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 Efficient Study of ACULAR in Inhibiting Proliferative Retinopathy in Prematurity (NCT00634972), a randomized phase 4 study. The primary outcome is Efficacy of ACULAR Compared to Placebo in Inhibiting the Development of Retinopahty of Prematurity in a High Risk Very Immature Preterm Group of Infants.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00634972 |
| Phase | Phase 4 |
| Condition | Retinopathy of Prematurity, Retinal Detachment, Blindness |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 83 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of South Alabama |
| Results posted | Yes |
2. Clinical Question
Population
High-risk, very immature preterm infants. The registry record does not report detailed eligibility criteria or a more specific description of this population.
Intervention
Topical ACULAR, described as a nonsteroidal anti-inflammatory eye drop medication. The intervention list also names REFRESH TEARS.
Comparator
Placebo, described in the study summary as an artificial tear. The registry record lists placebo as an intervention and identifies a placebo group.
Primary question
Whether ACULAR could inhibit the development of retinopathy of prematurity or reduce its severity, including the incidence of moderate to severe disease, defined in the hypothesis as grade II and above.
The study’s stated hypothesis was that ACULAR treatment would decrease the incidence of moderate to severe retinopathy of prematurity by 50%. This is a proposed effect, not a finding: the registry record says the study was prematurely interrupted because recruitment was insufficient to reach the preplanned power for a statistically significant result, and no data analysis was completed.
The primary outcome title describes efficacy compared with placebo in inhibiting development of retinopathy of prematurity in a high-risk, very immature preterm group. Its timeframe is recorded as 3-4 years. The registry record does not report outcome estimates, a treatment-effect comparison, or a statistical test. The clinical question therefore remains unanswered by the posted results; the stated hypothesis should not be read as evidence that the anticipated reduction occurred.
3. Trial Design
The registry identifies NCT00634972 as a phase 4, randomized, triple-masked, parallel study sponsored by the University of South Alabama. Its title concerns topical ACULAR and inhibition of proliferative retinopathy of prematurity. The study summary describes comparison with placebo, an artificial tear. The intervention list names ACULAR, REFRESH TEARS, and placebo, while the arm descriptions are blank. Further detail about the intended use of each listed intervention is not reported in the registry record.
Enrollment is recorded as 83. The record gives a start date of 2005-11 and a primary completion date of 2008-08, and the study status is terminated. Those dates and the enrollment entry describe the registry record; they do not establish that the planned recruitment target or follow-up was completed. The registry says recruitment did not reach the number required for the preplanned power and that the study was prematurely interrupted.
The design labels indicate randomized allocation, a parallel-group structure, and triple masking. The record does not identify which people were masked, describe the randomization procedure, state an allocation ratio, or give details of concealment. Those protocol features are not reported in the registry record. Although the study summary refers to ACULAR and placebo, the blank arm descriptions limit what can be said about the treatment regimens or how the listed interventions map to every arm.
The primary outcome timeframe is recorded as 3-4 years, but the registry does not provide a fuller schedule of visits or explain how the timeframe relates to treatment or assessment. It lists 1 outcome measure and 0 analyses. The outcome description states that no data analysis was completed. Thus, the design can be characterized from the recorded labels and summary, but the registry does not support a detailed reconstruction of the operational protocol or an efficacy analysis.
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 | 1 Drop of the ROP Study Drug | Placebo |
|---|---|---|
| STARTED | 40 | 43 |
| COMPLETED | 40 | 43 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The study was prematurely interrupted. As we could not achieve the recruitment of a sufficient number of patients that was required to reach the preplanned power for a statistically significant results, no data analysis was completed.
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.
| Characteristic | Unit | 1 Drop of the ROP Study Drug | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 40 | 43 | 83 | |
| Age, Categorical: <=18 years | Participants | 40 | 43 | 83 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 22 | 19 | 41 |
| Sex: Female, Male: Male | Participants | 18 | 24 | 42 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Efficacy of ACULAR Compared to Placebo in Inhibiting the Development of Retinopahty of Prematurity in a High Risk Very Immature Preterm Group of Infants, measured over 3-4 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome concerns the efficacy of ACULAR compared with placebo in inhibiting development of retinopathy of prematurity among high-risk, very immature preterm infants. The study summary frames the clinical target as prevention or reduced severity of retinopathy of prematurity. It specifies a hypothesis about the incidence of moderate to severe disease, defined as grade II and above, and proposes a 50% decrease. That target describes the investigators’ hypothesis; it is not an observed effect.
An endpoint of this kind is used to make the clinical question measurable: investigators need a defined disease outcome and assessment timeframe to compare groups. Retinopathy severity and whether disease develops are relevant to the stated aim of prevention or inhibition. The registry records the outcome timeframe as 3-4 years, but does not report the measurement unit, parameter, dispersion, assessment schedule, or further operational definition. The record also indicates that the primary outcome involves several categories or time points and is not reduced to one comparison.
Most importantly, the registry states that the study was interrupted before sufficient recruitment and that no data analysis was completed. It supplies no group-level outcome counts, effect estimate, confidence interval, or test result. The endpoint therefore identifies what the trial sought to assess, but the posted results do not show whether the groups differed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes an efficacy question but does not provide an efficacy result. The study was terminated, recruitment was insufficient to reach the preplanned power for a statistically significant result, and no data analysis was completed. There is consequently no reported comparison of ACULAR with placebo for the primary outcome. The registry does not report an effect estimate, confidence interval, p-value, or outcome counts by group.
The stated 50% decrease in moderate to severe retinopathy of prematurity is a hypothesis in the study summary. It is not an estimate from trial participants and must not be interpreted as the magnitude of a treatment effect. Likewise, absence of a reported efficacy analysis is not evidence that the treatments had the same outcomes, nor is it evidence that ACULAR did or did not alter disease occurrence or severity. The result is inconclusive because the outcome comparison was not completed in the record.
The enrollment entry is 83, and the serious-adverse-event display records 40 participants at risk in the group titled 1 Drop of the ROP Study Drug and 43 in the Placebo group. Those safety entries do not substitute for primary-outcome data. Their presence does not establish that the primary endpoint was assessed or analyzed, and the record does not explain how the safety groups relate to the complete study population beyond their group labels.
There is also no basis for assessing precision. A confidence interval would describe the range of effect sizes compatible with the analyzed data under the statistical model; no such interval is reported. Without outcome estimates or their uncertainty, readers cannot judge whether the available data would distinguish a clinically meaningful effect from little or no difference. The termination explanation establishes a recruitment and power problem, but it does not quantify the effect of that shortfall on any estimate.
Accordingly, the defensible statistical reading is limited: this randomized study was intended to compare topical ACULAR with placebo for retinopathy of prematurity, but the registry reports premature interruption and no completed outcome analysis. The record does not support a conclusion about comparative efficacy. The reported adverse-event counts can be described separately, with the limitations of their reporting, but they do not resolve the efficacy question.
9. Statistical Methods Explained
Statistical methods are difficult to evaluate when a study ends before its planned analysis. In this case, the registry explicitly says that recruitment was insufficient to reach the preplanned power for a statistically significant result and that no data analysis was completed. It lists 0 analyses. The registry record does not report a statistical analysis plan, a model for the primary outcome, a testing procedure, or a method for handling incomplete outcome observations.
What does statistical power mean?
In general, power is the chance that a planned statistical test will identify an effect of a specified size under stated assumptions. It is a feature of a study’s design and analysis plan, not a measure of whether a treatment worked. A study can have inadequate power because it recruits fewer participants than planned, because the outcome is less common or more variable than expected, or because the true effect is smaller than the effect used for planning. These are general statistical explanations, not findings about which factor occurred in this trial. The registry specifically identifies insufficient recruitment relative to the preplanned power, but does not report the target recruitment, the planned effect used in its original design, or the original power calculation.
Low power does not make an observed effect automatically biased, and it does not prove that an effect is absent. It generally means that an analysis may have difficulty distinguishing a real effect from random variation. Here, even that interpretation must remain general because no primary-outcome analysis was completed and no estimate or uncertainty interval is reported. There is no trial-specific test result from which to judge the evidence.
How should the sample-size illustrations be read?
Any sample-size values associated with planning illustrations are hypothetical calculations, not the achieved study power and not evidence about the trial’s success. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrations are described as based on a fraction of the observed effect. The registry record does not report the numerical effect used for these calculations in the information available for this analysis, so no value or implication can be inferred from that description alone.
A planning illustration for participants per arm for 80% power means the number of participants each group would require under the selected assumptions and effect size. Such a calculation is conditional: changing the effect size, variability, significance level, or allocation assumptions changes the requirement. It does not tell readers the power achieved by the trial as conducted. The registry’s explanation of premature interruption is the relevant account of the recruitment problem; a hypothetical planning calculation cannot replace the trial’s own design rationale, which is not reported in the registry record.
In general, a two-sided test considers departures in either direction, while a significance level sets a threshold used in a testing procedure. A normal approximation is a mathematical simplification that can be suitable under particular conditions. These general descriptions do not establish that the trial used these methods in its planned efficacy analysis. The stated values belong to the planning illustration, not a reported primary-outcome analysis.
Why does outcome structure matter?
The registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison. This matters because the definition of the endpoint determines what is compared and how uncertainty is calculated. For example, a categorical severity outcome may be analyzed differently from a continuous measurement or a time-to-event outcome. Multiple assessment times or outcome categories can also require a prespecified strategy for selecting or combining comparisons. The registry does not report such a strategy, and no analysis was completed.
In general, a confidence interval expresses uncertainty around an estimated effect under a specified method. It helps show whether the estimate is precise or compatible with a broad range of effects. A p-value, when reported, describes how unusual the data would be under a stated null model and assumptions; it does not measure the probability that a treatment works. Neither type of result is present for the primary endpoint. No statistical model, covariate adjustment, or estimation method is reported, so there is no basis to reconstruct them.
The distinction between planned design and completed analysis is central. Randomized allocation is recorded, but randomization alone does not provide an efficacy estimate. To assess a treatment comparison, readers would need outcome data, a clearly defined analysis population, and methods consistent with the endpoint and missingness. Those details are not reported, and the registry says that outcome analysis did not occur. The appropriate conclusion is therefore about the status and limits of the statistical evidence, not about the direction or size of a treatment effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity strategy. It indicates that the primary outcome involves several categories or time points and is not reduced to one comparison, but it does not describe which categories or times were designated for formal testing, whether any comparisons were prioritized, or how repeated testing would be handled. In general, when several outcomes or time points are tested, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the multiple comparisons. That is a general statistical concern, not a claim that a particular adjustment was needed or performed in this study.
Missing-data methods are not reported in the registry record. The outcome description says that recruitment was insufficient and no data analysis was completed, but does not state how many endpoint observations were missing, whether follow-up was incomplete, or what methods would have been used to address missingness. No assumption about missing outcomes or their treatment in an analysis can be made.
The record does not identify an intention-to-treat population, a per-protocol population, or another analysis population. It also does not explain how participants would be assigned to an analysis group if treatment was not started or follow-up was incomplete. These details are important because analysis populations can affect the interpretation of a randomized comparison. With no completed analysis and no reported population definition, no participant-flow or population-based efficacy estimate can be reconstructed.
The registry does record 1 outcome measure and 0 analyses. That count does not resolve how the multiple categories or time points within the primary outcome were to be handled. The statistical plan, multiplicity handling, missing-data strategy, and analysis populations are not reported in the registry record.
11. 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 |
|---|---|---|---|
| 1 Drop of the ROP Study Drug | 0 | 40 | 0.0% |
| Placebo | 0 | 43 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 1 Drop of the ROP Study Drug | 0 of 40 |
| Placebo | 0 of 43 |
The registry lists serious and other adverse-event counts for two groups. For the group titled 1 Drop of the ROP Study Drug, 40 participants are reported at risk, with 0 affected by serious adverse events and 0 affected by other adverse events. For the Placebo group, 43 participants are reported at risk, also with 0 affected by serious adverse events and 0 affected by other adverse events. These are the posted counts, not a comparative safety analysis.
A zero in the affected count means no events are recorded in that category for the group in this registry display. It does not, on its own, establish that no events occurred outside the definition, observation period, or reporting process used for this record. The registry does not report adverse-event definitions, collection methods, observation periods, or a statistical comparison between groups. Death counts are not reported in the registry record.
The counts should be read separately from the primary efficacy question. They do not show whether ACULAR affected retinopathy of prematurity, and the registry’s lack of an efficacy analysis does not change what the safety entries report. Because the arm descriptions are blank, the exact treatment details represented by the study-drug group are not fully described in the record.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, triple-masked, parallel study was registered to compare topical ACULAR with placebo for retinopathy of prematurity in high-risk, very immature preterm infants. It also establishes that the trial was terminated after recruitment fell short of the level required for the preplanned power and that no outcome analysis was completed. These are important details about what the study set out to do and what the registry reports happened.
The record does not establish whether ACULAR prevented retinopathy of prematurity, reduced its severity, or had outcomes similar to placebo. The proposed 50% decrease is a hypothesis, not a measured treatment effect. Because the primary outcome estimates, group outcome counts, confidence intervals, and test results are not reported, the direction, size, and precision of any comparative effect cannot be determined from the posted results.
It would also be incorrect to interpret the missing analysis as a finding of no effect. An uncompleted comparison cannot distinguish a real effect from no effect, and it cannot show how compatible the data would be with different possible effects. The reported enrollment and adverse-event counts do not answer the primary efficacy question.
In general, a terminated study can still contribute useful information about feasibility, recruitment, and reporting, but conclusions depend on what data and analyses are available. Here, the registry explains why the planned analysis was not completed, while leaving key details of the statistical plan and outcome data unreported. The careful conclusion is that the efficacy question remains unresolved in the registry record, rather than that either treatment was superior, equivalent, or ineffective.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a research question and an answer supported by analyzed data. The registry sets out a randomized comparison and a clinically focused outcome, but the study was interrupted before reaching the recruitment level required for its preplanned power. No data analysis was completed. A trial’s design labels and hypothesis do not supply the missing effect estimate.
Recruitment shortfalls can affect the ability to estimate treatment effects with useful precision. In general, fewer observations than intended can leave an analysis less able to separate an effect from random variation. That general principle helps explain why the registry links insufficient recruitment to the preplanned power. It does not establish the actual precision of this trial’s results, since no efficacy estimate or uncertainty interval is reported.
The record also emphasizes the value of transparent endpoint and analysis reporting. The primary outcome involves several categories or time points, but the registry does not describe how those components would be combined or tested. Statistical interpretation depends on knowing what was measured, which comparisons were planned, and how missing data and analysis populations were handled. Those details are not reported.
Finally, the safety counts and enrollment entry have distinct meanings from an efficacy result. Reporting them does not overcome the absence of a primary-outcome analysis. The key statistical lesson is not a conclusion about ACULAR, but the limits of inference when the planned outcome comparison was never completed and the registry record does not include results from that analysis.
14. 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 trial-specific limitation is that the registry reports premature interruption after recruitment failed to reach the level needed for the preplanned power. It states that no data analysis was completed. Consequently, the record contains no efficacy estimate, outcome counts by treatment group, confidence interval, or hypothesis-test result for the primary question.
Details needed to assess the planned methods are also absent. The registry does not report the original recruitment target, the original sample-size justification, the planned statistical model, or the full analysis plan. Although it describes sample-size illustrations, those are planning calculations rather than the trial’s achieved power. The actual rationale and calculations for the original design are not reported in the registry record.
The endpoint is not fully specified in the record. Its timeframe is recorded as 3-4 years, and it involves several categories or time points, but a detailed definition, assessment schedule, measurement unit, and comparison strategy are not reported. The record also does not report the allocation ratio, randomization procedure, masking roles, or fuller descriptions of the arms.
Information about missing outcomes, participant flow, analysis populations, and handling of protocol deviations is not reported. The safety display gives at-risk and affected counts, but does not provide event definitions, ascertainment periods, or a comparative safety analysis; death counts are not reported in the registry record. These gaps limit interpretation of both the planned analysis and the posted safety entries. They do not justify conclusions about outcomes that were not analyzed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficient Study of ACULAR in Inhibiting Proliferative Retinopathy in Prematurity — NCT00634972.
- Registry record last updated 2020-12-08; status last verified 2020-12.
- Results first posted 2020-12-08.
- 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.
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18. Record Summary
NCT00634972 was a phase 4 randomized, triple-masked, parallel study sponsored by the University of South Alabama. It evaluated topical ACULAR against placebo for preventing or inhibiting retinopathy of prematurity in high-risk, very immature preterm infants. Enrollment is recorded as 83; the study began in 2005-11, had a primary completion date of 2008-08, and is listed as terminated.
The study summary states a hypothesis of a 50% decrease in moderate to severe retinopathy of prematurity, defined as grade II and above. The primary outcome timeframe is 3-4 years. The registry says recruitment was insufficient to reach the preplanned power and that no data analysis was completed. It lists 1 outcome measure and 0 analyses; no efficacy estimate is reported.
The adverse-event display records 0 serious and 0 other adverse events in each listed group. Death counts are not reported in the registry record. The posted record therefore documents the intended comparison and the reason the planned analysis was not completed, but does not establish an efficacy result.