Changes in Retinal Function After Intravitreal Ranibizumab for Age-related Macular Degeneration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Changes in Retinal Function After Intravitreal Ranibizumab for Age-related Macular Degeneration (NCT00539734), a non-randomized na study. The primary outcome is Height (Amplitude) of Multifocal ERG Signal.

2. Clinical Question

This is a within-group before-and-after question. It describes retinal-function measurements at two time points in the study population; it does not by itself estimate how those measurements would have changed without treatment. Because there was no randomized control group, the design cannot separate change associated with treatment from change associated with other factors over time. The registry record also does not state how many participants contributed measurements at each time point or how missing measurements were handled. Those details matter when judging how representative the reported analysis would be of everyone enrolled, but they are not reported in the registry record.

3. Trial Design

The registry describes a completed, single-group, non-randomized study of ranibizumab in age-related macular degeneration. It lists planned enrollment of 25. The study is identified as unmasked, meaning that no masking is listed in the registry. There was no separate control arm in the design described, so the primary comparison was between measurements at baseline and 3 months.

The listed primary outcome is the height, or amplitude, of the multifocal electroretinogram signal. The registry specifies a mean and standard deviation as the summary measures and gives nanovolt/degree^2 as the unit. The primary outcome description says that the response at 3 months was compared with baseline data. It also states that the analysis was per protocol, but does not define the criteria for inclusion in that analysis.

The study dates in the registry are 2007-08 for start and 2008-12 for primary completion, and the study status is completed. The sponsor is Prince of Songkla University. The registry lists three outcome measures and one analysis, but the record does not give a full account of the analysis procedures or enumerate all outcome definitions in the posted information. Postoperative complication is named as a secondary outcome.

This design can describe change over time among the participants included in the analysis. Without random allocation to a concurrent control group, it does not provide a like-for-like comparison that would distinguish treatment-related change from other explanations. Details such as the schedule and number of injections, the eligibility criteria, the sample-size justification, and the statistical analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was per protocol

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 Height (Amplitude) of Multifocal ERG Signal, measured over baseline, 3 months.

The primary endpoint is the height, or amplitude, of the multifocal electroretinogram signal, expressed in nanovolt/degree^2. The registry describes a comparison of the response at 3 months after treatment with baseline data. It identifies the endpoint as continuous and specifies that results are to be summarized with a mean and standard deviation. The analysis population is described as per protocol.

In general, an electrophysiologic signal provides a quantitative measure of retinal response to stimulation. Measuring its amplitude at baseline and follow-up can describe whether the recorded response changed over the study period. A continuous measure can retain information about the magnitude of individual readings, rather than reducing results to categories such as improved or not improved. The mean describes the average measurement in the analyzed group, while the standard deviation describes how spread out measurements are around that mean.

The registry record does not report the baseline or 3-month mean, either standard deviation, the number of participants with measurements, or an estimated within-person change. It also does not provide a confidence interval or a test result for this endpoint. Consequently, the endpoint definition is available, but the posted record does not establish the direction, magnitude, or precision of the observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint summary describe?

The primary outcome is a continuous signal-amplitude measurement. The registry specifies reporting a mean and standard deviation at baseline and 3 months. In general, the mean is a measure of the center of a set of numerical observations. The standard deviation describes their dispersion around that center. Neither measure alone describes the uncertainty in a comparison of time points. The registry does not provide the numerical summaries or an estimate of change, so the extent of any change and its uncertainty cannot be evaluated.

The description refers to a comparison of the 3-month response with baseline data. That wording does not specify whether the analysis used participant-level paired measurements, a model for repeated measurements, or another procedure. In general, paired methods use the fact that two measurements come from the same participant, while independent-group methods treat observations as coming from separate groups. The appropriate approach depends on the data structure and analysis plan. The registry record does not report the method used, so no particular method should be attributed to this study.

What would a confidence interval mean?

In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the calculation method. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its limits. It is a way to communicate how compatible a range of estimates is with the observed data and the method. No confidence interval for the primary endpoint is reported in the registry record, so precision cannot be assessed using that tool.

What can a significance test establish?

In general, a significance test evaluates how compatible data are with a specified statistical model and null hypothesis. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. Interpretation also depends on the analysis design and assumptions. The registry record does not report a primary-outcome test statistic or p-value, and it does not give enough detail to identify the null hypothesis or inferential procedure. No significance claim can therefore be made from the posted record.

Why does the single-group design matter?

For this study, the listed comparison is over time within a single group, not between a treatment group and a randomized control group. In general, repeated measurements can account for the fact that readings from the same person may be related. But even a well-conducted within-person analysis cannot, by itself, distinguish the effect of treatment from all other changes occurring during follow-up. A concurrent comparison group can help address some alternative explanations, depending on how it is designed and analyzed. No such group is listed.

How should the planning illustration be understood?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration considers detecting a stated fraction of the observed effect. These are planning assumptions, not a report of the study’s own design justification or a measure of the study’s observed power. The registry record does not report the sample-size justification used for this trial.

The two-arm equal-allocation assumptions do not describe the listed single-group design. A hypothetical planning exercise based on those assumptions should not be read as evidence that the study actually randomized participants between arms or had a concurrent control group. The registry record does not provide the resulting planning sample sizes in the registry record for this analysis, and no new sample-size figures can be inferred from the endpoint description alone. Sample-size illustrations are prospective planning aids, not substitutes for the observed outcome estimate and its uncertainty.

In general, over-dispersion means that observed variability is greater than a model assumes. When that occurs, a model that understates variability can produce uncertainty estimates that are too small. The record does not identify a model for this endpoint or report an assessment of dispersion, so this concept is relevant only as a general statistical consideration, not as a finding about the study.

Finally, the registry identifies one analysis, but does not explain whether it was prespecified, adjusted, or exploratory. A single listed analysis count does not reveal the model, the estimation method, the handling of repeated observations, or the decision criteria. Those procedures are not reported in the registry record.

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("Ranibizumab Group")
n   <- c(25)
m   <- c(2.859)
sp  <- c(1.085)
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  Ranibizumab Group  25  2.859  1.085  2.411  3.307

11. Multiplicity, Missing Data and Analysis Populations

The record lists three outcome measures and one analysis, and names the multifocal electroretinogram signal amplitude as the primary outcome. Postoperative complication is identified as a secondary outcome. The other outcome definitions and any relationship among the outcomes are not fully described in the posted record. No multiplicity strategy is reported.

In general, multiplicity arises when researchers make several statistical comparisons or test several outcomes. The chance of a false-positive finding across a collection of tests can differ from the chance associated with a single test. A prespecified approach may define which outcomes are primary, whether adjustments are planned, and how secondary findings will be interpreted. Since no such approach is described in the registry record, readers should not assume that multiplicity was controlled or that a particular adjustment was used.

The primary analysis is labeled per protocol. The record does not define the analysis population, list exclusions, state how many participants were analyzed, or say whether participants without follow-up measurements were included in any other analysis. It also does not describe imputation, a missing-data model, or sensitivity analyses. These details are not reported in the registry record.

In general, missing outcome data can affect both the number of observations available and the interpretation of an estimate. The implications depend on why data are missing and on the assumptions used in the analysis. Without participant counts at baseline and follow-up, reasons for missingness, and the analysis method, it is not possible to evaluate those issues for this endpoint.

12. Safety Results

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

Other (non-serious) adverse events

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

The registry lists a Ranibizumab Group with 26 participants at risk for serious adverse events and 0 affected. For other adverse events, it also lists 26 at risk and 0 affected. No serious adverse event terms are listed. The death count is not reported in the registry record.

These figures describe what the registry records for the specified safety categories; they should not be read as proof that no adverse events of any kind occurred. The record distinguishes serious adverse events from other adverse events, and both categories have separate at-risk and affected counts. No further event definitions, observation details, or event descriptions are reported in the information available.

The at-risk count of 26 differs from the planned enrollment of 25. The registry record does not explain this difference, so the figures should be presented as recorded rather than reconciled by assumption. The counts also do not provide a comparative estimate: the study is listed as single-group and has no concurrent comparator group. Safety interpretation is therefore limited to the recorded counts and the extent of detail in the registry.

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

This study addresses whether multifocal electroretinogram signal amplitude changed between baseline and 3 months after ranibizumab treatment in people with age-related macular degeneration. The registry record identifies the endpoint, unit, summary measures, and per-protocol analysis population. It does not report the numerical primary results. Therefore, readers cannot determine the observed direction or magnitude of change, how variable the measurements were, or how precise an estimate might be.

Even if a numerical before-and-after change were available, the single-group, non-randomized design would limit what it could establish. In general, an observed change over time does not on its own show that the intervention caused the change. Without a concurrent control group, other time-related influences are not separated by the design. This is a design limitation, not a judgment about whether a change occurred.

The registry does not report a confidence interval, p-value, or other inferential result for the primary outcome. It is therefore not possible to characterize statistical uncertainty or make a claim about statistical significance from the posted record. The mean and standard deviation are named as summary measures, but their values are absent. The per-protocol label also does not reveal how many participants contributed data or how that population was defined.

The safety counts show 0 affected among 26 at risk for serious adverse events and 0 affected among 26 at risk for other adverse events. These entries should be interpreted narrowly as registry counts. They do not supply event details or a comparison with another group, and the death count is not reported in the registry record.

Accordingly, the record supports a description of the study question and design, but not a conclusion about the measured retinal-function result, its precision, or causality. Missing numerical outcome results should not be converted into a claim of no effect or no change.

14. Why This Trial Matters Statistically

Statistically, the study is useful as an example of how a defined outcome and follow-up comparison can still leave key interpretive questions unanswered when numerical results and analysis details are absent. The registry identifies a continuous electrophysiologic measure, its unit, the two time points, and a per-protocol analysis population. Those elements clarify what the primary endpoint was intended to capture, but they do not reveal the actual result or its uncertainty.

The design also illustrates the difference between documenting change and attributing change. A baseline-to-follow-up comparison in a single group can describe temporal variation in the analyzed participants. It cannot, by itself, isolate treatment effects from other influences over time. That distinction matters whenever results from uncontrolled before-and-after studies are interpreted.

The registry’s planning assumptions provide another statistical point: planning calculations depend on assumptions about allocation and analysis. Here, the stated illustration uses equal allocation between two arms, whereas the registered study is single-group. A planning illustration should not be mistaken for the actual trial design, its sample-size justification, or observed power. The sample-size justification is not reported in the registry record.

Finally, the difference between planned enrollment and the safety at-risk count, and the absence of endpoint analysis counts, show why participant flow and analysis-population definitions matter. The record does not explain these details. Taken together, the study’s statistical significance lies in the careful separation of what is specified, what is recorded as a count, and what remains unavailable for interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting the primary endpoint is that the numerical results are not reported in the registry record. There are no outcome means, standard deviations, estimated changes, endpoint-specific participant counts, confidence intervals, or p-values. The magnitude, direction, and precision of any observed difference therefore cannot be assessed.

The study is listed as non-randomized, unmasked, and single-group, with no concurrent control arm. The baseline-to-3-month comparison can describe change over time among analyzed participants, but the design does not separate treatment-associated change from other explanations for temporal change. This limitation applies even if a numerical difference were available.

The analysis is described as per protocol, but the record does not define that population, state how many participants were included, or explain how missing follow-up data were handled. The record also does not report the method for comparing repeated measurements, the statistical analysis plan, or a sample-size justification. These omissions prevent assessment of important assumptions and analysis choices.

Safety reporting is limited to event counts, with no serious adverse event terms listed and no death count reported. The recorded at-risk count is 26, while planned enrollment is 25; the registry does not explain the difference. Further outcome definitions, participant flow, and reasons for missing data are not reported in the registry record. These limitations constrain interpretation of both the primary outcome and the safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Changes in Retinal Function After Intravitreal Ranibizumab for Age-related Macular Degeneration — NCT00539734.
• Registry record last updated 2011-04-15; status last verified 2011-04.
• Results first posted 2011-04-08.
• 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

NCT00539734 is a completed, non-randomized, unmasked, single-group study of ranibizumab for age-related macular degeneration, sponsored by Prince of Songkla University. The registry lists planned enrollment of 25, a start date of 2007-08, and primary completion in 2008-12.

The primary outcome is multifocal electroretinogram signal amplitude in nanovolt/degree^2, comparing baseline with 3 months. The registry specifies a mean and standard deviation and says the analysis was per protocol. The numerical primary results and detailed analysis methods are not reported in the registry record. Postoperative complication is named as a secondary outcome.

The adverse-event record lists 0 serious adverse events among 26 at risk and 0 other adverse events among 26 at risk. No serious adverse event terms are listed, and the death count is not reported. The record does not explain why the safety at-risk count differs from planned enrollment.