Control of Pain in Intravitreal Injections Using Topical NSAIDs: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Control of Pain in Intravitreal Injections Using Topical NSAIDs (NCT04343222), a randomized phase 4 study. The primary outcome is McGill Pain Questionnaire (SF-MPQ) Scores at Baseline.

2. Clinical Question

The study's hypothesis was that a topical NSAID would alleviate pain experienced at intravitreal injection and after the injection. The two Bromfenac schedules place the active eye drop at different times relative to injection, while the artificial-tears schedule serves as the comparison regimen. The registry record does not report an analysis of change from baseline, a between-group effect estimate, or a statistical test of the stated hypothesis. The posted baseline means and ranges can describe the recorded scores in each group, but cannot answer whether the schedules differed in injection-related pain.

3. Trial Design

The COPIVIN Study is registered as a Phase 4, randomized, double-masked, parallel study. The registry record reports enrollment of 46 participants and a completed status. Its listed study dates are 2019-06-27 for start and 2019-12-19 for primary completion. The record says participants could expect to be on study for a day.

Participants were assigned to one of three regimens. Group A received Bromfenac 0.09% 30 minutes before the injection and artificial tears immediately after the injection and wash. Group B received artificial tears before injection and Bromfenac immediately after injection and wash. Group C received artificial tears at both specified times. Thus, the arms differ in whether Bromfenac is given before or after the injection, with artificial tears used at the other time, or whether artificial tears are used at both times.

Randomization can help balance measured and unmeasured characteristics across assigned groups on average; it does not ensure that groups have identical baseline values, especially in a study with limited enrollment. Double masking indicates that masking was part of the registered design, but the registry record does not specify who was masked or how masking was maintained. The allocation sequence and any details of concealment are not reported in the registry record.

The posted primary outcome is a baseline SF-MPQ score, reported as a mean and full range for each group. No inferential analyses are listed. The registry record does not report the planned statistical comparison, an analysis population, handling of repeated measurements, or a sample-size justification. Although the description refers to assessment before and after injection, the posted primary outcome timeframe is Baseline. This distinction limits what the displayed primary result can tell readers about pain following injection.

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 McGill Pain Questionnaire (SF-MPQ) Scores at Baseline, measured over Baseline.

The Short-Form McGill Pain Questionnaire (SF-MPQ) records pain using sensory and affective descriptors. The registry description says the questionnaire contains 15 descriptors, each rated from 0 to 3, with 0 meaning none, 1 mild, 2 moderate, and 3 severe. The total possible score range is 0-45, with higher scores indicating more intense pain. Combining descriptor ratings gives a structured way to represent patients' reported pain rather than relying only on an unstructured description.

The registry presents the primary outcome as “McGill Pain Questionnaire (SF-MPQ) Scores at Baseline,” with a mean and full range. A baseline score can describe reported pain before the study regimen's intended post-injection assessment, and can provide context for the groups' recorded starting values. In this record, the scores are 0.62 for Group A, 0.93 for Group B, and 0.53 for Group C; their reported full ranges are 0.0 to 3.0, 0.0 to 4.0, and 0.0 to 2.0, respectively.

The outcome description also refers to an analgesic effect pre- and post-injection, but the registered timeframe for this primary result is Baseline. A baseline score alone does not quantify change after treatment or a contrast between treatment schedules. The registry record does not report an outcome result at a post-injection timeframe or an analysis that relates baseline scores to later pain scores.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the study as randomized, double-masked, and parallel. These are design descriptions, not results. Random allocation is intended to make assigned groups comparable on average with respect to factors that could influence outcomes. In practice, chance differences can remain, and baseline summaries can describe the groups' observed starting values. Masking is intended to reduce the influence of expectations on care or outcome assessment, but the record does not specify which people were masked or how masking was implemented. In a parallel design, participants are assigned to a regimen rather than described as crossing through each regimen; details beyond the registered design label are not reported in the registry record.

What does the reported mean represent?

A mean is the arithmetic average of the recorded scores in a group. It provides a compact measure of the group's central score, but it does not describe every participant's response or the shape of the score distribution. For this outcome, the means reported are 0.62 for Group A, 0.93 for Group B, and 0.53 for Group C. The registry also reports a full range for each group. A range gives the endpoints of the observed values; it does not show how many observations fell at any score, nor does it quantify uncertainty in the group mean.

Means are often used to summarize a score when the score's numerical scale is treated as quantitative. The SF-MPQ is built from ratings of sensory and affective descriptors, each on a 0-3 scale, and the total score can range from 0-45. The record identifies the result parameter as a mean and reports no standard deviation, standard error, median, or other distribution summary. Consequently, the posted summaries do not allow a reader to reconstruct the score distribution or calculate a confidence interval for the mean without making assumptions that the registry does not report.

What would an inferential comparison add?

An inferential comparison would estimate how the outcome differs between assigned regimens and express uncertainty around that estimate. A confidence interval is a range of values compatible with the data and the assumptions of the analysis; it conveys precision as well as the direction and scale of an estimated effect. A hypothesis test addresses compatibility with a specified null hypothesis under a statistical model. Neither replaces judgment about whether the estimate is meaningful, and neither can be read from group means and ranges alone. The registry record reports no between-group effect estimate, confidence interval, or p-value for this primary result.

Analysis choices also depend on the exact outcome and timing. A baseline-only comparison describes starting scores. An analysis of post-injection scores, change from baseline, or repeated measurements would answer a different question and require the relevant outcome data and a defined method. Although the description mentions pre- and post-injection assessment, the registered primary timeframe is Baseline. The registry does not report whether any repeated-measures analysis was planned or conducted.

Why are assumptions and variability important?

Statistical methods rely on assumptions about the data and how observations relate to one another. For example, a method based on a normal approximation can be affected by skewed distributions, outliers, or scores concentrated at a boundary. The SF-MPQ total is bounded from 0-45, so possible values do not extend without limit. General statistical practice is to assess whether the chosen model represents the score distribution adequately and whether its uncertainty estimates are appropriate. The registry record does not report diagnostic checks or a model, so the suitability of any inferential method cannot be evaluated from this entry.

Over-dispersion is a general concern when variation in observed outcomes is greater than a model expects. If a model assumes less variability than the data contain, its uncertainty estimates can be too small, making apparent precision misleading. Conversely, a suitable model should reflect the actual variability and outcome structure. The posted full ranges offer only limited information about variability, and the record does not report a dispersion estimate or a model against which over-dispersion could be assessed. This is a general statistical consideration, not a finding about this study.

What can the planning illustrations establish?

Any sample-size illustration based on an observed effect is a planning exercise, not evidence that a study had a particular probability of detecting an effect. The registry states that its planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The stated illustration is not the trial's own design. It cannot establish observed power, and it does not substitute for a reported treatment-effect analysis.

The record does not report the statistical plan or a sample-size justification. It also does not report an analysis for the three-arm design that can be interpreted as the primary treatment comparison. Planning assumptions based on a two-arm comparison are not interchangeable with an analysis of all three regimens, and the registry's posted baseline outcomes do not supply an observed post-injection treatment effect to interpret. Any planning figures should therefore be understood only as hypothetical design calculations under the stated assumptions.

Overall, the methods information supports a description of the design and baseline summaries, but not a reconstruction of an inferential result. The registry record lists no analyses and provides no model specification, uncertainty estimates, or treatment contrasts. Those omissions make it impossible to determine from the record how the stated pain-relief hypothesis was statistically evaluated.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures and reports 0 secondary outcomes posted. It lists 0 analyses. The primary result identified in the record is the baseline SF-MPQ score. The record does not explain how the outcome measures relate to a prespecified hierarchy, which outcomes were intended to be confirmatory, or whether any adjustment for multiple testing was planned. Those details are not reported in the registry record.

Multiplicity is a general statistical issue that arises when several outcomes, time points, groups, or comparisons are examined. Each additional opportunity to identify a nominally unusual result can affect the overall chance of a false-positive finding if the analyses are treated as independent tests without adjustment. Statistical approaches can control this risk or set a hierarchy for interpretation, but the appropriate method depends on the planned questions and analyses. No multiplicity procedure is reported for this study, so it would be inappropriate to infer that an adjustment was or was not applied outside the registry information.

The entry does not report how missing outcome data were handled, whether any participants lacked a baseline or later score, or whether analyses used all randomized participants or another population. The analysis population is not reported in the registry record. The group counts shown for the primary result are reported as 16.0, 15.0, and 15.0, but those summaries do not establish how missing data were handled for other measurements or whether the posted results include every randomized participant.

There is also no reported imputation method, sensitivity analysis, or account of reasons for missingness. These details matter because analyses can be affected if missing outcomes are related to participants' pain or treatment experience. Without the relevant reporting, readers cannot assess potential bias from missing data or determine how robust an outcome estimate would be. Since no inferential treatment estimate is posted, the registry record also offers no analysis whose sensitivity to missingness can be evaluated.

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 0% reporting threshold.

The adverse-event record reports zero serious adverse events in each group and zero deaths in each group. It also reports zero other adverse events in each group. The recorded numbers at risk are 16 for Group A, 15 for Group B, and 15 for Group C for both serious and other adverse events. No serious adverse-event terms are listed.

These counts describe what is entered in the registry record. A count of zero means that no event in that category is recorded for the listed group in this results entry; it does not prove that an event is impossible or that there was no risk. Event counts can be difficult to interpret when the period of safety observation, definitions, ascertainment procedures, and completeness of reporting are not described. Those details are not reported in the registry record.

The adverse-event figures should also be kept separate from the pain outcome. The entry reports baseline SF-MPQ scores as its primary result and does not provide an inferential efficacy analysis. The absence of recorded adverse events does not establish a treatment effect, and the baseline scores do not determine the safety profile. The registry record supplies event counts and at-risk counts, but not further detail on the nature, timing, relatedness, or duration of adverse events.

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

The posted results establish that baseline SF-MPQ scores were reported for the three randomized groups. Group A's reported mean is 0.62 and its full range is 0.0 to 3.0. Group B's mean is 0.93 and its range is 0.0 to 4.0. Group C's mean is 0.53 and its range is 0.0 to 2.0. These are descriptive summaries of baseline scores on a questionnaire whose total possible range is 0-45.

They do not establish whether Bromfenac before injection, Bromfenac after injection, or artificial tears at both times is associated with a different level of pain during or after injection. The outcome is labeled Baseline, and the registry does not report post-injection scores, a change from baseline, or a treatment contrast. The direction and size of any treatment effect therefore cannot be determined from these primary results.

The means and ranges are not confidence intervals and do not show the precision of a comparison. There is no reported p-value or other inferential result for the primary outcome. Without an effect estimate and uncertainty interval, readers cannot judge how compatible the data are with different possible treatment effects. A visual or numerical contrast among descriptive summaries is not a substitute for an analysis that accounts for the study design and variability.

The randomized, double-masked design is relevant to how a treatment comparison might be conducted, but design labels alone cannot answer the efficacy question. The registry record does not report the analysis plan, the population used for analysis, the handling of missing outcomes, or multiplicity procedures. These absences restrict interpretation of the results posted to the registry; they do not show what analyses may or may not have been conducted elsewhere.

The adverse-event entry records no serious adverse events, other adverse events, or deaths in the listed groups. This is a description of the recorded counts, not proof that harm could not occur. Taken together, the registry record supports a narrow interpretation: it documents the study design, baseline pain-score summaries, and adverse-event counts, while leaving the intended comparison of pain outcomes unresolved.

13. Why This Trial Matters Statistically

This study raises a useful statistical distinction between a trial's research question and the outcome result that is actually posted. The stated question concerns pain associated with intravitreal injection and a topical NSAID regimen. The primary result is labeled as a baseline score. Keeping the question, measurement time, and reported analysis aligned is essential: baseline values describe the groups' starting scores, whereas a treatment-effect question requires an outcome contrast at a relevant time or a defined change over time.

The three regimens also make the comparison structure important. Bromfenac is assigned before injection in one group and after injection in another, while artificial tears are used at both times in the comparison group. A statistical analysis must make clear which contrasts answer which questions. The registry record does not report such contrasts, so readers should not infer a ranking or treatment effect from the baseline means.

The record illustrates why uncertainty matters alongside point summaries. Group means and observed ranges offer a compact description, but they do not quantify the precision of a difference between groups. Without an effect estimate and confidence interval, the evidence cannot be judged against a range of plausible effects. The absence of an inferential result is especially important when the stated outcome description includes assessment at more than one time.

It also highlights the value of transparent reporting on analysis populations, missing data, outcome selection, and multiplicity. Those elements help readers understand whether reported estimates correspond to the randomized groups, how incomplete measurements were addressed, and how multiple outcomes were interpreted. Such information is not reported in the registry record. The statistical importance of this trial therefore lies not in a demonstrated treatment contrast, but in the need to distinguish recorded baseline summaries from evidence that answers the intended clinical question.

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 limitation specific to interpretation is the mismatch between the stated aim and the posted primary outcome. The description refers to assessing Bromfenac's analgesic effect pre- and post-injection, while the primary outcome title and timeframe identify a baseline score. The registry record does not post post-injection scores or a change measure, so the reported result cannot address the pain response after injection.

The posted results are descriptive and provide only a mean and full range for each group. No dispersion measure beyond the range, confidence interval, effect estimate, or inferential test is reported. The range does not show the distribution of individual scores. This prevents an assessment of precision and limits understanding of score variability.

The record lists 6 outcome measures but has 0 secondary outcomes posted and 0 analyses. It does not report a statistical analysis plan, sample-size justification, analysis population, missing-data method, or approach to multiple outcomes and comparisons. It is therefore not possible to determine from this entry how the intended treatment comparison was specified or whether the posted summaries correspond to a particular planned analysis.

Although enrollment is reported as 46, the record does not explain recruitment or provide further information about the participants beyond the study description. Masking is listed as double, but who was masked and how masking was maintained are not reported. The registry also does not describe the safety observation period or event ascertainment methods. These reporting gaps should be distinguished from evidence of flaws in conduct: the registry entry does not provide enough detail to evaluate them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Control of Pain in Intravitreal Injections Using Topical NSAIDs — NCT04343222.
• Registry record last updated 2023-06-12; status last verified 2020-09.
• Results first posted 2020-10-19.
• 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 record describes the completed COPIVIN Study, a randomized, double-masked, parallel Phase 4 study of Bromfenac and artificial tears around intravitreal injections. It reports enrollment of 46 participants and three assigned regimens: Bromfenac before injection, Bromfenac after injection, or artificial tears at both specified times.

The primary outcome is titled as baseline SF-MPQ scores. The posted group means are 0.62, 0.93, and 0.53, with full ranges of 0.0 to 3.0, 0.0 to 4.0, and 0.0 to 2.0, respectively. No inferential analyses or post-injection treatment comparisons are reported in the registry record. The adverse-event entry records zero serious adverse events, zero other adverse events, and zero deaths in each group.

Accordingly, the record provides baseline descriptions and adverse-event counts, but does not report the analysis needed to assess the stated question about pain during or after injection.