The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy (NCT00732654), a randomized phase 1, phase 2 study. The primary outcome is Change in CM-specific Immunogloblin E (IgE).

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 1 and phase 2 trial, listed as completed. It enrolled 30 participants. The registry records no masking, so participants and study personnel were not described as blinded. The study start is listed as 2008-08 and primary completion as 2010-06.

Three arms appear in the posted outcome information: SLIT, SLIT/OIT B, and SLIT/OIT A. SLIT is identified as the control group. The arm descriptions indicate that the SLIT group received escalating sublingual milk-protein extract followed by daily maintenance. The two SLIT/OIT groups began with sublingual extract and then switched to oral milk powder with dose escalation. The stated powder goal is 1000 mg for SLIT/OIT B and 2000 mg for SLIT/OIT A. The descriptions are incomplete in the registry record, and the listed intervention goals do not fully establish the dose assigned to every arm.

Randomization supports an intended comparison across the assigned approaches, but the method used to generate or conceal the allocation is not reported in the registry record. The planned sample-size rationale, eligibility criteria, recruitment setting, and protocol details are also not reported in the registry record. The posted primary outcome includes 10 participants in SLIT, 9 in SLIT/OIT B, and 9 in SLIT/OIT A. The registry notes that data were not collected for one participant in SLIT/OIT A. These outcome counts should not be taken as a complete account of every analysis population, because the population definitions 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: 33 patients underwent screening Double-Blinded Placebo-Controlled Food Challenges (DBPCFCs). Two subjects failed screening because they tolerated at least 2.5g at the initial DBPCFC. One subject declined to continue in the study after the food challenge. 30 subjects were randomized.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data was not collected for one participant in the SLIT/OIT A group.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in CM-specific Immunogloblin E (IgE), measured over Change from baseline to after therapy (up to 18 months).

The primary endpoint is the change in cow’s-milk-specific immunoglobulin E (IgE), measured in kUa/L from baseline to after therapy, with the timeframe described as up to 18 months. The registry reports each arm’s median change and full range. IgE is a laboratory measure associated with allergic sensitization; measuring its change gives a biological marker that can be compared across the immunotherapy groups. It is not, by itself, a direct measure of symptoms, reactions during food exposure, or the ability to consume milk.

The reported medians are 0.8 for SLIT, -13.5 for SLIT/OIT B, and -9.4 for SLIT/OIT A. The corresponding full ranges are -390 to 10, -170.8 to 471.7, and -49.1 to 42.1. The record does not provide a confidence interval or a test result for these group summaries. The ranges are wide relative to the medians, particularly in the two SLIT/OIT groups, so the central values alone do not describe how variable individual changes were. The registry’s outcome description specifies change from baseline, but does not give further detail about the timing of measurements within the stated follow-up period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is expressed as a median change, with a full range for each arm. A median is a measure of central location: after observations are ordered from lowest to highest, it identifies the middle value. Unlike a mean, it is less influenced by the magnitude of an extreme observation. It still provides only one summary of the distribution, and with small groups it may shift substantially when individual values change.

A full range reports the lowest and highest observed values. It makes the span of the data visible, but gives no information about how many participants had values near either endpoint or how values were distributed between them. A wide range can reflect heterogeneous participant responses, extreme observations, or both. General statistical reasoning also cautions that ranges are especially sensitive to sample size: they are not a substitute for a standard deviation, interquartile range, or confidence interval. Those additional summaries are not reported for the primary endpoint.

The arm medians are 0.8 for SLIT, -13.5 for SLIT/OIT B, and -9.4 for SLIT/OIT A. Their full ranges are -390 to 10, -170.8 to 471.7, and -49.1 to 42.1. Because the values include both directions of change, a negative median does not mean every participant’s value decreased. Nor does a median’s sign show whether a group difference is statistically reliable. The posted values are summaries of changes from baseline, not raw IgE concentrations at follow-up.

For a comparison between groups, an estimate of the difference and an uncertainty interval would help distinguish the size of the observed contrast from its precision. A confidence interval is a range of values produced by a statistical procedure that, under its assumptions, is designed to cover the underlying parameter at a stated rate in repeated samples. It expresses uncertainty about an estimate; it does not mean that the true value has a particular probability of lying within one specific interval. No confidence interval for a group contrast is reported in the registry record. No p-value or test statistic is reported either.

The choice of statistical method depends on the outcome distribution, the target comparison, and the analysis plan. General statistical practice may use a model or a rank-based procedure for skewed data, but the registry record does not specify a method for this endpoint. Over-dispersion is a general concern when variability exceeds what a model assumes. If a model understates variability, its uncertainty estimates can be too narrow and its tests can appear more decisive than warranted. The record does not report a model or a dispersion assessment, so neither can be attributed to this trial.

The design is randomized and parallel, with three listed groups and no masking. Randomization can reduce confounding on average, but it does not guarantee balance in a small trial. The registry does not describe the allocation-generation procedure, allocation concealment, or any adjustment for baseline characteristics. It is also not reported whether the primary comparison was an overall comparison among all groups or separate comparisons of each immunotherapy approach with SLIT.

The registry’s planning note describes a sample-size illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such an illustration is a planning exercise based on assumptions, not a report of the trial’s design justification and not observed power. The registry record does not report the trial’s sample-size justification or a prespecified effect size. The illustration’s assumptions also do not establish which comparison or endpoint the trial was designed to detect.

Interpretation should distinguish descriptive results from confirmatory inference. The posted medians and ranges describe observed changes. Without a reported analysis method, contrast estimate, or uncertainty interval, they do not quantify the precision of differences between approaches. The registry record does not report interim analyses or the statistical plan, so it is not possible to assess whether analysis choices were prespecified or whether other analyses were conducted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures, but posts no secondary outcome results and no analyses. The primary outcome is identified as change in cow’s-milk-specific IgE. The record does not report the full hierarchy of outcomes, the number of comparisons planned, or which outcomes were designated primary at the time of analysis. It also does not report whether any multiplicity adjustment was planned or used.

Multiplicity is a general statistical concern when many outcomes, time points, subgroups, or treatment contrasts are tested. As the number of tests increases, the chance of at least one apparently unusual result can increase if each test is interpreted without accounting for the broader set. Adjustment methods and interpretation depend on which tests were planned and on the inferential goal. Since the registry does not report the analysis plan or a set of inferential results, the multiplicity approach cannot be assessed.

The primary outcome population includes 10 participants in SLIT, 9 in SLIT/OIT B, and 9 in SLIT/OIT A. The registry explicitly states that outcome data were not collected for one participant in SLIT/OIT A. It does not explain why the data were missing, when they became unavailable, or how the participant was handled in any analysis. The analysis population definitions and missing-data methods are not reported in the registry record.

Missingness can matter when the probability of an unavailable measurement is related to the participant’s outcome or treatment experience. General statistical methods address this in different ways, but their appropriateness depends on why data are missing and on assumptions that cannot be checked from the posted summary alone. The record does not report a sensitivity analysis or an imputation method. It is therefore not possible to tell how alternative handling of the missing measurement would affect the endpoint summaries.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse-event counts are 0 affected among 10 at risk in each of the OITA, OITB, and SLIT groups. The registry does not list any serious adverse-event terms. These counts describe what is recorded for the groups; they do not establish that serious events were impossible or that the approaches have identical safety profiles. The registry record does not report the serious-event definition, observation period, event adjudication process, or a comparative statistical analysis.

For other adverse events, the registry reports 10 affected among 10 at risk in each group. These figures indicate that the record marks every participant at risk in each group as affected by at least one other adverse event. They do not provide event types, numbers of events per participant, severity, timing, or relatedness to an intervention. Death counts are not reported in the registry record.

Adverse-event counts are not direct comparisons of risk unless the groups’ follow-up and event capture are understood. The registry does not report those details, so the counts should be read as a limited description of recorded events rather than a complete assessment of comparative safety.

12. What the Result Does, and Does Not, Mean

The registry record documents a randomized study comparing sublingual-only milk-protein immunotherapy with two approaches that began sublingually and then moved to oral milk powder. The primary posted outcome is median change in cow’s-milk-specific IgE, with full ranges for the three groups. These summaries are useful for describing the observed measurements, but they do not supply a formal estimate of the difference between treatment approaches or the precision of such an estimate.

The medians differ in direction and magnitude, and the ranges include values on both sides of zero. This illustrates why a group median should not be interpreted as a uniform response among participants. The record does not report confidence intervals, hypothesis tests, or an analysis model for the outcome. It therefore does not establish whether the observed arm summaries are distinguishable beyond sampling variation. The study’s stated aim is not itself evidence that the aim was achieved.

The endpoint also has a limited clinical interpretation. It measures a laboratory marker, not symptoms, reactions to milk exposure, or demonstrated ability to consume milk. A change in IgE cannot be treated as proof of a change in clinical sensitivity. The registry record does not provide a direct clinical outcome result that would bridge that distinction.

The trial enrolled 30 participants and reports a missing primary outcome measurement for one participant in SLIT/OIT A. The reason for missingness and the analysis population are not stated. Without that information, the extent to which missing data could influence the reported summaries is uncertain. The adverse-event record reports zero serious events in each group and other adverse events in all participants marked at risk, but lacks event descriptions and comparative analyses.

Accordingly, the posted information supports a descriptive account of the enrolled groups, the IgE summaries, and the recorded adverse-event counts. It does not support a definitive conclusion about comparative efficacy, clinical tolerance, or relative safety. Those questions require outcomes and analyses beyond what the registry record reports.

13. Why This Trial Matters Statistically

This trial is statistically notable because it places three immunotherapy approaches in a randomized parallel-group design while reporting a laboratory endpoint as medians and full ranges. Those summaries make clear that central change alone is not a complete account of the observations. The ranges extend in both negative and positive directions, and the groups are small, so individual data and uncertainty around group comparisons matter.

The record also illustrates the difference between having a randomized design and having enough posted analysis to interpret a treatment contrast. Randomization is a design feature; it does not by itself show the magnitude or precision of an effect. Here, the registry does not report a contrast estimate, confidence interval, p-value, or analysis method for the primary endpoint. A reader can describe the observed summaries but cannot use them to judge formal evidence for a between-group difference.

Another statistical issue is the relationship between a biomarker and a clinical outcome. Cow’s-milk-specific IgE is the posted primary measure, while the stated objective concerns decreased sensitivity. Those are not interchangeable quantities. Clear reporting of both laboratory and clinically interpretable outcomes can help distinguish biological change from changes that matter directly to participants.

Finally, the record shows why complete reporting of analysis populations, missing-data handling, adverse-event definitions, and prespecified comparisons is important. One primary outcome measurement was not collected in SLIT/OIT A, yet the reason and handling are not given. The posted safety counts lack event descriptions. Such gaps constrain interpretation even when the study design and the observed summaries are available.

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 registry record provides limited detail on how the trial was conducted and analyzed. Although allocation is described as randomized, the random-sequence method and allocation concealment are not reported. Masking is listed as none. Eligibility criteria, baseline characteristics, recruitment details, and the sample-size justification are not reported in the registry record, limiting assessment of who participated and how representative the groups may be.

The arm descriptions are incomplete, and the intervention listing includes several dose goals without a complete mapping to all arms. The primary outcome is reported as a median and full range, but no group-comparison estimate, confidence interval, p-value, or analysis method is posted. The registry does not report the timing of each participant’s endpoint measurement beyond the general timeframe of up to 18 months.

One participant in SLIT/OIT A has no collected primary outcome data. The reason, missing-data strategy, and analysis population are not reported. The record lists 4 outcome measures but posts no secondary outcome results or analyses. Interim analyses and the statistical analysis plan are not reported.

The safety data are also limited: serious-event terms are absent, other adverse events are not described by type or severity, and death counts are not reported in the registry record. Follow-up duration for safety and event-collection procedures are not reported. These limitations do not alter the posted counts, but they restrict what can be inferred from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy — NCT00732654.
• Registry record last updated 2017-05-15; status last verified 2017-04.
• Results first posted 2017-05-15.
• 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.

18. Record Summary

NCT00732654 is a completed randomized, open-label, parallel-group phase 1 and phase 2 study sponsored by Johns Hopkins University. It enrolled 30 participants with milk allergy. The listed arms are SLIT, SLIT/OIT B, and SLIT/OIT A; the registry identifies SLIT as the control. The trial began in 2008-08, with primary completion in 2010-06.

The primary outcome is median change in cow’s-milk-specific IgE from baseline to after therapy, described as up to 18 months. The posted medians are 0.8, -13.5, and -9.4, respectively, with full ranges of -390 to 10, -170.8 to 471.7, and -49.1 to 42.1. Outcome data were not collected for one participant in SLIT/OIT A.

The registry reports 0 serious adverse events among 10 at risk in each group and 10 affected by other adverse events among 10 at risk in each group. It does not post analyses or secondary outcome results. The record does not report inferential comparisons for the primary outcome.