Safety and Efficacy of BRM421 for Dry Eye Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of BRM421 for Dry Eye Syndrome (NCT03066219), a randomized phase 2 study. The primary outcome is Sign: Corneal Fluorescein Staining Score.

2. Clinical Question

The registry lists Dry Eye Syndrome as the condition and identifies the study as phase 2. Its stated objective concerns both signs and symptoms, while the primary endpoint addresses a sign: corneal fluorescein staining. Tear Film Break-up Time, Conjunctival Redness, and the Ocular Surface Disease Index are listed as secondary outcomes. The registry record does not provide results for those secondary outcomes in the information used for this analysis.

The study enrolled 157 participants. The endpoint results are reported separately for the BRM421 and placebo arms, with 76 and 75 participants, respectively. These arm-level numbers describe the posted endpoint results; they do not, by themselves, answer the comparative question. The registry record does not report an analysis that directly estimates the difference between the arms.

3. Trial Design

This was a phase 2, randomized, double-masked, parallel-group study of BRM421 ophthalmic solution and placebo. The official study title describes a multi-center clinical study using a controlled adverse environment model. The registry lists the condition as Dry Eye Syndrome and gives the study status as completed. BRIM Biotechnology Inc. is listed as the sponsor.

The study began on 2017-02-07, and primary completion is recorded as 2017-05-20. Total enrollment is listed as 157. The BRM421 arm is described as receiving BRM421 solution; the placebo arm is described as receiving the vehicle solution. The registry record does not give further details about treatment dose, frequency, duration, or the randomization procedure.

Randomized allocation is intended to assign participants to study arms by chance, helping make the groups comparable at the start of a trial. Double masking means the record identifies the study as masked for two parties, but does not specify which parties were masked. The parallel design means participants were assigned to one arm rather than crossing between treatments, according to the design classification in the registry.

The primary endpoint was change from baseline to week 4 in the mean corneal fluorescein staining score. Endpoint results are shown for 76 participants in the BRM421 arm and 75 in the placebo arm. The registry lists 157 enrolled overall, but does not explain the relationship between total enrollment and the endpoint arm counts. It also does not report a flow of participants through assignment, follow-up, or analysis, or state the analysis population used.

Although randomization and masking are relevant safeguards for a comparative trial, they do not replace a reported between-arm analysis. In this record, arm-specific mean changes and confidence intervals are posted, but a direct treatment contrast and its uncertainty are not reported. Details of the trial's protocol, statistical plan, and sample-size justification 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 Sign: Corneal Fluorescein Staining Score, measured over change from baseline to week 4.

The primary endpoint is a continuous measure: change from baseline to week 4 in corneal fluorescein staining score. It is described as a sign of dry eye, rather than a direct report of symptoms. Fluorescein staining is graded using the Ora Calibra Corneal and Conjunctival Staining Scale. The corneal surface is divided into superior, central, and inferior regions, and the total score is the sum of the scores for those regions.

Each region is graded on a scale with a minimum of 0 and a maximum of 4. The descriptions range from no staining at 0, through trace, mild, and moderate, to severe at 4. Half-grade increments may be used. The resulting total corneal score ranges from 0 to 12, with a higher possible value representing more staining within this scoring system.

A change-from-baseline endpoint describes how the recorded score changes over the specified follow-up period. The registry reports the mean change for each arm and a 95% confidence interval. The arm-level results are -1.06, with a 95% confidence interval from -1.5 to -0.62, for BRM421; and -1.16, with a 95% confidence interval from -1.61 to -0.71, for placebo.

Staining is used as an objective sign measure, complementing symptom measures such as the listed Ocular Surface Disease Index. A treatment comparison would need to estimate how the change differs between randomized arms. The registry record does not report that comparative estimate, so the arm-level changes alone do not establish the size or precision of a treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is analyzed?

Corneal fluorescein staining score is a continuous outcome. The registry identifies the reported quantity as a mean and specifies change from baseline to week 4. A mean describes the central value of the observations on the score scale. For a change outcome, the value concerns movement from the participant's baseline measurement to the measurement at the stated follow-up, aggregated across the arm.

Continuous outcomes are often summarized by a mean together with a measure of uncertainty or variation. In these results, the registry posts a 95% confidence interval for each arm but does not post a standard deviation. A confidence interval describes uncertainty around an estimated mean under the method's assumptions; it is not a range containing a specified proportion of individual participants' changes. The registry record does not report the exact procedure used to calculate the intervals.

What do the arm-specific estimates say?

The mean change is -1.06 for BRM421, with a 95% confidence interval from -1.5 to -0.62. For placebo, the mean change is -1.16, with a 95% confidence interval from -1.61 to -0.71. These estimates summarize each arm separately. They do not quantify the contrast between the arms, which is the quantity needed to directly assess whether mean change differed between randomized groups.

For a continuous endpoint, a two-arm comparison could be expressed as a difference in mean change, with an uncertainty interval and possibly a test result. The registry record does not post those quantities. It specifically notes that values were missing or not estimable for a two-arm comparison of this endpoint. No comparison should be reconstructed from the arm summaries as if it were the trial's reported analysis.

How should uncertainty be understood?

In general, a confidence interval reflects the precision of an estimate under a statistical model and its assumptions. A narrower interval indicates greater precision for that particular estimate than a wider interval, but precision alone does not establish clinical importance. These confidence intervals concern the separate arm means. They cannot be interpreted as the uncertainty interval for a treatment contrast, and they do not resolve whether the arms differ.

In general, variability among individual measurements affects how precisely a mean can be estimated. A sample mean can be similar across studies while its uncertainty differs if the amount of individual variation or the number of analyzed observations differs. The registry record does not report the standard deviation, participant-level data, or the analysis details needed to assess those features beyond the posted confidence intervals and arm counts.

What can the planning illustrations tell readers?

Any sample-size values associated with planning illustrations are not observed trial outcomes and are not observed power. The stated illustration assumptions use the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such an illustration asks what participant count would be needed under those assumptions for a planning scenario. It does not show that the trial was designed with those assumptions, nor does it establish the trial's probability of detecting an effect.

The registry record does not report the trial's own sample-size justification or design assumptions. The stated planning approach should therefore be distinguished from the protocol's design process. It is an illustration based on the posted effect, rather than evidence about the original sample-size calculation. No sample-size interpretation can replace a reported comparative estimate and its uncertainty.

Why does over-dispersion matter in general?

For continuous outcomes, over-dispersion is not a substitute for the reported outcome's variability; the relevant issue is whether the statistical model represents the observed variation adequately. More generally, when data vary more than a model assumes, standard errors can be understated and confidence intervals can be too narrow. This is a general statistical consideration, not a reported feature of this trial. The registry record does not describe a model, dispersion assessment, or evidence of over-dispersion for this endpoint.

What analysis details are unavailable?

The registry record does not report a model for the primary endpoint, covariate adjustments, handling of repeated measurements, or the procedure for dealing with missing endpoint values. It does not state whether the primary analysis was based on all randomized participants, participants with observed measurements, or another analysis population. It also does not post a primary between-arm test or explain the reason the two-arm result was missing or not estimable. Those omissions limit the ability to evaluate assumptions and reproduce the comparative analysis from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and identifies three secondary outcomes: Tear Film Break-up Time, Conjunctival Redness, and the Ocular Surface Disease Index. Results for those listed secondary outcomes are not reported in the registry record. The record does not describe how many hypotheses were planned, which outcomes were included in any testing hierarchy, or whether any adjustment for multiple comparisons was planned or used. It is therefore not possible to determine how multiplicity was handled.

Multiplicity matters in general when several outcomes or analyses are tested, because interpreting each result separately can increase the chance of a seemingly notable finding arising by chance. This is a general statistical concern, not evidence that a particular error occurred in this study. The registry record does not provide the statistical analysis plan needed to assess the intended approach.

The endpoint information includes arm-level counts and mean changes, but the analysis population is not identified. The registry record does not report how many participants were randomized to each arm, how many completed the week 4 measurement, or how missing measurements were handled. It does not describe imputation, exclusion rules, or sensitivity analyses for missing data. These details should not be inferred from the endpoint counts alone.

The registry lists no analysis entries, and a two-arm comparison for the continuous endpoint is described as missing or not estimable. The reason is not reported in the registry record. Without a defined analysis population, missing-data method, and comparative result, readers cannot assess whether the posted arm summaries represent all randomized participants or a subset with available measurements.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 0 of 78 participants at risk in the BRM421 ophthalmic solution group and 0 of 79 participants at risk in the placebo group. No deaths are reported in either group. These are counts as recorded; they do not provide a comparative estimate or establish that the risks are identical.

Other adverse events are listed for 4 of 78 participants at risk in the BRM421 group and 3 of 79 at risk in the placebo group. These are separate from the serious adverse event counts. The registry does not provide the event terms for serious events, and its list of top serious-event terms is empty. The record does not give further detail about event definitions, timing, severity grading, or how events were assessed.

Adverse-event counts are descriptive safety information. In general, the interpretation of an event count depends on the number of participants observed, follow-up, event definitions, and completeness of reporting. A zero count in a group does not establish that an event cannot occur. The registry record does not provide enough detail to evaluate all those factors or to compare safety statistically.

The safety counts should be read alongside, but separately from, the primary efficacy endpoint. They do not answer the primary question about change in corneal staining, and the primary endpoint results do not substitute for a fuller safety assessment.

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

The posted results describe mean change in corneal fluorescein staining score from baseline to week 4 within each study arm. The BRM421 arm has a reported mean change of -1.06, with a 95% confidence interval from -1.5 to -0.62; the placebo arm has a mean change of -1.16, with a 95% confidence interval from -1.61 to -0.71. The registry identifies 76 and 75 participants, respectively, for these arm-level results.

Those summaries do not establish the effect of BRM421 relative to placebo. The comparative quantity is the difference between the groups' changes, and the registry record does not report that estimate, its confidence interval, or a p-value. It also states that values for the two-arm comparison were missing or not estimable. Without that direct comparison, the arm-specific estimates cannot determine whether the groups differed statistically or how precisely any difference was estimated.

The record also does not show whether the posted result is adjusted for baseline score or other variables, which participants were included in the analysis, or how missing measurements were handled. Such details affect how a comparative estimate should be interpreted, but they are not reported in the registry record. The stated endpoint is limited to corneal staining at week 4 and cannot represent every outcome relevant to dry eye.

The trial objective includes signs and symptoms, and the record lists secondary outcomes related to tear film, conjunctival redness, and symptoms. Their results are not reported in the registry record. The available endpoint information therefore does not supply a complete account of all outcomes named in the study.

These results should be understood as a limited statistical record: arm-specific changes and confidence intervals are posted, while the main between-arm analysis is not. They do not support a definitive conclusion about a comparative treatment effect, nor do they provide a complete basis for judging the study's efficacy or safety. This is an interpretation of the recorded statistics, not medical advice.

13. Why This Trial Matters Statistically

This trial illustrates why randomized design and a reported comparison answer different statistical questions. Randomization assigns participants to groups by chance and is intended to support a fair comparison. However, the primary result posted in the registry consists of separate arm-level means and confidence intervals. Those summaries describe changes within groups, while the clinical question concerns the difference between groups.

The distinction matters because the uncertainty around each arm mean is not the same as uncertainty around the treatment contrast. A reader needs the comparative estimate and its precision to judge what range of differences is compatible with the data. The registry record does not post those values for the primary endpoint, and states that a two-arm comparison was missing or not estimable. The record therefore makes the absence of a direct contrast central to interpretation.

The endpoint also demonstrates how a clinical sign can be operationalized as a continuous score. Corneal fluorescein staining is graded across three regions and combined into a total score, with a defined scale and a week 4 change measure. Clear definition of the outcome helps readers understand what the mean represents, but it does not by itself establish the comparative result.

Finally, the record lists secondary outcomes and safety counts, yet does not report secondary outcome results or details of the analysis plan, missing-data handling, or multiplicity control. These gaps are important because conclusions depend not only on the endpoint definition but also on which participants and analyses contribute to the evidence. The trial is a useful example of reading arm-level summaries cautiously when the comparative analysis is unavailable.

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 is that the registry record does not report an estimable between-arm comparison for the continuous primary endpoint. The posted mean changes and confidence intervals apply separately to BRM421 and placebo. No contrast, confidence interval for the contrast, or p-value is reported. The reason the comparison is missing or not estimable is not reported in the registry record.

The record does not identify the analysis population or explain the relationship between total enrollment of 157 and the arm-level endpoint counts of 76 and 75. It does not report participant flow, completion counts, baseline score distributions, or whether the analysis adjusted for baseline values. Missing-data methods and sensitivity analyses are also not reported.

Although the study objective covers signs and symptoms, the primary endpoint is corneal staining change at week 4. Three secondary outcomes are named, but their results are not reported in the registry record. The record does not provide a statistical plan, multiplicity approach, or sample-size justification. The dose and frequency of the intervention and further eligibility criteria are also not reported.

These omissions limit assessment of precision, reproducibility, and the scope of the conclusions that can be drawn from the posted results. The registry lists safety counts, but does not provide further event definitions or details of ascertainment. The safety information is therefore also limited to the counts and at-risk denominators recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of BRM421 for Dry Eye Syndrome — NCT03066219.
• Registry record last updated 2026-05-01; status last verified 2019-10.
• Results first posted 2026-05-01.
• 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

The registry describes a completed phase 2, randomized, double-masked, parallel-group study of BRM421 ophthalmic solution versus placebo for Dry Eye Syndrome. Total enrollment is 157, and the study used a controlled adverse environment model. The primary outcome was mean change from baseline to week 4 in corneal fluorescein staining score.

The posted mean changes are -1.06 for BRM421 and -1.16 for placebo, with 95% confidence intervals from -1.5 to -0.62 and from -1.61 to -0.71, respectively. The registry record does not report an estimable two-arm comparison for this endpoint. Secondary outcomes are listed without results in the record. Serious adverse events and deaths are recorded as 0 in both groups; other adverse events are recorded for 4 participants in the BRM421 group and 3 in the placebo group.

The comparative efficacy estimate, analysis population, missing-data approach, multiplicity plan, and trial-specific sample-size justification are not reported in the registry record.