Persistence of Oral Tolerance to Peanut: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Persistence of Oral Tolerance to Peanut (NCT01366846), a non-randomized phase 2 study. The primary outcome is Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum.

2. Clinical Question

LEAP-On is described as evaluating whether tolerance persisted after a period without peanut consumption. The study followed participants who had consumed peanut and participants who had avoided it over the previous five years, then assessed outcomes after twelve months of cessation for the consumption group. That setup makes the earlier exposure history central to interpreting the comparison: the groups were not formed by random allocation in this study.

The primary classification used an oral food challenge at 72 months of age. Participants who did not react after the challenge were considered not to have peanut allergy. Participants who reacted were offered a double-blind, placebo-controlled challenge; a reaction during dose escalation classified them as having peanut allergy. When challenge data were inconclusive or unavailable, a diagnostic algorithm using skin prick test and peanut-specific IgE results was used.

The registry record does not report the primary outcome counts, a between-group effect estimate, or confidence intervals. It therefore supports describing the research question and endpoint, but not quantifying the primary result from the record.

3. Trial Design

ITN049AD, also called LEAP-On, is a completed phase 2 continuation study of ITN032AD, the LEAP study. The registry lists a parallel model, non-randomized allocation, and no masking. Enrollment is listed as 556. The study start is recorded as 2011-05 and primary completion as 2015-05.

The study addresses persistence of oral tolerance after a change in peanut exposure. According to the registry summary, participants who had consumed peanut during the previous five years stopped consuming it for twelve months. Participants who had avoided peanut continued avoidance. The intervention listing names avoidance of peanut, while the arm descriptions distinguish avoidance after continuous consumption from continued avoidance. These descriptions show why the groups should not be read as interchangeable arms: their histories before LEAP-On differed.

Because allocation was non-randomized, the comparison does not have the protection against baseline differences that random assignment is designed to provide. The record explicitly warns that the arms are not a like-for-like control comparison. Differences in observed outcomes could reflect prior group characteristics or other differences, as well as the exposure pattern being studied. The registry record does not report adjusted estimates or enough information to determine how such differences were handled analytically.

The primary endpoint is assessed at 72 months of age and is stratified by skin prick test status. The registry also lists secondary outcomes concerning peanut allergy at 60- and 72-month visits within the peanut avoidance after peanut consumption group, including a per-protocol population outcome. It lists six outcome measures and eight analyses, but detailed analysis specifications are not reported in the registry record.

The registry record gives a brief description of the earlier LEAP population and the study’s continuation purpose. It does not report a sample-size justification, the full eligibility criteria for LEAP-On, the recruitment process, or an account of masking procedures beyond the listing of no masking. The listed enrollment is not, by itself, evidence that all enrolled participants contributed data to the primary analysis.

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: In the LEAP trial, participants were stratified into strata based on a peanut allergen skin prick test (SPT). Participants were either SPT negative (0mm wheal) or SPT positive (1-4 mm wheal). Participants were then randomized into treatment groups within each stratum. This configuration was preserved in LEAP-On (this trial)

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat with available data at 72 months

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: Intent-to-treat

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum, measured over 72 months.

The primary endpoint is the number of participants classified as having peanut allergy at 72 months of age, reported by skin prick test stratum. It is a count outcome: it records how many participants in the analyzed population received the allergy classification, rather than measuring the severity of reactions or the time until an event.

The registry describes how classification was made. Participants first received an oral food challenge involving oral intake of 5g of peanut protein in a single dose. No reaction meant the participant was considered not to have peanut allergy. Those who reacted were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments; a reaction at any point during dose escalation meant the participant was considered to have peanut allergy. If challenge data were inconclusive or unavailable, a diagnostic algorithm based on skin prick test results and peanut-specific IgE values was used.

Using a defined challenge and classification procedure gives the endpoint a common clinical measurement basis across participants. The stratum reporting also makes the skin prick test grouping explicit rather than combining the listed strata into a single count. General statistical interpretation: counts are easiest to interpret alongside the number of participants contributing data in each group. The registry record does not report the primary counts or their denominators, so the endpoint’s observed results and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

LEAP-On uses a binary classification for the primary outcome: each participant with available outcome information is classified as having or not having peanut allergy at 72 months of age. The registry expresses the primary endpoint as a count of participants with peanut allergy, rather than as a continuous measurement. It specifies reporting by skin prick test stratum.

What does a count outcome represent?

A count tells the reader how many participants in a defined group met the outcome definition. It does not, by itself, show the chance of the outcome in that group. To interpret counts as proportions or compare the outcome frequency between groups, the corresponding denominators and an appropriate statistical estimate are needed. General statistical explanation: estimates of proportions or contrasts are more informative than raw counts when group sizes differ, because the same count can represent different frequencies in groups of different sizes.

The record does not give the primary counts or denominators by treatment history and stratum. It also does not state the primary effect measure or provide its uncertainty. It is therefore not possible to reconstruct an appropriate comparison from the registry description, and no new estimate should be inferred from enrollment or from the safety figures.

How was peanut allergy classified?

The primary assessment was an oral food challenge at 72 months of age. The registry states that participants received 5g of peanut protein in a single dose. If there was no reaction, the participant was classified as not having peanut allergy. Participants who reacted were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. A reaction at any point during dose escalation resulted in classification as having peanut allergy.

For participants whose challenge information was inconclusive or unavailable, the registry describes a diagnostic algorithm using skin prick test results and peanut-specific IgE values. This is a rule for outcome classification in those circumstances. The detailed algorithm, its decision thresholds, and the number of participants assessed through it are not reported in the registry record. It is not possible to determine how frequently this fallback procedure was used or whether its classifications differed from challenge-based classifications.

What does intent-to-treat with available data mean in this record?

The primary population is described as intent-to-treat with available data at 72 months. The wording signals that the outcome analysis was tied to the intended analysis population while also requiring outcome information to be available. It does not establish that every participant enrolled had an observed outcome. The record does not report the number missing, the reasons for missing primary outcome data, or a full missing-data procedure for the primary analysis.

General statistical explanation: missing outcome information can affect both the precision of an estimate and its interpretation, especially if availability is related to participants’ characteristics or outcomes. The registry’s diagnostic algorithm addresses inconclusive or unavailable challenge information for classification, but it does not explain how participants with no usable classification were treated in the analysis. Nor does it report sensitivity analyses for missing outcomes.

Why does non-randomized allocation matter?

The registry lists allocation as non-randomized and states that the arms are not a like-for-like control comparison. The groups had different prior exposure histories: one had consumed peanut during LEAP and then avoided it during LEAP-On; the other had avoided peanut and continued avoidance. In a randomized study, allocation is intended to balance measured and unmeasured baseline characteristics on average. In a non-randomized comparison, group differences may remain and can complicate causal interpretation.

General statistical explanation: adjustment for measured characteristics can sometimes address observed differences, but it cannot guarantee that unmeasured differences have been removed. The registry record does not report an adjusted primary analysis, the variables used for adjustment, or a causal analysis plan. It is therefore not appropriate to describe the group comparison as a randomized treatment effect.

What can be said about statistical planning?

The planning illustrations associated with the posted results use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They are based on a stated fraction of the observed effect. Such illustrations describe planning scenarios under those assumptions; they are not observed power and do not establish the probability that the study detected an effect. The registry record does not report a sample-size justification from the trial’s own design or enough detail to determine whether the planning illustrations reflect its original statistical plan.

General statistical explanation: a confidence interval communicates uncertainty around an estimate, while a p-value addresses compatibility between data and a specified null model under stated assumptions. Neither should be interpreted without the analysis definition and data context. The primary confidence interval and p-value are not reported in the registry record. The number of analyses is listed as eight, but the specific hypotheses, analysis hierarchy, and statistical methods for those analyses are not reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Negative Stratum - Peanut Avoidance Group", "Negative Stratum - Peanut Consumption Group", "Positive Stratum - Peanut Avoidance Group", "Positive Stratum - Peanut Consumption Group")
n      <- c(234, 224, 46, 46)
events <- c(34, 7, 18, 6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Negative Stratum - Peanut Avoidance Group  234  34  14.5  10.3  19.7  10.6  19.6  10.6  19.6
ARM  Negative Stratum - Peanut Consumption Group  224  7  3.1  1.3  6.3  1.5  6.3  1.5  6.3
ARM  Positive Stratum - Peanut Avoidance Group  46  18  39.1  25.1  54.6  26.4  53.5  26.4  53.6
ARM  Positive Stratum - Peanut Consumption Group  46  6  13.0  4.9  26.3  6.1  25.7  6.2  25.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and eight analyses. It identifies the primary endpoint and names secondary outcomes concerning peanut allergy at 60- and 72-month visits within the peanut avoidance after peanut consumption group, including an outcome in the per-protocol population. However, the registry record does not report a multiplicity strategy, such as a prespecified hierarchy, adjustment to control family-wise error, or a distinction between confirmatory and exploratory analyses. Without those details, the listed analyses should not automatically be treated as independent confirmation of a finding.

The primary population is described as intent-to-treat with available data at 72 months. The record does not report how many participants lacked primary outcome data, why information was unavailable, or how missing outcomes were handled in the primary analysis. For inconclusive or unavailable challenge data, it describes a diagnostic algorithm based on skin prick test and peanut-specific IgE results. It does not provide the algorithm’s detailed rules or the number of classifications made using that approach.

The phrase intent-to-treat with available data should not be read as evidence that every enrolled participant contributed a primary outcome. Nor does the registry description establish a particular imputation method or missing-data assumption. The per-protocol population is named for a secondary outcome, but the criteria defining that population are not reported in the registry record.

The record also does not report interim analyses, stopping rules, or a detailed statistical analysis plan. The planning illustrations use stated assumptions and should not be confused with those missing design details. These omissions limit assessment of how missing data, multiple outcomes, or analysis choices could affect the reported findings.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaphylactic reaction (4.3%), asthma (2.1%), wheezing (1.3%), tonsillitis (0.4%), thermal burn (0.4%).

The registry safety listing separates serious adverse events from other affected participants and reports the groups by negative or positive stratum and prior peanut exposure history. In the negative-stratum peanut avoidance group, 235 participants were listed as at risk and 12 as affected by serious adverse events; 206 were listed as affected by other events. In the negative-stratum peanut consumption group, the corresponding figures are 228 at risk, 7 with serious adverse events, and 182 with other events.

In the positive-stratum peanut avoidance group, the listing gives 47 at risk, 3 with serious adverse events, and 45 with other events. In the positive-stratum peanut consumption group, it gives 46 at risk, 2 with serious adverse events, and 38 with other events. These are the registry’s group-level counts; they are not the primary peanut allergy endpoint. The listed serious adverse event terms include Anaphylactic reaction at 4.3%, Asthma at 2.1%, Wheezing at 1.3%, Tonsillitis at 0.4%, Thermal burn at 0.4%, and Synovitis at 0.4%. The denominator and calculation basis for those term percentages are not reported in the registry record.

These figures should be read as descriptive safety data, not as a randomized comparison of risks. Allocation was non-randomized, and the registry cautions that the arms are not like-for-like controls. Death counts are not reported in the registry record. The listing does not establish a causal relationship between any event and peanut exposure.

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

The record establishes the study’s purpose, design, primary outcome definition, and selected safety counts. LEAP-On examined peanut allergy after participants with prior peanut consumption stopped consuming peanut for twelve months, while participants with prior avoidance continued avoidance. The primary endpoint was the number classified as having peanut allergy at 72 months of age, with results intended to be reported by skin prick test stratum.

The primary outcome counts and their denominators are not reported in the registry record. Neither an effect estimate nor its confidence interval or p-value is reported. Therefore, the record does not show the observed primary result’s direction, magnitude, or precision. It also does not support a statement about whether the primary comparison met a statistical significance threshold.

Even if the primary counts were available, the non-randomized design would remain important. The groups entered LEAP-On with different peanut exposure histories, and the registry explicitly warns that they are not a like-for-like control comparison. A difference between groups could reflect prior exposure or other characteristics as well as the exposure period under study. The registry record does not report an adjustment strategy that would resolve this concern.

The challenge and diagnostic procedures provide a defined way to classify allergy status. They do not answer questions about how representative the analyzed participants were, how missing outcomes affected results, or whether findings generalize beyond the study population. The record gives a brief account of the earlier LEAP population, but detailed LEAP-On eligibility and participant characteristics are not reported.

The safety counts describe serious and other adverse events in the listed groups. They should not be substituted for the primary outcome, interpreted as a randomized safety contrast, or used to infer causation. Overall, the registry record permits a careful account of what the study set out to measure and how it classified the outcome, but its reported information is insufficient to quantify the primary comparison or make a causal claim about the effect of stopping peanut consumption.

14. Why This Trial Matters Statistically

This study raises an important statistical distinction between observing an outcome after exposure changes and estimating the causal effect of that change. LEAP-On followed groups with different histories: participants who had consumed peanut and then avoided it, and participants who had avoided peanut throughout. Because allocation was non-randomized, the comparison carries the potential for group differences beyond the exposure period being examined. Recognizing that design feature is essential when interpreting any group contrast.

The endpoint also illustrates how clinical classification can combine direct challenge results with an algorithmic fallback. The registry specifies oral food challenge procedures and describes use of skin prick test and peanut-specific IgE information when challenge data were inconclusive or unavailable. That makes the outcome definition more informative than a simple label alone, while leaving unanswered how often the fallback was needed and how the algorithm classified particular cases.

Stratification is another important feature. The primary endpoint is reported by skin prick test stratum, which signals that the analysis distinguishes groups rather than presenting only a pooled count. Without the primary counts, denominators, and analysis details, readers cannot assess how the strata contributed to the overall evidence or how precise any comparison was.

The registry record also shows why outcome availability and analysis populations matter. The primary population is described as intent-to-treat with available data, while a secondary outcome is identified for a per-protocol population. These labels refer to different analytic populations, but the record does not provide their detailed definitions or the extent of missing outcome information. Statistical interpretation depends not only on how an endpoint is defined, but also on who contributes data and how incomplete information is handled.

Finally, planning illustrations should be distinguished from observed evidence. Their assumptions describe hypothetical planning scenarios and do not replace the trial’s own design justification or an estimate with uncertainty. Taken together, these features make LEAP-On useful for understanding endpoint construction and design limitations, while the absent primary results constrain what can be concluded from the registry record.

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 principal trial-specific limitation for interpreting the registry record is the non-randomized comparison. The peanut avoidance after consumption and continued avoidance groups reflect different prior exposure histories. The record explicitly states that they are not a like-for-like control comparison. This limits causal interpretation even if outcome counts are available elsewhere.

The primary outcome results are not reported in the registry record. Counts by skin prick test stratum, group denominators, effect estimates, and measures of uncertainty are absent in the registry record. The record therefore does not permit a quantitative interpretation of the primary endpoint. The analysis population is described as intent-to-treat with available data, but participant availability and the handling of missing primary outcomes are not detailed.

The registry describes an oral food challenge and a diagnostic algorithm for inconclusive or unavailable challenge information. It does not report the algorithm’s thresholds, how often it was used, or information that would allow comparison of challenge-based and algorithm-based classifications. The detailed definition of the skin prick test strata is also not reported in the registry record.

Although secondary outcomes are named, their results and analysis methods are not available in the registry record considered. The registry lists six outcome measures and eight analyses, but does not describe multiplicity control, an analysis hierarchy, interim analyses, or the statistical analysis plan. It also does not report the original sample-size justification. These omissions limit evaluation of selective analysis, precision, and the relationship between planning and reported outcomes.

The safety listing is descriptive, and the non-randomized design also constrains comparisons of adverse events. Death counts are not reported in the registry record, and the basis for the listed serious adverse event term percentages is not specified. These limitations should be kept distinct from the primary endpoint limitations: the safety data do not fill the gap in the primary allergy results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Persistence of Oral Tolerance to Peanut — NCT01366846.
• Registry record last updated 2017-03-10; status last verified 2017-01.
• Results first posted 2017-01-06.
• 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.

19. Record Summary

ITN049AD, titled Persistence of Oral Tolerance to Peanut and also known as LEAP-On, is a completed phase 2 continuation study of ITN032AD (LEAP). The registry lists enrollment of 556, non-randomized allocation, no masking, and a parallel model. Its purpose was to assess peanut allergy after participants who had consumed peanut stopped for twelve months, with a continued-avoidance group as the comparison.

The primary outcome is the number of participants with peanut allergy at 72 months of age, classified by oral food challenge or, when challenge data were inconclusive or unavailable, a diagnostic algorithm using skin prick test and peanut-specific IgE. The population is described as intent-to-treat with available data at 72 months.

The primary outcome counts and statistical comparison are not reported in the registry record. The record cautions that the arms are not a like-for-like control comparison. It lists secondary outcomes and descriptive adverse-event counts, but those do not provide the missing primary result or establish a causal effect.