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 Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study (NCT00649961), a na phase 2 study. The primary outcome is To Find the Dose of Melatonin Required to Achieve Physiological Blood Levels in the Preterm Infants Similar to That of the Mother..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00649961 |
| Phase | Phase 2 |
| Condition | Premature Birth, Brain Injury |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Imperial College London |
| Results posted | Yes |
2. Clinical Question
Population
The study focused on preterm infants born less than 31 weeks gestation and less than 7 days old. The brief summary describes this population as being at risk of brain injury and states that the study intended to include 24 babies. The recorded enrollment is 18.
Intervention
Infants received melatonin by injection in an open-label, single-arm study. The registry record identifies the intervention as a drug but does not report the dose levels, dosing schedule, or how doses were selected.
Comparator
No comparator group is recorded. The study is described as single group, with allocation listed as not applicable. Its design therefore does not provide a like-for-like comparison between infants receiving melatonin and infants receiving another intervention or no intervention.
Primary question
The primary objective was to find the melatonin dose needed to achieve blood levels in preterm infants similar to physiological levels in the mother. The endpoint is a blood concentration measured in pg/ml, summarized as a median with a full range over a timeframe of 6 months. The registry record does not report the observed concentrations or identify a dose that met the objective.
3. Trial Design
This is a phase 2, completed, single-group study sponsored by Imperial College London. The registry record gives a start date of 2010-05 and a primary completion date of 2011-02. It records enrollment of 18 and describes an open-label melatonin injection intervention. Masking is listed as none, and allocation is listed as not applicable.
The brief summary states that the study intended to study 24 babies. The recorded enrollment is 18; the registry record does not explain the difference between the intended number and the enrollment figure. The eligible infants are described as born less than 31 weeks gestation and less than 7 days old. No further eligibility criteria are reported in the registry record.
A single-group design describes observations among participants receiving the intervention, rather than a randomized comparison between groups. With no control group, any observed concentration could be described within the enrolled group, but the design alone cannot show how those concentrations would compare with outcomes under another treatment or without melatonin. Open-label status means masking is not part of the recorded design; further details about who knew the intervention assignment are not reported in the registry record.
The listed primary outcome concerns blood melatonin levels and has a timeframe of 6 months. The registry record lists one outcome measure and zero analyses. It does not report an outcome value, the specific timing of blood sampling, the doses administered, or the statistical analysis used to summarize the outcome. Completion status indicates the trial is marked completed in the registry; it does not, by itself, establish that the primary question was answered in the posted results.
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: Infants born less than 31 weeks gestation and less than 7 days old were eligible for the study, although those with: major congenital malformation; or cystic periventricular leucomalacia or haemorrhagic parenchymal infarcts on cranial enrolment were excluded.
Overall Study
| Stage | Melatonin Open Label Single Arm |
|---|---|
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
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: Infants born at less than 31 weeks gestation and less than 7 days after birth
| Characteristic | Unit | Single Arm |
|---|---|---|
| Participants analysed | 18 | |
| Age, Customized: Gestation at birth | weeks | 26.63 (24.71 to 30.28) |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 9 |
| Region of Enrollment: United Kingdom | participants | 18 |
6. Primary Endpoint
The registry lists the primary outcome as To Find the Dose of Melatonin Required to Achieve Physiological Blood Levels in the Preterm Infants Similar to That of the Mother., measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | pg/ml |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is intended to measure the blood concentration of melatonin in preterm infants, with the stated objective of finding a dose that achieves physiological blood levels similar to those of the mother. The unit is pg/ml. Concentration is relevant to this objective because the question concerns the level reached in the blood, rather than a clinical event or a comparison of symptoms.
The outcome is specified as a median with a full range over a timeframe of 6 months. A median describes the middle observation after values are ordered; it is less influenced by unusually high or low observations than an arithmetic mean. A full range describes the lowest and highest observed values, but does not show how observations are distributed between those endpoints. In a small group, the range can be particularly sensitive to individual observations. These are general statistical properties of the stated summary measures.
The registry record does not report the median, the full range, or numerical results by dose. It also does not report the exact measurement schedule, whether concentrations were summarized at multiple time points, or what criterion would count as sufficiently similar to the maternal level. Consequently, the endpoint definition identifies what the study was intended to measure, but the posted record does not allow readers to determine the concentrations observed or whether the dose objective was met.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry record states a dose-finding objective but does not report a numerical result for its primary endpoint. It gives the outcome’s unit, summary measure, and timeframe, yet no median concentration or full range is recorded. The dose levels and the results associated with them are also not reported in the registry record. The study’s primary question therefore cannot be answered from the posted results.
The recorded design is single group, open label, and without masking. This design can describe measurements made among the participating infants, but it does not include a concurrent control group for estimating what would have happened under a different intervention or no intervention. That distinction matters even if numerical endpoint results were available: a concentration observed after melatonin administration would be a within-group observation, not a controlled estimate of a difference attributable to melatonin.
The registry records enrollment of 18, while the brief summary says the study intended to study 24 babies. These figures describe different things: one is the recorded enrollment and the other is the stated intention in the summary. The registry record does not explain why they differ or provide additional information about recruitment, withdrawals, or the number contributing to the endpoint.
The record reports zero analyses. It therefore does not give an inferential result, such as an estimated contrast, confidence interval, or p-value. A confidence interval, in general, represents uncertainty around an estimate under a specified statistical method; without an estimate and analysis, precision cannot be evaluated. The absence of a reported analysis is not evidence that the underlying concentration was a particular value or that a particular dose was adequate.
Safety figures are also limited to the registry’s recorded counts: in the single arm, 18 were at risk for serious adverse events and 0 were affected; 18 were at risk for other adverse events and 0 were affected; deaths were recorded as 0. These are the counts posted for this study, not a comparative safety estimate. With no comparator and no further event details reported, they do not establish how the counts would differ under another care strategy.
Overall, the record supports a description of the study’s purpose, design, enrollment, and listed safety counts. It does not support a numerical conclusion about achieved blood levels, dose selection, statistical precision, or comparative effects. The completed status should be read as a registry status, not as a substitute for endpoint findings.
9. Statistical Methods Explained
The methods that can be described from the registry record are limited. The study is listed as phase 2, single group, open label, with no masking and allocation marked not applicable. Its primary outcome is a median blood concentration in pg/ml with a full range, over a timeframe of 6 months. The record lists one outcome measure and zero analyses. It does not provide an analysis plan or numerical primary outcome result.
What does a single-group design estimate?
In general, a single-group study can characterize measurements among the participants who receive the study intervention. It does not directly estimate a treatment contrast because there is no recorded comparison group. A treatment contrast is a difference between outcomes under two specified conditions. Without such a comparator, changes or observed levels cannot be separated from other influences using a between-group comparison. This is a general limitation of the design, not a finding about the biological effect of melatonin.
For this study, the stated objective is to identify a dose associated with blood melatonin levels similar to maternal physiological levels. The record does not state the dose sequence, dose allocation approach, timing of measurements, or criterion used to determine similarity. It also does not report results for any dose. The dose-finding process therefore cannot be reconstructed from the registry information.
Why report a median and full range?
In general, a median gives the middle observation in ordered data and can be useful when values are skewed or when extreme observations could pull an arithmetic mean. A full range gives the minimum and maximum values. These summaries are easy to interpret, but do not convey the full distribution or directly quantify the precision of the median. Other summaries, such as a confidence interval, can help express uncertainty, but none is reported for this endpoint in the registry record. No additional distributional information should be inferred from the choice of median and range alone.
The unit pg/ml identifies the scale of the concentration measurement. The timeframe of 6 months identifies the outcome period as registered, but the record does not clarify whether this means one measurement within that period, repeated measurements across it, or a summary across several times. The exact measurement schedule is not reported in the registry record.
What can significance testing tell readers?
In general, a statistical test evaluates how compatible observed data are with a stated null hypothesis under specified assumptions. A p-value is not a measure of effect size, clinical importance, or the probability that a hypothesis is true. A confidence interval is generally more informative about the range of estimates compatible with the data and the chosen method. Here, the registry record reports no analyses and no inferential statistics, so there is no posted p-value or interval to interpret.
The registry’s sample-size note describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of an observed effect, and distinguishes participant counts per arm from total event counts for time-to-event calculations. These assumptions describe an illustrative planning framework; they do not describe the recorded single-group trial design, which has no comparator arm. The registry record does not report a trial-specific sample-size justification, and the planning assumptions should not be read as evidence of observed power or as a description of the analysis actually used.
Why does over-dispersion matter in general?
In general, over-dispersion occurs when variability in data is greater than a statistical model assumes. If a model understates variability, its standard errors may be too small and its confidence intervals too narrow, making results appear more precise than warranted. Appropriate modeling depends on the data structure and outcome distribution. The registry record does not identify a model, report a dispersion assessment, or provide the underlying data, so no conclusion about over-dispersion or model adequacy can be made for this study.
More broadly, statistical methods depend on the observed data, measurement schedule, missingness, and analysis population. Those details are not reported in the registry record. Without them, readers cannot assess whether a particular estimator, model, or uncertainty calculation was appropriate. The primary endpoint definition and design can be described, but they do not supply the missing analysis details or numerical findings.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure and zero analyses. It does not report whether there were additional prespecified outcomes, secondary analyses, subgroup analyses, or repeated comparisons across doses or time points. A multiplicity adjustment or broader strategy for handling multiple statistical tests is therefore not reported in the registry record.
In general, multiplicity arises when several hypotheses or comparisons are evaluated. The more tests that are considered, the greater the chance that at least one result may appear unusual by chance if each is assessed separately. Methods for managing this issue can include defining a primary comparison in advance, adjusting significance thresholds, or emphasizing estimation and uncertainty. Which approach is suitable depends on the design and analysis plan. No such approach can be attributed to this study based on the registry information.
The record does not describe missing outcome data, withdrawals, exclusions, or the number of infants contributing measurements. It also does not report how missing values would be handled. Enrollment is recorded as 18, whereas the brief summary states an intention to study 24 babies; the record does not explain the difference. It would be inappropriate to infer that the difference reflects missing data, discontinuation, or any specific recruitment outcome.
Analysis populations are not described. The registry record does not say whether analyses were intended to include all enrolled infants, only infants with measured concentrations, or another defined population. In general, the analysis population affects the interpretation of estimates because it determines which participants contribute data. With no reported analyses or endpoint values, the population used for the primary outcome cannot be assessed.
These omissions limit appraisal of the endpoint’s completeness, the handling of repeated measurements, and the relationship between planned and analyzed participants. They do not demonstrate that particular procedures were or were not used; those details are simply 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 |
|---|---|---|---|
| Single Arm | 0 | 18 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Single Arm | 0 of 18 |
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 |
|---|---|
| Single Arm | 0 of 18 |
The registry lists one group, described as a single arm. For serious adverse events, 18 participants are recorded as at risk and 0 as affected. For other adverse events, 18 are recorded as at risk and 0 as affected. Deaths are recorded as 0. These are the safety counts in the registry record.
These figures should be interpreted as recorded counts for this study, not as evidence from a comparison between melatonin and another group. The study has no comparator arm, so it cannot provide a between-group estimate of safety differences. The record does not include serious adverse event terms, and the top serious terms list is empty. It does not describe event monitoring procedures, duration of observation for safety, or whether the counts represent all events collected under a defined reporting threshold.
Zero recorded affected participants means no events are entered in these fields; it does not establish that the risk of an event is zero. In general, an observed count is distinct from the underlying event probability, especially when the number observed is limited. The registry does not report a confidence interval or other uncertainty estimate for these safety counts. The figures should therefore be read narrowly as registry-reported counts, without extrapolating to other populations or settings.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed phase 2 study was registered to investigate melatonin dosing in preterm infants. Its primary objective was to find a dose associated with blood melatonin concentrations similar to maternal physiological levels. It identifies the population as infants born less than 31 weeks gestation and less than 7 days old, and describes an open-label, single-group melatonin injection intervention.
What the posted results do not establish is equally important. No median concentration, full range, dose-specific result, confidence interval, or test result is reported. Accordingly, the record does not identify a dose that achieved the stated objective, quantify how close observed infant levels were to maternal levels, or describe the precision of an estimate. The stated objective is not itself evidence that the objective was achieved.
The single-group design also does not provide a direct comparison with an alternative intervention or with no intervention. In general, comparative effects require a defined contrast between groups or conditions. Even a numerical concentration result from a single group would describe observations among those participants; it would not, by itself, establish what would have occurred under another condition.
The registry records 18 enrolled participants, while the brief summary says 24 were intended. It does not explain the difference. It also records zero affected participants in the serious and other adverse event fields and zero deaths. Those counts should not be interpreted as a guarantee of safety or as comparative evidence. They are descriptive registry entries, with no reported uncertainty estimates or further event details.
Thus, the record is useful for identifying the question, design, population, and limited posted safety counts. It does not provide enough outcome information to assess the primary dose-finding result or its statistical precision. No conclusion about clinical benefit or lack of benefit follows from the absence of numerical endpoint findings in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable because its stated aim is a dose-finding question, while the recorded design is a single group and the posted record gives no dose-specific endpoint results. Dose-finding depends on observing how measurements relate to administered dose. Without dose levels, measurement details, and corresponding concentration results, readers cannot evaluate that relationship or determine how a dose was selected.
The endpoint is a concentration rather than a randomized between-group contrast. A median and full range can describe the distribution in a group, but they do not on their own provide a treatment effect estimate or a measure of statistical precision. The record gives the intended summary form and measurement unit, yet does not report the values needed to interpret the endpoint. This illustrates the difference between registering an outcome and reporting its results.
The record also distinguishes an intended enrollment of 24 in the brief summary from a recorded enrollment of 18. Sample size affects how much information is available, but the record does not explain this discrepancy or report a trial-specific sample-size justification. The planning assumptions described in the registry use an equal-allocation, two-arm framework, whereas the recorded study is single group. This highlights why planning illustrations must be kept separate from the actual design and cannot be treated as observed power or as evidence that the study had a particular ability to detect an effect.
Finally, the safety counts are simple descriptive entries without a comparator or uncertainty estimates. Their interpretation is limited to the counts recorded. Taken together, these features make the registry useful for understanding the study’s purpose and design, while leaving the central statistical result unavailable. The distinction between design information, planning assumptions, and reported findings is essential to an accurate reading.
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.
Several limitations specific to this trial follow directly from the information recorded. First, the primary outcome has no numerical result in the registry record. The median and full range are specified as the summary format, but neither is reported. Dose levels and dose-specific concentrations are also not reported, preventing assessment of the stated dose-finding objective.
Second, the study is single group, with allocation listed as not applicable and masking listed as none. There is no recorded comparator group. This limits the study’s ability to estimate a comparative effect and leaves no controlled basis for separating observed concentrations from other influences. The registry does not report whether any external or historical reference was used to judge similarity to maternal levels.
Third, the brief summary states an intended enrollment of 24, whereas recorded enrollment is 18. The reason for this difference is not reported in the registry record. The record also does not specify how many enrolled infants contributed primary outcome data, whether measurements were repeated, or how missing observations were handled.
Fourth, the analysis methods are not reported. There are zero analyses listed, and no estimates, confidence intervals, p-values, or model details are given. The sample-size note describes a two-arm planning illustration, which does not match the recorded single-group design; no trial-specific sample-size justification is reported.
Finally, the safety information consists of counts without event terms or uncertainty estimates. The duration and procedures for safety ascertainment are not reported. These gaps constrain interpretation of both efficacy-related measurements and safety, without establishing what methods or events may have existed outside the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study — NCT00649961.
- Registry record last updated 2019-08-20; status last verified 2019-08.
- Results first posted 2014-02-28.
- 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
This completed phase 2 study, sponsored by Imperial College London, examined melatonin injection in preterm infants in an open-label, single-group design. The registry gives enrollment as 18, while the brief summary states an intention to study 24 babies. The primary objective was to find a dose associated with blood melatonin levels similar to maternal physiological levels. The endpoint is specified as a median with a full range in pg/ml over a timeframe of 6 months.
The registry record does not report the primary endpoint values, dose-specific findings, or statistical analyses. It records 18 participants at risk and 0 affected for serious adverse events, 18 at risk and 0 affected for other adverse events, and 0 deaths. There is no comparator group, so the design does not provide a controlled treatment comparison. The posted record describes the study’s question and structure but does not provide enough numerical outcome information to determine the dose-finding result or its precision.