Clareon PanOptix Pro vs. Clareon PanOptix - Study B: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clareon PanOptix Pro vs. Clareon PanOptix - Study B (NCT06401551), a randomized na study. The primary outcome is Mean Monocular Photopic Best Corrected Distance Visual Acuity (BCDVA).

2. Clinical Question

3. Trial Design

The study is titled “Clareon PanOptix Pro vs. Clareon PanOptix - Study B,” and its official title is “Contralateral Study of Clareon PanOptix Pro vs. Clareon PanOptix.” It is registered as NCT06401551 and lists Alcon Research as sponsor. The registry classifies it as randomized, double-masked, and parallel. Its phase is listed as NA.

The study compared two sequences of lens implantation. In one sequence, CPO Pro IOL was implanted in the first eye and CPO IOL in the fellow eye; in the other, CPO IOL was implanted in the first eye and CPO Pro IOL in the fellow eye. The second-eye operation was planned approximately 7-14 days after the first-eye operation. Cataract surgery is also listed as an intervention. The record does not explain the details of randomization or masking, including who was masked.

The registry lists enrollment as 71. The posted primary outcome results list 68 observations in each lens group. The analysis population is described as subjects with successful contralateral implantation and at least one postoperative visit, with both eyes assessed at the same postoperative visit. The registry record lists the study as completed, with a start date of 2024-06-18 and primary completion date of 2024-12-13.

The primary endpoint was mean monocular photopic best corrected distance visual acuity at Month 2 postoperative. The record lists one outcome measure and one analysis. It does not report the original sample-size justification or the detailed statistical plan. In particular, details such as the allocation procedure, any prespecified analysis population beyond the stated definition, and how the within-person relationship between the two eyes was handled 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: Of the 71 randomized participants, 2 were discontinued after randomization and prior to attempted implantation. This reporting group includes all participants with attempted implantation (69). Note: One participant was implanted in one eye only (i.e., with CPO Pro IOL).

Overall Study

Analysis population for the primary outcome, as defined in the registry: All Implanted Analysis Set: All subjects with successful contralateral implantation, with at least one postoperative visit (same postoperative visit for both eyes).

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: All Implanted Analysis Set: All subjects with successful contralateral implantation, with at least one postoperative visit (same postoperative visit for both eyes).

6. Primary Endpoint

The registry lists the primary outcome as Mean Monocular Photopic Best Corrected Distance Visual Acuity (BCDVA), measured over Month 2 postoperative.

The primary endpoint is mean monocular photopic best corrected distance visual acuity (BCDVA) at Month 2 postoperative, measured in logMAR. Visual acuity was assessed separately for each eye using ETDRS reading charts at a distance of 4 meters, under photopic, or well-lit, conditions, with correction in place. The endpoint therefore describes distance acuity under the specified testing conditions, rather than a measure of overall visual function.

The registry describes logMAR values as typically ranging from -0.3, corresponding to 20/10 vision on the Snellen chart, to 1, corresponding to 20/200 vision. Lower scores indicate better vision. The posted group means are -0.016 for CPO Pro IOL and 0.01 for CPO IOL, with standard deviations of 0.103 and 0.090, respectively. These are group summaries; they do not describe the acuity of every individual eye.

In general, a mean endpoint offers a compact way to compare the average measured outcome between groups, while the standard deviation describes how dispersed individual observations are around their group mean. Neither summary alone shows the full distribution of results. The endpoint is useful for evaluating the stated visual acuity outcome at a defined follow-up time. It does not, by itself, summarize other aspects of vision or establish how an individual subject experienced the procedure or lens.

7. Results Posted in the Registry

• CPO IOL: mean 0.01 versus -0.02 on control; difference 0.03 (95% CI -0.01 to 0.06), standardized effect d = 0.27; z-test p = 0.119.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure summarized by its mean and standard deviation. The registry describes the endpoint as mean monocular photopic BCDVA in logMAR. A mean represents the arithmetic average of the observations in a group, while a standard deviation describes the spread of observations around that average. These summaries help convey both the location and variability of the measured outcome, but they do not show the distribution in detail or indicate whether every subject had a value near the group mean.

What does the mean difference represent?

The posted recalculation compares CPO IOL with CPO Pro IOL, expressing the contrast as the CPO IOL mean minus the CPO Pro IOL mean. Its estimate is 0.026 logMAR. With this order of subtraction, a positive estimate means the observed mean is higher in the CPO IOL group. Because lower logMAR values indicate better visual acuity, the sign must be interpreted together with the endpoint’s scale and the stated group order. The estimate is a difference between group averages, not a change experienced by every subject.

In general, the standard error measures the uncertainty in an estimated quantity across repeated samples under a statistical model. It is not the same as the standard deviation: the standard deviation describes variation among observations, while the standard error describes uncertainty around an estimate. The record gives standard errors for the two arm means as 0.013 and 0.011. The recalculated comparison also reports a pooled standard deviation of 0.097 and a standardized effect size of 0.267. These are descriptive recalculations from the posted summary statistics, not additional outcomes measured in the trial.

How should the confidence interval be read?

In general, a confidence interval represents a range of values compatible with the observed data and the assumptions of the method. The recalculated 95% interval for the mean difference runs from -0.007 to 0.059. Its inclusion of zero indicates that the posted summary statistics do not rule out a zero mean difference under this calculation. The interval also includes values on both sides of zero, so the direction of the underlying difference is not estimated with high precision by this interval. A confidence interval is not a guarantee that the true value lies within its endpoints, and it does not account for limitations or biases that are not represented in the statistical model.

What does the reported test address?

The sponsor reports a one-sided t-test for non-inferiority, with a difference in means of -0.026 and an upper confidence limit of -0.005, described as 95.1%. A non-inferiority test asks whether the data are sufficiently inconsistent with a prespecified loss beyond an acceptable margin. The margin and other decision details are not reported in the registry record. The sponsor contrast has the reverse sign from the recalculation’s CPO IOL minus CPO Pro IOL contrast. Interpretation must therefore preserve the reported direction rather than compare the signs as if they used the same subtraction order.

The recalculated p-value is unadjusted and is 0.119. In general, an unadjusted p-value does not account for testing multiple outcomes or analyses. The registry lists one outcome measure and one analysis, but the broader multiplicity plan is not reported. The p-value is also tied to the particular model and assumptions used for its calculation. It should not be interpreted as a probability that one lens is superior, equivalent, or non-inferior.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. When that happens, uncertainty can be understated if the model does not account for the extra variability. This primary endpoint is continuous, and the posted calculation uses group means and standard deviations; the registry does not report an over-dispersion assessment. More generally, assumptions about the distribution of measurements, independence, and variance affect standard errors and confidence intervals. The paired-eye design makes dependence particularly relevant: two eye measurements from the same subject need not be independent. The registry record does not describe a paired analysis or explain how any within-subject correlation was handled.

What is not available about the analysis?

The record identifies the analysis population and reports the sponsor’s test, but it does not report a complete statistical analysis plan. The original sample-size justification, non-inferiority margin, detailed missing-data rules, handling of protocol deviations, covariate adjustment, and sensitivity analyses are not reported in the registry record. The absent details should not be inferred from the posted estimates. The reported summaries support a description of the observed group results and an unadjusted recalculation, but they do not establish that every aspect of the prespecified trial analysis can be reproduced independently.

10. Confidence Intervals and Precision

The recalculated mean difference is 0.026 logMAR for CPO IOL minus CPO Pro IOL. Its 95% confidence interval extends from -0.007 to 0.059. Because this interval includes zero, the recalculation does not narrowly establish the direction of a mean difference. The interval includes a small negative difference and positive differences through its upper bound. Its width reflects uncertainty around the estimate under the calculation’s assumptions.

In general, a confidence interval gives a range of values that are reasonably compatible with the observed data and statistical model. A wider interval indicates less precision than a narrower interval, but the interval does not account automatically for design features or sources of bias omitted from the model. In this study, the paired-eye structure is important: the two eye measurements from a subject may be related. The registry record does not say how that relationship was incorporated into the sponsor analysis or recalculation, so the precision should be understood in light of that reporting gap.

The sponsor’s reported one-sided non-inferiority analysis gives a mean difference of -0.026 and an upper confidence limit of -0.005, with a 95.1% confidence interval designation. Its contrast is in the opposite direction from the recalculated contrast. The sponsor result is the relevant posted analysis for its non-inferiority test, but the margin and full test specification are not reported in the registry record. Thus, the numerical bound alone is insufficient to independently judge the prespecified non-inferiority criterion.

Precision is distinct from clinical importance. The registry record does not report a threshold for a meaningful difference in logMAR, so the confidence interval cannot be classified against such a threshold. It describes statistical uncertainty in the mean contrast, not certainty about an individual subject’s result or about outcomes beyond Month 2 postoperative.

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 event counts. They are illustrations based on the observed effect, not the original study’s design calculation. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers an effect defined as a stated fraction of the observed effect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the illustrated number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true one and the model assumptions held. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. These are planning targets, not counts from the completed study. Smaller effects need more participants to detect under the same assumptions, which is why the planning figures increase as the assumed effect is reduced from 100% to 75% to 50% of the observed effect.

For 100% of the observed effect, the illustration lists 220 participants per arm for 80% power and 294 participants per arm for 90% power. For 75% of the observed effect, it lists 391 participants per arm for 80% power and 523 participants per arm for 90% power. For 50% of the observed effect, it lists 878 participants per arm for 80% power and 1,176 participants per arm for 90% power.

These values are not observed power. They do not describe the probability that the completed study detected its result, and they do not replace the reported confidence interval. They are scenario-based planning illustrations whose outputs depend on the stated assumptions and on the observed effect used as the reference.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.026; pooled standard deviation σ = 0.097.
2. n = 2 × (1.96 + 0.842)² × 0.097² / 0.026² = 219.5, rounded up to 220 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
delta <- 0.026                      # observed difference in means
sigma <- 0.0972175395697711                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(6401551)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 220 (80% power), 294 (90% power)
 75% of observed effect: n per arm = 391 (80% power), 523 (90% power)
 50% of observed effect: n per arm = 878 (80% power), 1,176 (90% power)
power.t.test: 220.4 
Simulated power at n = 220 per arm: 0.793 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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. Analyses Reported by the Sponsor

The sponsor’s posted analysis is a one-sided t-test for non-inferiority. It reports a difference in means of -0.026 and an upper confidence limit of -0.005, with a 95.1% confidence interval designation. The recalculated contrast is CPO IOL minus CPO Pro IOL and is 0.026, with a 95% confidence interval from -0.007 to 0.059 and an unadjusted p-value of 0.119. The directions are reversed: the sponsor’s -0.026 corresponds in sign to expressing the group contrast in the opposite order.

The recalculation is a simple unadjusted re-analysis of posted summary statistics. It is not a replacement for the sponsor’s prespecified test, and the sponsor’s own analysis takes precedence for the trial’s non-inferiority question. The estimates and interval endpoints are not identical, and the registry record does not explain the difference in methods or assumptions. It also does not report the non-inferiority margin, full analysis specification, or decision rule. Therefore, the posted sponsor result can be described, but its non-inferiority conclusion cannot be independently assessed from the registry record alone.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and one analysis. That is useful context, but it does not fully describe the trial’s approach to multiplicity. A multiplicity plan explains how statistical interpretation is handled when more than one hypothesis, endpoint, time point, subgroup, or analysis is considered. The record does not report whether any additional analyses were planned, whether the listed outcome was the only endpoint assessed, or whether any adjustment or hierarchy was prespecified. Those details are not reported in the registry record.

The recalculated p-value is unadjusted. In general, when multiple statistical tests are conducted, the chance of obtaining at least one small p-value can increase, depending on the tests and the plan. An adjustment may be used in some settings, but no particular approach can be inferred. The sponsor’s analysis is described as a one-sided non-inferiority t-test; the full statistical analysis plan and any multiplicity strategy are not reported.

The primary analysis population is described as subjects with successful contralateral implantation and at least one postoperative visit, with both eyes assessed at the same visit. The registry record does not provide the number excluded from the analysis population or a detailed account of missing outcome data. It does not report how missing values were handled, whether any imputation was used, or whether sensitivity analyses assessed the effect of missingness. Thus, the available result applies to the stated analysis population, and the consequences of missing outcome data cannot be evaluated from the registry record.

The record does not report whether the principal analysis followed an intention-to-treat principle, whether a per-protocol population was also analyzed, or how protocol deviations were treated. These details can be particularly important in non-inferiority trials, where exclusions and adherence may affect interpretation. The paired-eye design also raises an analysis question: two eyes from one subject can be correlated. The registry record does not explain whether the analysis accounted for that dependence. These omissions do not invalidate the posted results, but they limit independent assessment of the analysis choices and their effect on uncertainty.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cystoid macular oedema (1.5%), pneumonia (1.4%), thoracic vertebral fracture (1.4%).

The adverse-event summaries report no serious adverse events in the pretreatment group, with 69 at risk. For CPO Pro IOL ocular adverse events, 69 were at risk and 0 were affected by a serious adverse event. For CPO IOL ocular adverse events, 68 were at risk and 1 was affected by a serious adverse event. For systemic, nonocular adverse events, 69 were at risk and 2 were affected by a serious adverse event. Deaths are reported as 0 for each listed group.

The record lists cystoid macular oedema at 1.5%, pneumonia at 1.4%, and thoracic vertebral fracture at 1.4% among the top serious adverse-event terms. The registry does not provide further context in these fields about timing, relatedness, or how the term percentages map to the group summaries. These figures should therefore be read as reported safety counts and terms, not as evidence that an event was caused by a lens or procedure.

In general, an at-risk count is the number of participants included in a particular safety summary, while an affected count is the number recorded as having the event category. The categories have different at-risk counts, and the summaries are not a substitute for individual event histories or a comparative safety analysis. The registry record does not report a formal statistical comparison of adverse-event rates.

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

The posted results show mean Month 2 postoperative BCDVA values of -0.016 logMAR for CPO Pro IOL and 0.01 logMAR for CPO IOL. Lower logMAR indicates better visual acuity, so the observed group mean was lower for CPO Pro IOL. The unadjusted recalculation estimates a difference of 0.026 logMAR for CPO IOL minus CPO Pro IOL, with a 95% confidence interval from -0.007 to 0.059 and p = 0.119. These statistics describe the observed means and uncertainty under the recalculation; they do not establish the size of a clinically meaningful effect.

The sponsor reports a one-sided non-inferiority analysis with a difference in means of -0.026 and an upper confidence limit of -0.005. Because the non-inferiority margin and full test criteria are not reported in the registry record, the result cannot be independently classified against the sponsor’s intended decision threshold. The sponsor’s own analysis takes precedence for that test, while the recalculation serves as a separate, unadjusted description of the posted summaries.

The findings do not establish that the lenses are identical or that their effects are equivalent. A confidence interval that includes zero is not proof of equivalence, and the registry record does not report an equivalence margin. Nor do the posted results establish superiority or a clinically important difference. Those interpretations require prespecified criteria and context that are not reported.

The primary outcome concerns monocular photopic distance acuity at Month 2 postoperative in the stated analysis population. It does not, by itself, describe all aspects of vision, longer-term outcomes, or every subject’s experience. The record’s safety counts also do not establish causation or provide a formal comparative safety analysis. The results should be understood as summaries of the measured endpoint and reported adverse-event categories, with the analysis and reporting limitations described elsewhere in the registry record.

17. Why This Trial Matters Statistically

This study illustrates how a clinical comparison can have a design structure that matters to statistical interpretation. Each subject was assigned a lens sequence in which the two fellow eyes received different lenses. Since eye measurements from the same person may be related, the method used to handle that relationship can affect the estimated uncertainty. The registry record identifies the design and reports group summaries, but does not state whether the analysis accounted for within-subject dependence.

The endpoint also demonstrates the importance of reading an effect estimate with its scale and contrast direction. Lower logMAR values indicate better visual acuity, and the recalculated contrast is defined as CPO IOL minus CPO Pro IOL. Reversing that order reverses the sign. The sponsor’s non-inferiority result uses the opposite direction from the recalculation, so comparing estimates requires careful attention to which group is subtracted from which.

Finally, a non-inferiority claim depends on more than a point estimate or confidence bound: it requires a prespecified margin and analysis rule. Those details are not reported in the registry record. The trial therefore offers a useful statistical example of the distinction between a posted estimate, an unadjusted recalculation, and a decision based on a protocol-defined criterion. The planning illustrations also show how assumptions about the effect to detect relate to required sample sizes, while remaining separate from the completed study’s observed results.

18. 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 non-inferiority margin or the complete decision criteria for the sponsor’s one-sided test. This prevents independent evaluation of the sponsor’s non-inferiority conclusion. Although the sponsor reports a confidence bound, that bound cannot be interpreted against an unreported margin.

The primary endpoint is based on assessments of both eyes in the same subject. The record does not explain whether the statistical analysis accounted for correlation between fellow-eye measurements. It also does not provide enough detail to reproduce the sponsor analysis or determine why its interval differs from the simple recalculation based on posted summary statistics.

The original sample-size justification is not reported in the registry record. Planning illustrations based on the observed effect do not establish the assumptions used to design the study. Missing-data handling, the number and reasons for any exclusions, analysis populations beyond the stated All Implanted Analysis Set, and sensitivity analyses are also not reported. The registry lists one outcome measure and one analysis, but does not give a full multiplicity plan.

The primary result is limited to mean monocular photopic BCDVA at Month 2 postoperative. The registry record does not provide other posted outcome measures, and it does not establish longer-term results or outcomes beyond the stated endpoint. Adverse-event fields give category counts and selected serious-event terms but do not report a formal comparative safety analysis or details about event relatedness. These reporting gaps constrain interpretation without changing the numerical results that are posted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Clareon PanOptix Pro vs. Clareon PanOptix - Study B — NCT06401551.
• Registry record last updated 2026-06-02; status last verified 2026-05.
• Results first posted 2026-01-12.
• 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.

22. Record Summary

NCT06401551 is a completed, randomized, double-masked, parallel study comparing Clareon PanOptix Pro and Clareon PanOptix trifocal intraocular lenses in a contralateral-eye design. The registry lists enrollment of 71 and identifies Alcon Research as sponsor. The primary endpoint was mean monocular photopic BCDVA in logMAR at Month 2 postoperative, with lower values indicating better visual acuity.

The posted means were -0.016 for CPO Pro IOL and 0.01 for CPO IOL. The unadjusted recalculation gives a CPO IOL minus CPO Pro IOL difference of 0.026, with a 95% confidence interval from -0.007 to 0.059 and p = 0.119. The sponsor reports a one-sided non-inferiority analysis, but the margin and complete test criteria are not reported in the registry record. Interpretation is also limited by unreported details about paired-eye analysis, missing data, and the original sample-size justification.