Post-Market Clinical Investigation of the Clareon® IOL: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post-Market Clinical Investigation of the Clareon® IOL (NCT03316885), a na na study. The primary outcome is Percentage of First Implanted Eyes Achieving Best-Corrected Distance Visual Acuity (BCDVA) of 0.3 Logarithm Minimum Angle of Resolution (logMAR) or Better at 1 Year Post-Implantation.

2. Clinical Question

This is a single-group post-market investigation, not a randomized comparison. Its primary question is therefore descriptive and benchmark-based: it concerns the observed proportion meeting a specified visual-acuity threshold, interpreted against a historical reference rather than against outcomes in a concurrently enrolled control group. The registry record also describes longer-term visual-acuity and adverse-event evaluation, with visual acuity assessed at Years 2 and 3. Secondary outcomes include threshold-based BCDVA measures for first and second implanted eyes, as well as uncorrected distance visual acuity (UCDVA) measures.

The clinical question does not ask whether the device is superior to another lens under randomized conditions. Nor does the registry record establish that the historical endpoint represents an otherwise comparable group in this study. A benchmark comparison can indicate whether an observed proportion is compatible with a stated reference, but its interpretation depends on the definition and applicability of that reference. The numerical Year 1 proportion and its confidence interval are not reported in the registry record, so the primary question cannot be answered from the posted results described in the record.

3. Trial Design

NCT03316885 is a completed, post-market clinical investigation of the Clareon® IOL sponsored by Alcon Research. The registry lists enrollment of 245 and a study start date of 2018-03-14, with primary completion on 2019-10-18. The phase is listed as NA. The study model is single-group, with allocation listed as NA and masking listed as none.

The intervention description identifies the Clareon® aspheric hydrophobic acrylic intraocular lens, implanted using the Alcon Monarch III-D delivery system to replace the human crystalline lens during cataract surgery. Cataract Surgery is also listed as a procedure intervention. Because there is no concurrent control arm, the design does not provide a like-for-like randomized comparison between treatments. The primary endpoint instead references a historical safety and performance endpoint of 92.5% from EN ISO 11979-7:2014.

The stated primary purpose is to evaluate long-term visual acuity and adverse-event outcomes through 3 years. The primary visual-acuity endpoint is the percentage of first implanted eyes achieving BCDVA of 0.3 logMAR or better at Year 1 post-implantation, with its timeframe defined from second-eye surgery. The secondary purpose includes visual-acuity evaluation at Years 2 and 3. Listed secondary outcomes also include BCDVA threshold measures for first and second implanted eyes and UCDVA measures at follow-up visits.

The registry lists 12 outcome measures and 2 analyses. The analysis population named for the primary endpoint is the All Implanted Analysis Set with data. The registry record does not report a detailed protocol, the method used to select the historical benchmark population, or a statistical analysis plan describing the estimator and inferential procedures. Those details should not be inferred from the single-group design or from the endpoint description.

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 245 enrolled, 30 participants were discontinued from the study prior to attempted implantation with the IOL. This reporting group includes all participants with attempted implantation (215).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All Implanted Analysis Set with data

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/eyes with successful test article implantation

6. Primary Endpoint

The registry lists the primary outcome as Percentage of First Implanted Eyes Achieving Best-Corrected Distance Visual Acuity (BCDVA) of 0.3 Logarithm Minimum Angle of Resolution (logMAR) or Better at 1 Year Post-Implantation, measured over Year 1 post-implantation from second eye surgery.

The primary endpoint is the percentage of first implanted eyes achieving best-corrected distance visual acuity of 0.3 logMAR or better at Year 1 post-implantation, measured from second-eye surgery. BCDVA uses the correction obtained from manifest refraction. The registry description specifies 100% contrast electronic ETDRS charts at a distance of 4 meters, with acuity recorded in logMAR. It states that a 0.02 logMAR increment corresponds to a single ETDRS chart letter, and that 0.3 logMAR is equivalent to 20/40 Snellen visual acuity.

A threshold endpoint expresses the share of assessed eyes that meet a prespecified visual-acuity criterion. It is useful because it translates a measured acuity scale into an interpretable performance category. The endpoint is also the basis for the stated comparison with a historical safety and performance endpoint of 92.5%. That reference supplies context for the proportion, but it is not a concurrent control group and does not remove the limitations of a historical comparison.

For a percentage, the numerator is the number of eyes reaching the threshold and the denominator is the number of eligible eyes with relevant data under the endpoint definition. The registry names the All Implanted Analysis Set with data, but does not report the primary endpoint count, percentage, denominator, or confidence interval. The numerical result and its precision are therefore not reported in the registry record. The endpoint definition alone describes what was to be measured; it does not establish the observed level of visual acuity.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a percentage endpoint and a 95% confidence interval as the measure of dispersion. It does not state the estimator, the confidence-interval construction, or a formal hypothesis-testing procedure for the primary analysis. The distinctions below explain the relevant statistical concepts generally and separate them from methods that are actually documented.

What does the percentage represent?

For a binary threshold endpoint, each eligible eye either meets the specified criterion or does not. The estimated percentage is based on the number meeting the criterion relative to the number included in the endpoint analysis. This kind of outcome is easy to interpret clinically because it describes the proportion reaching a defined level, rather than only a mean score. Its interpretation still depends on the population included, the timing of assessment, and how missing observations are handled. The primary endpoint specifies the All Implanted Analysis Set with data, but does not report the actual denominator or the number meeting the criterion.

What does a confidence interval add?

In general, a confidence interval communicates uncertainty around an estimated quantity. For a percentage, it shows a range of values compatible with the data under the interval’s statistical assumptions and method. It is not a guarantee that the true value lies within the interval, and it does not replace consideration of the study design. A confidence interval can be useful for assessing precision even when a hypothesis test is not the main focus. The registry record names a 95% confidence interval for the primary endpoint, but neither the interval nor the endpoint estimate is reported there.

How should the historical reference be understood?

The primary endpoint description states that visual acuity was compared with a historical safety and performance endpoint of 92.5%, cited from EN ISO 11979-7:2014. In general, a one-sample comparison evaluates an observed study result against a fixed reference rather than against a concurrently observed control group. That approach depends on the reference being relevant to the study population, endpoint definition, assessment timing, and data collection. A benchmark comparison can provide a standard for interpretation, but it cannot provide the same protection against confounding or differences in care and measurement that random allocation to a concurrent control can offer. The registry record does not report details of the historical population or a method for evaluating its comparability.

What does the single-group design imply?

A single-group study can describe outcomes observed after an intervention, subject to how the study population and follow-up are defined. It cannot, by itself, isolate the effect of the device from other influences by comparing randomized groups. The allocation field is listed as NA, and the registry explicitly describes a single-group model. The record also notes that the arms are not a like-for-like control comparison. Accordingly, the primary result, if available, would need to be interpreted as a proportion in the study’s analysis population alongside the historical reference, rather than as a randomized treatment contrast.

What statistical planning information is documented?

A sample-size planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is described as computing from the observed effect, with the effect to detect expressed as a stated fraction of that observed effect. For time-to-event outcomes, the note says the planning quantity is the total number of events; for other outcomes, it is participants per arm. These are planning illustrations, not the trial’s own design, and they are not observed power. The trial itself is registered as single-group, so a hypothetical equal-allocation two-arm illustration should not be read as a description of the actual study design. Numerical planning outputs are not reported in the registry record.

In general, power is a design-stage property tied to assumptions about an effect, variability, significance level, and analysis. A calculation based on an effect observed in the study is retrospective and does not show that the study had a prespecified probability of detecting that effect. Planning for a fraction of an observed effect asks how a hypothetical future design might be sized under stated assumptions; it does not alter the uncertainty in the current study or establish confirmatory evidence.

Why can over-dispersion matter?

For count outcomes, a simple statistical model may assume that variability is tied closely to the mean. Over-dispersion means that the observed variability is greater than such a model expects. In general, ignoring over-dispersion can make standard errors too small and uncertainty appear less than it is. A suitable model may need to account for extra variability or clustering, depending on how events arise and are observed. The record identifies the primary endpoint as a percentage and does not report an over-dispersion analysis for it. The event summaries do not describe a count-model procedure, so no such method should be inferred.

The registry lists 12 outcome measures and 2 analyses, but the details of the analysis methods are not reported in the registry record. The record does not state whether the primary analysis used a hypothesis test, how any potential dependence between eyes was handled, or how repeated observations over time were modeled. These are distinct methodological choices, and their absence limits the ability to reproduce or fully evaluate the statistical analysis from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and 2 analyses. The primary endpoint is one Year 1 BCDVA threshold measure for first implanted eyes. Other listed outcomes include BCDVA threshold measures for first and second implanted eyes at Years 2 and 3, along with UCDVA measures at follow-up. Evaluating multiple outcomes can create a multiplicity issue: when many statistical questions are considered, the chance of at least one apparently notable result can increase. In general, investigators may address this by defining a hierarchy of outcomes, adjusting inference, or treating secondary analyses as exploratory. The multiplicity strategy is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The primary endpoint population is described as the All Implanted Analysis Set with data, but the record does not state how eyes without an available Year 1 measurement were treated, whether any imputation was used, or whether sensitivity analyses were conducted. A complete-case percentage can differ from a percentage based on an approach that makes assumptions about missing observations, so the handling details are relevant to interpretation.

The registry record does not report the statistical analysis population definitions for every outcome, the number assessed at each visit, or the analysis plan for repeated measurements. It also does not report interim analyses or a sample-size justification for the actual single-group study. These details should not be inferred from enrollment or from the endpoint descriptions. Without them, the record supports understanding the planned questions and some recorded safety counts, but not a full appraisal of analysis decisions, multiplicity control, or the potential impact of missing outcome data.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: intra-ocular injection (1.9%), myocardial infarction (1.4%), covid-19 (1.4%), cystoid macular oedema (0.9%), multiple organ dysfunction syndrome (0.9%).

The registry records adverse events in pretreatment, first-eye, second-eye, and systemic groups. In pretreatment, 215 were at risk for serious and other events, with 0 serious and 0 other affected. For SY60WF First Eye, 215 were at risk, with 6 affected by serious events and 34 by other events. For SY60WF Second Eye, 209 were at risk, with 4 affected by serious events and 39 by other events. For SY60WF Systemic, 215 were at risk, with 31 affected by serious events and 0 by other events; 10 deaths are recorded in that group. The registry lists 0 deaths in the other groups.

The serious-event terms with listed percentages are Intra-ocular injection at 1.9%, Myocardial infarction at 1.4%, COVID-19 at 1.4%, Cystoid macular oedema at 0.9%, Multiple organ dysfunction syndrome at 0.9%, and Biliary sepsis at 0.9%. These entries are event summaries, not proof that the device or procedure caused an event. The group labels and numbers at risk differ, and the record does not provide a randomized comparison or an adjusted causal analysis.

General caution is warranted when interpreting adverse-event counts: the number affected is not necessarily the same as the number of event episodes, and groups may reflect different types of follow-up. The registry record does not report further details needed to resolve those issues. The figures describe what is recorded in each group and should not be combined into a treatment-effect estimate.

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

The registry record establishes that NCT03316885 was a completed, single-group post-market investigation intended to assess visual acuity and adverse events after implantation of the Clareon® IOL. It defines a primary visual-acuity threshold, gives the timing and measurement approach, and identifies a historical reference of 92.5%. It also lists follow-up visual-acuity outcomes and records adverse-event counts for several groups.

What the record does not establish is the observed primary endpoint result. The Year 1 percentage and 95% confidence interval are not reported in the registry record. Therefore, the record does not show the proportion of first implanted eyes achieving BCDVA of 0.3 logMAR or better, the precision of that estimate, or its relation to the stated historical reference. Numerical results for the listed secondary visual-acuity outcomes are also not reported in the registry record.

Even if the primary estimate were available, a single-group comparison against a historical benchmark would not be equivalent to a randomized comparison against a concurrent control. In general, historical comparisons can be affected by differences in populations, measurement, follow-up, and clinical practice. The benchmark is useful context, but it cannot alone demonstrate that any observed outcome was caused by the lens.

The adverse-event information is likewise descriptive. Counts and listed serious-event percentages can help identify what the registry recorded, but without further information they do not establish attribution, comparative risk, or a causal relationship. The study record should therefore be read as evidence about the registered study design, endpoint definitions, and reported safety summaries, not as a complete account of treatment efficacy or comparative safety.

13. Why This Trial Matters Statistically

This study is statistically notable because it illustrates the distinction between a prespecified clinical benchmark and a concurrent control group. The primary question is framed around the percentage of first implanted eyes reaching a specific visual-acuity threshold, with comparison to a historical safety and performance endpoint. Such a design can be informative for describing outcomes against a standard, but it does not create the exchangeability that random allocation aims to achieve in a comparative trial.

The endpoint itself combines a clearly interpretable threshold with a precision measure: the percentage meeting the criterion and a 95% confidence interval. This pairing is valuable because a point estimate alone would not communicate uncertainty. In this record, however, the estimate and interval are not reported, so readers cannot assess either magnitude or precision. That absence sharply limits statistical interpretation, even though the endpoint definition and measurement details are stated.

The record also illustrates why outcome lists should be distinguished from reported results. It names multiple visual-acuity outcomes across eye order and follow-up times, and lists 12 outcome measures and 2 analyses. Without results and a stated multiplicity strategy, it is not possible to judge the pattern across outcomes or understand how inferential claims would account for multiple questions.

Finally, the safety summaries include event counts across eye-specific and systemic groups. Their differing denominators and group meanings reinforce that raw counts are not automatically comparable. Statistical interpretation requires attention to the defined population, time at risk, event ascertainment, and analysis method. Those considerations are central in clinical research, and the registry record offers a useful example of why design and reporting details matter as much as a numerical endpoint definition.

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 central limitation of the registry record is that the numerical result for the primary endpoint is not reported. The primary percentage and its 95% confidence interval are absent, as are the reported values for the secondary visual-acuity outcomes. Consequently, the record cannot support an assessment of the observed visual-acuity level, its precision, or how it compares with the historical reference.

The single-group design has no concurrently enrolled control group. The historical reference of 92.5% supplies a context for the primary endpoint, but the record does not describe the underlying historical population in enough detail to assess comparability. The record also does not report the protocol or statistical analysis plan, so the estimator, confidence-interval method, handling of repeated measures, and approach to any multiplicity are not available.

Although the primary analysis population is named as the All Implanted Analysis Set with data, the registry record does not report the number with endpoint data or the approach to missing observations. It does not provide visit-specific analysis denominators or sensitivity analyses for missing data. The detail needed to assess whether missingness could influence the observed percentage is therefore not reported in the registry record.

The safety summaries have additional limits: the record gives affected counts by group and selected serious-event terms, but does not provide a randomized safety comparison or a causal analysis. The adverse-event figures should not be interpreted as treatment-attributable effects. More detailed event definitions and analysis methods are not reported in the registry record, which limits comparisons across the eye-specific and systemic groups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Post-Market Clinical Investigation of the Clareon® IOL — NCT03316885.
• Registry record last updated 2023-08-21; status last verified 2023-08.
• Results first posted 2023-08-21.
• 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

NCT03316885 is a completed, single-group post-market clinical investigation of the Clareon® IOL sponsored by Alcon Research. The record lists enrollment of 245, a start date of 2018-03-14, and primary completion on 2019-10-18. Its primary endpoint is the percentage of first implanted eyes achieving BCDVA of 0.3 logMAR or better at Year 1 after second-eye surgery, with comparison planned against a historical reference of 92.5%.

The study also planned visual-acuity assessment at Years 2 and 3 and recorded adverse-event information. The registry record does not report the numerical primary endpoint estimate or its 95% confidence interval. It does not report numerical results for the listed secondary visual-acuity outcomes. The available safety figures are descriptive and do not establish causation. The single-group design and absence of a concurrent control limit comparative interpretation.