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 Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial (NCT02623426), a randomized phase 3 study. The primary outcome is Proportion of Baseline Central Subfield Thickness Observed at 12 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02623426 |
| Phase | Phase 3 |
| Condition | Uveitis, Macular Edema |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 194 |
| Arms in the primary outcome | 3 |
| Lead sponsor | JHSPH Center for Clinical Trials |
| Results posted | Yes |
2. Clinical Question
Population
People with uveitic macular edema that persisted or recurred after an intravitreal corticosteroid injection. A participant could have one or two eligible eyes, and eligible eyes received the participant’s assigned treatment.
Intervention
Intravitreal dexamethasone implant, 0.7 mg. This was one of three randomized treatment groups in a parallel comparative trial.
Comparator
The other groups received intravitreal methotrexate, 400 µg, or intravitreal ranibizumab, 0.5 mg. The registry reports dexamethasone comparisons against each of these groups.
Primary question
At the 12-week visit, how did central subfield thickness relative to baseline compare between dexamethasone and each of the two other treatments? Values below 1 represent a decrease from baseline, with lower values representing larger decreases.
The trial focused on a relative measure of retinal thickness rather than a change expressed in an absolute thickness unit. The central subfield thickness was assessed with optical coherence tomography, and masked readers measured the OCT outcomes. The primary time point was 12 weeks. The registry states that this time was selected in relation to the ranibizumab treatment schedule and the peak effect time for dexamethasone.
The key statistical contrast is therefore not simply whether each group changed from baseline. It is whether the groups differed in their baseline-relative thickness at the selected follow-up visit. The registry’s analyses compare dexamethasone with methotrexate and dexamethasone with ranibizumab. They do not report a comparison between methotrexate and ranibizumab. The results describe these measured outcomes and their uncertainty; they do not by themselves establish the broader clinical importance of any difference.
3. Trial Design
The Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial, known as MERIT, is a randomized, parallel-group Phase 3 trial. The registry lists an enrollment of 194 and three treatment groups: dexamethasone intravitreal implant, intravitreal methotrexate, and intravitreal ranibizumab. The planned allocation is described as 1:1:1. The masking designation is single; further detail about who was masked is not reported in the registry record.
The study concerned uveitic macular edema persisting or recurring after an intravitreal corticosteroid injection. Treatments were administered to eligible eye or eyes, with the same assigned treatment used for a participant’s eligible eyes. The posted arm descriptions give different dosing schedules. Dexamethasone was given at the first study visit, with retreatment required at the 8-week visit if retreatment criteria were met. Methotrexate was given at the first visit, with retreatment at the 4-week and 8-week visits if criteria were met. Ranibizumab was given at the first, 4-week, and 8-week visits. The arm descriptions are truncated in the registry record, so further schedule details are not reported there.
The primary outcome was measured at the 12-week visit. The brief summary describes an anniversary close-out after 6 months of follow-up, while the posted primary outcome concerns the earlier 12-week assessment. The registry lists the study as completed, with a start date of 2017-03-09 and a primary completion date of 2021-10-27. More detail about the trial’s conduct, recruitment, or analysis plan is not reported in the registry record. The registry reports outcome group sizes of 65 for dexamethasone, 66 for methotrexate, and 64 for ranibizumab.
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
| Stage | Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection | Intravitreal Methotrexate 400 µg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free | Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL |
|---|---|---|---|
| STARTED | 65 | 65 | 64 |
| 4 Week Visit | 65 | 64 | 63 |
| 8 Week Visit | 65 | 64 | 61 |
| COMPLETED | 64 | 63 | 61 |
| NOT COMPLETED | 1 | 2 | 3 |
Reasons for not completing this period:
| Reason | Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection | Intravitreal Methotrexate 400 µg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free | Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL |
|---|---|---|---|
| Lost to Follow-up | 0 | 0 | 1 |
| Withdrawal by Subject | 1 | 2 | 2 |
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: Randomized participants had 1 or both eyes with macular edema, defined as the presence of central subfield macular thickness greater than the normal range for the OCT machine being used
| Characteristic | Unit | Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection | Intravitreal Methotrexate 400 µg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free | Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL | Total |
|---|---|---|---|---|---|
| Participants analysed | 65 | 65 | 64 | 194 | |
| Age, Continuous | years | 59 (18 to 81) | 59 (20 to 83) | 57 (24 to 83) | 58 (18 to 83) |
| Sex: Female, Male: Female | Participants | 41 | 48 | 40 | 129 |
| Sex: Female, Male: Male | Participants | 24 | 17 | 24 | 65 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 2 | 2 | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 64 | 63 | 62 | 189 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 10 | 10 | 8 | 28 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 16 | 22 | 13 | 51 |
| Race (NIH/OMB): White | Participants | 38 | 28 | 41 | 107 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 4 | 2 | 7 |
| Region of Enrollment: Canada | participants | 4 | 3 | 1 | 8 |
| Region of Enrollment: United States | participants | 40 | 43 | 44 | 127 |
| Region of Enrollment: United Kingdom | participants | 9 | 8 | 8 | 25 |
| Region of Enrollment: Australia | participants | 2 | 2 | 3 | 7 |
| Region of Enrollment: India | participants | 10 | 9 | 8 | 27 |
| Intraocular pressure (IOP) | mm Hg | 15 (5 to 21) | 15 (5 to 23) | 14 (7 to 21) | 14 (5 to 23) |
| Visual acuity | Standard letters | 68 (25 to 89) | 64 (6 to 85) | 67 (6 to 88) | 66 (6 to 88) |
| Retinal thickness at the center subfield | um | 457 (241 to 1116) | 476 (276 to 991) | 401 (220 to 1091) | 453 (210 to 1116) |
| Concomitant systemic medication | Participants | 28 | 27 | 29 | 84 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Baseline Central Subfield Thickness Observed at 12 Weeks, measured over At 12-week visit.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Proportion of baseline retinal thickness |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the proportion of baseline central subfield thickness observed at the 12-week visit. It represents retinal thickness at follow-up relative to the baseline OCT measurement. A value of 1 corresponds to the baseline level; values below 1 indicate a decrease, and lower values indicate a greater decrease. The registry reports group means for this continuous outcome, along with 95% confidence intervals.
A relative measure can express change in a way that accounts for the starting thickness, rather than reporting only an absolute difference in thickness units. The endpoint was measured using optical coherence tomography, with masked readers assessing the images. Masked measurement can help reduce the influence of knowledge of treatment assignment on outcome assessment. The registry describes the endpoint as the primary outcome and states that the 12-week visit was selected because of the ranibizumab treatment schedule and the peak effect time for dexamethasone.
The analysis used measurements from baseline, week 4, week 8, and week 12 in a mixed effects model, including treatment group and the interaction between time and treatment. The treatment contrasts estimate the change from baseline to week 12 and compare those changes between groups. The reported group means are 0.65 for dexamethasone, 0.88 for methotrexate, and 0.79 for ranibizumab. These means describe the estimated proportion of baseline thickness; their uncertainty is represented by the reported 95% confidence intervals.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At 12 weeks, the estimated mean proportion of baseline central subfield thickness was 0.65 in the dexamethasone group, with a 95% confidence interval from 0.58 to 0.72. The corresponding estimate was 0.88 for methotrexate, with a 95% confidence interval from 0.81 to 0.96, and 0.79 for ranibizumab, with a 95% confidence interval from 0.7 to 0.89. Since values below 1 represent a decrease from baseline, all three reported group means are below baseline on this relative scale.
The registry reports two mixed effects model comparisons. For dexamethasone versus methotrexate, the reported ratio of the proportions of baseline was 1.36, with a 95% confidence interval from 1.19 to 1.56 and p < 0.001. For dexamethasone versus ranibizumab, the reported ratio was 1.22, with a 95% confidence interval from 1.04 to 1.43 and p = 0.012. The ratio is expressed in the order of dexamethasone relative to the comparator. Because a lower proportion means a larger decrease in thickness, a ratio above 1 is consistent with a higher residual proportion in the dexamethasone group than in the comparator group. The registry labels both contrasts as superiority analyses, with the preferred direction corresponding to the lower proportion.
Each reported confidence interval is entirely above 1, and each p-value is below 0.05. In the context of these model-based comparisons, the estimates therefore indicate evidence of a difference between dexamethasone and each comparator at the 12-week endpoint. A confidence interval describes uncertainty around an estimated quantity under the analysis model; it is not a range containing every individual participant’s result. The estimates do not quantify the likelihood that a treatment is beneficial for a particular person, and statistical evidence alone does not establish the clinical importance of the difference.
The registry does not report a methotrexate-versus-ranibizumab comparison. Nor does the record give an adjustment for making multiple comparisons, so the reported p-values should be read as the results of the listed contrasts, without assuming a multiplicity correction. The estimates concern the outcome and time point specified in the registry; the results do not establish whether the groups differed at other times or on outcomes not posted. The trial’s secondary outcome results are not posted in the registry record.
9. Statistical Methods Explained
The primary outcome is continuous: it is a relative measure of central subfield thickness. The registry describes the group result as a mean and reports a 95% confidence interval. A mean summarizes the center of a continuous distribution, while a confidence interval represents uncertainty in an estimated quantity under the assumptions of the statistical model. It is not a description of the spread of individual measurements. The registry does not report a separate measure of variability among individual participants for these outcome means.
Why use a mixed effects model?
The primary analysis used a mixed effects model with observations at baseline, week 4, week 8, and week 12. In general, mixed effects models can account for the fact that repeated observations from the same participant are related rather than independent. They can also represent systematic differences across time and treatment groups. The registry record does not give the full model specification, including the particular random-effects structure, covariance assumptions, or estimation details, so those features cannot be described further.
The model included time point and treatment group, as well as their interaction. In general, an interaction allows the pattern over time to differ by treatment group. In this trial’s stated approach, the interaction between time and treatment is used to estimate treatment effects. Contrasts of model parameter estimates were used for the baseline-to-week-12 change and between-group comparisons. This approach uses the planned repeated measurements to estimate the treatment contrasts at the primary time point, rather than treating each time point as an unrelated analysis.
How should the relative outcome be read?
The endpoint is the proportion of baseline thickness. A proportion below 1 indicates a decrease from baseline, and a lower value indicates a greater decrease. Thus, the group means describe how much of the baseline thickness was estimated to remain at the 12-week visit on this scale. The registry’s comparison statistic is a ratio of these proportions. A ratio of 1 represents equality on the ratio scale. A ratio above 1 for dexamethasone relative to a comparator indicates a higher estimated proportion for dexamethasone, which corresponds to a smaller decrease on this endpoint. The ratio is not a difference in thickness units and does not directly express a percentage-point change.
What do the confidence intervals and p-values say?
For dexamethasone versus methotrexate, the estimated ratio is 1.36 and the 95% confidence interval is 1.19 to 1.56; the reported p-value is p < 0.001. For dexamethasone versus ranibizumab, the ratio is 1.22 and the 95% confidence interval is 1.04 to 1.43; the p-value is 0.012. In general, a confidence interval gives a range of values reasonably compatible with the data and model at its stated confidence level. These intervals describe the model’s uncertainty about the ratio, not the range of participant-level outcomes. Both intervals exclude 1, the equality value for a ratio, and the reported p-values indicate evidence against equality under the corresponding model-based tests. The record does not state whether these tests were adjusted for the number of comparisons.
A p-value measures how incompatible the observed data are with a specified null hypothesis, assuming the model and its assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical relevance of a treatment difference. The ratio and confidence interval provide information about estimated direction and precision that the p-value alone does not convey. Interpretation should also account for the fact that the analyses concern a selected endpoint and time point.
What are the limits of the posted analysis detail?
The registry identifies a mixed effects model and describes its key terms, but a complete statistical analysis plan is not reported in the registry record. Details about model diagnostics, handling of missing outcome measurements, adjustments for multiplicity, and analysis populations are not reported in the registry record. Such details matter because model assumptions and analytic choices can affect estimates and uncertainty. For example, a repeated-measures model relies on assumptions about the observed data and their relationship over time; the registry does not state the assumptions used for missing measurements.
In general, over-dispersion is an issue when observed variability exceeds what a model assumes. It is especially relevant to count data models, whereas the primary endpoint is continuous and analyzed as a mean. The registry does not report over-dispersion as an issue for this endpoint. There is also no posted comparison between methotrexate and ranibizumab. No additional statistical conclusions about that pair can be inferred from the two reported contrasts.
The stated arm-level outcome counts are 65 for dexamethasone, 66 for methotrexate, and 64 for ranibizumab. These should be read as the numbers attached to the reported outcome estimates, not as confirmation that every randomized participant contributed every repeated measurement. The registry does not provide the flow of participants through follow-up or the number of measurements available at each time point. The analysis summary therefore supports interpretation of the reported model estimates, but not an independent assessment of all analysis decisions or missing-data assumptions.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| mixed effects model | Ratio of the proportion of baseline 1.36 | 1.19 to 1.56 | < 0.001 |
| mixed effects model | Ratio of the proportion of BL 1.22 | 1.04 to 1.43 | 0.012 |
The registry reports the sponsor’s primary comparisons from a mixed effects model. The dexamethasone-to-methotrexate ratio is 1.36, with a 95% confidence interval from 1.19 to 1.56 and p < 0.001. The dexamethasone-to-ranibizumab ratio is 1.22, with a 95% confidence interval from 1.04 to 1.43 and p = 0.012. These estimates are model-based comparisons using the repeated-measure outcome approach described in the registry.
A separate unadjusted recalculation from posted summary statistics is not estimable for these continuous two-arm comparisons, so there is no recalculated estimate to set alongside the sponsor’s model results. The registry does not identify a discrepancy between the reported analysis and any recalculation. The sponsor’s analysis should therefore be read as the available inferential result, with its model assumptions and the limits of the analysis detail described in the registry record. The recalculation does not supply a competing estimate or change the interpretation of the reported confidence intervals and p-values.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists two primary-outcome comparisons: dexamethasone versus methotrexate, and dexamethasone versus ranibizumab. It does not report a comparison between methotrexate and ranibizumab. The record does not say whether the two reported tests were treated as a family of comparisons or whether any adjustment to account for multiple testing was applied. Multiplicity procedures can affect how evidence is interpreted when several hypotheses are tested. Without a reported procedure, the p-values should be treated as the values reported for the individual comparisons, rather than assumed to have been adjusted.
Missing-data handling is not reported in the registry record. Although the mixed effects model included measurements at baseline, week 4, week 8, and week 12, the registry does not state how missing visits were handled, what assumptions were made about missingness, or whether sensitivity analyses were conducted. It also does not report the number of participants contributing data at each time point or a participant flow through follow-up. The posted arm counts attached to the outcome estimates do not by themselves establish that complete repeated measurements were available for everyone in those groups.
The analysis populations are not reported in the registry record. In particular, the registry does not specify whether the primary results were based on all randomized participants, participants who received treatment, or another defined population. The record also does not report an interim analysis plan, a sample-size justification, or a detailed statistical analysis plan. These omissions limit the ability to assess how the posted analysis was prespecified and how participants with incomplete measurements were incorporated.
The registry lists no posted secondary outcome results. This means that the posted results do not provide a broader set of outcome estimates against which to assess consistency across outcomes. It does not establish that no secondary outcomes were planned or measured; those details are not reported in the registry record. The available interpretation should remain focused on the stated primary endpoint and the two reported treatment contrasts.
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 |
|---|---|---|---|
| Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection | 6 | 65 | 9.2% |
| Intravitreal Methotrexate 400 µg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free | 7 | 65 | 10.8% |
| Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL | 3 | 64 | 4.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection | 0 of 65 |
| Intravitreal Methotrexate 400 µg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free | 0 of 65 |
| Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL | 0 of 64 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection | 12 of 65 |
| Intravitreal Methotrexate 400 µg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free | 24 of 65 |
| Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL | 14 of 64 |
Most frequent serious adverse event terms
| Event term | Organ system | Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection | Intravitreal Methotrexate 400 µg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free | Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL |
|---|---|---|---|---|
| Visual acuity decreased | Eye disorders | 0 of 65 | 4 of 65 | 1 of 64 |
| Intraocular pressure increased | Eye disorders | 3 of 65 | 0 of 65 | 0 of 64 |
| glaucoma | Eye disorders | 1 of 65 | 0 of 65 | 0 of 64 |
| Intraocular pressure decreased | Eye disorders | 1 of 65 | 0 of 65 | 0 of 64 |
| Iridotomy | Eye disorders | 0 of 65 | 1 of 65 | 0 of 64 |
| breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 65 | 1 of 65 | 0 of 64 |
| Catheterization cardiac for hypertension | Cardiac disorders | 0 of 65 | 0 of 65 | 1 of 64 |
| fall | Injury, poisoning and procedural complications | 1 of 65 | 0 of 65 | 0 of 64 |
| Post procedural infection | Injury, poisoning and procedural complications | 0 of 65 | 1 of 65 | 0 of 64 |
| Vasovagal response | Vascular disorders | 1 of 65 | 0 of 65 | 0 of 64 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ozurdex (0.7 mg Dexamethasone Pellet) Delivered Via Intravitreal Injection | Intravitreal Methotrexate 400 µg in 0.1 mL 0.9% Sodium Chloride Solution, Preservative-free | Intravitreal Ranibizumab (Lucentis) 0.5 mg in 0.05 mL |
|---|---|---|---|---|
| Post injection IOP increase >=30 mmHg | General disorders | 0 of 65 | 12 of 65 | 5 of 64 |
| Eye pain | Eye disorders | 5 of 65 | 5 of 65 | 4 of 64 |
| Ocular hypertension | Eye disorders | 3 of 65 | 2 of 65 | 1 of 64 |
| Uveitis | Eye disorders | 2 of 65 | 2 of 65 | 1 of 64 |
| Surgery to control IOP | Eye disorders | 1 of 65 | 4 of 65 | 0 of 64 |
| Headache | Nervous system disorders | 1 of 65 | 2 of 65 | 2 of 64 |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 1 of 65 | 1 of 65 | 2 of 64 |
| Vitreous or subconjunctival hemorrhage | Eye disorders | 3 of 65 | 0 of 65 | 1 of 64 |
| Dry eye | Eye disorders | 1 of 65 | 1 of 65 | 2 of 64 |
| Photopsia | Eye disorders | 3 of 65 | 1 of 65 | 0 of 64 |
Serious events with the highest arm-level rate: visual acuity decreased (6.2%), intraocular pressure increased (4.6%), catheterization cardiac for hypertension (1.6%), rectal hemorrhage (1.6%), glaucoma (1.5%).
The registry reports serious adverse events for the three treatment groups, using separate counts of participants at risk and participants affected. In the dexamethasone group, 6 of 65 were reported as affected; in the methotrexate group, 7 of 65; and in the ranibizumab group, 3 of 64. The registry reports zero deaths in each group. These are group-specific posted counts and should not be combined into a new overall total.
The registry also lists serious adverse event terms with percentages, including visual acuity decreased at 6.2% and intraocular pressure increased at 4.6%. The listed terms do not identify which treatment group each percentage belongs to in the posted safety summary. The terms and percentages should therefore not be interpreted as direct between-group comparisons or as a ranking of treatment risks.
Counts of participants affected do not describe the severity, duration, timing, or relatedness of each event, and the registry summary does not provide a comparative statistical analysis of safety. The reported figures are descriptive registry entries, not estimates that establish whether one treatment has more or fewer harms than another. Further detail about event definitions, adjudication, and the analysis population is not reported in the registry record.
13. What the Result Does, and Does Not, Mean
The posted primary outcome estimates show that the mean proportion of baseline central subfield thickness at 12 weeks was below 1 in each group. The model-based comparisons show higher estimated proportions for dexamethasone relative to methotrexate and relative to ranibizumab. Since lower proportions indicate larger decreases on this outcome, the direction of the reported contrasts favors the comparator groups on the relative-thickness endpoint. The confidence intervals and p-values describe the statistical uncertainty and evidence for these specific comparisons.
These findings do not by themselves establish the clinical importance of the estimated differences. The registry does not report a threshold for a clinically meaningful change in this endpoint, and the relative measure does not directly provide an absolute thickness difference. Statistical evidence is not the same as a patient-level prediction, and group averages do not describe the outcome for every participant.
The result is specific to the trial population, the treatments and dosing schedules studied, the OCT-based endpoint, and the 12-week time point. It does not establish how the groups compare at later visits or on other clinical outcomes. The record does not report the method used to handle missing measurements, the analysis populations, or any adjustment for multiple comparisons, which are relevant context for interpreting the model results.
The registry also does not report a methotrexate-versus-ranibizumab contrast. Nor do the posted serious adverse event counts support a definitive comparative safety conclusion. Overall, the results are best read as model-based evidence about relative central subfield thickness at the specified visit, alongside the stated uncertainty and limitations of the registry-level reporting. They do not establish broader treatment effects beyond the outcomes and comparisons reported.
14. Why This Trial Matters Statistically
This trial offers a useful example of how a clinical endpoint can be defined on a relative scale and analyzed across repeated visits. The primary measure is the proportion of baseline central subfield thickness, so its direction must be understood before interpreting a treatment ratio. A value below 1 indicates a decrease, and a lower value represents a greater decrease. In that context, ratios greater than 1 for dexamethasone relative to the other groups indicate a higher residual proportion for dexamethasone, not a larger decrease.
The analysis also illustrates why the treatment contrast and the endpoint scale need to be read together. Looking only at the ratio or at the word superiority could be misleading without knowing which direction of the endpoint is favorable. The group means, confidence intervals, and model-based comparisons provide complementary information: estimated levels on the relative scale, uncertainty around those levels, and comparisons between assigned groups.
The repeated-measure design makes the mixed effects approach relevant to the statistical question. The model uses observations across baseline and follow-up, while the time-by-treatment interaction permits treatment patterns over time to differ. At the same time, the registry’s limited reporting of missing-data assumptions, analysis populations, and multiplicity adjustment shows why an estimate should not be interpreted independently of its analytical context.
Finally, the safety counts demonstrate the distinction between descriptive reporting and formal comparative inference. Counts affected in each group are informative summaries, but without further analysis and detail they do not establish differences in safety. The trial’s statistical contribution in the registry is therefore best understood through a carefully defined endpoint, explicit contrast direction, and attention to the limits of what the record reports.
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.
Several limitations arise from the registry record’s level of detail. The mixed effects model is identified, and the main terms and time points are described, but the complete model specification is not reported. Details about random effects, covariance structure, estimation, model checking, and assumptions are not reported in the registry record. This makes it difficult to independently assess how the repeated observations were modeled.
The record does not report how missing measurements were handled, the number of observations available at each visit, or the analysis populations. It is therefore not possible from the posted information to determine how incomplete follow-up may have affected the estimates or whether the reported groups correspond to a particular prespecified population. A detailed participant flow and sensitivity analyses are not reported in the registry record.
Multiplicity is another uncertainty. Two dexamethasone comparisons are reported, but whether the p-values were adjusted for multiple testing is not reported in the registry record. No methotrexate-versus-ranibizumab comparison is posted. Secondary outcome results are also not posted, limiting the range of outcomes available for assessing the results alongside the primary endpoint.
The endpoint is a relative thickness measure at a single primary follow-up time. The registry does not state a threshold for clinical importance, and the primary outcome does not by itself convey all aspects of disease status or patient experience. The posted safety summary provides affected counts and selected event terms, but does not give event-level detail, relatedness, or a comparative safety analysis. Finally, the arm descriptions are incomplete in the registry record, which limits description of treatment scheduling beyond the details explicitly posted.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial — NCT02623426.
- Registry record last updated 2023-07-10; status last verified 2023-06.
- Results first posted 2023-07-10.
- 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
The MERIT Trial is a completed Phase 3 randomized, parallel-group trial of intravitreal dexamethasone, methotrexate, and ranibizumab for uveitic macular edema persisting or recurring after intravitreal corticosteroid injection. The registry lists an enrollment of 194 and a 1:1:1 allocation. The primary endpoint is the proportion of baseline central subfield thickness at 12 weeks, measured by OCT and assessed by masked readers.
The registry reports mixed effects model comparisons of dexamethasone with methotrexate and dexamethasone with ranibizumab. The estimated ratios are 1.36 and 1.22, respectively, with the reported 95% confidence intervals and p-values. The record does not report a methotrexate-versus-ranibizumab comparison. Details of missing-data handling, analysis populations, and multiplicity adjustment are not reported in the registry record. Serious adverse event counts are reported by group, with zero deaths listed in each group.