Validation of Indiana's Early Evaluation Hub System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Validation of Indiana's Early Evaluation Hub System (NCT06586788), a na na study. The primary outcome is Agreement Between Composite Eye-tracking Biomarker and Expert Autism-specialist.

2. Clinical Question

3. Trial Design

This is a completed, single-group diagnostic evaluation registered as NCT06586788, titled “Validation of Indiana's Early Evaluation Hub System.” Indiana University is the sponsor. The registry lists the study as starting on 2019-06-07 and reaching primary completion on 2022-09-23. The phase is recorded as not applicable. Enrollment is 154.

The study description says participating Early Evaluation Hubs referred a prospective, consecutive sample of children who received an evaluation at an Early Evaluation Hub. The study team then traveled to the hub to conduct a follow-up autism diagnostic assessment serving as the reference standard, as well as an eye-tracking biomarker battery serving as the index test. The primary outcome timeframe is Day 1. More detailed timing and operational procedures are not reported in the registry record.

The design is listed as single group, with no masking and no randomized allocation. The registry lists diagnostic tests named Eyelink Portable Duo and Integrated PCP Diagnosis and Eye-tracking Biomarker. The record does not describe a randomized assignment, a separate control group, or a between-group treatment comparison. The listed children undergoing developmental evaluation form the study group; the reference diagnosis is the comparator for evaluating test classification, rather than a parallel randomized arm.

The registry record lists two outcome measures and zero analyses. The primary outcome description identifies sensitivity and specificity as the measures of interest, but the record does not include numerical accuracy estimates, a classification count, or an analysis output. The second outcome measure's details are not reported in the registry record. As a result, the design and intended diagnostic question can be described, but the size and precision of the observed diagnostic performance cannot be assessed from this 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number of participants analyzed does not differ from the number of participants assigned to this arm.

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: Included participants

6. Primary Endpoint

The registry lists the primary outcome as Agreement Between Composite Eye-tracking Biomarker and Expert Autism-specialist, measured over Day 1.

The primary endpoint concerns agreement between a composite eye-tracking biomarker and an expert autism-specialist diagnosis. The registry describes the index test as a consolidated measure based on significant eye-tracking indices and the reference standard as an expert clinical autism diagnosis. The outcome description specifies sensitivity and specificity and lists the measurement unit as participants.

In general, sensitivity describes how often an index test identifies participants who meet the reference standard definition. Specificity describes how often it classifies as negative participants who do not meet that definition. These measures address different types of classification error, so reporting both helps characterize performance across reference-standard groups. They do not, by themselves, describe every aspect of a diagnostic test or its use in a particular setting.

Using an expert clinical diagnosis as the reference standard makes it possible to compare the biomarker's classifications with a clinical assessment. The registry's study objective links clinical evaluation with biobehavioral assessment in a community-referral setting. However, the registry record does not report the diagnostic threshold for the composite, the underlying classification counts, or numerical sensitivity and specificity. It also does not report confidence intervals. The endpoint's purpose is therefore clear, but the observed accuracy and its statistical precision cannot be determined from the reported record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Diagnostic accuracy is evaluated by comparing the index test with a reference standard. In this study, the index test is described as a composite eye-tracking biomarker, and the reference standard is an expert clinical autism diagnosis. The primary outcome description identifies sensitivity and specificity as the accuracy measures of interest. General statistical explanations below clarify what these measures mean; they do not substitute for results, which are not reported in the registry record.

What do sensitivity and specificity describe?

In general, sensitivity is the proportion of participants with a positive reference-standard diagnosis whom the index test also classifies as positive. Specificity is the proportion of participants without a positive reference-standard diagnosis whom the index test classifies as negative. Each measure uses a different reference-standard group as its denominator. Together they describe two distinct aspects of classification, but neither alone conveys all information relevant to test performance.

To calculate these measures, an analysis needs participant classifications under both the index test and the reference standard. Those classifications can be arranged into a cross-classification of positive and negative results. The registry record does not report that cross-classification, the total number with each reference diagnosis, or the numerical sensitivity and specificity estimates. It also does not report the operational threshold used to turn the composite biomarker into a positive or negative classification. Without these details, readers cannot independently inspect the pattern of agreement or identify the balance of false-positive and false-negative classifications.

Why does the reference standard matter?

Accuracy estimates describe agreement with the chosen reference standard, rather than agreement with an unknowable absolute truth. The record calls the expert autism-specialist assessment a gold-standard reference diagnosis and describes it as a follow-up assessment conducted by the study team at the Early Evaluation Hub. The index test and reference standard serve different roles in the comparison. The record does not report further information about diagnostic procedures, assessor training, diagnostic criteria, or whether assessors were unaware of index-test results. Those details can affect how readers assess the conduct and interpretation of a diagnostic-accuracy analysis.

The primary outcome timeframe is Day 1. The record also describes a follow-up reference assessment and an eye-tracking battery, but does not report more detailed scheduling or the order in which procedures were administered. No claim about the interval between assessments or the independence of their interpretation can be made from the registry record.

How should precision be assessed?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified analysis. For sensitivity and specificity, interval estimates help readers assess how much the observed accuracy could vary because of sampling uncertainty. They should be read alongside the point estimates and the underlying participant counts. The registry record does not report confidence intervals, standard errors, or numerical point estimates for this endpoint. Consequently, the precision of the intended accuracy estimates cannot be evaluated.

A larger analysis sample can often yield more precise estimates, but precision also depends on how participants are distributed across reference-standard categories and on the number of index-test classifications within those categories. The enrollment figure alone does not reveal those distributions. It would be inappropriate to infer precision from enrollment without the outcome counts and analysis results.

What do the design labels imply?

The registry identifies a single-group design, no masking, and no randomized allocation. For a diagnostic-accuracy question, this means that the comparison is between classifications produced by the index test and the reference standard among the study group. It is not a randomized comparison of two interventions. The study objective describes integrating clinical evaluation and biobehavioral markers, but the record does not report a comparison that estimates the causal effect of adopting one diagnostic pathway rather than another.

Masking is relevant in general because knowledge of one test's result can influence interpretation of another assessment. The record lists masking as none, but does not give more detail about assessor access to results or the sequence of assessments. The effect, if any, of this design feature on assessment is therefore not quantifiable from the registry record.

How should planning illustrations be understood?

General planning calculations can illustrate the sample size that might be required to detect a specified effect under chosen assumptions. The planning description associated with this record uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. These are planning assumptions, not evidence that the study was designed or conducted as a two-arm randomized trial. The registered study is single group, and the available information does not report a sample-size justification from the investigators or establish that these planning assumptions governed the protocol.

Any sample-size output based on an observed effect is a planning illustration. It is not observed power and does not demonstrate that an analysis found a statistically significant result. The registry record does not report the numerical primary result needed to interpret an observed-effect-based planning calculation in this specific diagnostic evaluation. Such calculations cannot replace the accuracy estimates, classification counts, or uncertainty intervals needed to answer the study question.

What analysis details are unavailable?

The registry lists zero analyses. It does not report the statistical procedure used to calculate sensitivity or specificity, the handling of missing or indeterminate test results, any confidence-interval method, or any prespecified analysis plan. The description of a composite based on significant eye-tracking indices does not specify how those indices were selected or combined. These omissions limit reproducibility and make it difficult to evaluate whether the reported endpoint, if available elsewhere, would reflect a prespecified or exploratory analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures, but it does not report details for the second outcome in the information available for this evaluation. It also lists zero analyses. The registry record does not report a multiplicity strategy, such as how interpretation would account for testing more than one outcome or multiple candidate eye-tracking indices. Because the composite is described as based on significant eye-tracking indices, the index-selection and combination procedures would be important for understanding the analysis, but they are not reported in the registry record.

Missing-data handling is not reported in the registry record. The record does not say whether any participants lacked an eye-tracking result, a reference-standard diagnosis, or usable paired measurements; nor does it describe exclusions, imputation, or treatment of indeterminate results. The enrollment figure cannot answer those questions.

The primary-outcome population statement says the number analyzed does not differ from the number assigned to the arm. The actual number assigned and the actual number analyzed are not stated in that outcome description. The registry does not provide a participant flow account or explain whether all enrolled children contributed paired index-test and reference-standard classifications. No interim analyses, subgroup analyses, or analysis-population definitions are reported in the registry record. These gaps restrict assessment of selection into the analysis and of how completely the intended population is represented in the endpoint.

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.

The safety figures describe the group titled Children Undergoing Developmental Evaluation. The registry records 154 participants at risk for serious adverse events and 0 participants affected. It also records 154 at risk for other adverse events and 0 affected, with 0 deaths. No serious adverse event terms are listed.

These are recorded event counts, not a complete account of every possible burden or consequence of study participation. The registry record does not describe adverse-event definitions, the observation period for these counts, collection procedures, or whether events were actively solicited. A zero count means that no events of the specified category were recorded in these entries; it does not by itself establish that no event occurred or that there was no risk. The record also does not provide further detail about event severity beyond the serious and other categories.

Because this is a diagnostic evaluation rather than a randomized treatment comparison, these safety figures should not be interpreted as a relative safety estimate between interventions. There is no parallel control group in the registered design, and the reported counts do not permit a comparative analysis. They are best read narrowly as the adverse-event counts recorded for the study group.

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

The registry record establishes the study's intended diagnostic question: whether a composite eye-tracking biomarker agrees with an expert autism-specialist reference diagnosis among children receiving developmental evaluation through Early Evaluation Hubs. It also identifies the setting as a high-risk community-referral sample in primary care and describes prospective, consecutive referral. Those details define the context in which the question was posed.

The record does not report numerical sensitivity or specificity, the participant classification counts used to derive them, or uncertainty intervals. Therefore, it does not allow readers to judge the level of accuracy, the kinds of classification errors, or the precision of any estimate. The completed status and enrollment count do not fill this evidence gap. They describe study status and participation, not the endpoint result.

The record also does not establish how the composite eye-tracking measure would perform in other settings or populations. The sample is described as a community-referral group of children undergoing developmental evaluation; the record does not provide characteristics that would support a more detailed assessment of generalizability. Nor does the single-group diagnostic design establish whether an integrated pathway changes clinical decisions or outcomes compared with another pathway.

In general, a diagnostic-accuracy estimate should be interpreted in light of the reference standard, test threshold, participant spectrum, missing data, and precision. Several of these details are not reported in the registry record. Accordingly, the available information supports a description of the study design and endpoint, but not a conclusion about the magnitude, reliability, or practical consequences of diagnostic performance. No treatment-effect conclusion follows from this record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it frames an eye-tracking biomarker as an index test to be assessed against an expert clinical reference diagnosis. That is a different inferential task from estimating whether a treatment changes an outcome. The central statistical quantities named in the registry are sensitivity and specificity, which depend on paired classifications for each participant and on the distribution of reference-standard diagnoses.

The study also illustrates why a study's objective and its reported results must be distinguished. The registry describes a prospective, consecutive referral sample and identifies the intended comparison, but does not report numerical accuracy estimates or analysis details. Without those results, neither the size of the observed agreement nor the uncertainty around it can be evaluated. Enrollment alone is not a substitute for the classification counts needed to interpret accuracy.

For readers assessing diagnostic studies, this record highlights the value of reporting the test threshold, reference-standard procedures, paired classification counts, missing-result handling, and interval estimates. These details support transparent appraisal and reproducibility. The registry record does not report these details in enough depth to assess them, so the statistical contribution that can be evaluated is limited to the stated design and question.

The design also matters to interpretation. A single-group diagnostic evaluation can assess classification agreement within its study sample, but it does not provide a randomized causal comparison of diagnostic strategies. Keeping that distinction clear prevents accuracy results, even if they are reported elsewhere, from being mistaken for evidence about comparative effects on care or outcomes.

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 most consequential limitation for interpreting the primary endpoint is the absence of numerical diagnostic-accuracy results in the registry record. The record names sensitivity and specificity but does not report their estimates, classification counts, or confidence intervals. As a result, the endpoint cannot be assessed for magnitude or precision from the registry information.

Further methodological details are also not reported in the registry record. These include the threshold for classifying the composite eye-tracking measure, the component indices and their combination procedure, the criteria and procedures for the expert diagnosis, and whether interpretation of one assessment was masked to the other. The registry says masking was none, but does not explain the practical implications for assessor access to results. It also does not describe handling of missing, unusable, or indeterminate assessments.

The study population is described as a prospective, consecutive community-referral sample of children receiving Early Evaluation Hub evaluations, with a high-risk primary-care context. However, demographic and clinical characteristics, referral patterns, and analysis-sample detail are not reported in the registry record. This restricts assessment of how representative the analyzed participants were of other groups or settings. The record also does not report a participant flow account that would clarify enrollment, test completion, and inclusion in the endpoint analysis.

The single-group design addresses agreement with a reference diagnosis, not comparative effects of alternative diagnostic pathways. The registry also lists two outcome measures but zero analyses, and does not report the analysis plan, multiplicity handling, or sample-size justification. These limitations constrain both reproducibility and the strength of any interpretation that might be drawn from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Validation of Indiana's Early Evaluation Hub System — NCT06586788.
• Registry record last updated 2024-10-31; status last verified 2024-10.
• Results first posted 2024-10-31.
• 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

NCT06586788 is a completed, single-group diagnostic evaluation sponsored by Indiana University. The registry lists enrollment of 154, a start date of 2019-06-07, and primary completion on 2022-09-23. The study concerns children undergoing developmental evaluation through participating Early Evaluation Hubs.

The primary outcome asks how a composite eye-tracking biomarker performs against an expert autism-specialist reference diagnosis, with sensitivity and specificity identified as the measures of interest. The registry describes prospective, consecutive referral and lists no masking or randomized allocation. It records 154 participants at risk for serious adverse events, 0 affected, 154 at risk for other adverse events, 0 affected, and 0 deaths.

Numerical diagnostic-accuracy results, confidence intervals, detailed analysis methods, and further endpoint details are not reported in the registry record. The available information therefore characterizes the study question and design but does not establish the observed accuracy or its precision.