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 2nd Study to Assess ISV-305 Compared to Vehicle for Treatment of Inflammation and Pain Associated With Cataract Surgery (NCT03192150), a randomized phase 3 study. The primary outcome is Number of Participants With Anterior Chamber Cell Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03192150 |
| Phase | Phase 3 |
| Condition | Inflammation and Pain Associated With Cataract Surgery |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 246 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sun Pharmaceutical Industries Limited |
| Results posted | Yes |
2. Clinical Question
Population
The primary endpoint was defined for the modified Intent to Treat population. This included randomized participants who underwent cataract surgery, received at least one dose of ISV-305 or vehicle, and had at least one post-surgery efficacy assessment of anterior chamber cells or pain. Participants who received rescue medications were included in this population, although the registry description of how they were treated is incomplete.
Intervention
ISV-305 was 0.1% dexamethasone in DuraSite 2. The study evaluated its ocular safety, tolerability, and efficacy in the setting of cataract surgery.
Comparator
The comparator was DuraSite 2 vehicle. The registry lists it as the vehicle intervention and identifies it as the control arm.
Primary question
The primary endpoint asks how many participants in each group had an anterior chamber cell grade of 0 in the study eye at Day 15, using last observation carried forward for missing Day 15 grades. The registry record does not report the arm-level primary endpoint counts or a statistical comparison, so the size and precision of any difference cannot be assessed from the posted results.
3. Trial Design
This was a Phase 3, randomized, multicenter, parallel-group study comparing ISV-305 with DuraSite 2 vehicle. The registry identifies masking as quadruple. The study was designed to assess ocular safety, tolerability, and efficacy for inflammation and pain associated with cataract surgery. Enrollment was 246. The record gives a study start date of 2018-01-03 and a primary completion date of 2019-11-18, and lists the study status as completed.
The intervention was ISV-305, described as 0.1% dexamethasone in DuraSite 2. The comparator was DuraSite 2 vehicle. The primary endpoint concerned anterior chamber cell grade in the surgery eye at Day 15. The study also listed a pain outcome: the number of participants with a pain score of 0 on a 0-100 mm Visual Analog Scale at post-surgical assessments on Days 1, 8, 15, 18, and 29.
Random assignment is intended to make treatment groups comparable, on average, with respect to measured and unmeasured factors at the start of a trial. Masking is intended to limit the influence of knowledge of treatment assignment on care, assessment, and reporting. These are general features of trial design; the registry record does not give further operational details about the randomization or masking procedures.
The registry lists two outcome measures and six analyses. It does not report the planned allocation ratio, the methods used to generate or conceal assignments, or a detailed statistical analysis plan. These details are not reported in the registry record and should not be inferred from the trial's design labels alone.
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 | ISV-305 | Vehicle |
|---|---|---|
| STARTED | 163 | 83 |
| COMPLETED | 108 | 29 |
| NOT COMPLETED | 55 | 54 |
Reasons for not completing this period:
| Reason | ISV-305 | Vehicle |
|---|---|---|
| Adverse Event | 14 | 12 |
| Lack of Efficacy | 23 | 30 |
| Lost to Follow-up | 1 | 1 |
| Withdrawal by Subject | 4 | 2 |
| Protocol Violation | 5 | 2 |
| Surgery Canceled | 6 | 2 |
| Other-Various Administrative Reasons | 2 | 5 |
Analysis population for the primary outcome, as defined in the registry: mITT Population - included randomized participants who underwent cataract surgery, received at least one dose of ISV-305 or vehicle, and had at least one post-surgery efficacy assessment (ACC or VAS). Participants who received rescue medications were included in the mITT Population, but were treated as failures.
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: Demographics were summarized for the Safety Population, which included all the randomized participants who received at least one dose of study treatment.
| Characteristic | Unit | ISV-305 | Vehicle | Total |
|---|---|---|---|---|
| Participants analysed | 152 | 79 | 231 | |
| Age, Continuous | years | 69.3 (SD 8.84) | 71.2 (SD 9.12) | 69.9 (SD 8.96) |
| Sex: Female, Male: Female | Participants | 88 | 40 | 128 |
| Sex: Female, Male: Male | Participants | 64 | 39 | 103 |
| Race/Ethnicity, Customized: African American or Black | Participants | 16 | 4 | 20 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Asian | Participants | 5 | 0 | 5 |
| Race/Ethnicity, Customized: White | Participants | 130 | 72 | 202 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Mixed | Participants | 0 | 2 | 2 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Anterior Chamber Cell Grade 0 in Study Eye at Day 15 (Last Observation Carried Forward) in the Modified Intent to Treat (mITT) Population, measured over Day 15.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with anterior chamber cell grade 0 in the study eye at Day 15. Anterior chamber cells were assessed by biomicroscopy in the eye that underwent surgery. The record describes use of a slit-lamp biomicroscope at x16 magnification, with two cell counts averaged to obtain a final count. That count was converted to a grade: grade 0 corresponded to no cells, while higher grades represented increasing cell counts. If an average fell between grade ranges, the higher grade was assigned.
A grade of 0 is a categorical endpoint, not a direct measure of the size of a change in cell count. Counting participants who meet a defined category can make a clinical assessment easier to interpret as a responder outcome. However, the registry record does not report how many participants in either arm achieved grade 0 or the statistical comparison between arms. It therefore does not establish the magnitude or precision of any group difference.
For a missing Day 15 assessment, the endpoint used the last non-missing scheduled post-baseline cell grade assessed before Day 15. This is the last observation carried forward approach. It substitutes an earlier measured value for the missing Day 15 value; it does not make the missing measurement an observed Day 15 assessment. Its implications depend on the pattern of missingness and how earlier measurements relate to the unobserved Day 15 grade.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint is defined clearly enough to identify what was intended to be counted: participants with grade 0 anterior chamber cells in the study eye at Day 15, in the modified Intent to Treat population, with missing Day 15 grades handled by last observation carried forward. The registry record does not report the number meeting this endpoint in either arm, an effect estimate, a confidence interval, or a p-value. Consequently, the primary comparison's direction, magnitude, and statistical precision are not available from the reported information.
This distinction matters because a trial's design and endpoint definition do not themselves provide evidence about the outcome. Randomization, masking, and a prespecified assessment time can support a credible comparison when implemented and analyzed appropriately, but interpretation also requires the observed results and the methods used to analyze them. The registry record does not report the statistical analysis plan, so it is not possible to determine from this information which inferential procedure was planned for the primary endpoint or whether any adjustment was used.
The registry lists a secondary pain outcome based on achieving a VAS score of 0 at multiple post-surgical assessments. That outcome is a separate measure from the Day 15 cell-grade endpoint. Although the assessment days are listed, the registry record does not report the arm-specific pain counts or comparisons. The presence of multiple assessment times raises a general interpretive issue: repeated outcomes can generate multiple opportunities to observe differences, so the analysis plan and any handling of multiplicity are important. The record does not describe that handling.
Safety information is reported for serious adverse events. In the ISV-305 group, 1 serious adverse event was reported among 152 participants at risk; in the vehicle group, 0 were reported among 79 participants at risk. No deaths were reported in either group. These counts describe the registry's serious-event reporting, but they do not establish whether a treatment caused an event, and the small event counts do not support a precise comparative safety estimate. The record also lists small intestinal obstruction and pneumonia among the top serious event terms, each at 0.7%; it does not provide enough detail in the registry record reported to assign those terms to a particular group.
Overall, the posted information establishes the trial question, design, endpoint definition, and some serious adverse event counts. It does not supply the primary efficacy results needed to assess the endpoint comparison. Conclusions about efficacy or the statistical strength of an efficacy finding cannot be drawn from the endpoint description alone.
9. Statistical Methods Explained
What does a binary endpoint count?
The primary outcome is a count of participants who reached a specified category, grade 0, at Day 15. In general, a binary outcome classifies each participant into one of two states for a particular analysis, such as meeting or not meeting a criterion. Reporting the number of participants meeting the criterion gives an event count. A group comparison can then describe how often the criterion was met across the randomized groups.
Counts are easier to interpret when the numbers assessed in each group and the analysis population are also clear. Estimates of a group difference and their confidence intervals can add information about uncertainty. A confidence interval is a range of values compatible with the data under the assumptions of the statistical method. It describes statistical uncertainty; it is not a guarantee that the true effect lies within the interval. The registry record does not report primary endpoint counts, an effect estimate, or a confidence interval, so the comparison cannot be reconstructed from the endpoint description.
What does the modified Intent to Treat population mean?
The mITT population in this record consists of randomized participants who underwent cataract surgery, received at least one dose of study treatment, and had at least one post-surgery efficacy assessment of anterior chamber cells or pain. This population definition excludes people who do not satisfy those stated conditions. It is therefore not identical, by definition, to an analysis of every randomized participant.
In general, retaining randomized participants in their assigned groups helps preserve the balance created by randomization. When an analysis population requires post-randomization events or assessments, such as receiving treatment and having an efficacy measurement, its composition can depend on events after assignment. The registry's mITT definition and its inclusion of participants who received rescue medications should be considered when interpreting the target population. The record's description of how rescue medication use was handled is truncated, and the full approach is not reported in the registry record.
What is last observation carried forward?
For a missing Day 15 cell grade, the described method used the last non-missing scheduled post-baseline cell grade recorded before Day 15. This is a simple imputation rule: an earlier observed grade is used in place of the missing endpoint value. It allows a participant with a missing Day 15 grade to contribute a value to the endpoint analysis, but that value is not a new measurement at Day 15.
As a general statistical matter, an imputation method relies on assumptions about how missing measurements relate to observed measurements and to the unobserved value. Carrying a prior value forward may fail to represent subsequent change. If missingness differs between groups or is related to outcome status, the resulting comparison can be affected. The registry record does not report the extent or pattern of missing Day 15 data, or sensitivity analyses testing alternative missing-data assumptions. It is therefore not possible to assess how much the imputation influenced the primary result.
Why do multiplicity and repeated assessment times matter?
The registry lists a pain outcome at Days 1, 8, 15, 18, and 29, as well as the primary cell-grade endpoint. In general, testing multiple outcomes or assessment times can increase the chance that at least one comparison appears statistically notable even when there is no underlying effect. Statistical plans may address this through a prespecified hierarchy, an adjustment to significance thresholds, or another strategy. The registry record does not report whether such a strategy was planned or used. It also does not identify which of the six listed analyses correspond to particular outcomes or comparisons.
The study's masking and randomization are design characteristics, not substitutes for reporting the analysis. The record does not state the statistical test, model, covariates, significance level for the primary analysis, or whether the primary comparison was adjusted. These details are not reported in the registry record. In the absence of that information and the primary outcome results, no independent inferential assessment can be made.
How should sample-size illustrations be read?
Planning calculations based on an observed effect are illustrations of the number of participants per arm that might be needed under specified assumptions. The registry's described illustration uses a two-sided significance level of 0.05, equal allocation between groups, a normal approximation, and alternative target effects defined as fractions of the observed effect. Such calculations are conditional on their assumptions and on the effect used as the reference.
These planning illustrations are not observed trial results, do not establish the trial's original design justification, and are not observed power. The registry record does not report the original sample-size justification or the assumptions used to plan enrollment. If the effect used for an illustration is imprecisely estimated, the resulting planning estimate is also uncertain. It should not be interpreted as proof that the trial was adequately or inadequately powered for its primary question.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint uses last observation carried forward when a Day 15 cell grade is missing. Specifically, the last non-missing scheduled post-baseline grade before Day 15 was carried forward. This describes the imputation rule, but the registry record does not report how many Day 15 values were missing, the reasons for missingness, or whether missingness differed between groups. It also does not report sensitivity analyses using alternative assumptions about missing data.
The primary population was mITT: randomized participants who underwent cataract surgery, received at least one dose of ISV-305 or vehicle, and had at least one post-surgery efficacy assessment of anterior chamber cells or pain. Participants who received rescue medications were included. The registry description does not fully specify how rescue medication use affected outcome handling, and further details are not reported in the registry record.
The record lists a primary endpoint and a pain outcome evaluated at several post-surgical days, alongside six analyses. In general, multiple outcomes and repeated time points raise multiplicity concerns because they create several possible statistical comparisons. The registry record does not report a multiplicity adjustment, a testing hierarchy, or the full statistical analysis plan. It is therefore not possible to determine how the analyses were prioritized or how any multiplicity was addressed.
The record also does not report whether interim analyses were planned or performed. No assumptions about interim monitoring or multiplicity control should be made in the absence of that information.
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 |
|---|---|---|---|
| ISV-305 | 1 | 152 | 0.7% |
| Vehicle | 0 | 79 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| ISV-305 | 0 of 152 |
| Vehicle | 0 of 79 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ISV-305 | 47 of 152 |
| Vehicle | 30 of 79 |
Most frequent serious adverse event terms
| Event term | Organ system | ISV-305 | Vehicle |
|---|---|---|---|
| Small intestinal obstruction | Gastrointestinal disorders | 1 of 152 | 0 of 79 |
| Pneumonia | Infections and infestations | 1 of 152 | 0 of 79 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ISV-305 | Vehicle |
|---|---|---|---|
| Anterior chamber cell | Eye disorders | 18 of 152 | 10 of 79 |
| Conjunctival hyperaemia | Eye disorders | 11 of 152 | 11 of 79 |
| Visual acuity reduced | Eye disorders | 12 of 152 | 10 of 79 |
| Corneal oedema | Eye disorders | 11 of 152 | 7 of 79 |
| Anterior chamber flare | Eye disorders | 10 of 152 | 7 of 79 |
| Intraocular pressure increased | Investigations | 12 of 152 | 4 of 79 |
| Conjunctival oedema | Eye disorders | 5 of 152 | 4 of 79 |
| Eye pain | Eye disorders | 1 of 152 | 8 of 79 |
| Headache | Nervous system disorders | 6 of 152 | 3 of 79 |
| Conjunctival haemorrhage | Eye disorders | 6 of 152 | 2 of 79 |
Serious events with the highest arm-level rate: small intestinal obstruction (0.7%), pneumonia (0.7%).
The serious adverse event figures are reported separately by group. In the ISV-305 group, 1 serious adverse event was reported among 152 participants at risk. In the vehicle group, 0 serious adverse events were reported among 79 participants at risk. The reported number of deaths was 0 in each group. These are counts, not estimates of a treatment effect.
The registry also identifies small intestinal obstruction and pneumonia as the top serious event terms, each reported as 0.7%. The available information does not establish which group or groups those terms refer to, so they should not be assigned to an arm. Nor does the record provide further context about timing, relatedness to treatment, or clinical course.
Serious adverse event counts are useful for describing events captured in a trial, but a small number of events gives limited information about comparative risk. A difference in counts alone does not show that treatment caused or prevented an event. The registry record does not report a statistical comparison of serious adverse events. These figures should be read as safety reporting within this study, not as a complete estimate of risk.
12. What the Result Does, and Does Not, Mean
The record describes a randomized, masked Phase 3 trial of ISV-305 versus DuraSite 2 vehicle for inflammation and pain associated with cataract surgery. It defines the primary endpoint as the number of participants with grade 0 anterior chamber cells in the study eye at Day 15, using a modified Intent to Treat population and last observation carried forward for missing endpoint assessments. It also identifies a pain outcome assessed at several post-surgical times.
These design and measurement details clarify what the study set out to assess. They do not show what the primary endpoint found. The registry record does not report the primary outcome counts by group, a comparison estimate, a confidence interval, or a p-value. It is therefore not possible to state from the reported information whether the groups differed on the primary endpoint, how large any difference was, or how precisely it was estimated. The pain outcome results are also not reported in the registry record.
The serious adverse event information gives counts by group and reports no deaths. Those figures provide descriptive safety information but do not establish causation or a precise comparative safety effect. The registry's event-term percentages likewise should not be interpreted as evidence about a particular group when the group assignment is not stated in the reported details.
More generally, a trial's sample size, phase, randomization, and masking do not replace outcome estimates and methods. Interpretation of a comparative result requires the results themselves, a clear account of the analysis population, and sufficient statistical detail to understand uncertainty and multiplicity. The registry record does not report several of those elements. No conclusion about efficacy or overall treatment benefit follows from the information described.
13. Why This Trial Matters Statistically
This trial raises several important statistical interpretation issues common in clinical studies. Its primary endpoint is a categorical responder-type measure derived from an anterior chamber cell assessment. The rule for converting cell counts into grades, including assigning the higher grade when an average fell between grade ranges, is relevant because the endpoint depends on a classification threshold. The reported endpoint definition makes the intended criterion identifiable, but outcome counts and comparative estimates are needed to evaluate the observed result.
The population and missing-data rules also matter. The mITT definition requires surgery, treatment exposure, and at least one post-surgery efficacy assessment, while missing Day 15 grades were handled by carrying an earlier grade forward. Each rule affects which observations contribute to the endpoint and how missing information is represented. Statistical interpretation should therefore consider both the analysis population and the assumptions behind imputation, rather than treating the endpoint as a direct summary of every randomized participant's observed Day 15 status.
The pain measure was scheduled at multiple post-surgical times, and the registry lists six analyses overall. Repeated outcomes make transparent reporting of the analysis plan especially important. Without a reported testing hierarchy or multiplicity strategy, readers cannot determine how comparisons were selected or interpreted. The record also does not report a primary analysis method, effect estimates, or uncertainty intervals.
Finally, the serious adverse event counts illustrate why rare events require cautious interpretation. A small number of reported events can describe what occurred in the trial, but cannot by itself support a precise comparative safety conclusion. The registry record is informative about the study's design and endpoint definitions, while leaving key efficacy and inferential details 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.
The most important limitation of the reported information is that the primary endpoint results are absent. No arm-level counts, comparative effect estimate, confidence interval, or p-value are reported in the registry record. The pain outcome results are also not reported. Without those results, the central efficacy comparison cannot be evaluated for direction, magnitude, or precision.
The registry identifies a modified Intent to Treat population and describes last observation carried forward for missing Day 15 grades, but does not report the amount or pattern of missing data. It does not provide sensitivity analyses or enough information to assess the impact of the imputation rule. The definition includes participants with at least one post-surgery efficacy assessment and excludes those who do not meet the stated criteria; how this selection affected group comparability is not reported.
The endpoint depends on a cell-count grading process. The record describes the measurement and grade thresholds, but does not report assessment reliability or how often the same examiner was used when that was not possible. It notes that the same examiner was used whenever possible, which leaves some possibility of examiner variation. The record does not report how frequently assessments were performed by different examiners.
The statistical analysis plan, primary test or model, multiplicity handling, and any interim analyses are not reported in the registry record. Further, the serious adverse event counts are sparse, and the available details do not establish event attribution or provide a comparative statistical analysis. These limitations constrain interpretation of efficacy and safety from the reported information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: 2nd Study to Assess ISV-305 Compared to Vehicle for Treatment of Inflammation and Pain Associated With Cataract Surgery — NCT03192150.
- Registry record last updated 2021-11-19; status last verified 2021-11.
- Results first posted 2021-01-11.
- 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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18. Record Summary
This completed Phase 3 study was randomized, multicenter, parallel-group, and quadruple-masked. It compared ISV-305, described as 0.1% dexamethasone in DuraSite 2, with DuraSite 2 vehicle for inflammation and pain associated with cataract surgery. Enrollment was 246. The study start date was 2018-01-03, and the primary completion date was 2019-11-18.
The primary endpoint was the number of mITT participants with anterior chamber cell grade 0 in the study eye at Day 15, with last observation carried forward for missing grades. A pain outcome was listed at Days 1, 8, 15, 18, and 29. The registry record does not report the primary endpoint results, pain outcome results, or a detailed statistical analysis plan. Serious adverse event counts were 1 among 152 participants at risk in the ISV-305 group and 0 among 79 participants at risk in the vehicle group; deaths were 0 in both groups.