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 Safety/Efficacy of Nepafenac Punctal Plug Delivery System Compared to Placebo to Control Ocular Pain/Inflammation After Cataract (NCT03496467), a randomized phase 2 study. The primary outcome is Assessment of Pain.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03496467 |
| Phase | Phase 2 |
| Condition | Pain, Inflammation |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 56 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mati Therapeutics Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People scheduled for routine unilateral cataract surgery were the intended study population. The registry record gives an enrollment of 56 but does not report further eligibility details or describe the characteristics of participants who entered the primary-outcome analysis.
Intervention
The intervention was the Nepafenac Punctal Plug Delivery System (N-PPDS), an L-shaped silicone punctal plug with a drug-eluting core containing active nepafenac. The brief summary says the plug was inserted in the lower punctum of the surgical eye before surgery and remained there for 2 weeks following surgery.
Comparator
The comparator was a placebo punctal plug delivery system (p-PPDS). The registry describes it as an L-shaped silicone plug with an insert containing no active ingredient. The brief summary says participants were randomized to N-PPDS or p-PPDS in a 2:1 allocation.
Primary question
The primary outcome was an assessment of pain at day 14, measured using a scale from 0 to 5, where 0 represents absence of pain and 5 represents definite, continuous, unbearable ocular or periocular pain. The registry record does not reduce the multiple categories or time points to one primary comparison, so it does not establish how the groups differed on this outcome.
3. Trial Design
This was a completed Phase 2, randomized, parallel-arm study comparing Nepafenac PPDS with Placebo PPDS after routine unilateral cataract surgery. The registry lists enrollment as 56. Its brief summary describes the study as multi-center and placebo-controlled, with randomization in a 2:1 allocation. The plugs were to be inserted in the lower punctum of the scheduled surgical eye 1 to 2 days before surgery and remain there for 2 weeks following surgery.
The registry's design fields classify masking as quadruple, while the brief summary describes the study as double-masked. These descriptions do not match; the record does not explain the difference. The record lists the study as completed and gives a start date of 2018-03-05 and a primary completion date of 2018-12-17.
The stated purpose was to assess safety and efficacy in controlling postoperative ocular pain and inflammation. The primary outcome is titled Assessment of Pain, with anterior chamber cells and flare listed as secondary outcomes. The registry record does not give further operational detail about how the secondary outcomes were scored or how they were incorporated into an analysis.
Randomization and masking can help reduce systematic differences in treatment assignment and outcome assessment, but they do not by themselves show that the groups were comparable in every respect or that an outcome favored either group. Interpreting those questions requires the outcome results and the analysis details. A single primary-outcome comparison is not available in the registry record, so the design information alone cannot answer the efficacy question.
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 | Nepafenac PPDS | Placebo PPDS |
|---|---|---|
| STARTED | 38 | 18 |
| COMPLETED | 34 | 14 |
| NOT COMPLETED | 4 | 4 |
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.
| Characteristic | Unit | Nepafenac PPDS | Placebo PPDS | Total |
|---|---|---|---|---|
| Participants analysed | 38 | 18 | 56 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 | 6 | 20 |
| Age, Categorical: >=65 years | Participants | 24 | 12 | 36 |
| Age, Continuous | years | 67.2 (SD 7.17) | 67.8 (SD 7.64) | 67.4 (SD 7.26) |
| Sex: Female, Male: Female | Participants | 19 | 11 | 30 |
| Sex: Female, Male: Male | Participants | 19 | 7 | 26 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 2 | 2 |
| Race (NIH/OMB): White | Participants | 38 | 15 | 53 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Region of Enrollment: United States | participants | 38 | 18 | 56 |
6. Primary Endpoint
The registry lists the primary outcome as Assessment of Pain, measured over day 14.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled Assessment of Pain and is reported as a count of participants. The stated assessment time is day 14. Pain is described on a scale from 0 to 5: 0 represents absence of pain, while 5 represents definite, continuous, unbearable ocular or periocular pain. The registry record does not state in the endpoint description how the scale values were grouped or which categories were used for a primary comparison.
Pain is relevant to the stated study question because the trial concerns postoperative ocular pain as well as inflammation. A scale can capture gradations in a participant's reported experience rather than recording only whether pain was present. However, a scale's clinical interpretation depends on its scoring, how observations are summarized, and how missing assessments are handled. Those analysis details are not reported in the registry record.
The registry record indicates that the primary outcome has several categories or time points and is not reduced to one comparison. It therefore does not provide a single treatment contrast, effect estimate, confidence interval, or p-value for this endpoint. The endpoint definition describes what was intended to be assessed, not the observed result or the size and precision of any difference between groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison of Nepafenac PPDS and Placebo PPDS, with postoperative pain assessed at day 14 and inflammation listed among the study's outcomes. It does not provide a single primary-outcome comparison for pain. The stated reason is that the outcome has several categories or time points and has not been reduced to one comparison. Consequently, the record does not support a conclusion about the direction, magnitude, or precision of a primary pain difference between groups.
No primary effect estimate, confidence interval, or p-value is reported in the registry record. Without a defined contrast and its results, there is no statistical basis in this record for saying whether the observed pain distributions differed, how large any difference was, or how compatible the data were with a range of possible effects. The scale description alone is not an outcome result.
The record lists anterior chamber cells and flare as secondary outcomes, but does not provide their results in the registry record described for this analysis. It also records no analyses. This means the available information does not permit an assessment of those outcomes or of any prespecified analysis strategy. It would be inappropriate to treat absence of a posted comparison as evidence that the groups were alike.
The safety figures are descriptive registry counts. For serious adverse events, the record lists 0 affected participants among 38 at risk in the Nepafenac PPDS group and 0 among 18 at risk in the Placebo PPDS group. For other adverse events, it lists 10 among 38 at risk and 3 among 18 at risk, respectively. Deaths are listed as 0 in each group. These counts do not establish a causal safety difference, and the record does not give event definitions, individual event details, follow-up completeness, or statistical comparisons.
Any sample-size figures associated with planning are illustrations based on stated assumptions, not observed trial power and not the original trial's design justification. The record says the illustration uses the observed effect, equal allocation, a normal approximation, and a two-sided significance level of 0.05, with the effect to detect expressed as a fraction of the observed effect. The protocol's sample-size justification is not reported in the registry record. Because the primary comparison is not available, the planning illustration should not be read as resolving the missing efficacy result.
9. Statistical Methods Explained
Interpreting a clinical trial requires a clear definition of what was compared, which outcome was analyzed, and how uncertainty was quantified. The registry describes random allocation to Nepafenac PPDS or Placebo PPDS and identifies pain at day 14 as the primary outcome. It does not, however, provide one primary comparison from the multiple categories or time points. The methods used for such a comparison are not reported in the registry record, so the posted information does not permit reconstruction of an efficacy analysis.
What does randomization contribute?
In general, randomization assigns participants to study groups by chance. It is intended to reduce systematic differences between groups at enrollment, including differences that investigators may not have measured. It does not guarantee that every characteristic will be balanced, particularly in a small trial, and it does not replace reporting the outcome data. The registry says allocation was randomized and the brief summary describes a 2:1 assignment, but the record does not give details of the randomization procedure or its implementation.
What does masking contribute?
In general, masking is intended to limit the influence of knowledge about treatment assignment on care, reporting, or outcome assessment. The design fields classify masking as quadruple, whereas the brief summary calls the study double-masked. The registry record does not explain this difference or specify which people were masked. The discrepancy should therefore remain visible rather than being resolved by assumption.
How should the pain scale be understood?
The outcome description uses a scale from 0 to 5, with anchors at 0 and 5. In general, a scale may be analyzed as its individual categories, as a summary score, or after combining categories. Each choice answers a different statistical question and may affect the interpretation. The registry record does not state which approach was used, how the categories were handled, or how multiple time points relate to the primary analysis. The reason given for not presenting one comparison is that the primary outcome has several categories or time points.
What would an effect estimate and confidence interval show?
In general, an effect estimate describes the size and direction of a contrast between groups for a specified outcome. A confidence interval describes the uncertainty around that estimate under the assumptions of the analysis. A narrow interval indicates greater statistical precision than a wide interval, while an interval spanning effects in different directions may leave the direction uncertain. Neither an estimate nor an interval can be interpreted without knowing the contrast, outcome definition, analysis population, and method. No primary effect estimate or confidence interval is reported in the registry record.
What can a p-value tell a reader?
In general, a p-value measures how incompatible the observed data are with a specified statistical model or null hypothesis, assuming the model and hypothesis are appropriate. It does not measure the probability that a treatment works, the size of an effect, or the importance of a result. A p-value also cannot correct for choosing among multiple outcomes or analyses after observing results. The registry record does not report a primary-outcome p-value or a statistical analysis plan.
Why does multiplicity matter?
In general, testing multiple outcomes, time points, or comparisons can increase the chance of at least one apparently unusual result when all tests are considered together. Statistical plans may address this through a prespecified testing hierarchy, adjustment, or other approach. The record lists a primary outcome with several categories or time points and secondary outcomes for anterior chamber cells and flare. It does not describe a multiplicity strategy, so the interpretation of any unreported or separately reported tests cannot be assessed from this record.
How should planning calculations be read?
The stated planning illustration uses the observed effect as its reference and assumes a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such calculations show what sample size might be needed under specified assumptions. They are not the same as the trial's actual design rationale, and they are not observed power. The registry record does not report the trial's own sample-size justification. The illustration cannot replace a reported outcome estimate, especially when the primary comparison itself is not available.
Why are adverse-event counts not a treatment-effect analysis?
Counts describe how many participants were recorded with an event among those listed at risk. In general, interpreting safety differences also depends on event definitions, duration and completeness of observation, severity, and the method used to compare groups. The registry provides serious-event, other-event, and death counts, but does not provide those additional details or a statistical comparison. These counts should be read descriptively and not as proof of either benefit or harm.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is Assessment of Pain at day 14, but the registry record states that the primary outcome has several categories or time points and is not reduced to one comparison. Without a specified contrast, a reader cannot determine which category, summary, or time point was intended to carry the primary inference. The record lists Assessment of Anterior Chamber Cells and Assessment of Flare as secondary outcomes, but their results are not reported in the registry record.
In general, multiplicity arises when several outcomes, time points, or statistical tests are considered. A prespecified strategy can define which result is primary and how additional tests are interpreted. The registry record does not report whether such a strategy was planned or used, nor does it report an adjustment method or analysis hierarchy. The appropriate multiplicity handling is therefore not reported in the registry record.
The record gives no analysis population, such as whether analyses were based on randomized participants, participants who received a plug, or participants with an observed day-14 assessment. It does not state how missing outcome data were handled, whether participants discontinued, or whether any sensitivity analyses were performed. These details are important because missing assessments and changes in the analysis population can affect the meaning of a comparison.
The record lists 0 analyses. This absence of posted analysis details should not be interpreted as evidence that no analyses were performed; it means the analysis methods are not reported in the registry record. No statistical plan, interim analysis approach, or missing-data method is reported.
11. 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 |
|---|---|---|---|
| Nepafenac PPDS | 0 | 38 | 0.0% |
| Placebo PPDS | 0 | 18 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Nepafenac PPDS | 0 of 38 |
| Placebo PPDS | 0 of 18 |
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 |
|---|---|
| Nepafenac PPDS | 10 of 38 |
| Placebo PPDS | 3 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Nepafenac PPDS | Placebo PPDS |
|---|---|---|---|
| elevated IOP | Eye disorders | 3 of 38 | 0 of 18 |
| iritis | Eye disorders | 2 of 38 | 1 of 18 |
| Pain/irritation/inflammation | Eye disorders | 3 of 38 | 0 of 18 |
| Headache | Nervous system disorders | 1 of 38 | 1 of 18 |
| posterior capsule rupture | Eye disorders | 0 of 38 | 1 of 18 |
| Cavity, 3rd molar | General disorders | 1 of 38 | 0 of 18 |
The registry lists serious adverse events by group. In the Nepafenac PPDS group, 0 participants were affected among 38 at risk; in the Placebo PPDS group, 0 were affected among 18 at risk. The death count is 0 in each group. For other adverse events, the record lists 10 affected among 38 at risk in the Nepafenac PPDS group and 3 among 18 at risk in the Placebo PPDS group.
These are counts, not estimates of a causal treatment effect. The registry record does not provide event descriptions, definitions, severity details, timing, or a statistical comparison. It also does not explain the categorization of events beyond distinguishing serious events from other adverse events. A count of zero serious events in the posted record does not establish that no unrecorded events occurred or that the groups have identical safety profiles.
In general, safety comparisons require attention to who was observed, how long observation continued, and how events were collected and classified. Those details are not reported in the registry record. The listed counts should therefore be read as descriptive reporting for this trial, not as proof of safety or of a difference between groups.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase 2 randomized study compared Nepafenac PPDS with Placebo PPDS after routine unilateral cataract surgery. It defines a day-14 pain assessment on a scale from 0 to 5 and lists anterior chamber cells and flare as secondary outcomes. It also gives group-level adverse-event counts. This information describes the study question, its broad design, and some reported safety data.
The record does not establish whether pain differed between groups. The primary outcome has multiple categories or time points and is not reduced to one comparison. No primary effect estimate, confidence interval, or p-value is reported in the registry record. The endpoint definition and allocation description cannot substitute for observed outcome results.
The absence of a single posted pain comparison is not evidence that there was no difference. Nor can it be taken as evidence that a difference existed. Without an interpretable contrast and its uncertainty, the direction and precision of any possible effect remain unknown from this record. The secondary outcomes likewise cannot be interpreted because their results are not reported in the registry record.
The safety counts document what the registry lists for serious adverse events, other adverse events, and deaths. They do not by themselves demonstrate that one study product caused more or fewer events. The registry record lacks the event-level details and analysis information needed for a fuller safety comparison.
Overall, the posted information supports a description of the randomized trial and its recorded safety counts, but not a conclusion about the primary pain outcome. The registry record also does not report the statistical plan, missing-data approach, analysis populations, or sample-size justification. These omissions limit how fully the study's findings and their uncertainty can be evaluated.
13. Why This Trial Matters Statistically
This trial raises several statistical issues that are common in clinical research. A randomized, parallel-arm design creates a framework for comparing treatment groups, but the value of that framework depends on a clearly specified endpoint and a reported analysis. Here, pain was assessed on a multi-category scale at day 14, while the registry notes several categories or time points and does not present one primary comparison. That makes the distinction between an outcome definition and an interpretable treatment contrast especially important.
The record also highlights why reporting a point estimate and its uncertainty matters. A label such as “Assessment of Pain” identifies the subject of measurement, but it does not tell readers how the groups compared or how precise that comparison was. Without the actual contrast and its uncertainty, readers cannot judge whether the observed data are compatible with meaningfully different possibilities.
Masking descriptions also warrant careful attention. The design fields say quadruple masking, while the brief summary says double-masked. This difference does not establish that masking failed, but it leaves a reporting ambiguity about who was masked. Clear descriptions help readers assess how knowledge of group assignment might have influenced care, assessment, or reporting.
Finally, the registry presents safety counts but not event definitions or comparative analyses. Descriptive counts are useful, yet their interpretation depends on who was followed, for how long, and how events were collected. The record's limitations illustrate why transparency about outcome handling, missing data, analysis populations, and statistical planning is essential alongside a trial's basic design description.
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 main trial-specific limitation in the registry record is that the primary pain outcome is not presented as one comparison. The endpoint is described at day 14 using a scale from 0 to 5, but the record says it has several categories or time points and is not reduced to a single comparison. This prevents an interpretation of the primary treatment contrast.
The registry lists secondary outcomes for anterior chamber cells and flare but does not provide their results in the registry record described for this analysis. It also lists no analyses. The statistical analysis plan, the handling of multiple outcomes or time points, and the method for any reported comparisons are not reported in the registry record.
Analysis populations and missing-data handling are also not described. The record does not state how many participants contributed primary-outcome data, how absent assessments were handled, or whether any sensitivity analyses were performed. These omissions limit assessment of the potential effect of incomplete outcome data.
There is a masking-description inconsistency: the design fields classify the trial as quadruple-masked, while the brief summary calls it double-masked. The record does not explain the difference. The safety data are limited to group counts; event descriptions, definitions, follow-up details, and comparative analyses are not reported. Finally, the trial's own sample-size justification is not reported in the registry record, and planning illustrations based on stated assumptions should not be treated as a substitute for it.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety/Efficacy of Nepafenac Punctal Plug Delivery System Compared to Placebo to Control Ocular Pain/Inflammation After Cataract — NCT03496467.
- Registry record last updated 2021-10-12; status last verified 2021-09.
- Results first posted 2021-10-12.
- 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.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
The registry describes a completed Phase 2 randomized, parallel-arm study of Nepafenac PPDS versus Placebo PPDS for postoperative ocular pain and inflammation after routine unilateral cataract surgery. Enrollment is listed as 56. The brief summary describes 2:1 randomization and plugs intended to remain in the lower punctum for 2 weeks following surgery.
The primary outcome is Assessment of Pain at day 14 on a scale from 0 to 5. The record does not present one primary comparison because the outcome has several categories or time points. It lists anterior chamber cells and flare as secondary outcomes, but their results are not reported in the registry record.
Safety counts include 0 serious adverse events in each group and 0 deaths in each group; other adverse events are listed as 10 among 38 at risk for Nepafenac PPDS and 3 among 18 at risk for Placebo PPDS. The primary efficacy comparison, statistical analysis plan, analysis populations, and missing-data methods are not reported in the registry record.