Multimodal Analysis and Electroretinogram in VKH From Acute Onset - Part I: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multimodal Analysis and Electroretinogram in VKH From Acute Onset - Part I (NCT03811366), a na na study. The primary outcome is Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months.

2. Clinical Question

3. Trial Design

This was a prospective, single-group study of patients with acute-onset VKHD. The registry lists the study as completed, with enrollment of 12 participants. Allocation is recorded as not applicable, and masking is listed as none. These features mean the study does not provide a randomized, masked comparison between treatment groups.

Participants were followed with clinical assessments, posterior-segment imaging, and full-field electroretinography for a minimum of 24 months. The primary outcome compares ERG scotopic parameters at 12 and 24 months. Clinical data were analyzed in groups defined by whether ERG findings were stable or worsening. The record notes that these are eye-based classifications and that one participant contributed one eye to each group; therefore, the group totals need not correspond to separate participants.

The treatment summary describes a three-day methylprednisolone pulse, followed by oral prednisone at 1mg/day with a slow taper. The median duration of prednisone treatment was 13 months. Non-steroidal immunosuppressive therapy was introduced for refractory disease or prednisone intolerance. Although the intervention is labeled corticosteroid monotherapy, the summary describes these additional treatments in specified cases.

The registry lists secondary outcomes involving anterior-chamber cells, dark dots on indocyanine green angiography, subfoveal choroidal thickness, perivascular leakage, choroidal neovascularization, cataract, and ocular hypertension. The registry record does not report a separate comparator, a randomized allocation procedure, or masking. It also does not report the statistical analysis plan or a sample-size justification.

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

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: Study of clinical, subclinical and electroretinographic outcomes of patients with acute Vogt-Koyanagi-Harada disease treated with corticosteroid monotherapy

6. Primary Endpoint

The registry lists the primary outcome as Variation (Worsening or Improvement) Between 24 and 12 Months of ERG Scotopic Parameters Comparing 24 and 12-months, measured over 12 and 24-months.

The primary endpoint measures percentage change in full-field ERG scotopic parameters between month 12 and month 24. The parameters listed are the amplitudes of the scotopic a and b waves, the amplitudes of the maximum scotopic a and b waves, and oscillatory potential. The registry states that the change is reported as the month-24 value divided by the month-12 value, multiplied by 100.

The endpoint is used to describe how retinal electrical-response measurements changed over follow-up. The registry also defines ERG worsening as a reduction of at least 30% in any listed scotopic parameter at month 12 and month 24. This definition establishes a classification rule; it does not by itself show how many eyes met the rule or the size of the observed change.

The numerical primary endpoint result is not reported in the registry record. Nor does the record provide an uncertainty estimate, such as a confidence interval, for the change. As a result, the endpoint description establishes what was intended to be measured, but the posted record does not allow readers to assess the magnitude or precision of the observed change from the primary outcome.

ERG is one component of the study’s multimodal follow-up, alongside clinical assessments and posterior-segment imaging. The record describes clinical data as analyzed according to ERG-based groups, but does not report the detailed analysis methods or the corresponding numerical results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s central measurement is a change in ERG scotopic parameters over time. The registry specifies measurements at 12 and 24 months and describes the reported change as the month-24 value divided by the month-12 value, multiplied by 100. In general, expressing a later measurement relative to an earlier one gives a scale-free description of change, but interpretation depends on the stated formula and the values being compared. The numerical result for this endpoint is not reported in the registry record.

What does the ERG worsening definition mean?

The registry defines worsening as a reduction of at least 30% in any of the specified scotopic ERG parameters at month 12 and month 24. This is a threshold-based classification rule, distinct from the continuous percentage-change measure. A threshold can make a result easier to classify, but it also compresses different magnitudes of change into categories. The registry record does not report how many eyes met the worsening definition or provide the individual parameter results.

The listed measures include amplitudes for scotopic a and b waves, maximum scotopic a and b waves, and oscillatory potential. They are related measures from the same examination rather than independent questions in every respect. In general, correlated endpoints may contain overlapping information. The record does not state how the analysis handled multiple ERG parameters or whether one parameter was designated as more important than the others.

Why does the single-group design matter?

A single-group longitudinal design follows participants over time without a concurrent control group. It can describe measurements and events observed during follow-up. It does not, by itself, distinguish changes associated with treatment from changes that might have occurred because of the disease course, additional treatment, measurement variability, or other factors. The study is prospective, but prospective follow-up alone does not create a causal treatment comparison.

The treatment summary describes corticosteroid therapy and notes that non-steroidal immunosuppressive therapy was introduced for refractory disease or prednisone intolerance. These treatment changes make the clinical context relevant when interpreting repeated outcomes. The registry does not report an analysis that separates results according to these treatment experiences, nor does it describe an adjusted treatment-effect estimate.

How should eye-level observations be understood?

The record specifically notes that one participant had one eye classified as ERG stable and the other as ERG worsening. Therefore, eye-based classifications can include two observations from the same participant, and the groups are not necessarily independent participant groups. In general, observations from two eyes of one person may be correlated because they share patient-level characteristics. Statistical methods that treat such observations as independent can understate uncertainty; methods that account for within-person correlation may be appropriate depending on the analysis. The registry record does not report whether or how this dependence was handled.

The record also does not state the number of eyes with usable measurements at each visit, how missing or unreadable ERG results were handled, or whether all enrolled participants contributed to every analysis. Those omissions limit assessment of the analysis population and of possible bias from incomplete follow-up.

What can be learned from statistical significance and precision?

In general, a significance test evaluates compatibility between observed data and a specified null hypothesis under the assumptions of the test. A p-value is not the probability that the null hypothesis is true, and statistical significance alone does not describe the size or clinical importance of an effect. A confidence interval complements an estimate by showing uncertainty under the method used. The primary endpoint’s p-value and confidence interval are not reported in the registry record, so neither significance nor precision can be assessed from the posted information.

Repeated outcomes and multiple analyses can raise multiplicity concerns. When many endpoints or comparisons are examined, the chance of at least one apparently unusual result can increase if no adjustment or prespecified hierarchy is used. This is a general statistical consideration, not a claim about the study’s analysis. The registry lists 10 outcome measures and 7 analyses, but does not report a multiplicity strategy, a prespecified hierarchy, or which analyses were confirmatory.

What do sample-size illustrations represent?

Any sample-size calculations based on an observed effect are planning illustrations, not observed power and not evidence that a study had adequate power after completion. The registry’s planning assumptions describe a two-arm, equal-allocation calculation, while this study is listed as a single-group study. Such illustrations should therefore not be treated as the trial’s design justification or as a direct description of the study’s actual analysis. The registry record does not report the trial’s own sample-size justification, planned power, or statistical analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 7 analyses. It does not report whether these outcomes were arranged in a prespecified hierarchy, whether a primary analysis was distinguished from exploratory analyses beyond the stated primary endpoint, or whether any multiplicity adjustment was used. When many outcomes or analyses are considered, general statistical practice treats the possibility of chance findings as an interpretive concern. The presence or absence of an adjustment in this study is not reported in the registry record.

The record does not report how missing outcome data were handled. It does not specify whether participants with incomplete follow-up were excluded, whether any values were imputed, or whether analyses used all available measurements. The number of participants enrolled is reported, but the analysis population for each outcome is not reported in the registry record. Thus, enrollment should not be taken as a statement that every participant contributed to every endpoint.

Eye-based group classification introduces another analysis-population issue. The record notes that one participant had one eye in the ERG stable group and the other eye in the ERG worsening group. It does not report the numbers of eyes analyzed, whether both eyes were included systematically, or how within-participant correlation was addressed. Those details matter when interpreting precision and when deciding whether a count refers to participants or eyes.

The registry record does not report a statistical analysis plan, a detailed missing-data strategy, or the handling of multiplicity. These omissions do not establish that no such procedures were used; they mean the procedures cannot be evaluated from the registry record.

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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 12 participants at risk for serious adverse events and reports 0 affected by serious adverse events. It lists 12 participants at risk for other adverse events and reports 6 affected. No serious adverse-event terms are listed among the top terms.

These are registry counts, not a complete description of the nature, timing, severity, or attribution of every event. The record does not report the specific other adverse events in the registry record, and it does not state whether an event was considered related to treatment. A count of 0 serious adverse events in this record should not be interpreted as proof that serious events cannot occur. It describes what the registry reports for this study, with the information recorded there.

The study is single-group, so these figures do not provide a randomized comparison of safety between treatments. The summary also describes non-steroidal immunosuppressive therapy in cases of refractory disease or prednisone intolerance, but the adverse-event counts are not broken down by treatment exposure in the registry record.

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

The study addresses how full-field ERG scotopic parameters changed between 12 and 24 months in a prospectively followed group with acute-onset VKHD. It also describes clinical and imaging follow-up and uses ERG-based classifications to group clinical data. These features provide context for understanding the research question and the types of measurements collected.

The primary endpoint’s numerical result is not reported in the registry record. Therefore, the posted information does not establish the direction or magnitude of the primary change, how precisely it was estimated, or how many eyes met the worsening definition. It also does not provide numerical results for the listed secondary outcomes in the registry record.

Because there is no separate control group, the study cannot determine from this design alone whether observed changes were caused by corticosteroid treatment. The treatment summary describes an initial corticosteroid regimen and additional immunosuppressive therapy in specified circumstances, but no controlled treatment contrast is reported. The study’s observations should be understood as follow-up findings in the treated study group, not as a randomized comparison of treatment strategies.

In general, a study can contribute descriptive information even when its design cannot support a causal comparison. The strength of any such description depends on the completeness of outcome reporting, the number of evaluable observations, and the methods used to address repeated measurements and missing data. Those analysis details are not reported in the registry record. The available record therefore supports a careful account of what was measured and how the study was organized, but not a conclusion about treatment effectiveness or the certainty of a treatment effect.

13. Why This Trial Matters Statistically

Statistically, this study combines repeated ERG measurements, clinical follow-up, and imaging in a prospective setting. The primary question is explicitly longitudinal: how scotopic ERG parameters at 24 months compare with those at 12 months. That makes the definition of change, the timing of measurements, and the handling of incomplete follow-up central to interpretation.

The record also highlights an important unit-of-analysis issue. ERG classifications are assigned by eye, and one participant had one eye in each classification group. This illustrates why participant counts and eye counts should not be treated as interchangeable. In general, two eyes from the same person may share information, and appropriate statistical interpretation depends on whether that dependence is considered.

The study also shows why endpoint definitions and endpoint results need to be read separately. The registry defines a threshold for ERG worsening and names the parameters included, but the numerical primary result is not reported. A clear definition helps readers understand the intended measurement; it cannot substitute for an estimate, its uncertainty, or the number of observations contributing to it.

Finally, the single-group design frames what can be learned. Prospective observation can describe outcomes over time, but without a concurrent comparator it does not isolate treatment effects. The registry record’s limited reporting of analysis methods, missing data, and multiplicity further constrains evaluation of precision and robustness. These are broadly useful considerations when reading longitudinal clinical research, especially when outcomes are measured at the eye level and several related endpoints are followed.

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 primary limitation for interpreting the posted results is that the numerical primary endpoint result is not reported in the registry record. The record also does not report a confidence interval, p-value, or the number of eyes contributing to the primary analysis. This prevents assessment of the observed change, its precision, and the number meeting the ERG worsening definition.

The study is single-group and has no separate control arm. Accordingly, changes during follow-up cannot be separated from the natural course of disease or other influences using a randomized between-group comparison. The treatment description also includes non-steroidal immunosuppressive therapy for refractory disease or prednisone intolerance, while the intervention is labeled corticosteroid monotherapy. The record does not report treatment-specific outcome analyses.

Eye-based classification is another specific interpretive concern. The registry notes that one participant contributed one eye to each ERG group, but does not report the total eye counts, the approach to within-participant correlation, or whether the analysis treated eyes as independent observations. Missing-data handling and the analysis population for each outcome are also not reported.

The registry lists multiple outcomes and analyses but does not report a multiplicity strategy or the detailed statistical analysis plan. The study’s sample-size justification is not reported in the registry record. These reporting gaps do not prove that the procedures were absent; they limit what can be evaluated from the registry information. The listed safety counts likewise lack event descriptions and treatment-specific attribution in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Multimodal Analysis and Electroretinogram in VKH From Acute Onset - Part I — NCT03811366.
• Registry record last updated 2025-04-17; status last verified 2025-04.
• Results first posted 2024-11-22.
• 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

NCT03811366 is a completed prospective, single-group study of acute-onset Vogt-Koyanagi-Harada disease, sponsored by the University of Sao Paulo. The registry reports enrollment of 12 participants, no masking, and a minimum 24-month follow-up involving clinical assessments, posterior-segment imaging, and full-field ERG.

The primary endpoint concerns percentage change in scotopic ERG parameters between 12 and 24 months. Treatment is described as a three-day methylprednisolone pulse followed by oral prednisone at 1mg/day with a slow taper; non-steroidal immunosuppressive therapy was introduced in specified cases. The registry lists secondary clinical and imaging outcomes.

The numerical primary endpoint result, confidence interval, detailed analysis plan, missing-data methods, and multiplicity strategy are not reported in the registry record. The registry reports 0 participants affected by serious adverse events and 6 affected by other adverse events.