Topical Interferon Gamma for Macular Edema Secondary to Uveitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical Interferon Gamma for Macular Edema Secondary to Uveitis (NCT01376362), a na phase 1, phase 2 study. The primary outcome is Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline.

2. Clinical Question

In plain terms, the study was intended to investigate safety and efficacy of ocular interferon gamma-1b for cystoid macular edema secondary to uveitis. The stated primary question is about change over time in an imaging measure, not a comparison between treatment and control. Any interpretation must keep that distinction in view: a before-and-after change in one group cannot by itself separate a treatment-associated change from natural variation, measurement variation, or other changes over time. Those are general considerations for single-group studies, not findings about what happened to participants in this study.

3. Trial Design

The registry identifies this as a completed Phase 1 and Phase 2 study sponsored by the National Eye Institute (NEI). Its model is single group, allocation is recorded as NA, and masking is listed as none. The study was not a randomized comparison and did not include a like-for-like control arm. Enrollment was 5. The listed start date is 2011-06, and primary completion is recorded as 2012-02.

The intervention was interferon gamma-1b, described as ocular instillations. The arm description says participants received 28 single-use dropperettes at the baseline visit, with approximately 0.2 mL in each dropperette. The description ends before the full instructions are given; the remaining dosing schedule and duration are not reported in the registry record. A complete account of adherence or treatment exposure is also not reported in the registry record.

The primary outcome compares excess central macular thickening in the study eye at baseline and one week, using OCT. The registry also lists outcomes involving the fellow eye, macular volume, and best-corrected visual acuity, at specified follow-up times. Overall, 17 outcome measures are listed. The registry contains 0 analysis entries, and it does not report numerical primary or secondary outcome results.

With one group and no control comparison, the design can describe change over time among the enrolled participants if those measurements are reported. It cannot, on its own, estimate how outcomes would have differed under a separate control condition. That is a general design limitation, rather than a judgment about the treatment. A sample-size justification, details of planned interim analyses, and a fuller statistical analysis plan are not reported in 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.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline, measured over Baseline and 1 Week.

The primary endpoint is change in excess central macular thickening in the study eye, measured by OCT at baseline and one week. The unit is micrometers (µm), and the registry describes the intended summary as a mean with standard deviation. OCT is a non-invasive imaging technique; the record describes spectral-domain OCT as capturing cross-sectional images of biological tissue using long-wavelength light. Central macular thickness provides an imaging measure of the structure under study.

Change from baseline is used to describe how a participant’s measurement differs between the initial assessment and follow-up. In general, this can be useful when the scientific question concerns a within-participant change over time. It does not, by itself, show what would have happened over the same period without the intervention. A control group or other appropriate comparative design is generally needed to estimate that contrast.

The registry specifies the measurement and timeframe but does not report the observed mean change, standard deviation, confidence interval, or test result. It also does not report details of the calculation used to define “excess” thickening. Consequently, the direction, magnitude, variability, and precision of the primary endpoint cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The registry identifies the primary outcome as a mean change in excess central macular thickening, measured in micrometers. A mean combines individual measurements into a summary of their central tendency. For a baseline-to-follow-up outcome, the individual change is generally the follow-up measurement relative to that participant’s baseline measurement, and the mean summarizes those changes across participants. The registry does not report the observed mean change or explain the detailed calculation of excess thickening.

A mean is useful for describing the average direction and size of change in the analyzed group, but it does not show whether every participant changed in the same direction. Nor does it communicate how much individual measurements varied. That is why the registry specifies a standard deviation as a dispersion measure. The standard deviation describes spread around the mean; it is not itself an estimate of the uncertainty in the mean. The registry does not report either value for the primary outcome.

What would a confidence interval add?

General statistical context: a confidence interval gives a range of values compatible with an estimate under the analysis method’s assumptions. A narrower interval indicates greater precision than a wider interval, while the interval’s location indicates which values remain plausible. It is not a guarantee that the true value lies in a particular interval, and it does not establish causation. No confidence interval for the primary outcome is reported in the registry record. Without an estimate and its uncertainty, the size and precision of the primary result cannot be assessed.

Why does the single-group design matter?

The study is recorded as single group, with allocation NA and no masking. In a single-group before-and-after design, a change in the measured outcome describes what occurred between assessments among participants with recorded measurements. It does not directly compare that change with what would have occurred in a control group over the same period. General statistical context: a control comparison can help distinguish changes associated with the intervention from changes that might occur over time for other reasons. Since there is no control arm in this design, a treatment-versus-control contrast is not available from the registry record.

Repeated measurements on the same participant are often statistically related. General methods may account for that pairing when estimating an average change or its uncertainty. The analysis method used in this study is not reported in the registry record, so it is not possible to say how the relationship between baseline and follow-up measurements was handled. Neither a particular test nor a model should be assumed.

How should variability be considered?

General statistical context: dispersion matters because measurements may vary among participants even when they are assessed in the same way. An average can conceal that variation. If variability is large relative to the estimated mean change, the estimate may be imprecise; if variability is smaller, it may be more precise, although precision also depends on the number of analyzed observations and the analysis method. The registry reports enrollment of 5, but does not report the number of participants with evaluable primary measurements or the observed dispersion. No calculation of precision can therefore be made from this record.

Over-dispersion is a general concept for data whose variability exceeds what a chosen statistical model assumes. If present, ignoring it can make uncertainty estimates too small and statistical tests too confident. The primary endpoint is continuous, and the registry does not identify an analysis model or report evidence of over-dispersion. This concept is relevant as general statistical background, but there is no basis in the record to assert that over-dispersion occurred or was addressed.

What is the role of a test result?

A statistical test evaluates how compatible data are with a specified null hypothesis under its assumptions. A p-value, if reported, would not measure the probability that the null hypothesis is true, nor would it quantify the size or importance of a change. The registry record has no analysis entries and reports no p-value for the primary outcome. There is therefore no test result to interpret. Even if a test result were available, it would need to be considered alongside the estimated change, its uncertainty, design limitations, and the prespecified analysis approach.

Sample-size planning is distinct from an observed result. The planning illustration described in the registry is based on an observed effect, uses a two-sided significance level of 0.05, assumes equal allocation between two arms, and uses a normal approximation. It describes hypothetical participants per arm for specified power and fractions of an observed effect; it is not a report of actual trial enrollment in a two-arm study. The trial itself is single group with enrollment of 5. The observed effect needed to interpret those planning illustrations is not reported in the registry record. Such planning values are not observed power and cannot substitute for an outcome estimate, confidence interval, or analysis of the enrolled participants.

The statistical analysis plan, including any specified model, confidence level, handling of repeated measures, interim analyses, and sample-size justification, is not reported in the registry record. General explanations above describe statistical concepts only; they do not identify methods used in this study.

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("Interferon Gamma-1b")
n   <- c(5)
m   <- c(-38.6)
sp  <- c(130.26)
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  Interferon Gamma-1b  5  -38.600  130.260  -200.339  123.139

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including outcomes for the study eye and fellow eye, measures of macular thickness and volume, and visual acuity. Multiple outcomes and follow-up times can create a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. General statistical approaches may address this by defining a primary analysis in advance, adjusting for multiple comparisons, or interpreting secondary findings as exploratory. The registry does not report whether a multiplicity strategy was planned or used.

The primary outcome is identified, but the registry contains 0 analysis entries and reports no numerical outcome results. It is therefore not possible to assess whether the reported endpoint hierarchy was followed in analysis, whether all listed outcomes were analyzed, or whether results were selectively omitted. A complete statistical plan and information on protocol changes are not reported in the registry record.

Missing-data handling and analysis populations are also not reported in the registry record. The enrollment count is 5, but that does not establish how many participants had complete baseline and follow-up measurements, whether all enrolled participants were included in each analysis, or whether any measurements were unavailable. General statistical context: missing measurements can affect both the composition of the analyzed group and the estimated change, especially if missingness is related to participants’ outcomes or circumstances. Without participant-level accounting, missingness details, and the analysis method, its potential impact cannot be evaluated.

The registry does not report an intention-to-treat, per-protocol, or other named analysis population. Those labels should not be inferred from the design or enrollment count.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The adverse-event summary lists 5 participants at risk in the interferon gamma-1b group. It reports 0 participants affected by a serious adverse event and 0 affected by other adverse events. The death count is not reported in the registry record. These counts describe the registry’s safety summary; they are not a complete account of event types, timing, severity, or individual exposure.

General statistical context: when a study includes few participants, a count of zero observed events does not establish that an event cannot occur or precisely characterize its frequency. Safety estimates are more informative when interpreted with the number exposed, duration and completeness of follow-up, event definitions, and detail about how events were collected. The registry record does not provide a fuller narrative of safety monitoring or follow-up, and the intervention description is incomplete. The zero counts should therefore be read as reported counts among those at risk, not as proof of an absence of risk.

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

The registry record describes a completed Phase 1 and Phase 2 single-group investigation of ocular interferon gamma-1b for macular edema secondary to uveitis. It identifies a primary imaging outcome: change in excess central macular thickening in the study eye from baseline to one week. It also lists 17 outcome measures and records enrollment of 5.

The record does not report the numerical primary outcome, a standard deviation, a confidence interval, or a statistical test result. As a result, it does not establish the direction or magnitude of the measured change, or how precisely that change was estimated. It also does not report numerical results for the listed secondary outcomes. The registry entry alone cannot support a claim that a particular change occurred.

The design is single group and unmasked, with no control arm. General interpretation: a before-and-after measurement can describe change over time, but does not distinguish an intervention-associated change from other possible influences on measurements over that period. The study therefore does not provide a randomized or like-for-like comparison of the intervention with a control condition. This is a limitation of what the design can estimate, not a conclusion about the intervention’s effect.

The safety summary records no serious or other adverse events among 5 participants at risk, while the death count is not reported. Such counts should be interpreted in light of the small enrollment and the limited safety detail in the registry. They do not establish that risk is absent.

In short, the record documents the study’s purpose, design, outcome definitions, and reported safety counts, but it does not provide the numerical efficacy results needed to quantify the primary change. Details of the statistical analysis, missing data, analysis populations, and multiplicity handling are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary question is a change-from-baseline question in a single group. That design can be useful for describing measurements over time, especially in an early-phase investigation, but it does not produce a controlled estimate of how outcomes differ between intervention and control conditions. Keeping the descriptive change separate from a comparative treatment effect is essential to sound interpretation.

The primary measure is an imaging outcome expressed in micrometers, summarized as a mean and standard deviation. Those summaries serve different purposes: the mean describes the central tendency of measured changes, while the standard deviation describes their spread. A complete interpretation would also need an uncertainty estimate and an account of the analysis population. Those numerical details are not reported in the registry record.

The registry also lists 17 outcomes. Multiple outcome measures can be informative, but they raise questions about which analyses were primary, how repeated measures and related outcomes were handled, and whether any multiplicity approach was specified. Those analysis details are not reported. The absence of numerical outcome results further prevents evaluation of whether findings were consistent across outcomes and follow-up times.

Enrollment was 5, which makes transparent reporting of individual-level accounting and precision especially important. The registry does not report how many participants contributed measurements to each outcome or how missing data were treated. It also has 0 analysis entries. The statistical value of the record is therefore principally its documentation of the study design and planned measurement focus, rather than a quantitative estimate of change.

These features illustrate a general lesson in clinical biostatistics: study design, outcome definition, analysis transparency, and uncertainty all shape what results can support. Here, the registry record makes the design constraints clear but does not contain the numerical findings required to assess the primary outcome.

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.

The main trial-specific limitation for interpreting results is the single-group design. There is no like-for-like control comparison, and allocation is recorded as NA. Any change from baseline would therefore be descriptive and could not by itself identify the intervention’s contribution. Masking is listed as none, which should also be considered when assessing a study’s procedures and measurements; the registry does not describe further steps to limit potential measurement or assessment bias.

Enrollment was 5. The registry does not report the number of participants with complete primary endpoint data, the spread of their measurements, or confidence intervals. It also reports 0 analysis entries. Consequently, the precision and robustness of any primary estimate cannot be assessed from the registry record. The record lists 17 outcomes, but does not report how multiplicity was addressed or how the primary and secondary analyses were carried out.

The intervention description is incomplete: it mentions 28 single-use dropperettes at baseline, but the rest of the instructions are not reported in the registry record. The registry does not describe adherence, exposure after baseline, or the detail of follow-up for outcome and safety collection. Missing-data methods, analysis populations, sample-size justification, and interim analyses are also not reported in the registry record.

Finally, the numerical outcome results themselves are not reported. This prevents assessment of direction, magnitude, variability, and statistical uncertainty for the primary endpoint and the listed secondary outcomes. These are limits of the available registry information and should not be mistaken for evidence of a particular outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Topical Interferon Gamma for Macular Edema Secondary to Uveitis — NCT01376362.
• Registry record last updated 2012-10-08; status last verified 2012-09.
• Results first posted 2012-10-08.
• 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

The registry describes NCT01376362, a completed Phase 1 and Phase 2 single-group study sponsored by the National Eye Institute (NEI). It investigated ocular interferon gamma-1b for macular edema secondary to uveitis. Enrollment was 5; allocation is listed as NA and masking as none.

The primary outcome was change in excess central macular thickening in the study eye, measured by OCT from baseline to one week and expressed in micrometers. The record lists 17 outcome measures and 0 analysis entries. Numerical efficacy outcomes, statistical analyses, missing-data handling, and analysis populations are not reported in the registry record.

The safety summary records 0 participants with serious adverse events and 0 with other adverse events among 5 at risk. The death count is not reported in the registry record. The single-group design does not provide a controlled treatment comparison.