assessment of the extent of this concern.

Third, the study includes 35 outcome measures, while the registry lists zero analyses. The analysis plan, multiplicity approach, missing-data procedures, and analysis populations are not reported. The population description refers to participants who completed surveys at each follow-up, but survey completion counts and reasons for missing observations are absent. These omissions limit evaluation of selection and reporting processes.

Fourth, the registry describes interviews, health-record review, and legal research but does not report their findings or analytic procedures. The scope of these components cannot be appraised from the study aims alone. Safety monitoring details and the observation period for adverse events are also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pediatric Reporting of Adult-Onset Genomic Results — NCT03832985.
• Registry record last updated 2026-04-09; status last verified 2026-03.
• Results first posted 2026-04-09.
• 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

NCT03832985, titled “Pediatric Reporting of Adult-Onset Genomic Results,” is registered as a completed, non-randomized, unmasked, parallel cohort study with enrollment of 162. The record describes six parent and adolescent groups categorized by adult-onset results, pediatric-onset results, or negative familial-variant testing. The listed conditions are Hereditary Breast and Ovarian Cancer Syndrome, Lynch Syndrome, and Familial Hypercholesterolemia.

The primary outcome is baseline HADS anxiety, summarized as a mean and standard deviation. The study description also includes surveys, interviews, electronic health record review, and legal research. The registry lists 35 outcome measures and zero analyses. Numerical primary outcome findings and the statistical analysis plan are not reported in the registry record.