Clinical Investigation of AcrySof® IQ ReSTOR® +3.0 D Multifocal Toric Intraocular Lens (IOL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Investigation of AcrySof® IQ ReSTOR® +3.0 D Multifocal Toric Intraocular Lens (IOL) (NCT01424189), a non-randomized na study. The primary outcome is Mean Monocular Uncorrected Distance Visual Acuity (UCDVA) at Fixed Distance at Visit 5.

2. Clinical Question

3. Trial Design

This completed clinical investigation, NCT01424189, evaluated the AcrySof® IQ ReSTOR® +3.0 D Multifocal Toric IOL against AcrySof® ReSTOR® Multifocal IOL Model SA60D3. The condition listed is cataracts. The registry names Alcon Research as sponsor and reports enrollment of 677 participants. The study started in 2011-07, reached primary completion in 2013-01, and has completed status.

The design is described as parallel, with non-randomized allocation and no masking. Participants were assigned to the ReSTOR Toric IOL or ReSTOR IOL arm. The toric model was determined by preoperative keratometric astigmatism; the arm descriptions state bilateral implantation for both lens groups. Because allocation was not randomized, the arm comparison may reflect differences between the participants selected for each lens as well as differences associated with the lenses. The record does not establish that the groups were comparable at baseline.

The primary outcome was mean monocular uncorrected distance visual acuity at a fixed distance at Visit 5, with the timeframe described as Month 12 from second-eye implantation. The analysis population included participants with successful IOL implantation in the first implanted eye and data at the visit. A secondary outcome listed was the rate of severe visual disturbances or distortions reported on the APPLES Questionnaire at Visit 5. The registry lists four outcome measures and two analyses, but a detailed analysis plan is not reported in the registry record.

The registry describes the primary endpoint measurement procedure, but it does not report the protocol’s rationale for enrollment, planned sample-size justification, interim analyses, or a complete account of how comparisons were adjusted. These omissions limit what can be concluded about the study’s planning and inferential approach.

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 677 participants enrolled, 103 were exited prior to randomization as screen failures. This reporting population includes all participants with successful IOL implantation in at least 1 eye (574).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis population includes all participants with successful IOL implantation in the first implanted eye with data at visit.

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: This analysis population includes all participants with successful IOL implantation in at least 1 eye.

6. Primary Endpoint

The registry lists the primary outcome as Mean Monocular Uncorrected Distance Visual Acuity (UCDVA) at Fixed Distance at Visit 5, measured over Month 12 from second eye implantation.

The primary endpoint is mean monocular uncorrected distance visual acuity at a fixed distance at Visit 5. “Monocular” means that each eye is measured separately. “Uncorrected” means visual correction is not used during the acuity measurement. The record specifies a 100% contrast ETDRS chart positioned 4 meters from the participant under well-lit conditions, with +0.25 diopter spherical power applied to correct for optical infinity.

Visual acuity was recorded in logMAR, the logarithm of the minimum angle of resolution. The registry explains that a 0.1 logMAR increment corresponds to 5 letters, or 1 line, on an ETDRS chart. Lower numeric logMAR values represent better visual acuity. This direction matters when reading a mean: a lower value indicates better measured acuity, not worse acuity.

A mean provides a summary of the measured acuity values in the analysis population. The registry identifies the endpoint statistic as a least-squares mean and its dispersion measure as a standard error. In general, a least-squares mean is a model-based mean, potentially adjusted for factors included in the model; the factors and model specification are not reported in the registry record. A standard error describes the precision of an estimated mean, rather than the spread of individual participants’ measurements.

The endpoint was prespecified for the first operative eye, and the analysis population required successful implantation in that eye and data at the visit. The timeframe was Month 12 from second-eye implantation. The endpoint estimates and their uncertainty are not reported in the registry record, so the magnitude and precision of the observed group results cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: visual acuity is represented on the logMAR scale, and the registry specifies a mean as the summary. For a continuous outcome, a group mean describes the central level of measured values. It does not describe every participant’s result, and it can conceal variation across individuals. The registry identifies a least-squares mean, which generally refers to a model-based estimate rather than simply the arithmetic average. The statistical model and any adjustment variables are not reported in the registry record, so the precise meaning of the adjustment cannot be reconstructed.

What does the standard error describe?

The reported dispersion type for the primary endpoint is standard error. In general, a standard error expresses the precision of an estimated quantity, such as a mean. It is not the same as a standard deviation, which describes variation among individual observations. A smaller standard error, in a comparable setting, indicates a more precise estimate; a larger one indicates more uncertainty about the estimated mean. The endpoint’s actual standard errors are not reported in the registry record.

A confidence interval is a range of values compatible with the data and the assumptions of the analysis, expressed at a stated confidence level. It communicates uncertainty around an estimate in a way that is often more informative than a test result alone. The registry record does not report a confidence interval for the primary endpoint. Without an estimate and its interval, readers cannot assess the range of plausible values for a group mean or a group contrast.

How should the logMAR scale be read?

The record states that lower logMAR values indicate better visual acuity. It also connects a 0.1 logMAR increment with 5 letters, or 1 line, on the ETDRS chart. These scale properties support interpretation of an estimate if one is reported. They do not supply the missing endpoint values. In particular, the direction of the scale should not be confused with the direction of an effect estimate: the registry does not report a comparative estimate whose sign could be interpreted.

The endpoint was measured monocularly, separately for each eye, without visual correction. The primary analysis was prespecified for the first operative eye, and the stated population included participants whose first implanted eye had successful IOL implantation and data at the visit. The timing was Month 12 from second-eye implantation. These specifications identify the measurement and analysis target, but the record does not explain the handling of participants who did not meet those analysis-population conditions.

What can be inferred from the study design?

The study is parallel and non-randomized, with no masking. A parallel design assigns participants to groups that are followed in their respective arms rather than describing a crossover. Non-randomized allocation means the assignment process did not use random allocation as described in the record. In general, randomization helps balance measured and unmeasured prognostic characteristics across groups on average. Without it, group differences may arise from how participants entered or were assigned to the arms. The record does not report enough detail to judge the extent of such differences or how the analysis addressed them.

No masking means the registry does not identify masking of participants, care teams, or outcome assessors. The record gives no further detail about who knew the assigned lens or how visual-acuity measurement was protected from assessment bias. The endpoint uses a chart-based measurement, but no conclusion about the conduct of assessment beyond the stated conditions is warranted.

What is not reported about the analysis?

The registry identifies a least-squares mean and standard error, but does not report the model formula, adjustment factors, assumptions checks, missing-data method, or a comparative test for the primary endpoint. It also does not report an analysis population for the other outcomes in sufficient detail. Therefore, a reader cannot determine from the registry record whether the reported primary statistic would account for baseline variables, site effects, repeated observations, or other features.

General statistical practice distinguishes a prespecified analysis from an analysis selected after looking at results. The registry says that the primary analysis was prespecified for the first operative eye, but does not provide a full statistical analysis plan or explain whether further analytic choices were prespecified. Interim analyses are not reported in the registry record. These omissions do not establish that such procedures were or were not used.

The record lists four outcome measures and two analyses. Counting listed outcomes does not reveal how many statistical tests were performed or whether multiplicity was addressed. When multiple outcomes or comparisons are tested, the chance of at least one false-positive result can increase if the tests are treated as independent confirmatory questions without adjustment. The registry record does not describe a multiplicity strategy, so no conclusion about adjustment is possible.

Planning illustrations based on an observed effect are not the same as an analysis of trial results and do not represent observed power. Such illustrations depend on their assumptions and are used to describe hypothetical planning requirements, not to establish whether the study found an effect. The registry’s design justification and any trial-specific sample-size rationale are not reported in the registry record. No inference about the study’s original planning can be made from an illustration alone.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("ReSTOR Toric IOL", "ReSTOR IOL")
n   <- c(373, 180)
m   <- c(0.126, 0.125)
sp  <- c(0.013, 0.015)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  ReSTOR Toric IOL  373  0.126  0.251  0.100  0.152
CARM  ReSTOR IOL  180  0.125  0.201  0.095  0.155

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and two analyses, but does not report how many formal tests were conducted, which outcomes were treated as confirmatory, or whether any multiplicity adjustment was used. In general, testing several outcomes or contrasts without accounting for the number of tests can increase the chance of a statistically significant finding arising by chance. Adjustment methods and prespecified hierarchies can address that issue, but the registry record does not identify a method or testing hierarchy. The listed APPLES Questionnaire outcome is secondary; its result is not reported in the registry record.

The primary analysis population is described as participants with successful IOL implantation in the first implanted eye and data at the visit. This definition clarifies who was included in that analysis, but the record does not report how many participants met it, how missing acuity observations were handled, or whether an alternative population was analyzed. It does not describe imputation, sensitivity analyses, or assumptions about why observations might be missing. Those details matter because estimates can depend on which participants contribute data and on how missing outcomes are treated.

The record reports enrollment of 677 participants, but does not provide the trial’s sample-size justification or explain whether enrollment was based on a prespecified target for precision or power. Any planning illustration is not a substitute for that design rationale and is not observed power. Interim analyses are not reported in the registry record. The available information therefore does not permit a complete assessment of multiplicity, missing-data handling, or the relationship between the planned and analyzed populations.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: surgical procedure repeated (second implanted eye) (1.6%), coronary artery disease (1.1%), halo vision (second implanted eye) (1.1%), surgical procedure repeated (first implanted eye) (1.1%), intraocular lens repositioning (first implanted eye) (1.0%).

The registry lists serious adverse events for the ReSTOR Toric IOL arm with 386 participants at risk and 45 affected, and other adverse events with 386 at risk and 48 affected. For the ReSTOR IOL arm, it lists 188 participants at risk and 21 affected for serious adverse events, and 188 at risk and 28 affected for other adverse events. These are counts as recorded; they should not be treated as evidence that an event was caused by the lens or procedure.

Selected serious-event terms and percentages are listed: Surgical procedure repeated (Second Implanted Eye), 1.6%; Coronary artery disease, 1.1%; Halo vision (Second Implanted Eye), 1.1%; Surgical procedure repeated (First Implanted Eye), 1.1%; Intraocular lens repositioning (First Implanted Eye), 1.0%; and Cystoid macular oedema (Second Implanted Eye), 0.8%. The registry record does not explain the denominator or selection rule for these terms, so the percentages should be read as registry listings rather than as directly comparable arm-specific rates.

Deaths are not reported in the registry record. The safety figures are descriptive, and the non-randomized design limits causal interpretation of differences between arms. Follow-up duration by event, severity criteria, relatedness assessments, and statistical comparisons are not reported in the registry record.

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

The registry record establishes that a completed, non-randomized, parallel clinical investigation compared bilateral implantation of an investigational multifocal toric IOL with bilateral implantation of a multifocal IOL identified as FDA-approved. It defines the primary endpoint as mean monocular uncorrected distance visual acuity, measured in logMAR at Visit 5, Month 12 from second-eye implantation. It also states how acuity was measured and which analysis population was intended.

Those design details do not reveal the primary endpoint result. The mean estimates, standard errors, comparative estimate, confidence interval, and test result are not reported in the registry record. Accordingly, the record does not support a quantitative conclusion about the visual-acuity difference between arms or its precision. The direction convention for logMAR is known, but there are no posted primary values to interpret using that convention.

The safety listings show the recorded numbers of participants at risk and affected in each arm and identify selected serious-event terms. They do not establish that a device caused an event, and they do not show a controlled comparison of risks. Because allocation was not randomized, differences between the groups could reflect factors other than the assigned lens. Baseline comparability and adjusted safety comparisons are not reported in the registry record.

The record also does not report the result for the APPLES Questionnaire outcome, a full statistical analysis plan, missing-data procedures, multiplicity handling, or trial-specific sample-size justification. These are important distinctions between a study’s stated question and the evidence available to answer it. The purpose and endpoint are described, but the posted information does not establish whether the primary comparison favored either arm, how certain any estimate was, or how secondary outcomes compare.

These observations are statistical interpretation of the registry record, not medical advice. They describe what can be concluded from the reported design and listings and identify where outcome information is absent.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly named clinical endpoint and a reported result must be considered together. The registry defines visual acuity measurement in detail, including the eye, correction status, chart conditions, scale, and timing. These features help readers understand what an eventual estimate would mean and how to read its direction. Yet without the estimate and its uncertainty, endpoint definition alone cannot answer the comparative question.

It also shows why allocation is central to interpretation. The comparison is parallel but non-randomized and unmasked. Those characteristics affect what can be inferred from between-arm differences, even if numerical results are available. Random allocation can help balance prognostic factors; a non-randomized comparison requires careful attention to selection and potential confounding. The registry does not report enough information to assess those factors or the adjustment strategy.

The safety listings further demonstrate the difference between event counts and causal evidence. Counts at risk and affected describe what was recorded in each group. They do not by themselves indicate whether events were caused by an intervention, whether the groups had comparable follow-up, or whether an apparent difference would be precise.

Finally, the record makes visible the importance of complete statistical reporting. Analysis populations, missing-data handling, multiplicity, confidence intervals, model details, and sample-size rationale all shape how results should be evaluated. When these details or the outcome estimates are absent, conclusions need to remain limited to the design and listed observations. The case is statistically useful because it separates a well-defined measurement question from the evidence needed to answer it.

15. 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 principal limitation for interpreting effectiveness is that the registry record does not report the primary endpoint estimates or a between-arm comparison. The endpoint’s standard error is identified as the dispersion measure, but no numerical standard error or confidence interval is reported. The listed primary question therefore cannot be resolved from the registry record.

Allocation was non-randomized, and masking was none. These design features limit the strength of causal interpretation. The registry does not report baseline characteristics or enough information to assess whether the arms were comparable, nor does it describe adjustment factors for the least-squares mean. It is therefore not possible to determine whether measured or unmeasured differences between participants could explain a group contrast.

The analysis population required successful implantation in the first implanted eye and data at the visit. The number meeting this definition and the handling of participants without eligible observations are not reported in the registry record. Missing-data methods, sensitivity analyses, and the analysis populations used for other outcomes are also not reported.

The registry lists a secondary APPLES Questionnaire outcome but does not report its result. It does not describe a multiplicity strategy, a complete statistical analysis plan, interim analyses, or the trial-specific sample-size rationale. The available safety listings lack details on event-relatedness assessments, follow-up by event, and the denominator used for the selected serious-event percentages. Deaths are not reported in the registry record. These gaps prevent a full assessment of efficacy, safety comparisons, and statistical robustness.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Investigation of AcrySof® IQ ReSTOR® +3.0 D Multifocal Toric Intraocular Lens (IOL) — NCT01424189.
• Registry record last updated 2018-06-29; status last verified 2018-05.
• Results first posted 2017-03-06.
• 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.

19. Record Summary

NCT01424189 is a completed, parallel, non-randomized clinical investigation sponsored by Alcon Research. It enrolled 677 participants with cataracts and compared bilateral implantation of the AcrySof® IQ ReSTOR® +3.0 D Multifocal Toric IOL with bilateral implantation of AcrySof® ReSTOR® Multifocal IOL Model SA60D3. The study started in 2011-07 and reached primary completion in 2013-01.

The primary endpoint was mean monocular uncorrected distance visual acuity in logMAR at Visit 5, Month 12 from second-eye implantation, prespecified for the first operative eye. Lower logMAR values indicate better visual acuity. The record identifies least-squares mean and standard error but does not report the endpoint estimates or comparative result. It also lists an APPLES Questionnaire outcome and descriptive adverse-event counts. The primary and secondary outcome results are not reported in the registry record, limiting interpretation of comparative effectiveness and safety.