Apremilast in the Treatment of Uveitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Apremilast in the Treatment of Uveitis (NCT00889421), a na phase 1, phase 2 study. The primary outcome is Improvement by 2 or More Lines of Best-corrected Snellen Visual Acuity in at Least One Eye.

2. Clinical Question

This is a question about a defined change in visual acuity during treatment, not a randomized estimate of apremilast’s effect relative to another treatment or to no treatment. In a single-group study, any observed change could reflect multiple influences, including the underlying course of uveitis, other care, measurement variability, or treatment. Without a comparator and an analysis that addresses those influences, the record cannot separate them.

The official title frames the intended population as people with vision-threatening disease that was refractory to other systemic immunosuppression. That wording describes the trial’s focus; the record does not provide enough participant-level information to determine how closely each enrolled person matched that description. It also does not report the number of eligible people who were approached, enrolled, treated, or assessed at the primary endpoint.

The registry lists enrollment of 3 and a primary endpoint timeframe of 6 months. It does not report an endpoint value, a response count, or a statistical estimate. The clinical question is therefore identifiable from the outcome definition, while its answer is not reported in the registry record.

3. Trial Design

The record describes an open-label trial of apremilast in the management of vision-threatening uveitis refractory to other modes of systemic immunosuppression. It lists Phase 1 and Phase 2, a single-group model, no masking, and allocation as NA. The treatment group consists of patients receiving apremilast. Enrollment is recorded as 3.

These design features matter when interpreting changes during treatment. In an open-label study, participants and study personnel are not masked to treatment assignment. In a single-group study, there is no separate concurrent control group in the record. Thus an outcome observed during treatment is a description of the treated group, not a direct estimate of how outcomes would have differed under a comparator. The registry record itself flags that the arms are not a like-for-like control comparison.

The record gives a study start of 2009-11 and a primary completion date of 2011-06. Its status is TERMINATED. These entries establish the recorded dates and status, but they do not explain why the trial was terminated, whether all planned follow-up was completed, or whether the termination affected data collection or analysis. Those details are not reported in the registry record.

There is no treatment schedule or dose in the intervention description, and the record does not state the planned duration of treatment. The primary outcome timeframe is 6 months; that timeframe should not be treated as proof that every participant was assessed at that point. The record does not report participant flow, follow-up completeness, protocol deviations, or the analysis population.

The study sponsor is Oregon Health and Science University. The registry lists five outcome measures and zero analyses. The named secondary outcome concerns the type, frequency, severity, and relationship of adverse events to study treatment. The record does not provide detailed results for that outcome. Overall, the design information identifies the broad clinical setting and the lack of a control comparison, but it does not supply the operational detail needed to reconstruct conduct or infer why the study ended.

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:

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: patients with refractory uveitis

6. Primary Endpoint

The registry lists the primary outcome as Improvement by 2 or More Lines of Best-corrected Snellen Visual Acuity in at Least One Eye, measured over 6 months.

The primary endpoint is improvement by 2 or more lines of best-corrected Snellen visual acuity in at least one eye, with a timeframe of 6 months. Best-corrected visual acuity measures visual acuity after correction is taken into account. The line-based criterion expresses a threshold for change: a participant meets the stated endpoint if the specified improvement is present in at least one eye. The definition does not require improvement in both eyes.

A threshold endpoint can make a clinical outcome easier to interpret than a continuous measurement alone. It identifies whether a prespecified level of change was reached, rather than describing only an average change across measurements. However, a threshold also compresses information. It does not show the size of change beyond the threshold, a smaller improvement, worsening, or whether the other eye changed differently. The registry record does not provide a more detailed endpoint description or state how eye-level measurements were handled when determining the participant-level outcome.

Visual acuity is relevant to a trial focused on uveitis described as vision-threatening because it directly concerns visual function. That general rationale does not establish that the endpoint captures every aspect of disease activity or patient experience. The record identifies no additional primary endpoint details, such as assessment procedures, confirmation requirements, or rules for incomplete measurements.

No result for this endpoint is reported in the registry record. There is no reported response count, estimate, confidence interval, or analysis at 6 months. Therefore the endpoint definition can be explained, but the record does not establish how many participants met it or how precisely any treatment-associated change was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a single-group, open-label design and a visual-acuity endpoint with a defined threshold. It does not describe the statistical analysis used for the primary outcome. The registry lists zero analyses, and the primary endpoint fields do not contain a result or analysis description. The concepts below explain how such data are generally considered; they are not claims about methods used in this trial.

What does a single-group design estimate?

A single-group study can describe outcomes among participants who receive the study intervention. If a change from baseline is measured, it can describe the change observed in that group. A causal treatment effect, however, is a comparison between the outcome under treatment and the outcome that would have occurred under a suitable alternative. For the same participant, both states cannot be observed at the same time. A concurrent comparison group helps estimate the alternative outcome. Without one, observed changes can be influenced by the condition’s natural course, other treatment, selection into the study, and measurement variation.

Open-label conduct is another consideration. When treatment status is known, expectations or decisions about care and assessment may be influenced by that knowledge. This is a general risk, not evidence that such influence occurred in this study. Masking is one way trials may limit certain forms of assessment or performance bias. The record lists masking as none.

How should a threshold endpoint be analyzed?

The endpoint uses a threshold: improvement by 2 or more lines in at least one eye at 6 months. An analysis could report how many participants met that criterion and the proportion of the analyzed group who met it, along with an uncertainty interval. This is a general description of possible reporting, not a reported analysis from this trial. The registry record gives no response count or estimate, so no such result can be interpreted.

Threshold outcomes are straightforward to communicate but discard some detail. A participant just meeting the threshold and a participant exceeding it by more may both be counted as meeting the endpoint. Those who improve without reaching the threshold may be grouped with those who do not improve, depending on the prespecified rules. The record does not give rules for missing eye measurements, discordant changes between eyes, or confirmation of a visual-acuity change. Those details are not reported in the registry record.

For a binary outcome, uncertainty is especially important when the cohort is small. The observed response count may be a very imprecise guide to the response probability in a broader population. A confidence interval expresses uncertainty around an estimate; a narrow interval generally indicates greater precision and a wide interval less precision. No interval is available for this primary endpoint because no endpoint estimate is reported. It would be inappropriate to infer precision from the enrollment number alone.

What does the registry say about planning illustrations?

The sample-size assumptions described for planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They state that the effect to detect is a stated fraction of the observed effect. Those are planning assumptions for an illustration, not evidence that the trial was designed as a two-arm study. The recorded design is single-group, and allocation is NA.

The illustrations are based on an observed effect, but the registry record reports no primary endpoint analysis or observed primary effect. Therefore, the assumptions do not provide a basis for describing an observed treatment effect from this trial. A planning sample size is not observed power. Observed power is not a substitute for an effect estimate and its uncertainty; with no reported primary result, no conclusion about the trial’s observed statistical power is supported.

In a general planning exercise, the assumed effect and variability influence the number of participants needed to detect a difference under chosen design assumptions. If the assumed effect is smaller, more information is generally needed to distinguish it from random variation. Such calculations depend on the comparator, outcome, allocation, analysis method, and assumptions. The record’s two-arm illustration assumptions do not match the listed single-group design, so they should not be read as a description of the actual study design or its own sample-size justification. The trial’s sample-size justification is not reported in the registry record.

Why does over-dispersion matter?

Over-dispersion is a general issue for count outcomes. It occurs when variation in observed counts is greater than a statistical model assumes. If a model assumes too little variation, it may produce uncertainty intervals that are too narrow or tests that are too optimistic. Methods that account for extra variation can improve uncertainty estimates. This concept does not imply that over-dispersion was assessed or relevant to the primary visual-acuity endpoint. The registry record does not report an over-dispersion assessment or a statistical model for the listed outcomes.

For a threshold visual-acuity endpoint, the main data would ordinarily be whether the criterion was met, not a count process with repeated event counts. The record does not state the analysis scale or model, so it is not possible to identify the method used. Nor does it report any adjustment for baseline characteristics, repeated measurements, or eye-level correlation. Those methods and decisions are not reported in the registry record.

Because the record contains no primary endpoint analysis, there is no sponsor estimate to compare with a recalculated estimate. A recalculation from summary statistics would require posted outcome data, and none are reported for the primary endpoint. No independent recalculation can replace a sponsor analysis when the two conflict; in a discrepancy, the sponsor’s own analysis takes precedence. That situation cannot be assessed from this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and zero analyses. It identifies the primary visual-acuity endpoint and a secondary outcome concerning the type, frequency, severity, and relationship of adverse events to study treatment. The registry record does not describe how the multiple outcomes were prioritized in analysis, whether any statistical adjustment was planned, or whether any analyses were conducted for the other outcome measures.

Multiplicity is a general concern when several outcomes, timepoints, subgroups, or statistical comparisons are examined. Looking across many tests can increase the chance of finding an apparently notable result by chance. Trial protocols may address this by defining a primary outcome, setting a testing order, or adjusting inference. The record identifies a primary endpoint, but it does not report a multiplicity strategy. It is not appropriate to infer one from the outcome listing alone.

Missing data are also consequential. If an outcome is unavailable for some participants, the analysis may depend on why it is missing and how the missingness is handled. Different assumptions or methods can lead to different estimates. The record does not report missing endpoint observations, follow-up completeness, imputation, sensitivity analyses, or a missing-data strategy. It also does not say whether all enrolled participants were included in an analysis.

Analysis populations are not reported in the registry record. It does not identify an intention-to-treat population, a treated population, or a per-protocol population, and it does not describe exclusions from analysis. These labels refer to general analysis approaches; their use cannot be assumed. Without the participant flow and analysis population, readers cannot determine who contributed to any endpoint estimate. In this case, no primary endpoint estimate is reported at all, so there is no analysis population to evaluate from the posted record.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s adverse-event summary lists zero participants with serious adverse events among 3 at risk. It also lists 1 participant with other adverse events among 3 at risk. These are recorded participant counts. They should not be treated as rates calculated for comparison, and no additional percentage is needed to interpret the entries.

The serious-event summary lists no serious adverse-event terms. The death entry is null, so deaths are not reported in the registry record. A missing death entry is not the same as a reported finding of no deaths. The record also does not provide event timing, duration, severity details, or the assessment of whether each event was related to treatment.

The named secondary outcome concerns the type, frequency, severity, and relationship of adverse events to study treatment, but the posted information does not provide detailed results for those features. The distinction between serious and other adverse events is important: zero participants listed with serious events does not mean that no adverse events occurred, since the record lists 1 participant with other events.

These counts are descriptive for a very small treated group and do not support a comparative safety conclusion. There is no separate control group in the record, and the limited counts cannot establish whether an event was caused by apremilast. The registry status is TERMINATED, but the reason for termination is not reported, so it should not be attributed to the safety entries.

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

The record establishes that an open-label, single-group trial of apremilast in uveitis was registered, that enrollment was 3, and that the primary endpoint was defined as improvement by 2 or more lines of best-corrected Snellen visual acuity in at least one eye at 6 months. It also records the study as TERMINATED and lists limited adverse-event counts. These registry entries describe the trial and its posted record; they do not answer whether the primary endpoint was met.

The record does not report a primary outcome result, a treatment effect estimate, an uncertainty interval, or an analysis. No conclusion about the size or precision of a visual-acuity change can be drawn from the endpoint definition alone. Enrollment does not reveal how many participants met the endpoint, whether measurements were available at 6 months, or how participants were handled in an analysis.

The design also limits what a within-group observation could establish. With no separate control group and no masking, the trial does not provide a like-for-like comparison in the registry record. In general, a change observed during treatment is not by itself evidence that the intervention caused that change. Other influences, including disease course, concurrent care, and measurement variability, can affect outcomes. The record does not report analyses that address those influences.

The adverse-event entries should likewise be read narrowly. They list zero serious events among 3 at risk and 1 participant with other events among 3 at risk; they do not establish comparative safety or causation. Deaths are not reported. The record does not explain termination, and no explanation should be inferred from status alone.

These limitations do not erase the value of a clearly stated endpoint or the fact that the study was undertaken in a challenging clinical setting. They define the boundary of what can be learned from the posted record. The record documents the trial’s broad design and selected safety counts, but it does not provide an efficacy result that can be evaluated or generalized.

13. Why This Trial Matters Statistically

This trial is statistically notable because its endpoint is specific while its posted analysis information is absent. The visual-acuity criterion states what would count as improvement, includes the condition that it occur in at least one eye, and identifies 6 months as the timeframe. A precise outcome definition is an important part of clinical-trial interpretation: it tells readers what observation the study intended to evaluate. It does not, on its own, show what was observed.

The trial also illustrates the distinction between describing a treated group and estimating a comparative treatment effect. A single-group design can be useful for describing experience in a focused population, particularly when a study is exploratory. But without a comparator, changes cannot be cleanly separated from the natural course of disease, other care, or measurement variation. Open-label conduct adds another possible source of influence on assessment or care, although the registry does not document that such influence occurred.

The small recorded enrollment makes transparent reporting of individual outcome counts and uncertainty especially important. Yet the registry reports no primary analysis, response count, or confidence interval. This leaves readers unable to judge either the observed result or its precision. The absence of a posted analysis is not evidence that the endpoint was or was not met; it is a limit on what the registry record can establish.

The planning assumptions also highlight why design assumptions must be kept distinct from the actual trial. The record describes illustrations using equal allocation between two arms, while the trial itself is listed as single-group. Such illustrations are not observed power and do not explain the study’s own sample-size justification, which is not reported.

For biostatisticians and clinical researchers, the case underscores the value of reporting outcome data, analysis populations, missing-data handling, and uncertainty alongside a study’s design and status. Those details are needed to assess what the evidence supports. Here, the record makes the question and design visible, but leaves the primary statistical answer unreported.

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.

Several limitations are specific to the available record. Enrollment is recorded as 3, and there is no participant flow describing how many people were screened, treated, followed, or assessed for the primary endpoint. The record therefore does not establish whether the enrolled group and any analyzed group were the same, or whether outcome observations were missing.

The trial is described as open-label and single-group, with no separate comparator reported. That prevents a like-for-like comparison in the registry record and limits causal interpretation. The record does not describe other therapies used during the study or how concurrent care was handled. Those details are not reported in the registry record.

The primary endpoint definition does not specify how visual acuity was measured, whether assessors were trained or masked, how changes across eyes were combined, or how incomplete measurements were treated. The record does not give baseline visual-acuity values, participant-level results, or any primary endpoint estimate. It also does not report a confidence interval or other measure of precision.

The study status is TERMINATED, but the reason, timing of the decision, and consequences for planned follow-up or analysis are not reported. The record lists five outcome measures and zero analyses, without a statistical analysis plan, multiplicity approach, or analysis-population definition. The sample-size justification is not reported, and the two-arm planning assumptions do not describe the listed single-group design.

Safety information is limited to the recorded counts. Serious adverse-event terms are not listed, deaths are not reported, and event-level detail is absent. These limitations mean the posted record supports a description of the registered study and selected safety entries, but not a complete assessment of efficacy, precision, or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Apremilast in the Treatment of Uveitis — NCT00889421.
• Registry record last updated 2014-07-08; status last verified 2014-06.
• Results first posted 2014-07-08.
• 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.

18. Record Summary

NCT00889421 is a trial titled “Apremilast in the Treatment of Uveitis,” sponsored by Oregon Health and Science University. The official title describes an open-label trial of apremilast for vision-threatening uveitis refractory to other modes of systemic immunosuppression. The registry lists Phase 1 and Phase 2, a single-group model, no masking, allocation as NA, enrollment of 3, and status TERMINATED.

The primary endpoint is improvement by 2 or more lines of best-corrected Snellen visual acuity in at least one eye at 6 months. The registry lists five outcome measures and zero analyses. No primary endpoint result is reported. Safety entries list zero participants with serious adverse events among 3 at risk and 1 participant with other adverse events among 3 at risk; deaths are not reported. The reason for termination, analysis populations, missing-data handling, and sample-size justification are not reported in the registry record.