Safety and Efficacy of a Violet Visible Light Blocking Intraocular Lens (IOL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of a Violet Visible Light Blocking Intraocular Lens (IOL) (NCT00747227), a randomized phase 3 study. The primary outcome is Best Corrected Distance Visual Acuity.

2. Clinical Question

The study is listed as a phase 3 randomized, double-masked, parallel-group evaluation of safety and effectiveness. The primary outcome is a threshold-based measure: it counts participants reaching the specified visual-acuity level rather than summarizing the full range of acuity readings. According to the posted primary results, all participants in both outcome groups met that threshold.

The question is therefore about the observed proportion reaching a prespecified clinical threshold in each lens group, and about the uncertainty around the between-group comparison. The registry also lists contrast sensitivity and satisfaction with overall eyesight as secondary outcomes. A numerical result for satisfaction is posted; a numerical result for contrast sensitivity is not reported in the registry record. The record does not describe a noninferiority or equivalence objective, so the findings should not be read as a formal demonstration that the lenses are equivalent.

3. Trial Design

The registry describes a phase 3, randomized, double-masked, parallel-group study with an enrollment of 250. Its stated purpose was to evaluate the safety and effectiveness of a modified light transmission monofocal intraocular lens compared with a conventional intraocular lens. The study is marked completed. The record lists the study start as 2006-12 and primary completion as 2009-03.

The two arms were the ZV9003 modified light transmission intraocular lens and the ZA9003 monofocal acrylic intraocular lens. Random allocation means the intended design assigns participants to study groups by chance. Double masking indicates that the registry classified the study as masked at two levels, but which people were masked and how masking was maintained are not reported in the registry record. The parallel model indicates that the groups were compared alongside one another rather than in a crossover design.

The primary outcome was assessed at one year and counted participants with best corrected distance visual acuity at the Snellen-equivalent threshold of 20/40 or better. The analysis population was restricted: the record says one subject was excluded because different lenses were implanted in the two eyes, and that all subjects included in the outcomes analysis had the same lens in both eyes. The posted primary result denominators are 119 and 120. These outcome denominators are not the same as the safety denominators, which are listed separately in the adverse-event record.

The registry identifies contrast sensitivity and participant satisfaction as secondary outcomes. The number of outcome measures is listed as four, but the full set of four titles and their analysis details are not reported in the registry record. No protocol-level allocation details, masking procedures, sample-size justification, or statistical analysis plan are reported there. The calculated tables and plots on this page display the posted results; they do not fill in those missing design details.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One subject was excluded from the analysis because the ZV9003 lens was implanted in the first eye and the ZA900 lens was implanted in the second eye. All subjects in the outcomes analysis had the same lens in 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.

6. Primary Endpoint

The registry lists the primary outcome as Best Corrected Distance Visual Acuity, measured over One year.

The primary endpoint is the number of participants whose best corrected distance visual acuity was Snellen-equivalent 20/40 or better at one year. Best corrected distance visual acuity assesses distance vision under the stated best-correction condition. This endpoint converts that assessment into a binary result: each participant either reaches the threshold or does not.

A threshold can be useful because it presents an outcome in a form that is easy to interpret clinically: the count indicates how many participants met a defined level. It also makes the group comparison an absolute difference in the proportion meeting the threshold. However, a binary endpoint does not show how far above or below the threshold each person’s acuity was, nor does it describe changes within categories. Two groups can have similar threshold counts while having different distributions of measurements that the binary classification does not preserve.

Here, the registry specifies the measure, threshold, and one-year timeframe. The posted results show 119 of 119 participants in the ZV9003 outcome group and 120 of 120 in the ZA9003 outcome group meeting the threshold. The record also notes that one participant was excluded because different lenses were implanted in the two eyes; the outcomes analysis included participants with the same lens in both eyes. That restriction is important when interpreting whom the endpoint results describe. The registry record does not report further detail about how acuity was measured, who assessed it, or how the threshold was selected.

7. Results Posted in the Registry

• ZA9003 Intraocular Lens: 100.0% (120/120) versus 100.0% (119/119) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Subject Satisfaction - Subjects Satisfied With Overall Eyesight Rated as "Good" or "Excellent".

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • ZA9003 Intraocular Lens: 95.0% (113/119) versus 94.9% (112/118) on control; risk difference 0.0 percentage points (95% CI -5.5 to 5.6), risk ratio 1.00 (0.94–1.06); unadjusted two-proportion z-test p = 0.988.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ZA9003 Intraocular Lens and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists contrast sensitivity and participant satisfaction as secondary outcomes, and it reports four outcome measures in total. The posted numerical information includes satisfaction, but a numerical contrast-sensitivity result is not reported in the registry record. The available secondary evidence is therefore incomplete as a summary of the full set of measures listed.

The satisfaction result shows a pattern consistent with the primary result in the limited sense that the posted groups are close on their recorded outcome. It is a different construct, however: satisfaction with overall eyesight is a participant rating categorized as good or excellent, whereas the primary endpoint is a visual-acuity threshold. Similar-looking group results across these measures do not make them interchangeable or show that one validates the other.

The satisfaction comparison is accompanied by an unadjusted result. Unadjusted secondary findings generally deserve less weight than a clearly prespecified primary comparison because a study may examine multiple outcomes, timeframes, or analyses. When multiple opportunities to find a difference are considered, the chance of at least one apparently notable result can increase. The registry record does not report a multiplicity adjustment or explain how the secondary outcomes were prioritized. That missing context limits the strength of any isolated secondary finding.

The record also does not report the statistical analysis methods for the secondary results, nor does it give the numerical results for all listed secondary measures. These gaps prevent a comprehensive assessment of consistency across outcomes. The secondary information can add descriptive context, but it should not be treated as a substitute for the primary result or as an independent confirmation of a broad claim. The tables on this page contain the endpoint-specific values; this reading focuses on how the outcomes relate and on the limitations of unadjusted secondary evidence.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Contrast Sensitivity
• Subject Satisfaction - Subjects Satisfied With Overall Eyesight Rated as "Good" or "Excellent".

9. Statistical Interpretation

10. Statistical Methods Explained

What does a binary endpoint represent?

The primary endpoint records whether each participant did or did not meet the visual-acuity threshold. In general, binary outcomes are summarized as counts and proportions within each group. Here, the posted counts are 119 of 119 and 120 of 120 meeting the threshold. The corresponding arm-level proportions are both 1.0 in the comparison data. This is a description of the participants included in the analysis, not a statement about unobserved participants or future patients.

In general, a risk difference compares the event proportions by subtracting one group’s proportion from the other’s. It expresses the absolute separation on the proportion scale. The registry comparison reports a risk difference of 0.0. Because both observed proportions are at the upper boundary of the scale, the data provide no observed difference to estimate. The particular statistical method used for the posted estimate and limits is not reported in the registry record.

What does a confidence interval usually convey?

In general, a confidence interval summarizes uncertainty around an estimated quantity under a stated statistical procedure. Its width depends on the amount and pattern of data as well as the method used. A narrow interval is not automatically persuasive if the method does not behave well for the observed data. For a binary outcome with all observations in the event category in both groups, methods based on ordinary approximations may encounter boundary issues. The registry record does not identify whether an exact, score-based, or other procedure was used for this primary comparison, so the displayed interval cannot be attributed to a particular method.

The posted primary interval has identical lower and upper limits at 0.0. It is therefore a zero-width interval as displayed, but it should not be read as showing that the true difference is known without uncertainty. The lack of observed non-events in the outcome denominators is central to interpreting this result. The record does not report an alternative interval or a sensitivity analysis.

What can be inferred from the secondary comparison?

The satisfaction endpoint is also binary: it counts participants whose overall eyesight satisfaction was rated good or excellent. Its posted comparison includes an estimated risk difference and confidence limits, as well as an unadjusted p-value. In general, a p-value measures how compatible data are with a specified null model under the test assumptions; it is not the probability that a treatment effect is real, and it does not measure clinical importance. The registry record does not identify the test used or report an adjusted analysis for this comparison.

Statistical significance, confidence intervals, and effect size answer different questions. An interval gives a range of values compatible with the analysis procedure, while a p-value summarizes evidence against a specified null hypothesis. Neither alone determines whether an observed difference matters clinically. The record does not report a prespecified threshold for a meaningful satisfaction difference.

What do the planning illustrations mean?

The sample-size section uses the observed satisfaction effect to create planning illustrations under stated assumptions: two-sided significance level 0.05, equal allocation, and a normal approximation. It shows planning for 100%, 75%, and 50% of the observed effect. These are not the trial’s original design justification and are not observed power. When the observed effect is very small, planning around that estimate can yield very large participant requirements; the resulting figures are sensitive to the effect chosen. The registry record does not report the trial’s own sample-size assumptions or justification.

In general, a sample-size calculation asks how many participants would be needed to detect a chosen effect under specified assumptions. It cannot establish that a study had a particular probability of success after the data have been observed. These illustrations should be treated as hypothetical planning scenarios, not evidence that the completed study was adequately or inadequately powered.

Which analyses are not documented?

The registry record lists zero reported analyses for the primary outcome and no reported analyses for the posted secondary outcome. It does not name the statistical test, interval procedure, covariate adjustment, handling of missing measurements, or approach to repeated measures. The comparison statistics should not be taken as proof that the record included a complete statistical analysis plan. Likewise, absence of a reported method does not establish that no method was used; it means the method is not reported in the registry record.

In general, interpreting a trial comparison involves checking the endpoint definition, analysis population, missing-data handling, model assumptions, and multiplicity plan. The registry provides some outcome definitions and denominators, but leaves several of those methodological questions unresolved. Accordingly, the clearest interpretation is descriptive: the posted counts show all analyzed participants met the primary threshold, while the record does not permit a detailed audit of the inferential procedure.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimated comparison. The posted primary risk difference is 0.0, and its reported lower and upper limits are both 0.0. Read literally, the displayed interval has no width. That display is difficult to reconcile with the usual role of an interval as a summary of sampling uncertainty, particularly because the primary outcome has no observed participants below threshold in either group.

The registry record does not report the method used to calculate the interval, so the reason it has identical limits cannot be determined from the posted information. It would be inappropriate to interpret the interval as proof of exact equality or complete certainty. The result is most safely described as no observed difference in the analyzed groups, with uncertainty about the true group difference not adequately conveyed by the displayed limits alone.

For the secondary satisfaction comparison, the posted interval is not zero-width: it extends on both sides of the estimated risk difference. In general, an interval spanning both negative and positive differences indicates that values in either direction are compatible with the interval procedure. It does not establish that all such values are equally plausible, and the interval’s interpretation depends on the method and assumptions. No interval method is identified in the registry record.

The analysis denominators also matter for precision. The primary comparison includes 119 and 120 participants, while the satisfaction comparison uses 118 and 119. The registry describes a participant excluded from the outcomes analysis because the two eyes received different lenses. The record does not explain the difference between the primary and secondary denominators, beyond reporting the outcome-specific counts. These results therefore have to be read outcome by outcome rather than assuming identical analysis sets.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome, secondary outcomes, and four outcome measures overall. The record does not report a multiplicity plan explaining whether the primary and secondary outcomes were tested as one family, whether any adjustment was planned, or which secondary outcome was considered most important. Without that information, secondary results should be regarded as exploratory or descriptive rather than as a set of confirmatory claims. This does not mean that no multiplicity plan existed; it means one is not reported in the registry record.

The record also lists zero reported analyses for the primary outcome and no reported analyses for the posted secondary result. It does not name the statistical tests, the confidence-interval procedures, any adjustment for baseline variables, or the analysis models. It therefore does not allow readers to verify whether methods were prespecified or whether the displayed comparisons follow a documented plan. Interim analyses and stopping rules are not reported in the registry record.

For the primary outcome, the registry explicitly states that one subject was excluded because the ZV9003 lens was implanted in the first eye and the ZA900 lens was implanted in the second eye. It further states that all participants in the outcomes analysis had the same lens in both eyes. This defines an analysis restriction, but the record does not describe a broader intention-to-treat analysis or provide a comparison of results with and without that participant.

Outcome-specific denominators differ between the primary and satisfaction results. The record does not explain all reasons for those differences, and it does not describe how missing outcome data were handled. There is no basis in the posted information to determine whether missingness was related to outcome or group. The safety summaries use separate at-risk counts and should not be assumed to represent the same analysis population as the visual-acuity endpoint.

These reporting gaps matter because the analysis population, missing-data approach, and multiplicity strategy can affect how confidently results are interpreted. They are limits of the information available in the registry record, not proof that the underlying study lacked these procedures.

13. 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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: retinal tear requiring secondary surgical intervention (0.8%).

The safety record lists one serious adverse event in each lens group among the participants at risk. It lists zero other adverse events in each group. A serious event is not necessarily caused by the study device; the figures alone do not establish causality. The registry also identifies retinal tear requiring secondary surgical intervention as the top serious-event term, at 0.8%. The posted summary does not provide enough detail to link that term to a particular group or to establish a causal relationship.

The safety denominators are 126 for ZV9003 and 124 for ZA9003. They differ from the primary visual-acuity outcome denominators, so the safety figures should not be combined with or substituted for the efficacy results. The record does not report death counts: the death fields are null, which should not be interpreted as zero deaths. The serious-event counts are small descriptive totals, and the registry record does not provide event-level timing, follow-up duration, attribution, or a statistical comparison. These figures summarize what was posted; they do not by themselves settle comparative safety.

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

The posted primary result has a straightforward descriptive meaning: in the outcome analysis, every participant in each group met the one-year visual-acuity threshold of Snellen-equivalent 20/40 or better. The estimated risk difference is reported as 0.0. This describes the observed comparison for this endpoint and analysis population.

It does not prove that the lenses produce identical outcomes in all respects. The endpoint reduces visual acuity to a single threshold, so it does not show the full distribution of acuity readings. The result also does not address every aspect of vision, participant experience, or safety. The registry lists other outcomes, but the numerical information is incomplete for the listed set.

The result is not a formal equivalence or noninferiority finding. Such a conclusion requires an appropriate design objective and a prespecified margin, neither of which is reported in the registry record. A displayed zero risk difference is not, on its own, proof that meaningful differences have been ruled out. The primary interval is also displayed with identical limits, and the method used to produce it is not reported; that interval should not be treated as a complete account of uncertainty.

The record describes an exclusion from the outcomes analysis for a participant with different lenses in the two eyes. Therefore, the result applies to the reported analysis population rather than automatically to all enrolled participants. The safety summaries use other denominators and provide limited event detail. Taken together, the posted data support a careful description of the observed threshold counts, but not a broader claim that one lens is superior, inferior, or interchangeable across all clinical outcomes.

15. Why This Trial Matters Statistically

This trial illustrates why the form of an endpoint matters. A binary threshold can make a result easy to communicate, but when all analyzed participants meet the threshold in both groups, the observed data contain no failures to help distinguish the groups. That boundary pattern creates challenges for uncertainty estimates and makes it especially important to know which interval method was used.

It also shows why an observed absence of difference is not the same as demonstrated equivalence. A formal equivalence question requires a prespecified framework, including a margin for what difference would be considered acceptably small. That framework is not reported in the registry record. The posted counts alone cannot supply it after the fact.

The study also provides a useful example of outcome-specific analysis populations. The primary visual-acuity and secondary satisfaction denominators differ, and the registry notes an exclusion related to different lenses implanted in the two eyes. Keeping those denominators distinct avoids implying that every outcome describes precisely the same participants.

Finally, the record demonstrates the value of transparent statistical reporting. It includes group counts, a comparison estimate, secondary data, and safety summaries, but does not report the analysis methods, multiplicity approach, or full analysis plan. These are not minor technical details: they shape how readers assess precision, robustness, and the weight to give secondary findings. Statistical interpretation depends both on the numerical results and on the methods needed to understand how those results were obtained.

16. 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.

Several limitations are specific to what is reported for this trial. First, the primary outcome is a binary threshold rather than the full visual-acuity distribution. The posted data therefore do not show how close participants were to the threshold or how measurements varied within the groups.

Second, all participants in the primary outcome denominators met the threshold. The resulting risk-difference interval is displayed as 0.0 to 0.0, but the registry record does not report its calculation method. This limits the ability to judge how well the displayed interval represents uncertainty in a boundary-data setting.

Third, one subject was excluded from the outcomes analysis because different lenses were implanted in the two eyes. The registry says the analysis included participants with the same lens in both eyes, but does not report a sensitivity analysis or a broader analysis including the excluded subject. The reasons for the different primary and secondary denominators are not fully explained.

Fourth, the numerical result for contrast sensitivity is not reported in the registry record, even though it is listed as a secondary outcome. The record does not report the statistical methods, multiplicity plan, sample-size justification, missing-data approach, or interim-analysis procedures. Safety reporting is also limited: the death fields are not populated, and detailed event-level information and attribution are not included in the posted summary. These reporting limits prevent a complete statistical and clinical assessment from the registry record alone.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Safety and Efficacy of a Violet Visible Light Blocking Intraocular Lens (IOL) — NCT00747227.
• Registry record last updated 2011-11-11; status last verified 2011-10.
• Results first posted 2011-11-11.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

20. Record Summary

This completed phase 3 study is listed as a randomized, double-masked, parallel-group evaluation of the ZV9003 modified light transmission intraocular lens and the ZA9003 monofocal acrylic intraocular lens. Enrollment was 250. The primary endpoint counted participants with Snellen-equivalent best corrected distance visual acuity of 20/40 or better at one year.

The posted primary data show that all participants in both outcome groups met the threshold, with a reported risk difference of 0.0 and limits of 0.0 and 0.0. The registry notes one exclusion from the outcomes analysis because different lenses were implanted in the two eyes. Satisfaction is reported as a secondary outcome; a numerical contrast-sensitivity result is not reported in the registry record.

The safety record lists one serious event in each group and zero other events, with separate at-risk denominators. Important details about statistical methods, multiplicity, missing data, and analysis planning are not reported. The results are therefore best read as a description of the posted outcomes, not as a formal equivalence conclusion.