Visual and Refractive Outcomes of The ClarVista HARMONI™ Modular Intraocular Lens System (HMIOL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Visual and Refractive Outcomes of The ClarVista HARMONI™ Modular Intraocular Lens System (HMIOL) (NCT03681886), a non-randomized na study. The primary outcome is Percentage of Eyes With Uncorrected Distance Visual Acuity (UCDVA) by Visit - Cohort 1.

2. Clinical Question

3. Trial Design

The study, NCT03681886, is titled “Visual and Refractive Outcomes of The ClarVista HARMONI™ Modular Intraocular Lens System.” It is recorded as completed, with ClarVista Medical as sponsor. The registry lists the start date as 2016-01-09 and primary completion as 2017-12-14. Phase is recorded as NA. Enrollment is listed as 150; that registry figure should not be mistaken for the denominator in any particular outcome analysis.

The design is non-randomized, unmasked, and single-group. These features matter when reading the results: the study does not establish a randomized comparison, and the registry does not identify a masked assessment process. The two described cohorts represent stages of care, not interchangeable arms. Cohort 1 received primary implantation and was followed through Month 1 before study exit, except that 1 site followed subjects through Month 12. Cohort 2 was a subset of Cohort 1 that underwent optic exchange at Month 1 after primary implantation and was followed through Month 1 after the exchange. Thus, people in the optic-exchange cohort had a prior primary implantation; the cohorts are not independent groups.

The study purpose was to evaluate visual and refractive outcomes with HMIOL implantation, assembly, and optic exchange among subjects undergoing cataract surgery. The primary endpoint addresses visual acuity after primary implantation in Cohort 1. It does not directly give a comparative estimate against another lens or a concurrent control group. The registry lists 13 outcome measures and 0 analyses. The primary outcome description states that formal statistical hypothesis testing was not planned. Further details about the study’s statistical plan 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 150 subjects enrolled, 72 were exited from the study prior to attempted implantation with the HARMONI™ Modular Intraocular Lens (HMIOL) System. This reporting group includes all subjects / eyes with attempted implantation.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Per Protocol: All subjects/eyes with successful implantation of HMIOL with no major protocol deviations and available 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: Safety Population: All subjects/eyes with attempted HMIOL implantation (successful or aborted after contact with the eye)

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Eyes With Uncorrected Distance Visual Acuity (UCDVA) by Visit - Cohort 1, measured over Day 1 post primary implantation, Week 1 post primary implantation, Month 1 post primary implantation, Month 3 post primary implantation, Month 6 post primary implantation, Month 12 post primary implantation.

The primary endpoint is the percentage of eyes with uncorrected distance visual acuity at specified visits after primary HMIOL implantation in Cohort 1. The listed visits are Day 1, Week 1, Month 1, Month 3, Month 6, and Month 12 post primary implantation. Acuity was tested using a chart at a 20-foot equivalent distance, with an optical infinity adjustment of +0.25 diopter. Results were recorded in Snellen notation. The description identifies 20/20 as “normal” vision and explains that a larger denominator indicates lower visual acuity.

Reporting percentages by visit can describe how many measured eyes fall into acuity categories at each follow-up point. This is useful for making the time course of the measured outcome understandable, especially when a clinical endpoint is naturally expressed as a proportion of eyes meeting a specified acuity level. It does not, on its own, show why an observed value changed, whether a change is attributable to the lens, or how the outcome compares with an alternative treatment.

The registry record does not report the acuity percentages, counts, category cutoffs used for the reported endpoint, or the number of eyes assessed at each visit. Those missing outcome details prevent evaluation of the observed distribution and its precision. The endpoint description says no formal statistical hypothesis testing was planned. It is therefore appropriate to treat the endpoint as a descriptive measure as defined in the record, rather than as evidence of a tested difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a percentage of eyes with uncorrected distance visual acuity at visits after primary implantation. The following statistical concepts are general explanations of how such outcomes are commonly interpreted; they are not claims that additional analyses were performed in this study.

What does a percentage describe?

A percentage expresses a count relative to a denominator. For an eye-based endpoint, the denominator is the number of eyes assessed for the relevant outcome at a visit, and the numerator is the number meeting the specified acuity criterion. Both parts are important: the same percentage can arise from different numbers of observations, and its uncertainty depends in part on how many eyes contributed. The registry record does not report the visit-specific counts, denominators, or acuity percentages, so none can be reconstructed from the enrollment figure.

The endpoint is repeated across visits. Each visit describes acuity at a particular follow-up time, not a new randomized comparison. If the number or identity of eyes observed changes between visits, percentages across visits may reflect both outcome changes and changes in who remains assessed. A longitudinal analysis could account for repeated measurements and within-eye dependence, but the registry record does not report such an analysis or its method. The endpoint description instead says that no formal statistical hypothesis testing was planned.

What does a confidence interval communicate?

General: a confidence interval is a way to express the statistical uncertainty around an estimate under specified assumptions. For a proportion, it can indicate a range of values compatible with the observed data and the chosen interval method. A narrow interval generally indicates more precision than a wide interval, but an interval does not correct bias from selection, missing observations, or lack of a suitable comparator. No confidence interval for the primary outcome is reported in the registry record.

Why does the analysis population matter?

The primary endpoint population is identified as per protocol: subjects or eyes with successful implantation, no major protocol deviations, and available data. This is a rule for inclusion in the endpoint population, not a report of its size. General: restricting analysis to participants with available measurements can make an estimate depend on who returned or had usable data. If availability is related to health status or outcome, the measured results may not represent those with missing measurements. A reader would need visit-specific denominators and information about missingness to assess this concern. Those details are not reported in the registry record.

Another general consideration is that two eyes from the same subject, if both are included, may have correlated outcomes. Treating correlated eyes as fully independent can understate uncertainty. The registry describes the endpoint in terms of eyes and the per-protocol population in terms of subjects or eyes, but does not report whether one or both eyes per subject contributed, nor how any within-subject dependence was handled. No assumption about that handling should be made.

What does the cohort structure allow?

General: random allocation helps balance measured and unmeasured prognostic factors on average, supporting a more credible estimate of a causal contrast. Here, allocation is recorded as non-randomized and the model as single-group. Cohort 2 is a subset of Cohort 1 that underwent optic exchange, rather than a separately randomized group. Comparisons between their outcomes, or between time points, may be affected by selection and clinical circumstances. They do not have the same interpretation as a randomized treatment comparison.

The registry records masking as none. General: masking can reduce the chance that knowledge of treatment influences outcome assessment or reporting, depending on who is masked and how the outcome is measured. Visual acuity is assessed with a chart, but the record does not describe assessor masking or other procedures that might influence measurement. No further masking details are reported.

How should planning illustrations be understood?

General: a sample-size calculation is a planning exercise that asks how many observations might be needed to detect a chosen effect under stated assumptions. It is not an observed study result, and it is not “observed power.” The planning assumptions recorded for this study’s illustration include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Such an illustration is not the trial’s own design justification. It also does not turn this non-randomized, single-group study into a valid two-arm comparison. The registry does not report a sample-size justification for the original study.

For non-time-to-event outcomes, the planning assumptions specify participants per arm; time-to-event illustrations specify a total number of events. These are general planning conventions. Any planning output should be read as conditional on its assumptions, not as evidence that the present study had a particular power or that its endpoint met a hypothesis-testing threshold. The primary endpoint description states that formal hypothesis testing was not planned, and the registry lists 0 analyses.

Finally, registry entries distinguish endpoint definitions from analyzed results. An outcome may be described in detail without a numerical result, denominator, uncertainty estimate, or analysis method being reported. For this study, the available record defines the primary visual-acuity outcome and its timing, but does not report the outcome values needed for an inferential assessment.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint description states that no formal statistical hypothesis testing was planned. The registry lists 13 outcome measures and 0 analyses. It does not report a statistical testing hierarchy, a family-wise error strategy, or another multiplicity adjustment. The presence of several outcomes or visits does not establish that they were tested, and no unreported testing plan should be inferred. For the primary endpoint, the record supports a descriptive framing rather than a claim of confirmatory statistical testing.

The primary population is per protocol: subjects or eyes with successful implantation of HMIOL, no major protocol deviations, and available data. This definition makes clear that the endpoint is not necessarily based on everyone enrolled. However, the record does not state the number of subjects or eyes included at each visit, how many had missing measurements, or how missing values were handled. It does not report imputation, sensitivity analyses, or reasons for missingness. These items are not reported in the registry record.

General: missing-data methods matter because a complete-case estimate describes those with observed measurements, and may not represent all eligible participants if missingness is related to outcome. Imputation or sensitivity analyses can explore how conclusions depend on assumptions, but they do not eliminate uncertainty about unobserved values. Without the number and pattern of missing measurements, it is not possible to assess the impact of missingness.

The registry does not report additional analysis-population definitions for the other outcomes. The number enrolled, the per-protocol endpoint definition, and the event-specific at-risk figures serve different purposes and should not be substituted for one another.

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 non-serious adverse event terms

The registry records serious and other adverse events separately for Non-Ocular and Ocular groups. For Non-Ocular, 78 were at risk: 0 had a serious adverse event, 0 had another adverse event, and 0 deaths were recorded. For Ocular, 100 were at risk: 0 had a serious adverse event, 12 had another adverse event, and 0 deaths were recorded. These are the event figures and at-risk counts stated in the registry.

A count of 0 serious events means that none were recorded among the stated at-risk group in this record. It does not establish that the underlying risk is zero. Similarly, 12 other events in the Ocular group is a count, not a measure of severity or a causal conclusion. The record does not describe the individual events, their timing, seriousness criteria, relatedness to the device or procedure, or whether multiple events could occur in the same subject. The groups should not be compared as if they were randomized arms: the study was non-randomized and single-group, and the optic-exchange cohort was a subset of the primary-implantation cohort. These counts therefore describe recorded safety experience, not a controlled estimate of relative risk.

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

The registry record establishes what the study set out to assess: visual and refractive outcomes associated with HMIOL implantation and optic exchange in subjects undergoing cataract surgery. It defines a primary measure of uncorrected distance visual acuity and lists its follow-up visits. It also describes the study as completed, non-randomized, unmasked, and single-group. These details help frame the intended interpretation, but they do not supply the missing visual-acuity results.

The primary outcome percentages, eye counts at each visit, and confidence intervals are not reported in the registry record. As a result, the size and precision of the measured visual-acuity outcomes cannot be determined from this record. The registry’s enrollment figure is not a substitute for outcome-specific denominators, particularly because the primary endpoint uses a per-protocol population defined by successful implantation, no major protocol deviations, and available data.

The record also does not provide a randomized comparison. The optic-exchange cohort was a subset of the primary-implantation cohort, so it cannot be interpreted as an independent control group. The design cannot by itself separate treatment effects from other differences between people, eyes, or follow-up times. This is a limitation on causal interpretation, not a claim that no useful descriptive information could be collected.

The safety entries show 0 serious adverse events and 0 deaths in each listed group, with 12 other adverse events recorded in the Ocular group and 0 in the Non-Ocular group. These counts should be read with their respective at-risk figures and without inferring comparative or causal effects. They do not provide descriptions of event type or circumstances.

Accordingly, the registry record supports statements about the study’s aims, design, endpoint definition, and reported safety counts. It does not establish the magnitude or precision of the primary visual-acuity outcome, demonstrate a comparison with another treatment, or permit a formal hypothesis-testing conclusion for that endpoint.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly defined outcome and a reported result. The primary endpoint specifies the measure, population, and assessment schedule: percentage of eyes with uncorrected distance visual acuity in Cohort 1 at visits from Day 1 through Month 12. It also describes the acuity assessment. Yet without the actual percentages and eye counts, a reader cannot evaluate the level of acuity observed or the precision of those estimates. Endpoint detail alone does not permit a quantitative appraisal.

The cohort structure also illustrates why design labels matter. Non-randomized allocation and a single-group model do not support the same causal interpretation as a randomized comparison. The optic-exchange cohort is a subset of the primary-implantation cohort, which makes it especially important not to mistake cohort labels for independent treatment arms. The record’s planning assumptions involving equal allocation between two arms are illustrations rather than evidence that the study itself had a randomized two-arm design.

The per-protocol definition gives another useful lesson: the analyzed population may differ from the enrollment figure. Successful implantation, protocol adherence, and available data are part of the stated inclusion rule, but the endpoint denominators are not reported. Without those denominators, percentages and their uncertainty cannot be independently understood.

Finally, the safety record separates serious events, other events, and deaths. Presenting each with its at-risk figure helps prevent a count from being mistaken for a rate or causal comparison. The record illustrates that careful interpretation depends on both the design and the detail available, not merely on whether an outcome is named or an event count is displayed.

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 primary endpoint is defined, but its observed percentages and visit-specific eye counts are not reported in the registry record. No confidence intervals or other precision estimates are reported for this outcome. This is the central limitation for interpreting visual-acuity results: the record does not permit an assessment of either the observed levels or their uncertainty.

The endpoint population is per protocol and requires successful implantation, no major protocol deviations, and available data. The record does not state how many eyes met these criteria or how many contributed at each follow-up visit. It also does not report missing-data handling, reasons for unavailable measurements, or sensitivity analyses. The enrollment figure of 150 should not be treated as the denominator for each outcome.

The study was non-randomized, unmasked, and single-group. There is no like-for-like randomized control comparison. Cohort 2 consisted of a subset of Cohort 1 undergoing optic exchange, which limits interpretation of any comparison between those cohorts. The registry does not report details about assessor masking or procedures to reduce measurement bias.

The record states that formal statistical hypothesis testing was not planned for the primary endpoint, lists 13 outcome measures, and lists 0 analyses. It does not report further statistical methods, adjustment for multiplicity, or an original sample-size justification. The planning assumptions are illustrative and should not be treated as the study’s design rationale or as observed power.

For safety, event counts are reported, but descriptions, timing, severity details, relatedness, and handling of recurrent events are not reported in the registry record. These gaps limit how much can be inferred from the counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Visual and Refractive Outcomes of The ClarVista HARMONI™ Modular Intraocular Lens System (HMIOL) — NCT03681886.
• Registry record last updated 2021-01-05; status last verified 2020-12.
• Results first posted 2021-01-05.
• 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

NCT03681886 evaluated visual and refractive outcomes associated with the HARMONI Modular Intraocular Lens System during cataract surgery. The registry lists ClarVista Medical as sponsor, a non-randomized, unmasked, single-group design, enrollment of 150, and completed status. The primary endpoint was the percentage of eyes with uncorrected distance visual acuity in Cohort 1 at visits from Day 1 through Month 12 after primary implantation. The registry states that formal hypothesis testing was not planned for this endpoint.

The optic-exchange cohort was a subset of the primary-implantation cohort. The registry lists 13 outcome measures and 0 analyses, but does not report the primary endpoint’s outcome values, eye counts by visit, or confidence intervals. Safety entries record 0 serious adverse events and 0 deaths in both groups, alongside 12 other adverse events in the Ocular group and 0 in the Non-Ocular group. The study design and unreported outcome detail limit comparative and quantitative interpretation.