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 Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity (NCT02390531), a randomized phase 1 study. The primary outcome is Number of Participants With Successful Treatment of ROP.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02390531 |
| Phase | Phase 1 |
| Condition | Retinopathy of Prematurity |
| Allocation | Randomized |
| Design model | Sequential |
| Masking | Quadruple |
| Enrollment | 120 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Jaeb Center for Health Research |
| Results posted | Yes |
2. Clinical Question
The study asked whether a lower dose of intravitreal bevacizumab could meet the trial’s definition of successful treatment for severe retinopathy of prematurity (ROP), with the aim of identifying a dose for evaluation in larger studies. It compared eight dose groups: 0.250 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg. The record describes each arm as a dosage of injected bevacizumab to be studied.
The primary question concerned the number of participants whose ROP treatment was successful at 4 weeks post-injection. Success required improvement by the 4-day examination and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks of injection. The registry description says a dose would be considered effective if it successfully treated at least 80% of subjects. This is a stated criterion, not a reported finding: the number of participants meeting the endpoint in each dose group is not reported in the registry record.
The broader research question also included VEGF and Avastin levels, additional treatment for study eyes, adverse events or complications since the 4-week examination, visual fixation status at 12 months, and whether infants experienced at least one event. These secondary outcomes could describe biological exposure, subsequent eye treatment, safety, and later visual status. Their results are not reported in the registry record.
The question is therefore dose-finding and descriptive as presented in the record. It is not possible to determine from the posted information which dose, if any, met the success criterion, or to compare doses on the primary endpoint.
3. Trial Design
This was a phase 1, randomized, quadruple-masked, sequential trial of bevacizumab in infants with retinopathy of prematurity. The registry lists an enrollment of 120 and identifies the sponsor as Jaeb Center for Health Research. The recorded study dates are 2015-04-28 for study start and 2019-06-04 for primary completion; the study status is completed.
Eight bevacizumab dose arms are listed, from 0.250 mg through 0.002 mg. The arm descriptions identify each dose as the dosage of injected bevacizumab to be studied. Although the trial is described as sequential, the registry record does not report the sequence rules, how decisions between stages were made, or whether assignment probabilities changed as the trial proceeded. Randomization is reported, but the randomization procedure and allocation ratios are not reported in the registry record.
Masking is reported as quadruple. The record does not identify the four masked roles or explain how masking was maintained across the different dose groups. It also does not report a control or placebo arm; the listed arms are bevacizumab doses.
The primary assessment was at 4 weeks post-injection, with improvement assessed at the 4-day examination as part of the success definition. The registry also lists a visual fixation outcome at 12 months. Other outcome time points, beyond those stated for particular outcomes, are not reported in the registry record. Seven infants were excluded from the primary outcome population for reasons described in the endpoint record: deaths before the 4-week examination, an unconfirmed failure, an incorrect dose in the study eye, and treatment of the fellow eye without the stated ROP indication. The record does not provide outcome counts by dose.
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.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | Bevacizumab (0.250 mg) | Bevacizumab (0.125 mg) | Bevacizumab (0.063 mg) | Bevacizumab (0.031 mg) | Bevacizumab (0.016 mg) | Bevacizumab (0.008 mg) |
|---|---|---|---|---|---|---|
| STARTED | 11 | 16 | 24 | 10 | 14 | 9 |
| COMPLETED | 11 | 14 | 24 | 9 | 13 | 9 |
| NOT COMPLETED | 0 | 2 | 0 | 1 | 1 | 0 |
Reasons for not completing this period:
| Reason | Bevacizumab (0.250 mg) | Bevacizumab (0.125 mg) | Bevacizumab (0.063 mg) | Bevacizumab (0.031 mg) | Bevacizumab (0.016 mg) | Bevacizumab (0.008 mg) |
|---|---|---|---|---|---|---|
| Death | 0 | 2 | 0 | 1 | 0 | 0 |
| Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Seven infants were excluded (4 infants died prior to 4-week outcome examination; 1 failed, but it was not confirmed by second examiner; 1 was injected with the wrong dose in the study eye; and 1 had the fellow eye treated in the absence of type 1 ROP within one week of the study eye).
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.
Only the first 6 of 9 groups are shown.
| Characteristic | Unit | Bevacizumab (0.25 mg) | Bevacizumab (0.125 mg) | Bevacizumab (0.0625 mg) | Bevacizumab (0.031 mg) | Bevacizumab (0.016 mg) | Bevacizumab (0.008 mg) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 11 | 16 | 24 | 10 | 14 | 9 | |
| Age, Continuous: Gestational age at enrollment | Weeks | 24.81 (SD 1.49) | 25.21 (SD 2.22) | 24.82 (SD 1.42) | 24.73 (SD 1.12) | 24.48 (SD 1.14) | 24.63 (SD 1.48) |
| Sex: Female, Male: Female | Participants | 6 | 4 | 12 | 4 | 3 | 7 |
| Sex: Female, Male: Male | Participants | 5 | 12 | 12 | 6 | 11 | 2 |
| Race/Ethnicity, Customized: White | Participants | 7 | 10 | 12 | 2 | 9 | 3 |
| Race/Ethnicity, Customized: Black/African American | Participants | 2 | 2 | 3 | 4 | 2 | 2 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 2 | 3 | 3 | 2 | 2 | 1 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 0 | 2 | 1 | 1 | 1 |
| Race/Ethnicity, Customized: Native Hawaiian/Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: American Indian/Alaskan Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: More than 1 race | Participants | 0 | 1 | 3 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Unknown/Not Reported | Participants | 0 | 0 | 1 | 1 | 0 | 2 |
| Birth Weight | grams | 726.27 (SD 219.23) | 801.31 (SD 514.35) | 652.08 (SD 156.88) | 680.60 (SD 167.17) | 677.93 (SD 147.02) | 539.44 (SD 133.19) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Successful Treatment of ROP, measured over 4 weeks post-injection.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with successful treatment of ROP at 4 weeks post-injection. It is a participant count, not a measure of how much an individual infant’s condition changed. Success combines an early response with the absence of specified worsening or need for additional treatment during the stated period.
For infants with plus disease, early improvement meant that plus disease was no longer present by the 4-day post-injection examination. For infants with type 1 ROP without plus disease—zone I, stage 3—the definition required a significant reduction in the severity and/or extent of extraretinal neovascularization. If pre-plus was present before injection, improvement also required reduced abnormal vascular dilation and/or tortuosity. The definition then required no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks of injection.
A combined endpoint of this kind can capture both an early clinical response and whether that response is sustained over the specified follow-up. It is used in this trial to assess whether a dose meets the stated treatment-success criterion. The registry says a dose would be considered effective if at least 80% of subjects were successfully treated. The observed number of successes and the proportion meeting that criterion are not reported in the registry record, so the endpoint definition alone cannot establish whether any dose met it.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial’s design, dose groups, endpoint definition, and some safety counts, but it does not provide the primary outcome results. In particular, it does not report the number of participants with successful treatment in each dose group, the total assessed for that endpoint in each group, or an estimate of success with a confidence interval. The stated criterion of successful treatment in at least 80% of subjects is a planned benchmark; without outcome counts, it cannot be compared with observed results.
The record lists 120 participants enrolled and notes that seven infants were excluded from the primary outcome population. It gives reasons for those exclusions, but does not report how many participants remained in each dose group for analysis. The seven exclusions comprise four infants who died before the 4-week outcome examination, one failure not confirmed by a second examiner, one infant injected with the wrong dose in the study eye, and one infant whose fellow eye was treated without type 1 ROP within one week of the study eye. These details matter when judging which participants contributed to the endpoint, but they do not reveal the outcome among those included.
Randomization and masking are recorded, but the registry does not provide estimates comparing doses or an analysis plan. The fact that there are multiple dose groups does not by itself tell readers how the investigators evaluated dose patterns, accounted for the sequential design, or handled multiple comparisons. Those procedures are not reported in the registry record. Nor does the record report a statistical test, confidence interval, or other inferential result for the primary endpoint.
Safety information is reported separately as numbers at risk and numbers affected for serious and other adverse events, alongside deaths by dose group. These counts provide a descriptive account, not a causal comparison. The record does not give enough detail to determine event timing, whether participants could contribute multiple events, or the methods used to attribute events to treatment. The listed percentages for selected serious-event terms also have no denominator explained in the registry record.
Consequently, the posted information cannot establish which dose had the highest success, whether any dose met the stated benchmark, or whether outcomes differed between doses. It supports a description of the trial’s intended question and some reported safety counts, but the primary efficacy findings and their precision are not reported in the registry record.
9. Statistical Methods Explained
Statistical methods determine how trial observations are converted into estimates and how uncertainty is represented. For this trial, the registry record identifies randomization, quadruple masking, a sequential model, a participant-count primary endpoint, and a stated threshold for considering a dose effective. It does not report the detailed statistical plan, so the methods below explain general concepts rather than asserting which analyses investigators used.
What does a participant count show?
The primary endpoint is a count of participants whose treatment met a defined success rule. A count is easiest to interpret when read with the number assessed in the same group: the count indicates how many met the rule, while the group size indicates the number who could have met it. A proportion expresses the count relative to that group size. The registry record does not report the group-specific counts or denominators, so neither proportions nor comparisons can be recovered from the record.
The endpoint itself combines several conditions. A participant had to show the specified improvement by the 4-day examination and avoid the specified recurrence or severe neovascularization requiring additional treatment within 4 weeks of injection. Because the success rule requires all of its components, a failure to meet any required component means the overall endpoint is not met. Separate component results would help explain why participants did or did not meet the combined definition, but those component results are not reported in the registry record.
How should uncertainty be understood?
A confidence interval is a statistical range that conveys uncertainty around an estimated quantity, such as a success proportion or a difference between groups. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its endpoints. No confidence interval for the primary outcome is reported in the registry record, so the precision of the dose-specific success estimates cannot be assessed.
A hypothesis test can assess how compatible observed data are with a specified null hypothesis, but its p-value does not measure the size or clinical importance of an effect. A p-value also does not replace an estimate and its uncertainty. The registry record reports no primary outcome test or p-value. It would therefore be inappropriate to infer statistical significance, or lack of significance, from the available endpoint description.
What does randomization contribute?
In general, random allocation can help balance measured and unmeasured characteristics across treatment groups, on average, and supports comparisons that are less vulnerable to confounding than nonrandomized comparisons. Its protection depends on appropriate allocation and analysis. The record says the trial was randomized, but does not report the randomization method, allocation ratio, or analysis population. The word randomized alone does not reveal whether all planned procedures were followed or how the analysis handled participants who received an incorrect dose.
Masking can reduce the influence of knowledge about assigned treatment on care, outcome assessment, or reporting. The registry labels the trial quadruple-masked, but does not define the four roles or describe masking procedures. The record therefore identifies masking as a design feature without allowing a detailed assessment of its implementation.
What does a sequential design imply?
In general, a sequential design allows a study to proceed through stages, with decisions made as information accumulates. Depending on the prespecified rules, sequential designs may affect allocation, stopping, or the interpretation of statistical evidence. The registry does not report the stage structure, decision boundaries, stopping rules, or how the sequential feature was incorporated into analysis. No specific implication for the trial’s estimates or error rates can be established from the design label alone.
How should the sample-size assumptions be read?
The registry record describes 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 effects defined as stated fractions of the observed effect. For non-time-to-event outcomes, its convention is participants per arm; for time-to-event outcomes, the convention is total events. These are general planning assumptions, not the trial’s reported sample-size justification or an observed power calculation. The record does not report the trial’s own sample-size justification, and it does not report primary endpoint results needed to assess the observed effect.
Planning calculations based on an observed effect should not be interpreted as evidence that the completed trial had a particular probability of detecting an effect. Sample size is a design quantity, while observed results and their uncertainty are determined by the trial data and analysis. The registry record does not report an analysis using a prespecified target effect or a formal power calculation for this trial.
Why do event counts need context?
For binary outcomes, an event count is meaningful alongside the number of participants at risk and a clear event definition and observation period. For adverse events, additional context includes whether the count refers to people with at least one event or total events, whether repeat events are included, and whether events were judged related to treatment. Those details are not all reported for the safety figures. The displayed serious and other affected counts should therefore be read as registry-reported counts, not as rates or adjusted comparisons.
10. Multiplicity, Missing Data and Analysis Populations
The study has a primary endpoint, multiple bevacizumab dose groups, and several listed secondary outcomes. When many doses or outcomes are compared, the chance of finding at least one apparently notable result by chance can increase. Statistical approaches can address multiplicity by defining a primary comparison, adjusting tests, or interpreting results as exploratory. The registry record does not report a multiplicity strategy, a hierarchy of secondary outcomes, or which dose comparisons were planned.
The record lists 14 outcome measures and zero analyses. The latter means no analyses are posted in the registry record; it does not establish that no analyses were conducted. Results for the primary endpoint and secondary outcomes are not reported in the registry record. Without estimates, denominators, confidence intervals, or analysis descriptions, readers cannot assess the multiplicity of any reported efficacy comparisons.
Missing data and analysis populations also affect interpretation. Seven infants were excluded from the primary outcome population. The stated reasons are four deaths before the 4-week examination, one unconfirmed failure, one wrong dose in the study eye, and one fellow-eye treatment in the absence of type 1 ROP within one week of study-eye treatment. The registry does not report how these participants were handled in any statistical analysis, whether other outcome data were missing, or whether sensitivity analyses were performed.
The record also does not describe an intention-to-treat population, a per-protocol population, or rules for including participants who did not receive their assigned dose. These are important distinctions: analysis populations can change which participants contribute to an estimate and what comparison it represents. No particular analysis population or missing-data method should be inferred from the exclusions alone.
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 |
|---|---|---|---|
| Bevacizumab (0.25 mg) | 1 | 11 | 9.1% |
| Bevacizumab (0.125 mg) | 3 | 16 | 18.8% |
| Bevacizumab (0.0625 mg) | 3 | 24 | 12.5% |
| Bevacizumab (0.031 mg) | 1 | 10 | 10.0% |
| Bevacizumab (0.016 mg) | 1 | 14 | 7.1% |
| Bevacizumab (0.008 mg) | 1 | 9 | 11.1% |
| Bevacizumab (0.004 mg) | 5 | 12 | 41.7% |
| Bevacizumab (0.002 mg) | 4 | 24 | 16.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Bevacizumab (0.25 mg) | 0 of 11 |
| Bevacizumab (0.125 mg) | 3 of 16 |
| Bevacizumab (0.0625 mg) | 2 of 24 |
| Bevacizumab (0.031 mg) | 2 of 10 |
| Bevacizumab (0.016 mg) | 1 of 14 |
| Bevacizumab (0.008 mg) | 0 of 9 |
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 |
|---|---|
| Bevacizumab (0.25 mg) | 4 of 11 |
| Bevacizumab (0.125 mg) | 3 of 16 |
| Bevacizumab (0.0625 mg) | 4 of 24 |
| Bevacizumab (0.031 mg) | 1 of 10 |
| Bevacizumab (0.016 mg) | 4 of 14 |
| Bevacizumab (0.008 mg) | 1 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Bevacizumab (0.25 mg) | Bevacizumab (0.125 mg) | Bevacizumab (0.0625 mg) | Bevacizumab (0.031 mg) | Bevacizumab (0.016 mg) | Bevacizumab (0.008 mg) |
|---|---|---|---|---|---|---|---|
| Bronchopulmonary dysplasia | Respiratory, thoracic and mediastinal disorders | 0 of 11 | 3 of 16 | 3 of 24 | 1 of 10 | 0 of 14 | 0 of 9 |
| Upper respiratory tract infection | Infections and infestations | 0 of 11 | 0 of 16 | 3 of 24 | 1 of 10 | 0 of 14 | 0 of 9 |
| Infantile apnoea | Respiratory, thoracic and mediastinal disorders | 0 of 11 | 2 of 16 | 0 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Necrotising enterocolitis neonatal | Gastrointestinal disorders | 0 of 11 | 1 of 16 | 1 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Vomiting | Gastrointestinal disorders | 0 of 11 | 1 of 16 | 1 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | 0 of 11 | 0 of 16 | 1 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | 0 of 11 | 1 of 16 | 0 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Bronchiolitis | Infections and infestations | 0 of 11 | 0 of 16 | 0 of 24 | 1 of 10 | 0 of 14 | 0 of 9 |
| Cardiac Arrest | Cardiac disorders | 0 of 11 | 0 of 16 | 1 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Dysphagia | Gastrointestinal disorders | 0 of 11 | 0 of 16 | 0 of 24 | 1 of 10 | 0 of 14 | 0 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bevacizumab (0.25 mg) | Bevacizumab (0.125 mg) | Bevacizumab (0.0625 mg) | Bevacizumab (0.031 mg) | Bevacizumab (0.016 mg) | Bevacizumab (0.008 mg) |
|---|---|---|---|---|---|---|---|
| Any Adverse Event | Eye disorders | 4 of 11 | 3 of 16 | 4 of 24 | 1 of 10 | 4 of 14 | 1 of 9 |
| Conjunctival haemorrhage | Eye disorders | 0 of 11 | 1 of 16 | 2 of 24 | 1 of 10 | 0 of 14 | 0 of 9 |
| Feeding Intolerance | Gastrointestinal disorders | 2 of 11 | 0 of 16 | 1 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Gastroesophageal reflux disease | Gastrointestinal disorders | 0 of 11 | 2 of 16 | 1 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Retinal Detachment | Eye disorders | 2 of 11 | 0 of 16 | 0 of 24 | 0 of 10 | 1 of 14 | 0 of 9 |
| Retinal Haemorrhage | Eye disorders | 0 of 11 | 0 of 16 | 0 of 24 | 0 of 10 | 2 of 14 | 1 of 9 |
| Bronchopulmonary dysplasia | Respiratory, thoracic and mediastinal disorders | 0 of 11 | 1 of 16 | 1 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Conjunctivitis | Eye disorders | 0 of 11 | 1 of 16 | 0 of 24 | 1 of 10 | 0 of 14 | 0 of 9 |
| Deafness | Ear and labyrinth disorders | 0 of 11 | 0 of 16 | 2 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
| Inguinal Hernia | Gastrointestinal disorders | 0 of 11 | 1 of 16 | 1 of 24 | 0 of 10 | 0 of 14 | 0 of 9 |
Serious events with the highest arm-level rate: respiratory distress (33.3%), bronchopulmonary dysplasia (18.8%), infantile apnoea (12.5%), upper respiratory tract infection (12.5%), enterococcal infection (11.1%).
The registry reports serious-event and other-event counts for each dose group, including the number at risk, the number affected, and deaths. These figures are descriptive counts as posted. They should not be treated as event rates or as evidence that one dose caused more or fewer events than another: the record does not report a comparative statistical analysis, event timing, or how repeat events were counted.
For the 0.250 mg group, 11 were at risk for serious events and 1 was affected; 11 were at risk for other events and 4 were affected, with 0 deaths. The corresponding serious-event and other-event counts are 16 at risk and 3 affected, and 16 at risk and 3 affected, for the 0.125 mg group, with 3 deaths. For the group labeled 0.062 mg in the safety record, the counts are 24 at risk and 3 affected for serious events, and 24 at risk and 4 affected for other events, with 2 deaths.
For the 0.031 mg group, 10 were at risk and 1 was affected for serious events, and 10 were at risk and 1 was affected for other events, with 2 deaths. For 0.016 mg, the respective counts are 14 and 1, and 14 and 4, with 1 death. For 0.008 mg, they are 9 and 1, and 9 and 1, with 0 deaths. For 0.004 mg, they are 12 and 5, and 12 and 5, with 0 deaths. For 0.002 mg, they are 24 and 4, and 24 and 9, with 1 death.
The registry also lists selected serious-event terms with percentages, but the denominator and method for those percentages are not reported in the registry record. No causal conclusion follows from these counts alone.
12. What the Result Does, and Does Not, Mean
The registry record provides a structured account of a randomized, quadruple-masked phase 1 dose-finding trial and defines how primary treatment success was to be judged. It also records an enrollment of 120, several secondary outcomes, and dose-group safety counts. These details help readers understand what the study set out to assess and what kinds of observations were collected.
The record does not report the primary success counts, group denominators for that endpoint, or statistical estimates. It therefore cannot show whether any dose met the stated criterion of successful treatment in at least 80% of subjects. It also cannot support a ranking of doses, an estimate of how outcomes differed by dose, or a conclusion about the precision of any treatment effect. Those limits concern the information recorded, not the possible existence of analyses outside the registry record.
The safety counts have a similarly bounded meaning. They describe numbers at risk and numbers affected, along with deaths, but the record does not explain enough about event definitions, timing, repeat events, or attribution to support causal comparisons. The counts should not be read as proof that a dose was safer or less safe than another.
The study’s stated purpose was to identify a lower dose for testing in larger studies. A phase 1 dose-finding question is distinct from a definitive comparative efficacy question. Even if primary results were available, interpretation would depend on the number assessed, uncertainty around estimates, the analysis plan, and how the sequential design and multiple dose groups were handled. Those statistical details and the primary results are not reported in the registry record.
Accordingly, the posted information is informative about design and endpoint definitions but incomplete for evaluating efficacy. No treatment recommendation or conclusion about clinical benefit can be drawn from the record alone.
13. Why This Trial Matters Statistically
This trial is statistically notable for combining a randomized, quadruple-masked design with multiple dose groups and a sequential model. Each feature affects how evidence should be interpreted. Randomization and masking are relevant to bias control, while a sequential structure may require rules that account for accumulating information. The registry reports these design labels but not the procedures needed to assess their implementation.
The primary outcome also illustrates how a clinical endpoint can combine early response and follow-up. Improvement by the 4-day examination was not sufficient by itself: the definition additionally required no specified recurrence or severe neovascularization requiring additional treatment within 4 weeks of injection. Such a rule can make an endpoint clinically focused, but it also means that its interpretation depends on consistent assessment of each component and clear handling of incomplete follow-up.
Multiple dose groups raise questions about how comparisons are organized and how uncertainty is controlled across them. The record does not state which comparisons were primary, how multiplicity was handled, or how the sequential design affected the statistical plan. Without posted efficacy estimates and methods, readers cannot distinguish a dose pattern from random variation or judge the precision of apparent differences.
The registry does report a threshold for considering a dose effective, but a threshold is not a result. Evaluating it requires the observed success count and denominator, alongside uncertainty and a clearly defined analysis population. Those primary results are not reported in the registry record. The case demonstrates why endpoint definitions and design labels are important but cannot substitute for outcome data and transparent analysis methods.
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 most important limitation of the registry record for interpreting this trial is that primary outcome results are not reported. There are no dose-specific counts of successful treatment, endpoint denominators, estimates, confidence intervals, or primary outcome tests. As a result, the stated success benchmark cannot be evaluated from the posted information.
The record identifies a sequential model but does not describe its stages, decision rules, stopping boundaries, or impact on allocation and analysis. It reports randomization and quadruple masking without the randomization procedure, allocation ratio, or the roles that were masked. These omissions limit assessment of how the design was implemented and how it should inform statistical interpretation.
Seven infants were excluded from the primary outcome population, with reasons listed, but the record does not explain their treatment in the analysis or report sensitivity analyses. It also does not report the number assessed in each dose arm. The record therefore does not show how exclusions and any other missing outcome data affected the endpoint estimates.
Safety reporting includes affected counts and deaths, but does not describe event timing, repeat-event handling, attribution to treatment, or the denominator for the percentages attached to selected serious-event terms. These omissions prevent detailed comparison of safety patterns. The registry also lists 14 outcome measures but no posted analyses, leaving the results for secondary outcomes unavailable in the record.
Finally, no trial-specific sample-size justification or detailed statistical analysis plan is reported in the registry record. The planning assumptions described for an illustration should not be mistaken for the trial’s own design rationale or for evidence of observed power.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity — NCT02390531.
- Registry record last updated 2022-11-03; status last verified 2022-11.
- Results first posted 2022-11-03.
- 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
The record describes NCT02390531, a completed phase 1 trial of bevacizumab for severe retinopathy of prematurity. It was randomized, quadruple-masked, and sequential, with an enrollment of 120. The listed dose arms range from 0.250 mg to 0.002 mg. The study start is recorded as 2015-04-28, and primary completion as 2019-06-04.
The primary endpoint was the number of participants with successful treatment at 4 weeks post-injection, using an improvement and no-recurrence definition. The registry says a dose would be considered effective if it successfully treated at least 80% of subjects. Seven infants were excluded from the primary outcome population for the reasons recorded in the endpoint description.
Secondary outcomes include VEGF and Avastin levels, additional treatment, adverse events or complications, visual fixation status, and whether infants had at least one event. The record includes dose-group safety counts but does not report primary outcome results, secondary outcome results, or statistical analyses. The trial’s statistical analysis plan, multiplicity procedures, and sample-size justification are not reported in the registry record.