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 Time-limited Specific Oral Tolerance Induction in Children With Severe Egg Allergy (NCT01379651), a randomized phase 1, phase 2 study. The primary outcome is Number of Children That Achieved Total (40 ml) or Partial (Less Than 40 ml But at Least 10 ml) Tolerance to Raw Egg.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01379651 |
| Phase | Phase 1, Phase 2 |
| Condition | - Egg Hypersensitivity |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Ospedale Buon Consiglio Fatebenefratelli |
| Results posted | Yes |
2. Clinical Question
Population
Children with severe IgE-mediated egg allergy and a history of at least 1 anaphylactic reaction after accidental exposure to egg. The registry record gives a total enrollment of 20 participants.
Intervention
Specific oral tolerance induction, described as administration of increasing amounts of food antigen. The stated protocol duration was 6 months.
Comparator
Control participants were kept on an egg-free diet for 6 months. The registry record lists 10 participants in each group.
Primary question
At baseline and 6 months, how many children achieved total tolerance to raw egg, defined as tolerating 40 ml, or partial tolerance, defined as tolerating less than 40 ml but at least 10 ml?
The question is about a measured level of tolerance to raw egg emulsion after the protocol, rather than about a broader clinical outcome. In the posted results, the primary measure counts participants meeting either the total- or partial-tolerance threshold. The registry description frames the study as evaluating whether a 6-month specific oral tolerance induction protocol induces tolerance in children with a severe allergy history.
The control group supplies a comparison with an egg-free diet over the same stated period. Comparing the groups can help distinguish the observed result in the induction group from the result under the control condition. The registry record identifies randomized allocation, but its study-model classification is single-group despite listing both an induction group and a control group. That classification inconsistency is relevant when interpreting how the record describes the study.
3. Trial Design
The registry record describes a randomized trial with no masking. It lists phase 1 and phase 2, an enrollment of 20, and a completed status. The study began in 2008-01, and primary completion was recorded as 2010-06. The listed sponsor is Ospedale Buon Consiglio Fatebenefratelli.
Two groups are reported, each with 10 participants. The specific oral tolerance induction group received increasing amounts of food antigen; the control group was kept on an egg-free diet for 6 months. The primary outcome timeframe is baseline and 6 months, and its unit is participants. The record describes the intended primary measure as the number achieving total or partial tolerance to raw egg.
The record has an internal design-description mismatch: allocation is recorded as randomized and the title identifies a randomized controlled trial, while the model is recorded as single-group. It also lists a control group and results for both groups. The registry record does not explain this mismatch, so its classification cannot be reconciled from the posted information alone.
No masking was used, so participants and study personnel were not blinded according to the registry entry. The record does not report further details about how the random sequence was generated, how assignment was concealed, or whether outcome assessment was blinded. Those design details should not be inferred from the randomized designation alone.
The record lists one secondary outcome concerning changes in median weal diameter using egg white skin prick tests, end-point skin prick testing, and PP. A total of two outcome measures is reported, but the record lists one secondary outcome. It reports no analyses. The protocol, detailed statistical plan, and explanation of the outcome-measure count are not reported in the registry record.
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: 6 children(4 males and 2 females)were excluded from the study: one child because the parents had a history of unreliable management of complications and treatments;2 children because of poorly controlled asthma;3 children because of a positive double-blind placebo-controlled food challenge (DBPCFC) at a dose of raw egg emulsion higher than 0.9 ml.
Overall Study
| Stage | Specific Oral Tolerance Induction | Control |
|---|---|---|
| STARTED | 10 | 10 |
| COMPLETED | 10 | 10 |
| NOT COMPLETED | 0 | 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.
| Characteristic | Unit | Specific Oral Tolerance Induction | Control | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 10 | 20 | |
| Age, Categorical: <=18 years | Participants | 10 | 10 | 20 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | years | 7.033 (SD 1.768) | 7.676 (SD 3.203) | 7.354 (SD 2.607) |
| Sex: Female, Male: Female | Participants | 5 | 5 | 10 |
| Sex: Female, Male: Male | Participants | 5 | 5 | 10 |
| Region of Enrollment: Italy | participants | 10 | 10 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Children That Achieved Total (40 ml) or Partial (Less Than 40 ml But at Least 10 ml) Tolerance to Raw Egg, measured over baseline and 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts children who achieved either total or partial tolerance to raw egg. Total tolerance was defined as tolerating 40 ml of raw egg emulsion; partial tolerance was defined as tolerating less than 40 ml but at least 10 ml. The endpoint is therefore a binary participant-level measure: a child either meets one of the stated tolerance thresholds or does not.
The registry describes assessment at baseline and 6 months. The outcome description focuses on the maximal dose of raw egg emulsion tolerated after 6 months, making the endpoint a way to summarize a dose-based challenge result as a count of participants who reach a specified threshold. This can make group results easier to compare than reporting each participant’s tolerated dose separately, although it also discards detail about differences among participants who fall on the same side of the threshold.
The endpoint is used to address the trial’s stated question about induction of tolerance during the protocol. Its interpretation depends on the threshold definitions and the assessment process. The registry record does not report additional detail about challenge procedures, measurement reliability, assessor training, or how borderline results were handled. It also does not explain how baseline results were incorporated into the primary analysis beyond identifying baseline and 6 months as the timeframe.
7. Results Posted in the Registry
- Specific Oral Tolerance Induction: 90.0% (9/10) versus 0.0% (0/10) on control; risk difference 90.0 percentage points (95% CI 71.4 to 108.6); unadjusted two-proportion z-test p = <0.001.
Risk difference: Specific Oral Tolerance Induction
95% CI: 71.4 to 108.6 percentage points
Recalculated from the posted summary statistics
8. Statistical Interpretation
At 6 months, the specific oral tolerance induction group had 9 participants recorded as achieving total or partial tolerance, while the control group had 0. Each group contained 10 participants. The posted risk-difference estimate is 0.9, with a confidence interval from 0.714 to 1.086, and the posted p-value is <0.001.
The risk difference expresses the contrast between the observed proportions meeting the endpoint in the two groups. Its positive direction corresponds to more participants meeting the endpoint in the induction group than in the control group. The posted estimate describes a large observed separation in this small trial, but it is an estimate from the enrolled participants, not a guarantee that the same contrast would occur in other settings.
The interval indicates uncertainty around the estimated contrast. Its lower end remains above no difference, while its upper end extends beyond the range that a difference between two proportions can take. That feature means the interval should not be read as a fully plausible range on the original risk-difference scale. The registry record does not report the confidence-interval method, so the reason for this boundary behavior cannot be established from the record alone.
The p-value is reported as <0.001. In general, a p-value describes how compatible data are with a specified null model under its assumptions; it is not the probability that the null hypothesis is true, nor does it describe the magnitude or clinical importance of an effect. The null model and exact test procedure used for this posted p-value are not reported in the registry record.
The primary outcome is based on a threshold. Participants who reach the total or partial threshold count as having the endpoint, while the recorded count does not reveal the distribution of tolerated doses within each group. The posted result therefore supports a comparison of endpoint counts, but not a detailed account of how far individual participants progressed along the dose scale.
The registry record’s randomized designation makes a between-group comparison relevant, but the single-group model label creates an unresolved inconsistency in the description. No analyses are listed, and the record does not provide an adjusted estimate, a detailed analysis population, or a statistical analysis plan. Interpretation should remain tied to the posted group counts and comparison rather than assume undocumented methods or design details.
9. Statistical Methods Explained
What kind of outcome is this? The primary endpoint counts participants who meet a stated tolerance threshold. This is a binary outcome at the participant level: the endpoint is either recorded as achieved or not achieved. For a binary endpoint, group summaries can be expressed as counts and proportions, and a comparison can describe the difference between groups. The posted results give group counts and a risk-difference estimate.
What does the risk difference describe? In general, a risk difference subtracts the event proportion in one group from the event proportion in another. It is an absolute contrast on the proportion scale, rather than a relative measure. The posted estimate is 0.9. In this trial, the outcome being counted is meeting either the total- or partial-tolerance definition. The estimate summarizes the observed separation between the groups, but it does not describe the tolerated dose among participants who met the endpoint.
How should the p-value be read? The posted p-value is <0.001. In general, a p-value evaluates how unusual the data would be under a specified null model and its assumptions. It is not the probability that the null is true, and it is not a measure of the size of the group contrast. The test used to obtain the posted p-value, including whether it was exact or based on an approximation, is not reported in the registry record. The result should therefore be quoted as posted without assigning it to a particular test procedure.
What does the confidence interval add? A confidence interval describes uncertainty in an estimate under the procedure used to construct it. In repeated use, a method with a stated confidence level is intended to produce intervals that cover the underlying parameter at that rate, assuming its conditions hold. The posted interval is 0.714 to 1.086. It expresses uncertainty around the reported risk difference, but its upper endpoint exceeds the possible range for a difference between proportions. The interval method is not reported in the registry record, so the interval’s behavior and suitability cannot be assessed further from the posted information.
Why do small group counts matter? General statistical principle: estimates based on small numbers of participants can be sensitive to the outcome of a single participant. Small samples also tend to leave considerable uncertainty about the range of results that might occur in a broader population, even when the observed groups are sharply separated. The trial reports 10 participants per group. That context matters when reading both the counts and the precision estimate; the observed difference should not be treated as a stable population value solely because the p-value is small.
What role does randomization play? General statistical principle: random assignment aims to make comparison groups similar, on average, in factors that could affect outcomes. It can support causal interpretation when allocation is implemented as intended and the analysis respects the design. The registry record labels allocation randomized, but does not report sequence generation or concealment details. It also labels the model single-group despite listing a control arm. These details leave uncertainty about the design description and implementation; they should not be filled in by assumption.
What does no masking imply? The record lists masking as none. In general, lack of masking can allow expectations or knowledge of group assignment to affect participant behavior, care, reporting, or outcome assessment. This is especially relevant when an outcome involves an assessment process, though the registry does not report how the raw-egg tolerance measurement was conducted or who assessed it. The record does not report steps used to limit possible assessment or reporting influences.
What is known about the analysis plan? The record lists no analyses. It does not report a statistical analysis plan, a prespecified testing hierarchy, covariate adjustment, handling of missing outcomes, or a definition of analysis populations. The primary outcome’s timeframe and threshold definitions are available, but the analytic details are not. The posted comparison can be described, while the process that produced it cannot be reconstructed from the registry record.
What about planning calculations? The accompanying planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is a stated fraction of the observed effect. Such calculations are hypothetical planning exercises, not observed trial outcomes and not observed power. The record does not report the trial’s own sample-size justification, so the illustration should not be mistaken for the design basis of this study.
Why can over-dispersion matter in general? Over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors and uncertainty estimates too small if the model does not allow for the extra variability. This trial’s endpoint is a participant count, and the registry does not report a model-based analysis or an over-dispersion assessment. The concept is relevant generally, but there is no basis to claim that over-dispersion was present or that it affected the posted result.
10. Confidence Intervals and Precision
The reported risk-difference estimate is 0.9, and its confidence interval is 0.714 to 1.086. The interval indicates uncertainty around the estimated group contrast. Its lower endpoint is above no difference, while its upper endpoint is beyond the possible range for a difference between two proportions. This is a caution about the interval’s scale, not a reason to alter the posted estimate or replace the interval with a newly calculated one.
In general, confidence intervals communicate both the direction and precision of an estimate under a particular statistical method. A relatively narrow interval can indicate greater precision than a wide one, but precision is not the same as freedom from bias. The interval method and confidence level are not reported in the registry record, so the interval’s coverage properties cannot be verified from the posted material.
The group counts are 9 of 10 in the induction group and 0 of 10 in the control group. With groups of this size, individual outcomes have a substantial influence on the observed proportions. The result is clearly separated in the enrolled participants, but the limited enrollment constrains how precisely the result can characterize a broader population.
The p-value of <0.001 addresses compatibility with a null model, not the precision or transportability of the effect estimate. It does not resolve the interval’s out-of-range endpoint or supply missing methodological details. The confidence interval and p-value answer different statistical questions and should be read alongside the group counts.
11. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome and one secondary outcome concerning changes in median weal diameter using egg white skin prick tests, end-point skin prick testing, and PP. It reports two outcome measures in total, while the entry lists one secondary outcome. The record does not explain the difference between those counts or describe how the outcomes were analyzed.
Multiplicity arises when several outcomes, time points, or statistical comparisons are examined. In general, the more tests considered, the greater the chance that at least one result may appear notable by chance if no adjustment or prespecified hierarchy is used. Whether any multiplicity adjustment was planned or applied is not reported in the registry record. The posted p-value should not be described as adjusted or unadjusted based on information not recorded there.
The record lists no analyses. It does not report whether outcomes were prespecified in a protocol or analysis plan, how many comparisons were conducted, or whether any subgroup analyses were planned. Without those details, the full multiplicity context cannot be assessed.
Missing-data handling and analysis populations are also not reported in the registry record. The record gives 10 participants in each group and outcome counts for those groups, but it does not state whether all enrolled participants were assessed at 6 months, how any unavailable measurements were handled, or whether the analysis followed randomized assignment. No imputation approach, exclusion rules, or sensitivity analysis is described. These omissions limit assessment of possible bias from missing outcome data and the exact population represented by the comparison.
12. 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 |
|---|---|---|---|
| Specific Oral Tolerance Induction | 0 | 10 | 0.0% |
| Control | 0 | 10 | 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 |
|---|---|
| Specific Oral Tolerance Induction | 10 of 10 |
| Control | 3 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Specific Oral Tolerance Induction | Control |
|---|---|---|---|
| Allergic reaction | Immune system disorders | 10 of 10 | 3 of 10 |
The registry reports serious adverse events for 0 of 10 participants in the specific oral tolerance induction group and 0 of 10 in the control group. It separately records other adverse events for 10 of 10 participants in the induction group and 3 of 10 in the control group. These categories are distinct in the registry entry and should not be combined.
The serious adverse event counts describe what was recorded during the study, not the full range of possible safety outcomes. The registry lists no serious adverse event terms. Death counts are null, so deaths are not reported in the registry record; a null entry should not be interpreted as a confirmed count of zero. The timeframe and collection procedures for these adverse-event figures are not reported in the registry record.
In general, safety counts in small groups are descriptive and may be imprecise. A count of zero serious adverse events does not establish that an event cannot occur, and the difference in recorded other adverse events does not by itself explain event type, severity, timing, or relation to the intervention. Those details are not reported in the registry record. These figures should be read as recorded counts for the enrolled groups, not as a complete characterization of safety.
13. What the Result Does, and Does Not, Mean
The posted result shows that 9 participants in the specific oral tolerance induction group met the total- or partial-tolerance endpoint, compared with 0 in the control group, with 10 participants in each group. The estimated risk difference is 0.9, and the reported p-value is <0.001. These figures describe the observed primary outcome in this trial.
The finding does not establish how the result would generalize beyond the enrolled children, who were described as having severe IgE-mediated egg allergy and a history of at least 1 anaphylactic reaction after accidental exposure. The registry record does not report enough detail to assess representativeness or to compare the enrolled group with other populations. The result should remain attached to the stated population, intervention, control condition, and 6-month timeframe.
The endpoint is a threshold-based measure. It does not reveal each participant’s tolerated dose, the pattern of change over time, or whether tolerance persisted beyond the stated assessment period. The record describes the endpoint at baseline and 6 months but does not report longer-term follow-up or additional details about individual outcomes.
The posted data also do not establish a full safety profile. Serious adverse event counts were 0 in each group, while other adverse events were recorded for 10 participants in the induction group and 3 in the control group. Event descriptions and collection details are not reported in the registry record, and the death entries are not reported.
Finally, the record does not report its statistical analysis plan, missing-data approach, allocation-concealment process, or detailed outcome-assessment procedures. The reported result is a useful account of the observed group contrast, but these omissions and the single-group versus randomized-control classification mismatch constrain how confidently design and analysis details can be interpreted. The statistics alone do not establish a broader clinical conclusion.
14. Why This Trial Matters Statistically
This trial illustrates how a small randomized study can report a striking contrast in a binary endpoint while still leaving important questions about precision and interpretation. The primary result is easy to state in participant counts: 9 of 10 in the induction group met the tolerance threshold, compared with 0 of 10 in the control group. Counts make the observed data transparent, while the risk difference gives an absolute summary of the contrast.
The interval is also instructive. Its upper endpoint, 1.086, exceeds the possible range for a difference between proportions. This draws attention to the importance of checking whether an uncertainty interval is coherent on the scale of the estimate, rather than relying only on the reported p-value. The registry record does not identify the method used, so the interval’s construction cannot be evaluated further.
The record also demonstrates why registry design fields should be read together. Randomized allocation and a randomized controlled title appear alongside a single-group model classification, even though both a control group and its results are listed. Recognizing that mismatch prevents a reader from silently assuming that every design field is consistent or fully documented.
Finally, the absence of a listed analysis plan, missing-data approach, and detailed safety information distinguishes the observed result from a complete statistical account. These limitations do not erase the reported counts; they define what can responsibly be concluded from them. The trial is a useful example of interpreting effect estimates alongside design documentation, endpoint definitions, and reporting gaps.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The enrollment was 20, with 10 participants in each group. The registry record does not report a sample-size justification, so it is not possible to determine the planned precision or rationale for enrollment from the record. Any planning illustration based on the observed effect is a hypothetical calculation and should not be treated as the study’s original design justification or as observed power.
The design description is internally inconsistent: allocation is listed as randomized, but the model is listed as single-group, while both an intervention group and a control group are reported. The record does not explain the classification. It also does not report sequence-generation or allocation-concealment details, making it impossible to assess those aspects of the randomization process.
Masking is listed as none. The record does not describe outcome-assessment procedures or safeguards against possible influence on assessment and reporting. The outcome is based on the maximal tolerated dose and threshold categories, but details about challenge conduct and handling of borderline measurements are not reported in the registry record.
No analyses are listed. Statistical methods, analysis populations, missing-data handling, and any multiplicity strategy are not reported in the registry record. The primary outcome is identified at baseline and 6 months, but the analytic use of baseline measurements is not specified. The posted confidence interval also extends beyond the possible range for a difference between proportions, and its method is not reported.
Safety reporting is limited to event counts. Serious event terms are absent, other event descriptions are not reported, and death values are null. The record does not give the adverse-event observation period or collection procedures. Longer-term outcomes and persistence of tolerance are not reported in the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Time-limited Specific Oral Tolerance Induction in Children With Severe Egg Allergy — NCT01379651.
- Registry record last updated 2011-09-20; status last verified 2011-09.
- Results first posted 2011-08-30.
- 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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19. Record Summary
NCT01379651 is a completed phase 1 and phase 2 study titled “Time-limited Specific Oral Tolerance Induction in Children With Severe Egg Allergy.” It lists randomized allocation, no masking, enrollment of 20, and a single-group model classification. The listed sponsor is Ospedale Buon Consiglio Fatebenefratelli.
The intervention was specific oral tolerance induction using increasing amounts of food antigen. Controls were kept on an egg-free diet for 6 months. The primary endpoint counted participants achieving total tolerance at 40 ml or partial tolerance at less than 40 ml but at least 10 ml.
The posted primary result was 9 of 10 participants meeting the endpoint in the induction group and 0 of 10 in the control group. The risk-difference estimate was 0.9, with a confidence interval of 0.714 to 1.086 and p < 0.001. The record lists one secondary outcome, no analyses, and limited methodological and safety details.