Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation to Treat Radiation Retinopathy.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation to Treat Radiation Retinopathy. (NCT02222610), a randomized phase 2 study. The primary outcome is Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0..

2. Clinical Question

The study concerns treatment schedules for subjects with radiation retinopathy. Its primary outcome is the mean change in ETDRS visual acuity from day 0 to 104 weeks, measured in letters read on the ETDRS chart. The results are reported separately for three cohorts; the registry record does not provide an estimable two-arm comparison for this continuous outcome.

3. Trial Design

This was a randomized, active-controlled, phase II study with a parallel-group model and no masking. The registry record lists 40 participants as enrolled and the study status as completed. The recorded start date is 2014-09-23, and primary completion is listed as 2019-03. The sponsor was Greater Houston Retina Research.

Three cohorts are described. Cohort A received monthly intravitreal injections of 0.5 mg ranibizumab for 48 weeks. Beginning at week 52, participants could enter a treat-and-extend regimen if the macula met the described dry criterion. Cohort B received monthly 0.5 mg ranibizumab for 48 weeks, with peripheral targeted retinal photocoagulation one week after the initial injection. Cohort C received three consecutive monthly ranibizumab doses, followed by as-needed ranibizumab; it also included targeted retinal photocoagulation one week after the initial injection.

Thus, the cohorts differ in whether photocoagulation was included and in the described injection schedules. The primary result is not reported as a direct contrast between Cohort A and either combination cohort. For the 104-week visual-acuity outcome, the registry lists 8.0 participants in Cohort A, 11.0 in Cohort B, and 10.0 in Cohort C. The registry record does not report the allocation ratio, the randomization procedure, concealment details, or a justification for the planned enrollment.

The registry describes an active-controlled design, but the posted primary results are cohort-specific means and standard deviations rather than a treatment-effect estimate with an accompanying uncertainty interval. Details beyond the cohort schedules described in the registry record 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.

Baseline to W48

Baseline to W104

Analysis population for the primary outcome, as defined in the registry: Subjects analyzed only include those that completed the W104 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.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0., measured over 104 weeks.

The primary endpoint is mean change in Early Treatment Diabetic Retinopathy Study visual acuity at 104 weeks from day 0. It is measured in letters. The ETDRS best-corrected visual-acuity assessment uses an ETDRS chart and records the number of letters a subject can read. A change score expresses the follow-up result in relation to the day 0 measurement: a negative mean indicates a lower letter score on average at follow-up, while a positive mean indicates a higher score on average.

A letter-based measure gives a numerical summary of visual-acuity change that can be averaged across participants. This is useful for describing the direction and spread of changes within a cohort, although a group mean does not show each participant's experience or the full distribution of outcomes. The standard deviation reported alongside a mean describes variability among observed values; it is not the same as a confidence interval for the mean.

The registry specifies that the primary-outcome population includes only subjects who completed the week 104 visit. It reports the mean and standard deviation for each cohort, but does not report confidence intervals, an inferential comparison, or an adjusted treatment-effect estimate. Consequently, the endpoint summaries describe the observed completer groups and do not by themselves quantify how precisely the cohort means estimate outcomes beyond those participants.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it is a numeric change in ETDRS visual-acuity letters. The registry identifies the summary as a mean and reports a standard deviation for each cohort. This is a straightforward descriptive approach for a continuous measure. It gives a central value and a measure of participant-to-participant variability, but it does not by itself answer whether cohort outcomes differ statistically.

What does a mean change describe?

A mean is the arithmetic average of the measurements in the analyzed group. Here, the measurements are changes in letters from day 0 to 104 weeks. The reported value is therefore a summary of the participants included in each cohort's outcome analysis. It does not mean that every participant changed by that amount, and it does not show the range of individual changes.

The standard deviation describes how spread out the participant-level changes are around the cohort mean. A larger standard deviation indicates more variability in the observed measurements. It is not a measure of the precision of the mean itself. General statistical context: the standard error and confidence interval are tools for representing uncertainty in an estimated mean; neither is posted for this endpoint. Because the cohorts have modest reported analysis counts and their observed variability differs, the mean and standard deviation alone do not communicate the full uncertainty needed for a formal comparison.

How should a treatment comparison be assessed?

A comparative analysis would estimate a contrast between treatment groups and report its uncertainty, commonly with a confidence interval and an inferential test. The record reports cohort-specific means, standard deviations, and participant counts, but the continuous outcome is identified as lacking values or an estimable result for a two-arm comparison. No treatment-effect estimate, confidence interval, or p-value is reported. The cohort summaries should therefore not be converted into claims of statistical superiority or equivalence.

General statistical context: a confidence interval gives a range of values compatible with the data and the analysis assumptions, and its width reflects precision. A narrow interval represents more precise estimation than a wide one. No interval is available for these primary results, so the precision of the means and any between-cohort contrast cannot be read directly from the registry record. A failure to report a comparison is not evidence that the groups are the same.

What does the planning illustration mean?

The stated planning approach is an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes scenarios for detecting a stated fraction of the observed effect. Such planning values are hypothetical sample-size illustrations, not observed results and not observed power. The registry record does not report the trial's own sample-size justification, and the planning assumptions do not establish that those assumptions were used to design or conduct the trial.

General statistical context: sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. It is not a measure of the certainty of the result after the study has been completed. An illustration based on an observed effect is especially dependent on that estimate, which may be imprecise. No numerical planning estimates are stated in the registry record, so no participant requirement should be inferred from the method description alone.

Why does the analysis population matter?

The primary outcome population is defined as subjects who completed the week 104 visit. The primary summaries consequently concern that group rather than all enrolled participants. If completion is related to outcome or treatment experience, a completer-only summary may differ from an analysis that includes all randomized participants. Whether that concern applies in this study cannot be determined from the posted record. The reasons for noncompletion, the number with missing primary outcomes by cohort, and the methods used to handle missing data are not reported in the registry record.

General statistical context: an analysis population is the set of participants whose data are used for a particular result. Different population definitions can answer different questions. For example, an analysis including all randomized participants can preserve the comparison created by randomization, while a completer analysis describes participants with observed follow-up. The registry identifies the completer population for the primary endpoint, but does not describe an additional intention-to-treat analysis or other population-based analyses.

What can the adverse-event summaries establish?

The registry reports counts of participants at risk and counts affected for serious and other adverse events in each cohort, as well as selected serious-event terms. These counts are descriptive. They do not, on their own, adjust for exposure time or establish that an event was caused by a treatment. General statistical context: adverse-event comparisons can be influenced by the size of groups, follow-up duration, event definitions, and how events are collected. The registry record does not provide enough detail to assess those aspects or to make an adjusted safety comparison.

The record lists zero analyses. It does not report inferential tests for the primary endpoint or a detailed statistical analysis plan. The choice of statistical tests, any adjustments, handling of repeated measurements, and any interim analyses are not reported in the registry record. Those omissions limit what can be concluded about the intended analysis and how the posted results were selected or interpreted.

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("Cohort A", "Cohort B", "Cohort C")
n   <- c(8, 11, 10)
m   <- c(-1.9, -3.9, 1.3)
sp  <- c(7.4, 16.5, 11.8)
sd  <- sp      # posted standard deviations
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  Cohort A  8  -1.900  7.400  -8.087  4.287
CARM  Cohort B  11  -3.900  16.500  -14.985  7.185
CARM  Cohort C  10  1.300  11.800  -7.141  9.741

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures: the primary ETDRS visual-acuity change and four secondary outcomes. The secondary outcomes concern intravitreal injection counts, retinal hemorrhage, intraretinal exudates, and central mean thickness. The record lists zero analyses, and the posted results do not include estimates for those four secondary outcomes. It does not report a strategy for controlling multiplicity across outcomes or comparisons. Without such information, the family of planned statistical tests and any adjustment for multiple testing are not reported in the registry record.

The primary endpoint is defined for subjects who completed the week 104 visit. The record does not report how many participants lacked that measurement by cohort, why measurements were missing, or how missing observations were handled. It does not report imputation, sensitivity analyses, or a statistical model designed to address missing data. As a result, the available primary summaries describe the reported completer groups, and the potential influence of missing outcomes cannot be assessed from the registry record.

The record does not report whether an intention-to-treat population or another analysis population was used. It also does not describe prespecified subgroup analyses, interim analyses, or a detailed statistical analysis plan. Those items are not reported in the registry record; their absence from the posted information should not be interpreted as proof that no such plans or procedures existed.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: metastatic uveal melanom (12.5%), worsening of hypertension (12.5%), acute chronic diastolic heart failure (6.2%), acute chronic renal failure (6.2%), broken wrist (6.2%).

The registry reports serious adverse events and other adverse events separately for each cohort. For serious adverse events, the at-risk and affected counts are 8 and 1 in Cohort A, 16 and 2 in Cohort B, and 16 and 5 in Cohort C. For other adverse events, the corresponding counts are 8 and 3, 16 and 7, and 16 and 6. The registry lists 0 deaths in Cohort A, 0 in Cohort B, and 1 in Cohort C.

These are counts, not comparative estimates adjusted for the amount of follow-up or other differences among participants. The record also lists selected serious-event terms with percentages: Metastatic Uveal Melanom, 12.5%; Worsening of Hypertension, 12.5%; Acute Chronic Diastolic Heart Failure, 6.2%; Acute Chronic Renal Failure, 6.2%; Broken Wrist, 6.2%; and Central Retinal Artery Occlusion, 6.2%. The listed term percentages should be read as registry-reported figures; the record does not supply further detail about their calculation in the material reported.

General statistical context: adverse-event counts describe events recorded during a study, but do not alone establish causation. The registry record does not report an adjusted safety comparison or sufficient detail to evaluate differences in exposure or event ascertainment. These figures should therefore be interpreted as descriptive records of events, not as evidence that an intervention caused or prevented them.

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

The posted primary results show the mean 104-week ETDRS visual-acuity change within each of three cohorts. Cohort A's mean was -1.9 letters, Cohort B's was -3.9 letters, and Cohort C's was 1.3 letters. The reported standard deviations were 7.4, 16.5, and 11.8, respectively. These values describe the analyzed participants and show that the observed changes varied within each cohort.

The findings do not establish that the cohort with the numerically higher mean had a better outcome than another cohort in a statistical sense. The registry record does not report a two-arm comparison, an uncertainty interval, or an inferential test for the primary endpoint. A difference between displayed means cannot be interpreted as a statistically established treatment effect without an appropriate comparison and an estimate of its uncertainty.

The primary analysis includes only participants who completed the week 104 visit. This means the result is not a complete summary of all 40 participants enrolled. The record does not explain the missing outcomes or provide an analysis showing how missingness might affect the results. It is therefore not possible to determine from these summaries how well the completer results represent all enrolled participants.

The results also do not establish equivalence, non-inferiority, or the absence of an effect. Each of those conclusions requires a defined analysis and appropriate uncertainty assessment; neither is reported for this primary outcome. The registry record does not report the detailed statistical plan, a sample-size justification, or a multiplicity approach. These gaps constrain interpretation but do not alter the descriptive values that are posted.

The adverse-event figures are also descriptive. They show recorded affected counts and selected serious-event terms, but do not establish that an event was caused by a study treatment. Taken together, the registry supports a description of the reported completer outcomes and event counts. It does not provide enough comparative or uncertainty information to determine whether the treatment schedules differ in visual acuity or safety.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a randomized design and a reported treatment comparison. Randomization is a design feature, but the posted primary results are cohort-specific summaries. Without a treatment-effect estimate and its uncertainty, the means alone do not deliver a formal randomized comparison. Readers should distinguish the presence of randomization in the design from the statistical evidence actually reported for the endpoint.

The endpoint population is also important. The registry defines the primary results using participants who completed week 104, while the trial lists 40 enrolled participants. Completer-only results can describe observed follow-up measurements, but do not automatically answer the question for everyone enrolled. Information about missing outcomes and alternative analyses would help readers understand how much the endpoint results depend on follow-up completion.

The study reports a continuous outcome with cohort means and standard deviations. These summaries are useful for describing direction and variability, but confidence intervals would clarify precision, and a comparative estimate would address the treatment contrast. Neither is reported. The comparatively broad spread of individual measurements represented by the standard deviations reinforces why the mean alone should not be read as a precise prediction for an individual participant.

Finally, the record lists multiple outcome measures but does not report a multiplicity strategy or results for the four secondary outcomes. Transparent reporting of the analysis plan, missing-data methods, and inferential results would help define the scope of evidence. The posted record supports careful descriptive interpretation, while leaving several key questions about comparative uncertainty unanswered.

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 are specific to the available record. First, the primary result is based only on participants who completed the week 104 visit. Cohort-specific analysis counts are 8.0, 11.0, and 10.0, while 40 participants are listed as enrolled overall. Reasons for missing week 104 data and the handling of those data are not reported in the registry record.

Second, the registry reports means and standard deviations but no confidence intervals or inferential comparison for the primary endpoint. The continuous outcome is specifically marked as lacking an estimable two-arm comparison. Therefore, precision and comparative uncertainty cannot be evaluated from the posted primary results. No adjusted analysis is reported.

Third, three cohorts have different treatment schedules. Cohort A received ranibizumab without targeted retinal photocoagulation, while Cohorts B and C included the procedure and had different injection schedules. The record does not provide a statistical contrast that isolates the effect of photocoagulation from differences in injection schedule. It also does not report an allocation ratio or details of the randomization procedure.

Fourth, the registry lists four secondary outcomes but does not post their numerical results in the information reported. A multiplicity strategy, detailed statistical analysis plan, sample-size justification, interim analyses, and the handling of repeated measurements are not reported in the registry record. These omissions limit assessment of planned analyses and of the breadth of the reported evidence.

Finally, adverse-event counts are descriptive. The registry does not report an adjusted safety comparison or details sufficient to assess differences in exposure and event collection. The listed event counts and percentages should not be interpreted as causal comparisons between cohorts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation to Treat Radiation Retinopathy. — NCT02222610.
• Registry record last updated 2021-03-25; status last verified 2021-03.
• Results first posted 2021-03-25.
• 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

NCT02222610 is a completed randomized, active-controlled, phase II parallel study with no masking. It enrolled 40 participants with radiation retinopathy. The study compared ranibizumab schedules alone and in combination with targeted retinal photocoagulation across three cohorts.

The primary outcome was mean change in ETDRS visual-acuity letters at 104 weeks from day 0. The registry reports cohort-specific means and standard deviations among subjects who completed the week 104 visit: Cohort A, -1.9 letters (standard deviation 7.4; 8.0 analyzed); Cohort B, -3.9 letters (standard deviation 16.5; 11.0 analyzed); and Cohort C, 1.3 letters (standard deviation 11.8; 10.0 analyzed). No inferential comparison or confidence interval is reported for this endpoint.

The registry lists four secondary outcomes and selected adverse-event counts, but does not report the secondary-outcome values in the information summarized. Missing-data methods, multiplicity handling, and a detailed statistical analysis plan are not reported in the registry record.