Evaluation of Loteprednol Etabonate Versus Vehicle for the Treatment of Inflammation and Pain Following Cataract Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Loteprednol Etabonate Versus Vehicle for the Treatment of Inflammation and Pain Following Cataract Surgery (NCT01060072), a randomized phase 3 study. The primary outcome is Resolution of Anterior Chamber Cells..

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 3, randomized, double-masked, parallel-group study sponsored by Bausch & Lomb Incorporated. Its title describes an evaluation of loteprednol etabonate versus vehicle for inflammation and pain following cataract surgery. The brief summary likewise states that the study compares the safety and efficacy of loteprednol etabonate with vehicle for postoperative inflammation and pain.

The two listed arms received loteprednol etabonate 0.5% ophthalmic suspension or the vehicle of loteprednol etabonate ophthalmic suspension. The parallel-group model means the registry describes participants as assigned to one of these arms, rather than a crossover comparison. Randomization and double masking are recorded, but the method used to generate the allocation sequence, conceal allocation, and maintain masking is not reported in the registry record.

The record reports enrollment of 407. The primary outcome was resolution of anterior chamber cells at Visit 5, identified as postoperative day 8, and the primary population is identified as ITT. Three secondary outcomes are listed: resolution of anterior chamber cells, Grade 0 pain, and resolution of anterior chamber flare. The registry reports five outcome measures overall, but does not provide additional outcome details in the registry record for this analysis.

The study status is completed. Its recorded start is 2010-02, and its primary completion is 2010-09. These entries describe the registry timeline, not the duration of treatment or the follow-up period for every outcome. The protocol’s original sample-size justification, detailed schedule of visits, and planned statistical analysis 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.

Before assignment: A total of 407 participants, who were candidates for routine, uncomplicated cataract surgery, were enrolled in the study, 400 participants completed the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to treat (ITT) population

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 Resolution of Anterior Chamber Cells., measured over Visit 5 (Postoperative day 8).

The primary endpoint is the number of participants with complete resolution of anterior chamber cells (ACC) at Visit 5, postoperative day 8. The registry defines the population as ITT and describes cell grading on a 0–4 scale, with 0 meaning no cells and 4 meaning >30 cells. For this endpoint, resolution means the grade has reached 0. The reported values are participant counts, rather than a mean score or time-to-event measure.

Anterior chamber cells are a recorded feature relevant to the study’s focus on postoperative inflammation. Using a prespecified threshold such as complete resolution turns a graded observation into a binary outcome: each participant either meets the resolution definition at the specified visit or does not. In general, this can make an outcome easier to interpret as a count of participants meeting a criterion, while also discarding information about intermediate grades. The registry’s primary endpoint therefore answers a specific question about complete resolution at one visit, not about the full course of cell grades over time.

The record lists the outcome unit as participants and the parameter as a number. It does not report details of the assessment procedure, assessor training, or handling of observations that were unavailable at the visit. Those details matter for understanding how the endpoint was measured and analyzed, but are not reported in the registry record.

7. Results Posted in the Registry

• Loteprednol Etabonate: 31.1% (64/206) versus 13.9% (28/201) on control; risk difference 17.1 percentage points (95% CI 9.2 to 25.1), risk ratio 2.23 (1.50–3.32); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this?

The primary outcome is binary: each participant either had complete resolution of anterior chamber cells at Visit 5 or did not. The registry reports counts of participants meeting the criterion in each arm. For a binary outcome, a proportion is the number meeting the criterion divided by the number in the relevant group. The posted comparison expresses the difference between the arms as a risk difference and also reports relative measures. No new calculations are needed to interpret the posted quantities.

General statistical explanation: a risk difference describes the absolute separation between two proportions. It is expressed on the same scale as the proportions and is zero when the two proportions are equal. A risk ratio compares one proportion with the other; a value of one corresponds to equal proportions. An odds ratio compares odds, where odds are the number meeting the criterion relative to the number not meeting it. A value of one likewise corresponds to equal odds. These scales answer related but distinct questions. The risk difference is often the most direct scale for understanding the absolute contrast, while relative measures describe the contrast in proportional or odds terms.

How should the uncertainty be understood?

A confidence interval gives a range of values compatible with the observed data under the method used to construct it. General statistical explanation: intervals that are narrower indicate greater precision on the scale being reported, while wider intervals indicate more uncertainty. A confidence interval is not a guarantee that the true value lies within its endpoints, and it is not a range containing a fixed proportion of individual participant outcomes. The registry reports confidence intervals for the relative measures and for the risk difference, but the confidence-interval construction method is not reported in the registry record.

The reported confidence intervals for the risk ratio and odds ratio lie above one. In general, that means the interval excludes the equal-value reference for those relative measures. The risk-difference interval is also reported, but the particular method used to estimate it is not specified in the registry record. The estimates and intervals communicate more than a significance label alone: the estimates show the direction and scale of the observed comparison, while the intervals show uncertainty around them.

What does the p value add?

The registry posts an unadjusted p value of <0.001 for the primary comparison. General statistical explanation: under a null hypothesis and a specified statistical model, a p value summarizes how unusual data at least as incompatible with that null would be. A small p value can be evidence against the null model, but it is not the probability that the null hypothesis is true, the probability that the result occurred by chance, or a measure of the effect’s importance. The registry record does not state the test used to obtain this p value. It also does not report whether the primary comparison was adjusted for covariates.

What does the intention-to-treat label tell us?

The primary outcome population is labeled ITT. General statistical explanation: an intention-to-treat approach ordinarily analyzes participants according to their randomized assignment, regardless of later treatment adherence. The label alone does not establish the exact analysis rules used in this trial. In particular, it does not explain how missing endpoint observations, withdrawals, or other deviations were handled. Those details are not reported in the registry record, so the label should not be taken as a complete description of the analysis.

What can be concluded about the statistical plan?

The posted result includes counts, a risk difference, relative measures, confidence intervals, and an unadjusted p value. The registry record does not report the statistical test, model, confidence-interval method, covariate adjustment, interim analyses, or a detailed prespecified analysis plan. It also reports zero posted analyses in the record summarized for this analysis. That does not justify inferring which methods were used beyond the quantities explicitly posted. The statistical interpretation should remain tied to the endpoint, population, visit, and comparisons that the registry identifies.

General explanation: analysis choices can matter because different methods may handle small samples, missing observations, repeated measurements, or adjustment differently. A binary endpoint such as this one does not require an assumption about a continuous-outcome distribution merely because statistical estimation is involved. Still, the assumptions behind the reported intervals and p value cannot be evaluated fully without the method details. The randomized, double-masked, parallel-group labels describe design features; they do not substitute for the missing analysis specification.

10. Confidence Intervals and Precision

Precision concerns how tightly the data estimate the comparative result. The registry reports a confidence interval for the risk difference and confidence intervals for the risk ratio and odds ratio. For the risk ratio, the estimate is 2.23 and the interval runs from 1.496 to 3.325. For the odds ratio, the estimate is 2.785 and the interval runs from 1.695 to 4.575. Both relative-measure intervals exclude one, the value corresponding to no relative difference. The risk-difference interval likewise supports a positive direction for the posted contrast, though the interval-construction method is not reported in the registry record.

These intervals indicate uncertainty around estimates from the observed participants; they do not describe the range of outcomes for individual participants. The breadth of an interval depends on factors including the amount of information in the data and the method used to estimate uncertainty. General statistical explanation: more information often leads to greater precision, while less information generally leaves more uncertainty. The record gives the arm counts and endpoint counts, but does not document the confidence-interval procedure or the handling of any missing outcome values.

The reported p value, <0.001, addresses evidence against a null comparison under the method used. It does not replace the confidence intervals, which communicate uncertainty on the estimate’s scale. Nor does a confidence interval establish whether an observed difference is important in a clinical sense. That judgment would require context and criteria that are not reported in the registry record. The intervals should therefore be read as statistical precision for this endpoint and visit, not as a complete account of the result’s practical meaning.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants across both arms and not total events. They are illustrations based on the observed effect, with the effect to detect set to 100%, 75%, or 50% of that observed effect. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The original trial’s sample-size justification and design assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated planning assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning number for a 90% chance. These are design targets, not probabilities that the trial’s observed result is correct. The figures are 93 and 123 participants per arm for planning around 100% of the observed effect; 153 and 205 for 75% of the observed effect; and 318 and 425 for 50% of the observed effect, respectively.

Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants per arm. The planning figures are not observed power; they illustrate how sample-size requirements change under the listed assumptions. They do not show the trial’s original planning rationale or demonstrate that the study was designed around its eventual result. No additional curve-specific numerical values are reported in the registry record.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.139; treatment proportion p₁ = 0.311; average p̄ = 0.225.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5905 = 1.1574.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5780 = 0.4864.
4. n = (1.1574 + 0.4864)² / (0.1714)² = 92.0, rounded up to 93 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.139303482587065                          # control proportion
p1 <- 0.310679611650485                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1060072)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 93 (80% power), 123 (90% power)
 75% of observed effect: n per arm = 153 (80% power), 205 (90% power)
 50% of observed effect: n per arm = 318 (80% power), 425 (90% power)
power.prop.test: 92 
Simulated power at n = 93 per arm: 0.809 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and three secondary outcomes: resolution of anterior chamber cells, Grade 0 pain, and resolution of anterior chamber flare. It reports five outcome measures overall. The record summarized for this analysis includes the primary endpoint result, but does not report results for the secondary outcomes. The number of posted analyses is zero. These entries do not establish how many comparisons were actually planned or performed outside the registry record.

Multiplicity arises when several outcomes, visits, or statistical comparisons are examined. General statistical explanation: as the number of tests increases, the chance of obtaining at least one apparently unusual result under a collection of null hypotheses can increase. Prespecifying a primary outcome and setting out how secondary outcomes will be interpreted can help readers distinguish the central comparison from exploratory findings. Whether this trial used a multiplicity adjustment or another strategy is not reported in the registry record. The posted p value is identified as unadjusted, and should not be described as adjusted for the other outcomes.

The primary population is identified as ITT. However, the record does not state the number of participants with missing primary outcome data, the reasons for missingness, how missing values were handled, or whether sensitivity analyses were conducted. It also does not report details of the analysis population for secondary outcomes. Missing observations can affect the interpretation of a binary endpoint if their frequency or distribution differs between arms; without the relevant details, that possibility cannot be evaluated from this record.

The registry does not report a complete statistical analysis plan, interim analyses, covariate adjustment, protocol deviations, or methods for handling multiple outcomes. Those are unknowns, not evidence that a particular procedure was or was not used. The most defensible interpretation is limited to the primary endpoint, ITT label, and posted comparison, while recognizing that multiplicity and missing-data procedures are not documented in the registry record.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (0.5%), hypokalemia (0.5%), diverticulitis (0.5%), cholecystitis (0.5%), myocardial infarction (0.5%).

The registry reports serious adverse events affecting 3 participants among 206 at risk in the loteprednol etabonate arm and 1 participant among 201 at risk in the vehicle arm. For other adverse events, the posted figures are 10 participants among 206 at risk in the loteprednol etabonate arm and 24 among 201 at risk in the vehicle arm. These are counts and group sizes, not measures that describe severity beyond the serious-versus-other classification recorded.

The record lists Dehydration, Hypokalemia, Diverticulitis, Cholecystitis, and Myocardial infarction among the top serious terms, each shown at 0.5%. The available information does not assign those terms to an arm, so they should not be attributed to either group. Death counts are not reported in the registry record.

Adverse-event counts are descriptive safety data. They do not by themselves establish whether an event was caused by study treatment, and the registry information does not provide event timing, duration, outcomes, or participant-level details. The figures should be read within the limits of the reported classifications and available follow-up information.

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

The posted primary result describes a difference between randomized arms in the number of participants meeting a specific endpoint: complete resolution of anterior chamber cells at postoperative day 8. The observed counts were 64 of 206 participants in the loteprednol etabonate arm and 28 of 201 in the vehicle arm. The reported risk difference and relative measures, together with their confidence intervals and the unadjusted p value, characterize the comparison statistically. They do not answer every question about postoperative inflammation, pain, safety, or the course of recovery.

The endpoint is a threshold at a single visit. It distinguishes participants who reached grade 0 from those who did not, but does not show the distribution of grades among those who did not reach grade 0. It also does not indicate when resolution occurred, whether it persisted, or how participants’ symptoms changed over time. The listed secondary outcomes include Grade 0 pain and resolution of anterior chamber flare, but their results are not reported in the record summarized for this analysis.

The randomized and double-masked design labels describe features intended to support a fair comparison, but the registry does not give the operational details needed to assess how those features were implemented. The record also lacks details about missing data, the statistical test, and multiplicity procedures. These gaps limit what can be said about robustness beyond the reported result.

Statistical evidence about a trial endpoint is not the same as a treatment recommendation. The posted data describe one study’s comparison at a particular time point and do not establish how the result applies to every patient, setting, or outcome. Clinical importance requires context beyond a p value or an interval, and that context is not fully reported in the registry record.

16. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint definition matters in clinical research. “Resolution” is operationalized as complete resolution of anterior chamber cells, defined by grade 0 on a 0–4 scale, at a named visit. That definition makes the primary comparison interpretable as counts meeting a threshold. At the same time, a binary threshold leaves out information about intermediate grades and changes over time. Readers need both the endpoint definition and its timing to understand what the statistical comparison represents.

The result also demonstrates the value of considering absolute and relative measures together. The risk difference describes separation between the arms on the proportion scale, while the risk ratio and odds ratio express the comparison relatively. Their interpretations differ, so reporting more than one measure can help convey the result’s shape. Confidence intervals add information about precision that a p value alone cannot provide. Here, the registry includes all of these forms of comparison, but does not identify the methods used to calculate the intervals or test.

Finally, the record shows why statistical transparency includes more than outcome estimates. A primary population is named, and design features are recorded, but the analysis plan, missing-data handling, multiplicity strategy, and original sample-size justification are not reported. Those omissions leave important questions about how the posted results were generated and how secondary outcomes should be interpreted. The planning illustrations are useful for understanding how assumed effect size and power affect sample requirements, but they are not a substitute for the trial’s original design rationale.

17. 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 registry record does not report the original sample-size justification, so the planning illustrations based on the observed effect should not be mistaken for the trial’s design rationale. The trial enrolled 407 participants, but enrollment alone does not show whether the study met its intended statistical targets. The registry’s randomized, double-masked, parallel-group labels are not accompanied by details on sequence generation, allocation concealment, or masking procedures.

The primary result is for complete resolution of anterior chamber cells at one visit, postoperative day 8. It does not describe the full grade distribution, change from an earlier visit, or persistence of resolution. Although the registry lists secondary outcomes for pain and anterior chamber flare, their results are not reported in the record. It therefore cannot support conclusions about those outcomes.

Important analysis details are also absent. The statistical test and confidence-interval methods are not reported, nor are covariate adjustment, multiplicity procedures, interim analyses, or the handling of missing endpoint data. The primary population is labeled ITT, but the exact analysis rules are not described. The registry reports an unadjusted p value, which does not clarify how other outcomes or analyses were treated.

Safety information is limited to counts of participants affected, group sizes at risk, and a list of serious-event terms. Event timing, duration, outcomes, causal assessments, and deaths are not reported. These limitations restrict interpretation to the posted counts and defined endpoint; they do not establish that unreported procedures or events did or did not occur.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Evaluation of Loteprednol Etabonate Versus Vehicle for the Treatment of Inflammation and Pain Following Cataract Surgery — NCT01060072.
• Registry record last updated 2012-01-13; status last verified 2011-12.
• Results first posted 2012-01-13.
• 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.

21. Record Summary

NCT01060072 is a completed phase 3 randomized, double-masked, parallel-group study sponsored by Bausch & Lomb Incorporated. The registry describes a comparison of loteprednol etabonate 0.5% ophthalmic suspension with its vehicle following cataract surgery. Recorded enrollment is 407; the study start is 2010-02 and primary completion is 2010-09.

The primary outcome is the number of ITT participants with complete resolution of anterior chamber cells at Visit 5, postoperative day 8. The registry reports 64 participants in the loteprednol etabonate arm and 28 in the vehicle arm meeting that criterion, with a risk difference, relative measures, confidence intervals, and an unadjusted p value of <0.001. Three secondary outcomes are listed, but their results are not reported in the record summarized for this analysis.

The registry also reports serious and other adverse-event counts. Detailed statistical methods, missing-data procedures, multiplicity handling, and the original sample-size justification are not reported in the registry record.