This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Suprachoroidal Injection of Triamcinolone Acetonide in Subjects With Macular Edema Following Non-Infectious Uveitis (NCT02255032), a randomized phase 2 study. The primary outcome is Change From Baseline in Central Subfield Thickness, Measured Using Optical Coherence Tomography, After Treatment With CLS-TA in Subjects With Macular Edema Following Uveitis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02255032 |
| Phase | Phase 2 |
| Condition | Uveitis, Macular Edema, Uveitis, Posterior |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 22 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Clearside Biomedical, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Subjects with macular edema following non-infectious uveitis were studied. The registry lists several uveitis conditions, including posterior, anterior, intermediate, and panuveitis. The primary outcome population is described as the Intent-to-Treat set: randomly assigned subjects who received at least one dose of study drug.
Intervention
The intervention was a single unilateral suprachoroidal injection of 4 mg CLS-TA. The registry describes this as 40 mg/mL in 100 µL.
Comparator
The other randomized group received a single unilateral suprachoroidal injection of 0.8 mg CLS-TA, described as 8 mg/mL in 100 µL. Both groups received CLS-TA; the registry does not describe a placebo or untreated comparator.
Primary question
The primary outcome was change from baseline in central subfield thickness, measured by optical coherence tomography, after 2 months. The clinical question is whether these two dose groups showed different changes. The posted analysis does not report a direct between-group test, so it does not answer that comparative question statistically.
The registry identifies the study as randomized, masked, multicenter, and parallel-group. Its stated purpose was to evaluate safety and efficacy in subjects with macular edema following uveitis. The posted primary outcome is a continuous measurement, reported as a mean with standard deviation. Negative change values indicate that the measured thickness was lower at follow-up than at baseline. This direction describes the measurement; by itself, it does not establish a treatment effect or explain the clinical importance of the change.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group Phase 2 study sponsored by Clearside Biomedical, Inc. The registry lists enrollment as 22 and the study status as completed. The study began in 2014-10, with primary completion in 2015-12. The intervention descriptions specify one unilateral suprachoroidal injection in each group: 4 mg CLS-TA or 0.8 mg CLS-TA.
The listed primary outcome was change from baseline in central subfield thickness measured using optical coherence tomography. The outcome timeframe was 2 months. The registry describes the analysis population as randomly assigned subjects who received at least one dose of study drug. It reports 16 subjects in the 4 mg outcome group and 5 in the 0.8 mg outcome group. The registry record does not explain the relationship between the listed enrollment and the outcome-group counts, or give reasons for any difference.
The study has two active-dose groups rather than a placebo group, so the posted outcome summaries describe changes within those groups. Randomization can support a comparison between assigned groups when an appropriate between-group analysis is reported, but the registry's posted analysis is a paired test for the 4 mg group alone. It therefore does not provide a direct statistical comparison of the two doses. Details of sequence generation, allocation concealment, masking procedures, and the intended sample-size justification are not reported in the registry record.
The record lists one outcome measure and one analysis. It does not establish from that count whether other analyses were conducted but not posted. Interpretation is limited to the outcome, time point, population description, and analysis information present 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
| Stage | 4 mg CLS-TA | 0.8 mg CLS-TA |
|---|---|---|
| STARTED | 17 | 5 |
| COMPLETED | 17 | 5 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat set includes all randomly assigned subjects who received at least one dose of study drug.
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: Intent-to-Treat set includes all randomly assigned subjects who received at least one dose of study drug.
| Characteristic | Unit | 4 mg CLS-TA | 0.8 mg CLS-TA | Total |
|---|---|---|---|---|
| Participants analysed | 17 | 5 | 22 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 13 | 4 | 17 |
| Age, Categorical: >=65 years | Participants | 4 | 1 | 5 |
| Age, Continuous | Years | 52.2 (SD 19.65) | 51.8 (SD 16.87) | 52.1 (SD 18.67) |
| Sex: Female, Male: Female | Participants | 8 | 4 | 12 |
| Sex: Female, Male: Male | Participants | 9 | 1 | 10 |
| Region of Enrollment: United States | participants | 17 | 5 | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Central Subfield Thickness, Measured Using Optical Coherence Tomography, After Treatment With CLS-TA in Subjects With Macular Edema Following Uveitis, measured over 2 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Microns |
| Endpoint classification | Continuous Endpoint |
Central subfield thickness is a structural measurement obtained using optical coherence tomography. For this trial, the endpoint is the change from baseline in that measurement after 2 months, expressed in microns. A change score represents the follow-up measurement relative to the participant's baseline measurement; a negative value means the follow-up thickness was lower than baseline.
As a continuous endpoint, thickness can be described by a group mean and standard deviation. The mean summarizes the average change in the group, while the standard deviation describes how much individual measurements varied around that mean. These summaries address different questions: the mean gives the central tendency, and the standard deviation describes dispersion.
General explanation: an imaging measurement can provide a quantitative way to assess anatomical change over time. Its interpretation still depends on study design, measurement reliability, the analysis population, and whether the observed change is compared appropriately between randomized groups. A within-group change does not isolate the effect of treatment from other influences on change over time. The registry does not report a threshold for clinical importance or additional context for interpreting the size of a change in microns.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the 4 mg CLS-TA group, the posted mean change in central subfield thickness was -164.4 microns, with a standard deviation of 173.1. For the 0.8 mg group, the posted mean change was -78.2 microns, with a standard deviation of 121.9. The negative means indicate decreases from baseline on average in both groups. These summaries are descriptive; they do not by themselves show whether the groups differ beyond what might occur through sampling variation.
The registry reports a paired, two-sided t-test for the 4 mg group. Its reported mean difference in final values is -164.44 microns, with a 95% confidence interval from -256.7 to -72.2 and a reported p-value of 0.002. This analysis concerns change within the 4 mg group, not a test of the 4 mg group against the 0.8 mg group. The interval is entirely below zero, which is consistent with a mean decrease from baseline in that group under the analysis reported. It does not answer whether one dose produced a greater change than the other.
General explanation: a confidence interval describes the range of values compatible with the data and the statistical model at the stated confidence level. It conveys uncertainty about an estimated mean change; it is not a range containing a specified proportion of individual participants' changes. A p-value describes how unusual the data would be under a stated null hypothesis and model. It does not measure the probability that the null hypothesis is true, nor does it establish clinical importance.
The different group means should not be treated as a calculated treatment contrast. The registry explicitly indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. No between-group confidence interval or test is posted. Consequently, the outcome summaries permit a description of each group's observed change, but the comparative question remains unresolved by the reported analysis.
The group sizes and standard deviations also matter when judging precision. The outcome summaries are based on 16 subjects in the 4 mg group and 5 in the 0.8 mg group. Smaller groups and substantial individual variability can leave estimates imprecise. The reported standard deviations are large relative to the group means, indicating variation in observed change; they do not establish why participants' changes differed. The registry does not report individual-level data or additional analyses to clarify that variation.
These findings should be read as registry-reported results for one outcome at one stated time point. They do not establish comparative benefit, clinical relevance, or outcomes beyond the posted measurement. The record does not report secondary outcomes.
9. Statistical Methods Explained
What does a paired t-test assess?
The registry names a paired t-test, two-sided, for the 4 mg CLS-TA group. In general, a paired test uses the relationship between measurements from the same participant, such as baseline and follow-up measurements. It assesses whether the average within-participant change is compatible with a null value of no average change. The paired structure is appropriate to repeated measurements because the two measurements from a participant are related rather than independent.
A paired t-test relies on assumptions about the distribution of participant-level differences and the way observations enter the analysis. General explanation: departures from assumptions can affect the calibration of the test, particularly when there are few observations or unusual values. The registry record does not report diagnostic checks, alternative analyses, or details about how missing paired measurements were handled.
What does the reported confidence interval mean?
The 95% confidence interval for the 4 mg group's mean change ranges from -256.7 to -72.2 microns. General explanation: a confidence interval combines an estimate with its sampling uncertainty. Under the model and repeated-sampling interpretation, intervals constructed in this way would capture the underlying parameter at the stated frequency. It does not mean that most individual changes lie inside the interval, and it does not account automatically for design limitations, missing data, or selection of results.
The interval is for a within-group estimate. It is not a confidence interval for the difference between the two randomized groups. A comparative interval would need to estimate the contrast between groups and incorporate uncertainty from both groups. That comparison is not reported in the registry record.
How should the p-value be read?
The reported test is two-sided, meaning that the test considers departures in either direction from the null value. General explanation: the p-value is calculated under a specified null hypothesis and statistical model. It describes how compatible the observed data are with that null under those assumptions. It is not the probability that the result occurred by chance, the probability that the treatment is ineffective, or a measure of effect size. A p-value for within-group change cannot substitute for a test of the difference between randomized groups.
The registry identifies the analysis parameter as a mean difference in final values and reports the paired test. The outcome summaries separately provide the group mean change and standard deviation. The record does not give further detail to reconcile the wording of the analysis parameter with the endpoint description. Accordingly, the reported analysis should be described as the registry states it rather than reinterpreted as a between-group estimate.
Why do standard deviations matter?
Standard deviation describes variability among observed values around a group mean. It is not the standard error of the mean and is not itself a confidence interval. General explanation: the standard error reflects both variability and the amount of information available, whereas the standard deviation describes variation among observations. Greater dispersion can make an estimate less precise, all else being equal. The registry reports standard deviations of 173.1 microns for the 4 mg group and 121.9 microns for the 0.8 mg group; it does not report a separate standard error for the two-arm contrast.
In some data, observations vary more than a simple statistical model expects. General explanation: over-dispersion refers to greater variability than assumed by a model and can make standard errors too small if not addressed. The posted outcome is summarized as a mean and standard deviation, and the record does not report a model for over-dispersion or a diagnostic assessment. There is no basis in the registry record to say whether over-dispersion was assessed or relevant to the analysis.
What is the role of a between-group analysis?
Randomization is intended to make the assigned groups comparable, on average, with respect to baseline characteristics. A direct analysis of the randomized groups is needed to estimate the comparative effect represented by their difference in outcome. General explanation: a difference in within-group changes is not equivalent to a formal between-group test; uncertainty depends on both groups and on the chosen model. The registry states that values are missing or not estimable for a two-arm comparison of this continuous endpoint. Therefore no comparative estimate, confidence interval, or p-value can be interpreted from the posted record.
What can be said about sample-size planning?
Any sample-size figures associated with planning illustrations are planning estimates, not observed power. General explanation: a planning calculation uses assumptions about the effect to detect, variability, allocation, significance level, and desired power. It does not indicate the probability that a completed trial's result is true or the probability that the trial detected an effect. The registry record does not report the trial's own sample-size justification, targeted power, or design assumptions. The planning assumptions described for illustrations use the observed effect, equal allocation, a two-sided significance level of 0.05, and a normal approximation; they should not be mistaken for the study's original design plan.
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.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| 4 mg CLS-TA | 16 | -164.440 | 173.148 | -256.704 to -72.176 |
| 0.8 mg CLS-TA | 5 | -78.200 | 121.890 | -229.546 to 73.146 |
R code and output
arm <- c("4 mg CLS-TA", "0.8 mg CLS-TA")
n <- c(16, 5)
m <- c(-164.44, -78.2)
sp <- c(173.148, 121.89)
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 4 mg CLS-TA 16 -164.440 173.148 -256.704 -72.176
CARM 0.8 mg CLS-TA 5 -78.200 121.890 -229.546 73.14611. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Paired t-test, two-sided | Mean Difference (Final Values) -164.44 | -256.7 to -72.2 | 0.002 |
The registry's sponsor-reported analysis is a paired, two-sided t-test for the 4 mg CLS-TA group. It reports a mean difference in final values of -164.44 microns, a 95% confidence interval from -256.7 to -72.2, and a p-value of 0.002. This is a within-group analysis, not a direct comparison with the 0.8 mg group.
The posted arm summaries report mean changes of -164.4 microns for 4 mg and -78.2 microns for 0.8 mg. Those descriptive summaries do not provide the uncertainty for a between-group contrast. The registry record marks values as missing or not estimable for a two-arm comparison of this continuous endpoint, so no unadjusted two-arm re-calculation is available to compare with the sponsor's analysis. The record does not flag a discrepancy between a sponsor estimate and a recalculation.
The sponsor's reported result therefore takes precedence as the analysis actually posted, but its scope should remain clear: it addresses change in the 4 mg group. It should not be recast as evidence from a randomized dose comparison. The registry record does not report why the two-arm result is unavailable.
12. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and one reported analysis, with no secondary outcomes posted. This does not establish that no other outcomes or analyses were considered; details of any broader analysis plan are not reported in the registry record. The record also does not report a multiplicity adjustment or explain whether multiple endpoints, time points, or analyses were prespecified. Without that information, the potential impact of selecting among analyses cannot be assessed.
The primary outcome population is described as the Intent-to-Treat set, defined in the registry as randomly assigned subjects who received at least one dose of study drug. This definition excludes randomized subjects who received no dose, so it is not an all-randomized population in the usual sense of that label. The registry gives outcome-group counts of 16 for 4 mg and 5 for 0.8 mg. It does not report the disposition of every randomized subject or explain how the listed enrollment relates to those analyzed counts.
Missing-data methods are not reported in the registry record. It is not stated whether any baseline or follow-up measurements were missing, whether participants discontinued, or how incomplete paired observations were handled. No imputation method, sensitivity analysis, or assessment of missingness is described. These omissions matter because a change-from-baseline analysis requires measurements at relevant time points or a stated method for incomplete data.
The registry also does not report a statistical analysis plan, prespecified handling of protocol deviations, or an analysis of the 0.8 mg group corresponding to the posted paired test. The available record therefore supports a limited account of the population definition and posted analysis, but not a full assessment of missing-data assumptions or selective reporting.
13. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 4 mg CLS-TA | 1 | 17 | 5.9% |
| 0.8 mg CLS-TA | 0 | 5 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 4 mg CLS-TA | 0 of 17 |
| 0.8 mg CLS-TA | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 4 mg CLS-TA | 14 of 17 |
| 0.8 mg CLS-TA | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | 4 mg CLS-TA | 0.8 mg CLS-TA |
|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | 1 of 17 | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 4 mg CLS-TA | 0.8 mg CLS-TA |
|---|---|---|---|
| Conjunctival haemorrhage | Eye disorders | 1 of 17 | 2 of 5 |
| Eye pain | Eye disorders | 3 of 17 | 0 of 5 |
| Macular oedema | Eye disorders | 0 of 17 | 3 of 5 |
| Macular oedema | Eye disorders | 2 of 17 | 1 of 5 |
| Uveitis | Eye disorders | 3 of 17 | 0 of 5 |
| Uveitis | Eye disorders | 1 of 17 | 1 of 5 |
| Injection site pain | General disorders | 1 of 17 | 1 of 5 |
| Hypertension | Vascular disorders | 2 of 17 | 0 of 5 |
| Palpitations | Cardiac disorders | 1 of 17 | 0 of 5 |
| Anterior chamber cell | Eye disorders | 1 of 17 | 0 of 5 |
Serious events with the highest arm-level rate: atrial fibrillation (5.9%).
For serious adverse events, the registry lists 1 affected subject among 17 at risk in the 4 mg CLS-TA group and 0 among 5 at risk in the 0.8 mg group. It reports zero deaths in both groups. The registry also lists atrial fibrillation at 5.9% among the top serious adverse event terms, but the record does not specify in that listing which group the term belongs to.
For other adverse events, the registry lists 14 affected subjects among 17 at risk in the 4 mg group and 5 among 5 at risk in the 0.8 mg group. These are descriptive counts in the registry record, not a formal comparison of safety between doses. No statistical test or adjustment for differences in exposure or follow-up is reported.
General explanation: adverse-event counts depend on how events were defined, collected, and attributed, as well as on the number of participants observed and the duration of observation. A zero count does not establish that an event cannot occur, and counts from groups of different sizes should not be compared as if they were equally precise. The registry record does not provide event narratives, severity details beyond the serious-event classification, or additional information needed to assess causality. These figures describe what was posted and do not establish a complete safety profile.
14. What the Result Does, and Does Not, Mean
The posted results show mean decreases from baseline in central subfield thickness in both dose groups at the 2-month outcome time point. The 4 mg group mean change was -164.4 microns, and the 0.8 mg group mean change was -78.2 microns. The reported standard deviations indicate variability in the observed changes within each group.
The sponsor-reported paired analysis for the 4 mg group gives a confidence interval that lies below zero and a p-value of 0.002. This supports a statistical finding of mean within-group change under the reported test and its assumptions. It does not establish that the 4 mg dose caused the change, because change over time in a single group is not a randomized comparison. It also does not establish that 4 mg is superior to 0.8 mg.
The registry does not report a direct statistical comparison between dose groups for the primary continuous endpoint. Although both groups have descriptive summaries, a valid comparative conclusion requires an estimated between-group contrast and its uncertainty. The registry explicitly says that values for such a comparison are missing or not estimable. The difference in the displayed group means should therefore not be treated as a tested treatment effect.
The study's scope is limited to the listed population, endpoint, and timeframe. The record does not report a clinical-importance threshold for central subfield thickness, secondary outcomes, or longer-term outcome results. It also does not provide enough information to assess the effects of missing measurements, other analyses, or the reasons the two-arm comparison is unavailable.
In statistical terms, the posted record documents within-group change and selected safety counts. It does not settle the comparative question between doses or establish how the measured changes relate to outcomes important to patients. These distinctions separate what the registry reports from conclusions that would require additional results or evidence.
15. Why This Trial Matters Statistically
This record illustrates why the analysis question matters as much as the numerical result. The primary clinical question concerns two randomized dose groups, but the posted inferential analysis concerns change within the 4 mg group. A statistically clear within-group result is not automatically a statistically clear difference between groups. Keeping those estimands distinct prevents a one-arm test from being interpreted as a randomized comparison.
The record also demonstrates the difference between descriptive and inferential information. Group means and standard deviations describe the observed outcome distributions. A between-group estimate with uncertainty would address whether the groups differed in change, but that result is not reported. The registry's explicit note that a two-arm result is missing or not estimable makes the boundary of interpretation particularly important.
The study is described as randomized and masked, features that can support rigorous comparison when the corresponding analysis is available. Yet design features do not replace reporting the comparative estimate, analysis population, missing-data handling, and prespecified statistical plan. The record's incomplete detail on these topics limits independent assessment of the primary comparison.
Finally, the safety counts show why denominators and uncertainty matter in small studies. Counts can describe observed events, but they do not alone establish comparative risk or rule out uncommon events. Overall, the statistical lesson is to match each claim to the analysis actually reported: within-group change, between-group difference, and safety description are distinct questions.
16. 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 principal limitation for interpreting the primary endpoint is that the registry does not report a two-arm comparison. The posted summaries permit description of mean change in each dose group, but not a statistical conclusion about the difference between doses. The sponsor's paired test is confined to the 4 mg group.
The outcome-group counts are limited, particularly for the 0.8 mg group, and the reported standard deviations indicate appreciable variability in change. These features can limit precision. The record does not report individual-level data, a comparative confidence interval, or a sensitivity analysis that would help assess uncertainty in the dose comparison.
The registry's analysis-population definition includes randomly assigned subjects who received at least one dose. The record does not explain the difference between the enrollment listing and the outcome-group counts, or provide a complete participant disposition. It does not report missing-data methods, the number of incomplete measurements, or whether all relevant participants contributed paired measurements.
Additional design and analysis details are absent: the sample-size justification, statistical analysis plan, allocation procedures, masking procedures, checks of test assumptions, and any multiplicity strategy are not reported in the registry record. The record also does not report a clinical-importance threshold for the imaging outcome, secondary outcomes, or further follow-up results. These limitations prevent a fuller assessment of the intended comparative inference, robustness, and clinical meaning of the posted findings.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: Suprachoroidal Injection of Triamcinolone Acetonide in Subjects With Macular Edema Following Non-Infectious Uveitis — NCT02255032.
- Registry record last updated 2021-02-08; status last verified 2021-01.
- Results first posted 2021-02-08.
- 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.
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20. Record Summary
NCT02255032 is a completed, randomized, quadruple-masked, multicenter, parallel-group Phase 2 study of CLS-TA for macular edema following non-infectious uveitis. The study compared single unilateral suprachoroidal injections of 4 mg and 0.8 mg CLS-TA. The primary outcome was change from baseline in optical coherence tomography central subfield thickness after 2 months.
The registry reports mean decreases in both groups and a paired, two-sided test for the 4 mg group. It does not report a direct two-arm analysis of the continuous endpoint. Safety listings include serious and other adverse-event counts and zero deaths in both groups. Missing-data methods, the study's sample-size justification, and several details of the statistical plan are not reported in the registry record.