This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (LUCERNE) (NCT03823300), a randomized phase 3 study. The primary outcome is Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03823300 |
| Phase | Phase 3 |
| Condition | Wet Macular Degeneration |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 658 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants with neovascular age-related macular degeneration were enrolled. The primary analysis population was the intention-to-treat population: all randomized participants, grouped according to their assigned treatment. The registry reports 658 participants enrolled overall. The primary endpoint description identifies the study eye as the eye in which best corrected visual acuity was assessed.
Intervention
The experimental treatment was faricimab. The registry summary says its administration intervals were specified in the protocol, but the actual interval schedule is not reported in the registry record. A sham procedure is also listed among the interventions; the arm descriptions do not explain how it was used.
Comparator
The active comparator was aflibercept administered once every 8 weeks, described in the registry summary as Q8W. The study is identified as randomized and parallel, with treatment assigned to participants at randomization. The primary analysis grouped participants according to that assignment.
Primary question
The primary question was whether change in best corrected visual acuity in the study eye, averaged over Weeks 40, 44, and 48, differed between the assigned treatments. Visual acuity was scored using ETDRS letters. The registry reports adjusted mean change estimates and an adjusted between-group mean difference with a confidence interval. Although the reported comparison is classified as non-inferiority, the non-inferiority margin is not reported in the registry record, so the margin-based decision criterion cannot be independently assessed from these details.
3. Trial Design
This was a Phase III, randomized, parallel-group study comparing faricimab with the active comparator aflibercept in participants with neovascular age-related macular degeneration. The registry reports an enrollment of 658 and a completed study. Its listed start date is 2019-03-11 and its primary completion date is 2020-10-05. Those dates describe the registry record; they do not, by themselves, establish how long each participant was followed.
The primary endpoint was assessed through Week 48, while selected secondary outcomes extend to an average over Weeks 52, 56, and 60. The registry summary describes the study as evaluating efficacy, safety, durability, and pharmacokinetics. The listed interventions include faricimab, aflibercept, and a sham procedure. However, the arm descriptions contain no details, and the administration interval for faricimab is not reported in the registry record. No assumptions about injection schedules or sham-procedure use should therefore be inferred from the intervention list alone.
The registry fields identify the allocation as randomized and the masking as triple. The official title describes the trial as double-masked. These descriptions do not match, and the registry record does not explain the difference or specify which individuals were masked. It is therefore safest to report both descriptions without resolving the inconsistency. The study is also described as multicenter in its official title.
The primary analysis population was the intention-to-treat population, defined in the record as all randomized participants analyzed according to assigned treatment. The primary endpoint description reports 331 participants in the faricimab arm and 327 in the aflibercept arm. The population counts used for some safety outcomes and secondary analyses differ from those primary-analysis arm counts; the registry record does not explain every reason for those differences. A planned sample-size target, design assumptions for the trial itself, and details of any interim analyses 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: A total of 1012 patients were screened, 354 of whom failed screening, most commonly due to not meeting inclusion criteria. A total of 658 treatment-naive patients with nAMD were randomized 1:1 into the study: 331 to the faricimab arm and 327 to the aflibercept arm.
Overall Study
| Stage | Arm A: Faricimab | Arm B: Aflibercept |
|---|---|---|
| STARTED | 331 | 327 |
| Received at Least One Dose of Study Drug | 331 | 326 |
| Completed up to Week 48 | 321 | 309 |
| COMPLETED | 297 | 273 |
| NOT COMPLETED | 34 | 54 |
Reasons for not completing this period:
| Reason | Arm A: Faricimab | Arm B: Aflibercept |
|---|---|---|
| Withdrawal by Subject | 16 | 22 |
| Death | 10 | 14 |
| Adverse Event | 3 | 5 |
| Physician Decision | 1 | 7 |
| Lost to Follow-up | 1 | 3 |
| Protocol Violation | 1 | 1 |
| Lack of Efficacy | 1 | 1 |
| Not Eligible | 0 | 1 |
| Other | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.
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: Intent-to-Treat (ITT) Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.
| Characteristic | Unit | Arm A: Faricimab | Arm B: Aflibercept | Total |
|---|---|---|---|---|
| Participants analysed | 331 | 327 | 658 | |
| Age, Continuous | Years | 74.8 (SD 8.4) | 76.1 (SD 8.6) | 75.5 (SD 8.5) |
| Sex: Female, Male: Female | Participants | 203 | 188 | 391 |
| Sex: Female, Male: Male | Participants | 128 | 139 | 267 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 35 | 46 | 81 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 287 | 274 | 561 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 9 | 7 | 16 |
| Race/Ethnicity, Customized: White | Participants | 278 | 270 | 548 |
| Race/Ethnicity, Customized: Asian | Participants | 38 | 34 | 72 |
| Race/Ethnicity, Customized: Unknown | Participants | 12 | 17 | 29 |
| Race/Ethnicity, Customized: Black or African American | Participants | 2 | 5 | 7 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Multiple | Participants | 0 | 1 | 1 |
| Region of Enrollment: United States and Canada | Participants | 135 | 132 | 267 |
| Region of Enrollment: Asia | Participants | 35 | 33 | 68 |
| Region of Enrollment: Rest of the World | Participants | 161 | 162 | 323 |
| Number of Participants by the Eye (Right or Left) Chosen as the Study Eye: Right Eye | Participants | 168 | 170 | 338 |
| Number of Participants by the Eye (Right or Left) Chosen as the Study Eye: Left Eye | Participants | 163 | 157 | 320 |
| Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye | ETDRS Letters | 58.7 (SD 14.0) | 58.9 (SD 13.3) | 58.8 (SD 13.6) |
| Number of Participants by the BCVA Letter Score Categories in the Study Eye: ≥74 Letters | Participants | 45 | 39 | 84 |
| Number of Participants by the BCVA Letter Score Categories in the Study Eye: 73 to 55 Letters | Participants | 181 | 183 | 364 |
| Number of Participants by the BCVA Letter Score Categories in the Study Eye: ≤54 Letters | Participants | 105 | 105 | 210 |
| Number of Participants by the Low Luminance Deficit (LLD) Letter Score Categories in the Study Eye: <33 Letters | Participants | 238 | 234 | 472 |
| Number of Participants by the Low Luminance Deficit (LLD) Letter Score Categories in the Study Eye: ≥33 Letters | Participants | 89 | 93 | 182 |
| Number of Participants by the Low Luminance Deficit (LLD) Letter Score Categories in the Study Eye: Missing/Invalid | Participants | 4 | 0 | 4 |
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography: Occult | Participants | 171 | 140 | 311 |
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography: Classic | Participants | 98 | 109 | 207 |
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography: Minimally Classic | Participants | 30 | 31 | 61 |
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography: Retinal Angiomatous Proliferation (RAP) | Participants | 14 | 15 | 29 |
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography: Predominantly Classic | Participants | 6 | 16 | 22 |
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography: Polypoidal Choroidal Vasculopathy (PCV) | Participants | 5 | 8 | 13 |
| Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography: Missing | Participants | 7 | 8 | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48, measured over From Baseline through Week 48.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | ETDRS Letters |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures change from baseline in best corrected visual acuity in the study eye, averaged over Weeks 40, 44, and 48. Visual acuity was assessed using the Early Treatment Diabetic Retinopathy Study chart at a starting distance of 4 meters. Scores range from 0 to 100 ETDRS letters, with a higher score indicating better visual acuity. A gain from baseline therefore represents improvement in the measured score, while a decline represents a lower score than at baseline.
Using an average across multiple scheduled visits provides a summary of visual acuity over the specified assessment period rather than relying on a single visit. The registry describes the endpoint as a continuous measure and reports adjusted mean changes with 95% confidence intervals. The primary analysis used a repeated-measures model that incorporated measurements over time and adjusted for specified baseline and study factors. The stated timeframe is from baseline through Week 48.
This endpoint is a measure of visual acuity, not a complete account of every aspect of the disease or a participant’s experience. It also does not, on its own, describe durability, safety, or pharmacokinetics, which the registry lists among the broader study aims. The clinical importance of a particular difference in ETDRS letters and the threshold used to make a non-inferiority decision cannot be determined from the endpoint definition alone; the non-inferiority margin is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The adjusted mean change in the faricimab group was 6.6 ETDRS letters, with a 95% confidence interval from 5.3 to 7.8. The corresponding adjusted mean change reported for aflibercept was also 6.6, with a 95% confidence interval from 5.3 to 7.8. The reported adjusted mean difference was 0.0, and its 95% confidence interval ranged from -1.7 to 1.8. These results describe the estimated average changes and the uncertainty around them; they do not establish that the treatments are identical.
A confidence interval gives a range of values compatible with the analysis under its statistical assumptions. The interval for the difference includes values on both sides of zero, so the posted estimate is compatible with a small difference in either direction as well as no difference. It is important to interpret the interval in relation to the study’s decision criterion. The registry classifies the reported comparison as non-inferiority, but the non-inferiority margin is not reported in the registry record. Without that margin, the interval alone does not show whether the specified non-inferiority criterion was met.
The record does not report a p-value for the primary comparison. A p-value is not needed to describe the estimate and its confidence interval, and it would not resolve the missing-margin issue. In a non-inferiority analysis, the key question is whether the interval excludes differences beyond a prespecified unacceptable boundary. The record’s classification indicates the analysis type, but the boundary itself and enough detail to verify the decision are absent.
The primary estimates are adjusted rather than simple differences in the observed arm averages. The described model accounts for treatment, visit, their interaction, baseline visual acuity and other baseline categories, and region. The endpoint analysis also used measurements across visits and specified approaches to intercurrent events. Accordingly, the adjusted comparison should be read as the model-based estimate defined by the registry’s analysis description, not as a direct subtraction of two unadjusted values.
The posted results are consistent with similar estimated average changes in the two randomized groups. Precision is described by the confidence interval, not by the rounded point estimate alone. The interval permits a range of possible between-group differences, and its clinical interpretation depends on a margin that is not reported. The result should therefore be stated narrowly: the posted analysis estimates a 0.0 adjusted mean difference, with the stated interval, for the primary visual-acuity endpoint and assessment period.
9. Statistical Methods Explained
The primary endpoint is continuous: each participant has a visual-acuity score measured in ETDRS letters, and the analysis concerns change from baseline. The reported arm summaries are adjusted means, with 95% confidence intervals. A mean describes the center of the measured changes across the analysis population; it does not imply that every participant experienced a change equal to that mean. The confidence interval expresses uncertainty around the estimated mean under the analysis model. It is not a range containing every participant’s score or change.
The primary description names a Mixed Model of Repeated Measures, or MMRM. In general, a repeated-measures model uses measurements collected at multiple visits while accounting for the fact that observations from the same participant are related. It can estimate treatment patterns over time and compare groups while using the available repeated measurements. Here, the reported model included treatment arm, visit, and the interaction between visit and treatment arm, alongside baseline covariates. The interaction allows the estimated difference between treatment groups to vary across visits rather than forcing a single identical contrast at every visit.
The listed adjustment factors include baseline BCVA as a continuous measure and as categories, baseline LLD categories, and region. Adjusting for prespecified baseline characteristics can account for differences in prognostic factors and improve the precision or stability of an estimate. The registry identifies the categories used for baseline BCVA and LLD and lists regional groupings. It does not report a coefficient for each adjustment factor in the primary outcome summary, so the treatment estimate should not be interpreted as a description of those factors’ individual effects.
An unstructured covariance structure was used. In general, a covariance structure describes how repeated measurements from the same participant relate to one another. An unstructured form allows those relationships to vary without imposing a simpler pattern, but it relies on the model being estimable from the available data. The record does not give additional model diagnostics or explain whether alternative covariance structures were examined.
The registry describes two strategies for intercurrent events. A treatment-policy strategy used all observed values for non-COVID-19-related intercurrent events. A hypothetical strategy censored values after COVID-19-related intercurrent events. In general, an estimand strategy clarifies which outcomes are included when events occur after treatment assignment. The registry also says missing data were implicitly imputed by MMRM and invalid BCVA values were excluded. This description does not provide a detailed missing-data sensitivity analysis or establish that missingness assumptions were correct.
The primary confidence interval is labeled 95%, and the endpoint description states that it is a rounding of a 95.03% confidence interval. That detail matters when interpreting the displayed precision: the posted rounded limits are not an independently calculated interval with extra digits. The adjusted mean difference is reported as 0.0, with limits of -1.7 and 1.8. The interval communicates uncertainty about the between-group contrast; it does not communicate the spread of participant-level changes.
The reported analysis type is non-inferiority. In general, a non-inferiority analysis asks whether the data rule out a disadvantage larger than a prespecified margin, rather than testing only whether the treatments differ from one another. A confidence interval must be judged against that margin and the direction in which the comparison is defined. The margin and its rationale are not reported in the registry record. Consequently, the reported estimate and interval can be described, but the formal threshold-based conclusion cannot be reconstructed from the available record alone.
Some secondary binary outcomes are accompanied by comparisons and planning illustrations based on simple, unadjusted summary statistics. Those recalculations are not substitutes for the sponsor’s reported analyses. In general, an unadjusted comparison does not account for stratification or covariate adjustment used in a trial’s primary analysis. The planning illustrations use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the detectable effect set to a stated fraction of the observed effect. They are planning scenarios, not observed power, and do not describe the enrollment target or assumptions used to design this trial. The trial’s own sample-size justification is not reported in the registry record.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | Adjusted mean difference 0.0 | -1.7 to 1.8 | not reported |
The registry reports the sponsor’s primary comparison as an adjusted mean difference of 0.0 ETDRS letters, with a 95% confidence interval from -1.7 to 1.8, and classifies the analysis as non-inferiority. The arm-specific adjusted mean changes are each reported as 6.6, with 95% confidence intervals from 5.3 to 7.8. No p-value is reported for this primary comparison.
The posted primary comparison is the appropriate result to emphasize because it reflects the trial’s reported adjusted analysis. No discrepancy is flagged between that reported result and the available summary, so there is no competing recalculation that would replace the sponsor’s analysis. In particular, the arm-level mean estimates should not be subtracted to create a new comparison: the reported adjusted difference and its interval are the relevant model-based quantities.
The registry’s non-inferiority classification should still be read alongside an important limitation. The non-inferiority margin and its rationale are not reported in the registry record. A reader can accurately report the sponsor’s estimate, interval, and analysis classification, but cannot verify from these fields whether the interval met the prespecified margin. The sponsor’s analysis is reported; the threshold needed to interpret its formal non-inferiority decision is not.
11. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study evaluates several outcomes, time points, or comparisons. Even if each analysis is considered separately, examining many results can increase the chance that at least one appears unusual by chance. This is especially relevant when outcomes are related or when the analysis includes multiple thresholds and assessment periods, as in the posted visual-acuity outcomes.
The registry lists 43 outcome measures, 42 posted secondary outcomes, and 16 analyses. The primary endpoint is clearly identified, but a complete hierarchy for secondary outcomes, rules for selecting among time points, or a multiplicity adjustment plan is not reported in the registry record. The registry also does not report interim analyses or stopping boundaries. Absence of these details from the record should not be taken as evidence that no such plans existed; it means they cannot be evaluated from the registry record.
The primary endpoint description gives an analysis population, adjustment factors, covariance structure, and strategies for intercurrent events. It states that missing data were implicitly imputed by MMRM and that invalid BCVA values were excluded. However, the registry record does not report detailed missingness patterns, sensitivity analyses under alternative assumptions, or the robustness of the result to different handling of missing observations. MMRM can use available repeated measurements under its model assumptions, but it does not make missing data assumptions irrelevant.
The primary analysis population is defined as all randomized participants, analyzed according to assigned treatment. The secondary and safety summaries have their own denominators, which differ across outcomes. The record does not provide a full account of every participant’s availability for each analysis or explain all denominator differences. Readers should therefore interpret each result with its stated population and denominator rather than assume all outcomes include the same participants.
These missing details limit how completely a reader can assess confirmatory status, robustness, and the handling of multiplicity. They do not erase the reported estimates. They do mean that secondary findings, especially unadjusted comparisons, should be considered supportive or descriptive unless a fuller analysis plan establishes their inferential role.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm A: Faricimab | 91 | 331 | 27.5% |
| Arm B: Aflibercept | 101 | 326 | 31.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A: Faricimab | 10 of 331 |
| Arm B: Aflibercept | 14 of 326 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A: Faricimab | 178 of 331 |
| Arm B: Aflibercept | 165 of 326 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A: Faricimab | Arm B: Aflibercept |
|---|---|---|---|
| Neovascular age-related macular degeneration | Eye disorders | 8 of 331 | 4 of 326 |
| Cardiac failure congestive | Cardiac disorders | 3 of 331 | 6 of 326 |
| COVID-19 pneumonia | Infections and infestations | 2 of 331 | 7 of 326 |
| Pneumonia | Infections and infestations | 2 of 331 | 6 of 326 |
| COVID-19 | Infections and infestations | 3 of 331 | 4 of 326 |
| Cerebrovascular accident | Nervous system disorders | 2 of 331 | 5 of 326 |
| Atrial fibrillation | Cardiac disorders | 3 of 331 | 3 of 326 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 4 of 331 | 2 of 326 |
| Cardiac failure | Cardiac disorders | 2 of 331 | 3 of 326 |
| Coronary artery disease | Cardiac disorders | 2 of 331 | 3 of 326 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A: Faricimab | Arm B: Aflibercept |
|---|---|---|---|
| Neovascular age-related macular degeneration | Eye disorders | 80 of 331 | 62 of 326 |
| Conjunctival haemorrhage | Eye disorders | 35 of 331 | 37 of 326 |
| Cataract | Eye disorders | 38 of 331 | 26 of 326 |
| Nasopharyngitis | Infections and infestations | 27 of 331 | 22 of 326 |
| Urinary tract infection | Infections and infestations | 19 of 331 | 29 of 326 |
| Vitreous detachment | Eye disorders | 22 of 331 | 21 of 326 |
| Fall | Injury, poisoning and procedural complications | 18 of 331 | 22 of 326 |
| Dry eye | Eye disorders | 15 of 331 | 21 of 326 |
| Posterior capsule opacification | Eye disorders | 15 of 331 | 19 of 326 |
| Hypertension | Vascular disorders | 15 of 331 | 18 of 326 |
Serious events with the highest arm-level rate: neovascular age-related macular degeneration (2.4%), covid-19 pneumonia (2.1%), cardiac failure congestive (1.8%), pneumonia (1.8%), sepsis (1.5%).
The registry lists serious adverse events for 91 of 331 participants at risk in the faricimab group and 101 of 326 at risk in the aflibercept group. Other adverse events are listed for 178 and 165 participants, respectively. Deaths are listed for 10 participants in the faricimab group and 14 in the aflibercept group. These are reported counts with the registry’s stated at-risk denominators; they are not estimates of treatment effects or adjusted comparisons.
The serious-event terms with the highest listed percentages include neovascular age-related macular degeneration at 2.4%, COVID-19 pneumonia at 2.1%, congestive cardiac failure at 1.8%, pneumonia at 1.8%, sepsis at 1.5%, and cerebrovascular accident at 1.5%. These percentages describe listed event terms, not the probability that a treatment caused an event. A term appearing in both the disease and safety records does not establish causation.
Safety counts require caution because the registry summary does not provide event timing, duration, severity distributions beyond the serious-event classification, or adjusted between-group comparisons. The group denominators for safety differ from the primary endpoint analysis counts. Counts alone cannot determine whether events were caused by treatment or whether a difference is meaningful. They should be read as descriptive reporting, alongside the limitations of the available safety detail.
13. What the Result Does, and Does Not, Mean
The primary result describes average change in best corrected visual acuity for the randomized groups over the defined assessment period. Both arms have a reported adjusted mean change of 6.6 ETDRS letters. The adjusted mean difference is reported as 0.0, with a 95% confidence interval from -1.7 to 1.8. This supports a narrow description of the posted estimate: the model-based average changes were similar, and the interval reflects remaining uncertainty about the difference.
It does not prove that the treatments are exactly equivalent. A point estimate of 0.0 is rounded, and a confidence interval includes a range of possible underlying differences. Whether that range is sufficiently narrow for a non-inferiority conclusion depends on the prespecified margin. Because the margin is not reported in the registry record, the formal non-inferiority criterion cannot be checked from the reported interval alone, even though the analysis is labeled non-inferiority.
The endpoint also does not represent every participant’s experience. A group mean can conceal variation in individual changes, and a confidence interval around that mean is not an individual prediction interval. The visual-acuity measure does not cover every aspect of neovascular age-related macular degeneration, treatment burden, quality of life, safety, or pharmacokinetics. Those topics require their own outcomes and analysis.
The secondary outcomes provide related but distinct descriptions of visual acuity. They do not automatically validate the primary finding, particularly where many outcomes are considered and multiplicity handling is not reported. Safety counts likewise describe observed events and should not be interpreted as proof that treatment caused or prevented them. Overall, the registry supports reporting the stated estimates and their uncertainty, while leaving the margin-based conclusion, broader clinical meaning, and some analysis details unresolved.
14. Why This Trial Matters Statistically
This trial is statistically informative because its primary outcome is measured repeatedly and summarized across a defined assessment period, rather than relying on a single isolated score. The MMRM description makes clear that the comparison used measurements over time and adjusted for baseline characteristics and region. That analytical structure matters when interpreting the adjusted mean difference: it is a model-based contrast, not simply a subtraction of arm summaries.
The reported result also illustrates why non-inferiority claims need more than a near-zero estimate. A small estimated difference can be compatible with a range of possible effects, and that range must be compared with a prespecified margin. Here the registry reports the analysis type and interval but not the margin. This leaves an essential part of the decision framework unavailable to readers using the registry record alone.
Related secondary outcomes provide useful context, but they raise familiar issues of multiplicity, correlation, and differing estimands. Multiple thresholds and time points can generate a large set of results that are not independent. Without a reported adjustment plan, secondary comparisons are better treated as descriptive than as a set of separate confirmatory claims.
The record also demonstrates the importance of distinguishing planned design assumptions from post hoc planning illustrations based on observed effects. Such illustrations can help show how sample requirements vary under hypothetical assumptions, but they do not reveal the trial’s original design target, do not constitute observed power, and cannot explain why the trial enrolled its recorded number of participants. The original sample-size justification is not reported in the registry record.
Finally, the mismatch between the registry masking field and official-title wording, together with incomplete arm descriptions, shows how registry entries can leave important operational details unclear. Transparent reporting of those details, analysis plans, and decision thresholds is important for interpreting results reproducibly.
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 registry record does not report the non-inferiority margin or its rationale. This prevents an independent assessment of the margin-based decision despite the recorded non-inferiority classification and the posted confidence interval. The primary comparison has no reported p-value, although the estimate and interval remain interpretable without one.
The registry’s masking descriptions are inconsistent: the masking field says triple, while the official title says double-masked. The record does not reconcile these terms or state which parties were masked. Arm descriptions are blank, and the exact faricimab dosing interval is not reported in the registry record. The presence of a sham procedure in the intervention list does not establish how it was administered or to whom.
The primary outcome analysis description is more detailed than the information available for several other aspects of the trial. The registry does not report the study’s sample-size justification, interim-analysis plan, a complete multiplicity strategy, detailed missing-data sensitivity analyses, or model diagnostics. Some secondary results are reported as CMH weighted-percentage differences, while simple recalculations from posted counts are unadjusted; they should not be treated as identical analyses.
Participant denominators differ across the primary endpoint, secondary outcomes, and safety summaries. The record identifies the primary population but does not explain every denominator difference or provide a full account of missing observations for each analysis. The posted safety information is also limited for causal interpretation: event timing and adjusted comparisons are not described in the available summary. These limitations concern what can be evaluated from the registry record and should not be mistaken for proof that an unreported procedure or analysis was not conducted.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (LUCERNE) — NCT03823300.
- Registry record last updated 2025-07-11; status last verified 2025-07.
- Results first posted 2022-05-04.
- 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.
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19. Record Summary
NCT03823300 is a completed Phase III randomized parallel-group study of faricimab and aflibercept in neovascular age-related macular degeneration. The registry reports an enrollment of 658, with a primary completion date of 2020-10-05. The primary outcome was change from baseline in study-eye best corrected visual acuity, averaged over Weeks 40, 44, and 48.
The adjusted mean change was 6.6 ETDRS letters in each arm. The adjusted mean difference was 0.0, with a 95% confidence interval from -1.7 to 1.8. The analysis is classified as non-inferiority, but the margin needed to assess that criterion is not reported in the registry record. Secondary visual-acuity outcomes and descriptive safety counts are also posted. Missing details about multiplicity, sample-size justification, masking terminology, and some analysis populations limit independent evaluation of the full design and interpretation.