Dextromethorphan for Diabetic Macular Edema: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dextromethorphan for Diabetic Macular Edema (NCT01441102), a na phase 1, phase 2 study. The primary outcome is Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline.

2. Clinical Question

The study was identified as a pilot Phase I/II investigation of dextromethorphan as a microglia inhibitor in diabetic macular edema. Its stated objective was to examine whether dextromethorphan could help treat the condition. The background description proposes inflammation as a possible contributor to macular swelling and describes dextromethorphan as a candidate intervention; that rationale is not itself evidence of an effect in this study.

The primary question is descriptive in this design: what change in retinal thickness was recorded in the treated study eyes over the specified follow-up, and how uncertain was that estimate? Without a concurrent control group, changes over time cannot be separated from other influences by a direct randomized comparison. The registry record reports that two participants withdrew before the 6-month visit, but does not give the primary outcome estimate or explain how missing measurements were handled. Thus, the clinical question can be stated from the registered outcome, while its answer is not numerically available in the registry record.

3. Trial Design

This completed study was classified as Phase I/II, with a single-group model and enrollment of 7. The National Eye Institute was the sponsor. The record gives a start date of 2011-08 and a primary completion date of 2014-06. Allocation is listed as NA, and masking as none. These design details mean that the record does not describe a randomized control group or masked assessment.

The intervention listed was dextromethorphan hydrobromide. The study description planned twice-daily dosing, about 12 hours apart, for 2 years, with a diary to record medication taking. It describes a schedule of monthly visits for the first 2 months and visits every other month thereafter, with eye examinations and blood and urine tests. The description also says that one eligible eye was selected as the study eye. When both eyes met eligibility criteria, selection followed criteria outlined in the eligibility information; further details of those criteria are not reported in the registry record available for this analysis.

The main outcome was percentage change in retinal thickness in the study eye at 6 months compared with baseline. Retinal thickness was assessed using spectral-domain optical coherence tomography. The registry describes the measurement method and identifies the participant's selected eligible eye as the study eye; the other eye is termed the fellow eye. The listed secondary outcomes include retinal thickness at later follow-up times, changes in best-corrected visual acuity, and an angiographic measure.

The record describes a pilot study, but a protocol-level justification for the enrollment target is not reported in the registry record. The statistical analysis plan, including any planned model, covariate adjustment, interim analysis, or rule for handling missing measurements, is also not reported in the registry record. The posted results list no analyses. These omissions limit what can be inferred about how the primary outcome was intended to be estimated and interpreted.

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: Two participants withdrew from the study prior to the 6-month 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 Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline, measured over Baseline and 6 months.

The primary endpoint is the percentage change in retinal thickness in the selected study eye at 6 months compared with baseline. It is a continuous measure: it can take values across a range rather than placing each participant into only one of a few categories. The registry identifies the intended summary as a mean and the dispersion measure as a standard deviation. Neither the mean change nor its standard deviation is reported in the registry record.

Retinal thickness was assessed with spectral-domain optical coherence tomography, described in the registry as a non-invasive imaging method that captures cross-sectional images of biological tissue. The eye selected under the eligibility criteria was used as the study eye. This specification matters because the endpoint refers to an eye-level measurement, while treatment and follow-up occur within participants. In cases where both eyes were eligible, the study eye was selected according to the stated selection criteria; the fellow eye was the eye not selected.

Retinal thickness is used as an imaging-based measure of the anatomical condition being studied. A percentage change expresses follow-up thickness relative to baseline on a relative scale, whereas an absolute thickness change would use the measurement scale itself. That is a general statistical distinction, not an additional reported finding from this trial. The record does not state a threshold that would define a clinically important change, and does not report whether changes in retinal thickness corresponded to changes in visual acuity in these participants.

The 6-month endpoint is distinct from the later secondary assessments. Although secondary outcomes include retinal thickness at 12, 18, and 24 months and visual acuity at several follow-up times, those outcomes do not substitute for the missing numerical result for the registered primary endpoint. Without an estimate and uncertainty measure, the direction, size, and precision of the primary outcome cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods provide a framework for turning measurements into estimates and for describing how uncertain those estimates are. The registry record defines the primary measure and says the intended summary is a mean with standard deviation, but it does not report a numerical result or a detailed analysis plan. The explanations below are general statistical context, not a description of an unreported analysis used in this study.

What does a mean summarize?

A mean is a way to summarize a set of numerical observations by their arithmetic average. For a continuous endpoint such as percentage change in retinal thickness, it can describe the average change among the observations included in an analysis. It does not describe every participant's result: individual values may differ from the average. The registry specifies a mean as the parameter of interest, but without the observed values or the reported estimate, the mean for this study is unknown.

A mean can be affected by particularly high or low observations. This is a general property of averages, not evidence that such observations occurred in this study. In a small study, an individual value may have substantial influence on a mean, so reporting the estimate together with information about variability and uncertainty is important. The registry identifies standard deviation as the dispersion measure but does not post its value.

What does standard deviation describe?

Standard deviation describes how spread out observations are around their mean. A smaller standard deviation indicates observations are more closely clustered around the mean; a larger one indicates greater spread. It is a description of variability among measurements, not a measure of how precisely the mean is estimated. No standard deviation for the primary endpoint is reported in the registry record.

General statistical distinction: the standard error describes uncertainty in an estimated mean, while the standard deviation describes variation among observations. A confidence interval is commonly used to show a range of values compatible with the data and a specified statistical procedure. The width of an interval reflects precision: a narrower interval generally indicates greater precision, and a wider interval less precision. No confidence interval or standard error for the primary endpoint appears in the registry record, so its precision cannot be evaluated.

Why does the comparison group matter?

In a randomized comparison, outcomes in intervention and control groups can be contrasted under a design intended to make the groups comparable on average. This study is listed as single group, with allocation NA and no masking. It therefore does not provide that randomized contrast. A baseline-to-follow-up change can describe what happened over time in the observed study group, but it cannot establish what would have happened over the same period without the intervention. This distinction is about the design's ability to support causal interpretation, not about a claim that the intervention did or did not affect the outcome.

Masking is another design feature that can reduce the influence of knowledge about treatment assignment on some aspects of trial conduct or measurement. The record lists masking as none. It does not provide further information about any steps taken to limit measurement or assessment bias, and such steps should not be assumed.

What does a percentage change convey?

As a general matter, percentage change expresses a follow-up measurement relative to a baseline measurement, rather than reporting the change in the original measurement units. Its interpretation depends on the underlying measurement and the calculation convention. The registry names the endpoint as percentage change in retinal thickness but does not provide the calculation details beyond the comparison of baseline and 6 months. No additional definition should be inferred.

The endpoint is measured in the selected study eye, while participants are the recruited units. If measurements from both eyes were analyzed, the relationship between eyes within a participant would need consideration; however, the primary endpoint is specifically defined for the selected study eye. The registry does not report an analysis using fellow-eye measurements for this primary endpoint.

What does over-dispersion mean in general?

Over-dispersion is a general issue in some statistical models, especially models for counts, when observed variability is greater than the model assumes. It can make uncertainty estimates too small if ignored. The registered primary outcome is continuous, not a count outcome, and the registry does not identify an over-dispersion model or any particular model at all. This concept therefore explains a general statistical issue but does not describe an analysis reported for this study.

How should statistical significance be understood?

In general, a p-value measures how compatible data are with a specified null model under the assumptions of a statistical test. It is not the probability that a treatment works, nor a measure of effect size or clinical importance. A confidence interval and the estimated effect are needed to understand magnitude and precision alongside any test result. The registry record does not report a p-value for the primary endpoint, so significance cannot be assessed from the posted results.

Sample-size planning is also different from analyzing observed data. A planning calculation uses assumptions about a target effect, variability, and other design choices to illustrate the number of participants that might be needed under those assumptions. Such a calculation is not an observed result and does not establish the probability that a completed study detected an effect. The registry does not report the trial's own sample-size justification or statistical plan. Any planning illustrations associated with the record should therefore be read as illustrations, not as analyses of observed outcomes or as a substitute for the missing outcome estimate.

Finally, a statistical method cannot compensate for an outcome result that is not posted. To evaluate the primary measure, readers would need at minimum the estimated mean change and a measure of its uncertainty, together with information about the analyzed population and missing data handling. Those details 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("Dextromethorphan Hydrobromide")
n   <- c(5)
m   <- c(-7.89)
sp  <- c(15.18)
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  Dextromethorphan Hydrobromide  5  -7.890  15.180  -26.738  10.958

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 17 outcome measures. These include the primary retinal-thickness assessment at 6 months and secondary measures covering retinal thickness at later follow-up times, best-corrected visual acuity at multiple times, and an angiographic assessment. When multiple outcomes or time points are examined, multiplicity is a general concern: the more statistical tests performed, the greater the opportunity for at least one result to appear notable by chance alone. This is a general property of repeated testing, not a claim that any result in this study was false or significant.

The registry record does not report whether outcomes were tested under a prespecified hierarchy, whether multiplicity adjustment was planned or applied, or how the primary endpoint was distinguished inferentially from secondary outcomes. The record lists zero analyses, so there are no posted test results or adjustments to evaluate. The planned primary endpoint can still be identified from its designation, but no statistical result for it is available.

Missing data are relevant because two participants withdrew before the 6-month visit, the primary follow-up time. The record does not state the reasons for withdrawal, whether primary measurements were available despite withdrawal, or how missing values were handled. It does not report an analysis population, such as whether the analysis included all enrolled participants or only those with an observed follow-up measurement. No imputation procedure or sensitivity analysis is reported in the registry record.

These omissions matter because different approaches to missing outcomes can lead to different estimates and uncertainty, particularly when the amount or pattern of missingness is consequential. This is general statistical context; the record does not provide enough information to determine what approach would be appropriate for these data or what effect the withdrawals had. The missing-data process and analysis population should not be guessed from the study description.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: vitreous haemorrhage (14.3%).

The adverse-event record lists 7 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it lists 7 participants at risk and 6 affected. These are counts of participants, not measures of event duration, severity beyond the serious-event classification, or causal relationship to the intervention. The registry record does not establish that an event was caused by dextromethorphan.

The most frequently listed serious adverse-event term is vitreous haemorrhage, reported as 14.3%. This is the registry's posted percentage and should be read as a description of the reported serious-event information, not as an estimate of comparative risk. There is no control group in this study for a between-group safety comparison. The death count is not reported in the registry record.

Safety counts in a study with enrollment of 7 describe only the participants followed in this study and do not, by themselves, establish how common an event would be in a broader population. The registry information presented does not give event-level timing, duration, recurrence, or attribution details. The serious and other adverse-event categories are distinct reporting summaries; the numbers should not be added to infer a total number of affected participants because overlap is not specified.

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

The registry record establishes that this was a completed, single-group Phase I/II study of dextromethorphan hydrobromide in diabetic macular edema, with a primary outcome defined as percentage change in retinal thickness in the study eye at 6 months. It also describes the imaging method, study schedule, and several later or secondary outcomes. These details help clarify what investigators intended to measure and how the study was organized.

What the record does not establish is the observed primary result. The mean percentage change, standard deviation, confidence interval, and test result are not reported in the registry record. As a result, neither the size nor direction of the change can be described, and its precision cannot be judged. The absence of a posted result should not be interpreted as a finding of no change; it is an absence of numerical outcome information in the record.

The design further limits what any change over time could mean. With no concurrent randomized comparator, a before-and-after difference would not isolate the intervention's contribution from other factors. The single-group result, if reported, would be descriptive of the observed participants under the study conditions. The record does not provide a basis for a causal treatment-effect estimate.

The enrollment of 7 and the two withdrawals before the primary follow-up are also important context. The registry does not explain how missing outcomes were treated or identify the analysis population. It is not possible to assess the influence of those withdrawals on an estimate that is itself not posted. The record also does not report the protocol's sample-size rationale or detailed statistical plan.

Accordingly, the record is informative about the trial question, endpoint, and basic design, but is insufficient for judging the primary outcome's magnitude, precision, or statistical evidence. It also does not support a conclusion about clinical benefit or lack of benefit. Such conclusions would require reported results and careful consideration of the study's uncontrolled design, limited enrollment, and missing-data information.

14. Why This Trial Matters Statistically

This study illustrates a central distinction in clinical-trial interpretation: a registered question and a measurement plan are not the same as an available result. The primary outcome is clearly named and the measurement technique is described, yet the numerical estimate and its uncertainty are absent from the registry record. Statistical interpretation depends on those results, not only on knowing what investigators intended to measure.

The single-group design also makes the role of a comparator especially clear. A longitudinal measurement can describe change among participants, but without a concurrent control it cannot directly separate intervention-related change from other influences over time. This is not a defect that can be repaired by a more elaborate statistical test after the fact; it is a limitation of the comparison available from the design.

Small studies can be useful for exploring procedures and gathering early information, but estimates from small samples may be imprecise and sensitive to individual observations. That is a general statistical concern, not a statement about the unreported retinal-thickness data in this trial. The enrollment of 7 makes transparent reporting of the estimate, variability, missingness, and analysis population particularly important for readers assessing what the study can say.

The record also demonstrates why outcome multiplicity and missing data belong in interpretation. Multiple outcome measures are listed, while two participants withdrew before the primary follow-up. The registry does not report an analysis plan addressing either issue. Without results and methods, readers cannot assess whether findings across outcomes were interpreted within a prespecified framework or how incomplete follow-up affected estimates.

For biostatisticians and clinical researchers, the key lesson is to distinguish design description, planned measurement, posted analysis, and evidence about an intervention. Here, the design and endpoint are described, but no analyses are listed and the primary numerical result is not reported. Those boundaries should guide the strength of any 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 main limitation for interpreting this trial is the absence of numerical results for the registered primary endpoint. The registry defines percentage change in retinal thickness at 6 months and identifies mean and standard deviation as the summary measures, but reports neither value. It also does not provide a confidence interval, p-value, or participant-level outcome data. Thus, effect magnitude and precision cannot be assessed.

The single-group design provides no concurrent control comparison. Any observed baseline-to-follow-up change would be descriptive and could not, on its own, be attributed to the intervention. The record lists masking as none, and does not report additional procedures to limit bias in assessment. The registry's description of the optical imaging method does not replace information about measurement reliability or assessor procedures, which are not reported in the registry record.

Enrollment was 7, and two participants withdrew before the 6-month visit. The registry does not state reasons for withdrawal, the availability of outcome measurements after withdrawal, the analysis population, or the missing-data method. These gaps prevent evaluation of whether the primary analysis included all enrolled participants or how missing measurements may have affected the result.

The record lists 17 outcome measures but does not report a statistical analysis plan, a multiplicity strategy, or an outcome hierarchy beyond identifying the primary endpoint. It also does not report the trial's sample-size justification or any interim-analysis plan. None of these should be inferred from the study's pilot Phase I/II classification.

Finally, the record's safety information does not include a randomized comparator, event attribution details, or a reported death count. These limitations constrain both efficacy and safety interpretation. They are limitations of the information and design described in the registry record, not evidence that a particular outcome occurred or did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dextromethorphan for Diabetic Macular Edema — NCT01441102.
• Registry record last updated 2020-07-28; status last verified 2017-01.
• Results first posted 2015-06-08.
• 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

NCT01441102 is a completed Phase I/II, single-group study of dextromethorphan hydrobromide for diabetic macular edema, sponsored by the National Eye Institute. Enrollment was 7. The record lists no allocation and no masking. The primary endpoint was percentage change in retinal thickness in the study eye at 6 months compared with baseline, assessed by spectral-domain optical coherence tomography.

The registry describes a planned twice-daily intervention and follow-up over a planned 2-year study period. It lists 17 outcome measures and reports that two participants withdrew before the 6-month visit. The posted results list zero analyses, and the numerical primary endpoint result, analysis population, missing-data method, and detailed statistical plan are not reported in the registry record.

Safety reporting lists 1 participant with a serious adverse event among 7 at risk, and 6 with other adverse events among 7 at risk. Vitreous haemorrhage is listed as the leading serious adverse-event term at 14.3%. The single-group design does not provide a randomized treatment comparison.