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 Long-term Safety and Efficacy Outcome Study Comparing Children Previously Enrolled in Study ROPP-2008-01 for the Prevention of Retinopathy of Prematurity (ROP) (NCT02386839), a na phase 2 study. The primary outcome is Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 6 Months Corrected Age (CA).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02386839 |
| Phase | Phase 2 |
| Condition | Retinopathy of Prematurity (ROP) |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 76 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Shire |
| Results posted | Yes |
2. Clinical Question
Population
Children previously enrolled in study ROPP-2008-01 who had written informed consent for this long-term outcome study. The registry record describes an enrolled set of 76 participants overall, while the numbers at risk differ by outcome and group. The follow-up included children whose earlier care was standard neonatal care and children whose earlier care included rhIGF-1/rhIGFBP-3.
Intervention
The intervention of interest is prior short-term exposure to rhIGF-1/rhIGFBP-3 in ROPP-2008-01. This record concerns long-term follow-up; it does not describe a new treatment assignment during the follow-up study. The study aimed to assess later efficacy and safety outcomes associated with the earlier treatment experience.
Comparator
The comparison group comprises children who received standard neonatal care in the earlier study. The groups are classified by antecedent care, and this follow-up record does not describe random allocation. The registry explicitly notes that the arms are not a like-for-like control comparison, so differences between them cannot be interpreted as if they arose from a randomized comparison.
Primary question
The primary outcome asks how many participants had visual acuity assessed by an age-appropriate method at 6 months corrected age (CA). Assessment methods included teller acuity cards, the LEA symbols test and charts. Visual acuity was categorized as normal, below normal or poor using the measurement thresholds described in the registry record. The participant counts for these categories are not reported in the registry record, so the primary outcome cannot be interpreted quantitatively from the posted information.
3. Trial Design
This is a completed Phase 2 long-term outcome study, sponsored by Shire, with an enrollment of 76. Its purpose was to evaluate longer-term efficacy and safety outcomes after short-term exposure to rhIGF-1/rhIGFBP-3 or standard neonatal care in the earlier study ROPP-2008-01 (NCT01096784). The study ran from 2015-03-26 to primary completion on 2021-09-28.
The follow-up groups are defined by what participants received in the earlier study: antecedent standard of care and antecedent rhIGF-1/rhIGFBP-3. The registry lists a single-group model, allocation as NA, and no masking. It also cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The group labels therefore describe prior treatment history rather than a newly randomized treatment contrast in the follow-up.
The primary outcome was the number of participants with visual acuity assessed at 6 months CA. The listed secondary outcomes cover changes in body weight, height and head-circumference Z-scores; cognitive development assessed at 24 months CA and 5 years CA; physical examination findings; cerebral palsy diagnosis by neurological examination at 24 months CA; and hearing screening status. The registry lists 40 outcome measures, but does not report their results in the information available for this record.
The registry reports no statistical analyses. Details such as the planned analysis model, adjustment variables, handling of missing observations and sample-size justification are not reported in the registry record. The primary outcome counts by visual-acuity category are also not reported in the registry record. Consequently, the design and stated objectives can be described, but the posted information does not support an estimate of the primary outcome or a causal comparison of the antecedent groups.
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.
Before assignment: A total of 76 participants who previously treated with rhIGF 1/rhIGFBP-3 or Standard Neonatal Care in ROPP-2008-01 (NCT01096784) study were enrolled in this long-term safety and efficacy study.
Overall Study
| Stage | Antecedent Standard of Care | Antecedent rhIGF-1/rhIGFBP-3 |
|---|---|---|
| STARTED | 36 | 40 |
| COMPLETED | 20 | 25 |
| NOT COMPLETED | 16 | 15 |
Reasons for not completing this period:
| Reason | Antecedent Standard of Care | Antecedent rhIGF-1/rhIGFBP-3 |
|---|---|---|
| Death | 1 | 0 |
| Withdrawal by Subject | 9 | 10 |
| Lost to Follow-up | 4 | 4 |
| Other (Site Terminated by Sponsor) | 1 | 0 |
| Other (Covid 19 Pandemic) | 0 | 1 |
| Other (unspecified) | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Enrolled set included all participants for whom written informed consent was obtained for this long-term outcome study. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at the specified categories.
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.
Population: Enrolled set included all participants for whom written informed consent was obtained for this long-term outcome study.
| Characteristic | Unit | Antecedent Standard of Care | Antecedent rhIGF-1/rhIGFBP-3 | Total |
|---|---|---|---|---|
| Participants analysed | 36 | 40 | 76 | |
| Age, Continuous | Weeks | 7.15 (SD 5.622) | 6.73 (SD 6.224) | 6.93 (SD 5.911) |
| Sex: Female, Male: Female | Participants | 13 | 14 | 27 |
| Sex: Female, Male: Male | Participants | 23 | 26 | 49 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 6 | 13 | 19 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 28 | 27 | 55 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 4 | 0 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 | 1 | 6 |
| Race (NIH/OMB): White | Participants | 26 | 34 | 60 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 5 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 6 Months Corrected Age (CA), measured over At 6 Months CA.
| 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 visual acuity assessed using an age-appropriate method at 6 months corrected age. Visual acuity describes how well a participant sees at different distances. The registry lists teller acuity cards, the LEA symbols test and charts as assessment methods, and classifies measurements as normal, below normal or poor.
Corrected age is used to place developmental assessments in context for children born preterm. The registry defines corrected age in weeks as chronological age in weeks minus 40 plus gestational age in weeks. The listed visual-acuity thresholds distinguish normal, below-normal and poor categories. In the description, normal includes measurable acuity at or above 20/40 or at or above 15 cycles per degree; below normal includes a range from 20/200 to less than 20/40 or from 3 to less than 15 cycles per degree; poor includes acuity at or below 20/200 or at or below 3 cycles per degree.
As a count endpoint, the outcome is intended to describe how many assessed participants fall into the relevant visual-acuity categories, rather than the average acuity measurement. Such categories can make clinical status easier to describe, but interpretation depends on knowing the number assessed and the count in each category. Those counts are not reported in the registry record. The endpoint's definition is available, but its observed distribution and the precision of any estimate cannot be determined from the posted information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies visual acuity at 6 months CA as the primary outcome, but it does not report the number of participants in each visual-acuity category. It therefore offers no posted primary-outcome result from which to describe the frequency of normal, below-normal or poor acuity, or to compare those frequencies between antecedent-care groups. This is a limit of the posted record, not evidence that the outcome was not assessed.
The registry describes 76 enrolled participants overall. For the safety counts, 36 participants in the antecedent standard-of-care group and 40 in the antecedent rhIGF-1/rhIGFBP-3 group were at risk for the listed serious adverse-event summaries. The record lists 3 participants with serious adverse events in the standard-of-care group and 2 in the prior-treatment group. It lists 5 and 2 participants, respectively, with other adverse events, and 1 and 0 deaths, respectively. These are descriptive counts. They do not establish that a difference between groups was caused by prior treatment.
The record states that allocation was NA and identifies the follow-up as a single-group model. Although it presents two groups according to earlier care, it explicitly warns that this is not a randomized, like-for-like control comparison. In general, nonrandomized groups may differ in ways that affect later outcomes. Without details about baseline comparability, confounder adjustment and the analysis plan, group differences would not isolate an effect of the earlier treatment.
No statistical analyses are reported. There are no posted inferential estimates, confidence intervals or p-values for the primary outcome. A confidence interval, in general, describes the uncertainty around an estimate under a specified statistical model; without an estimate and interval, the precision of the visual-acuity findings cannot be assessed. The record also does not report the number analyzed for the primary endpoint, so the extent of missing outcome information cannot be established from the posted record.
The listed secondary outcomes indicate a broad follow-up covering growth, cognitive development, physical and neurological examinations, and hearing. Their results are not reported in the registry record. The existence of these outcome measures alone does not establish what was observed, whether a difference occurred, or how uncertain any finding may be. The appropriate interpretation is therefore limited: the study's follow-up questions and some safety counts are described, while the primary outcome findings and statistical comparisons are unavailable in the registry record.
9. Statistical Methods Explained
What does the design imply for comparisons?
The record labels the study model as single group and allocation as NA, while describing two groups based on antecedent care in ROPP-2008-01. This distinction matters. The follow-up observes children with different prior treatment histories; it does not describe random assignment to treatment within this study. Randomization, in general, aims to make comparison groups similar on average with respect to measured and unmeasured factors. Without it, group differences can reflect prior health, care or other factors as well as treatment history. The registry itself warns that the arms are not a like-for-like control comparison. A causal treatment effect should not be inferred from a simple contrast of these groups.
What information would an analysis need?
The primary outcome is a count of participants classified by visual-acuity category. To interpret such an endpoint, an analysis generally needs the number assessed in each group, the number in each category, and a clear denominator. If participants can fall into only one category, category counts can describe the observed distribution; if the endpoint is summarized as a binary event, the event definition must be explicit. Here, the registry names categories and assessment methods but does not report the outcome counts or the number analyzed. The statistical analysis plan and any model for comparing groups are not reported in the registry record.
General statistical practice distinguishes descriptive summaries from inferential comparisons. Counts describe what was observed in the analyzed participants. Inferential methods estimate uncertainty and may test a specified hypothesis, subject to model assumptions. The registry reports 0 analyses, and no p-values, confidence intervals or adjusted estimates are listed. Thus, there is no posted inferential result to interpret. Absence of a reported analysis does not establish that no analysis was performed outside the registry; it means the analysis is not reported in the registry record.
How should uncertainty be understood?
In general, a confidence interval gives a range of values compatible with an estimate under the statistical model and its assumptions. A wide interval indicates less precision than a narrow one, though interpretation depends on the outcome and design. No primary-outcome estimate or interval is reported, so neither the direction nor the precision of a primary comparison can be judged. The sample-size illustrations use general planning assumptions: two-sided significance level 0.05, equal allocation between groups, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are planning illustrations, not the trial's own design justification and not observed power. The registry does not report a trial-specific sample-size justification.
For count outcomes, the denominator is essential. The overall enrollment does not necessarily equal the number with an observed endpoint, because some enrolled participants may not contribute data to a particular measure. The record's definition distinguishes the enrolled set from those evaluable for the outcome, but the primary outcome counts and number analyzed are not reported. No missing-data method is described. It is therefore not possible to assess whether the analyzed participants represent all enrolled participants or how incomplete follow-up might affect the result.
Why can repeated outcomes raise multiplicity questions?
The registry lists 40 outcome measures, including several secondary developmental and examination outcomes. In general, testing many outcomes can increase the chance of obtaining at least one apparently unusual result by chance, especially when each test is interpreted separately. Study teams may address this with a prespecified hierarchy, adjusted thresholds or a clear distinction between confirmatory and exploratory analyses. The registry record does not report a multiplicity strategy, hypothesis hierarchy or analysis plan. No adjustment method should be assumed.
What do the safety counts represent?
The serious adverse-event figures are counts among participants at risk in each antecedent group, and the other adverse-event and death figures are also presented as counts. A count is not itself an adjusted comparison. General safety interpretation considers the event definition, observation period, completeness of reporting, denominator and participant characteristics. The record names the groups and counts but does not provide inferential comparisons or detailed adjustment methods. A descriptive difference in counts cannot establish causation, particularly in a nonrandomized follow-up.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 40 outcome measures, including the primary visual-acuity endpoint and secondary growth, cognitive, physical, neurological and hearing outcomes. Considering many outcomes can create multiplicity: in general, the more separate hypotheses examined, the greater the chance that at least one result may appear notable by chance. Appropriate interpretation depends on which outcomes were prespecified as primary or confirmatory and whether a hierarchy or adjustment strategy was used. The multiplicity approach and detailed statistical analysis plan are not reported in the registry record. No correction method should be presumed.
The record describes an enrolled set of 76 participants and distinguishes the enrolled population from those evaluable for an outcome. However, the number analyzed for the primary visual-acuity outcome and the category counts are not reported. The registry does not describe how missing observations, withdrawals or incomplete follow-up were handled. It is therefore not possible to assess the completeness of the primary endpoint data, compare those retained with those not assessed, or determine the potential direction of bias from missingness.
Analysis populations are not fully specified in the registry record. The record gives a general definition of the enrolled set, but does not provide outcome-specific analysis populations for the reported results. The number of analyses is listed as 0. No methods for covariate adjustment, imputation, sensitivity analysis or multiplicity control are reported in the registry record. These omissions prevent a detailed assessment of how the study addressed missing data and multiple outcomes.
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 |
|---|---|---|---|
| Antecedent Standard of Care | 3 | 36 | 8.3% |
| Antecedent rhIGF-1/rhIGFBP-3 | 2 | 40 | 5.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Antecedent Standard of Care | 1 of 36 |
| Antecedent rhIGF-1/rhIGFBP-3 | 0 of 40 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Antecedent Standard of Care | 5 of 36 |
| Antecedent rhIGF-1/rhIGFBP-3 | 2 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | Antecedent Standard of Care | Antecedent rhIGF-1/rhIGFBP-3 |
|---|---|---|---|
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | 2 of 36 | 2 of 40 |
| Sudden infant death syndrome | General disorders | 1 of 36 | 0 of 40 |
| Adenoidal hypertrophy | Respiratory, thoracic and mediastinal disorders | 1 of 36 | 0 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Antecedent Standard of Care | Antecedent rhIGF-1/rhIGFBP-3 |
|---|---|---|---|
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | 5 of 36 | 2 of 40 |
Serious events with the highest arm-level rate: tonsillar hypertrophy (5.6%), sudden infant death syndrome (2.8%), adenoidal hypertrophy (2.8%).
For serious adverse events, the registry lists 3 participants among 36 at risk in the antecedent standard-of-care group and 2 among 40 at risk in the antecedent rhIGF-1/rhIGFBP-3 group. It lists 5 participants with other adverse events among 36 at risk in the first group and 2 among 40 at risk in the second. Deaths are listed as 1 in the first group and 0 in the second. These are descriptive participant counts; the registry does not report statistical comparisons for them.
The registry also lists tonsillar hypertrophy at 5.6%, sudden infant death syndrome at 2.8%, and adenoidal hypertrophy at 2.8% among the top serious adverse-event terms. These entries identify reported event terms and percentages, but the excerpt does not give further detail about event timing, severity beyond the serious-event classification, recurrence, or group-specific distribution for each term. Such details are not reported in the registry record.
In general, safety counts should be read alongside their denominators, follow-up duration, definitions and completeness of ascertainment. The listed at-risk counts differ between groups, and the groups were not formed by random assignment in this follow-up. These figures alone cannot establish a treatment-related effect or support a causal comparison.
12. What the Result Does, and Does Not, Mean
The record establishes that a long-term follow-up study was completed to assess outcomes among children previously treated with rhIGF-1/rhIGFBP-3 or standard neonatal care in ROPP-2008-01. It identifies visual acuity at 6 months CA as the primary endpoint and names a range of developmental, growth, examination and hearing outcomes. It also posts descriptive safety counts for the antecedent groups.
However, the primary visual-acuity counts are not reported in the registry record. Without those results, the posted information does not show how many participants were classified as normal, below normal or poor, or how the observed categories were distributed between groups. No primary-outcome statistical analysis is reported, so the precision of any estimate and the strength of evidence for a difference cannot be assessed. The secondary outcome results are also not reported in the registry record.
The safety counts show the numbers listed in each group, but they do not prove that prior treatment caused more or fewer events. This follow-up was not randomized, and the registry cautions that its groups are not a like-for-like control comparison. Differences in participant characteristics, follow-up or other factors could affect observed group counts. No adjusted analysis is posted to address such possibilities.
Accordingly, the registry record supports a description of the study's purpose, design labels, outcome definitions and selected safety counts. It does not support a conclusion about comparative long-term efficacy, nor does it establish that a treatment is effective or ineffective. The lack of posted outcome findings should be understood as a reporting limitation: it does not mean that the outcomes were absent, that no analysis was conducted outside the registry, or that no events occurred.
13. Why This Trial Matters Statistically
This study is statistically important as an example of the distinction between a long-term follow-up and a randomized treatment comparison. Participants were grouped by their earlier care in ROPP-2008-01, while the follow-up record identifies a single-group model and allocation as NA. The registry explicitly cautions that the arms are not a like-for-like control comparison. That context is essential when interpreting any differences in later outcomes: descriptive group contrasts do not by themselves isolate treatment effects.
The record also illustrates why an endpoint definition is not the same as an endpoint result. It describes age-appropriate visual-acuity assessment and the categories used, but does not report the numbers in those categories. Without the observed counts and analysis population, readers cannot evaluate the outcome frequency, uncertainty or completeness of follow-up. The same distinction applies to the listed secondary measures: their presence in a registry record does not communicate their results.
Finally, the entry makes the limits of registry reporting visible. No analyses are reported, and the methods for missing data, multiplicity and adjustment are not stated. In general, such details are important for evaluating precision and the credibility of multiple outcome comparisons. The posted safety counts remain useful as descriptive information, but should be interpreted in light of nonrandomized group formation and absent inferential analyses. Statistical interpretation depends not only on the number of outcomes listed, but also on transparent reporting of who was assessed, what was observed and how uncertainty was handled.
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 principal limitation for interpreting efficacy is that the primary visual-acuity category counts are not reported in the registry record. The number analyzed for this endpoint is also not stated, so neither the observed distribution nor its precision can be assessed. Results for the listed secondary outcomes are likewise not reported in the registry record.
The follow-up groups are based on antecedent care rather than random allocation in this study. The registry warns that they are not a like-for-like control comparison. The record does not report baseline comparisons, confounder adjustment or a model for estimating group differences. As a result, the posted information cannot establish a causal effect of prior treatment on long-term outcomes.
The statistical analysis plan, missing-data methods, multiplicity strategy and trial-specific sample-size justification are not reported in the registry record. These omissions limit assessment of the planned hypotheses, analysis populations and robustness of any findings. The registry lists 40 outcome measures but reports 0 analyses, leaving no inferential results to assess. The safety information consists of counts and selected serious adverse-event terms; further details about event timing and group-specific term counts are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long-term Safety and Efficacy Outcome Study Comparing Children Previously Enrolled in Study ROPP-2008-01 for the Prevention of Retinopathy of Prematurity (ROP) — NCT02386839.
- Registry record last updated 2022-05-18; status last verified 2022-04.
- Results first posted 2022-04-25.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02386839 is a completed Phase 2 long-term outcome study sponsored by Shire, with enrollment of 76. It followed children previously treated with rhIGF-1/rhIGFBP-3 or standard neonatal care in ROPP-2008-01. The registry lists a single-group model, allocation as NA and no masking, and cautions that the antecedent groups are not a like-for-like control comparison.
The primary endpoint was participant visual acuity at 6 months CA. The registry lists 40 outcome measures and 0 analyses. Primary visual-acuity results, secondary outcome results, and details of the analysis and missing-data methods are not reported in the registry record. Descriptive safety counts are listed for serious adverse events, other adverse events and deaths; these do not establish a causal treatment comparison.