Follow up of LEAP Participants and Their Families: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Follow up of LEAP Participants and Their Families (NCT03546413), a registered phase not stated study. The primary outcome is Percentage of LEAP Participants With Peanut Allergy.

2. Clinical Question

3. Trial Design

LEAP Trio (ITN070AD), registered as NCT03546413, is described as a prospective, cross-sectional follow-up of LEAP Participants and their families. Its stated purpose was to improve understanding of whether early-life peanut introduction may promote maintenance of tolerance in adolescence, and to serve as an additional safety evaluation of the original nutritional intervention. The record lists an enrollment of 1868. The study started on 2018-07-05, reached primary completion on 2022-08-31, and has status COMPLETED.

The study includes LEAP Participants, their younger and older siblings, and their parents. Each family group is labelled according to whether the LEAP Participant was originally randomized in LEAP to Peanut Avoidance or Peanut Consumption. Those labels describe the history of the original LEAP assignment. For LEAP Trio, allocation is not stated in the registry record, and the record cautions that the arms are not a like-for-like control comparison. The follow-up should therefore be understood as an observational assessment organized around prior assignment, rather than as a new randomized treatment comparison.

The primary endpoint concerns peanut allergy status among LEAP Participants at Visit 144. The record also lists outcomes concerning weekly peanut protein consumption, skin prick test wheal size, peanut-specific IgE, eczema severity and prevalence, asthma, and rhinitis. These outcomes cover both clinical conditions and measurements relevant to peanut allergy assessment. The registry record does not report the analysis methods used for those outcomes, the number of participants with usable data for each one, or the results of the primary or secondary analyses. Enrollment is not the same as the number contributing to a particular endpoint.

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.

Only the first 6 of 8 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All LEAP Trio participants in the LEAP Participant cohort for whom data was available to make a determination of peanut allergy status at LEAP Trio Visit 144.

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: All LEAP Trio enrolled participants

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of LEAP Participants With Peanut Allergy, measured over Assessments were performed on consented LEAP Participants at the time of the LEAP Participant's Visit 144 (when the LEAP Study (NCT00329784) Participant was approximately 12 years old (age approximately 144 months))..

The primary endpoint is the percentage of LEAP Participants with peanut allergy at LEAP Trio Visit 144. It is intended to describe allergy status at the follow-up assessment, among participants for whom the record says data were available to make that determination. The registry record does not report the endpoint value, its uncertainty, or a comparison between the original Peanut Avoidance and Peanut Consumption groups.

Peanut challenge was used to determine allergy status where possible. Participants meeting criteria for peanut oral allergy syndrome without primary peanut allergy were not considered peanut allergic. A participant was considered peanut tolerant if they reported consuming at least 2 g of peanut protein without reaction on at least one occasion in the last year. If oral challenge was not possible and the tolerance criteria were not met, status was determined using an internally and externally validated prediction model. The model used peanut wheal size and peanut-specific IgE measurements, including Ara h1, Ara h2, and Ara h3.

As a general statistical matter, a percentage expresses the frequency of an outcome in a defined population. Its interpretation depends on a clear outcome definition and on knowing which participants contributed data. Here, the stated criteria make the endpoint definition more specific than a simple report of allergy history. However, the registry record does not report how many participants were assessed, how many had indeterminate status, or the resulting percentage. Without those results, neither the magnitude nor the precision of the endpoint estimate can be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the primary outcome as a percentage of participants with an event: in this case, the percentage of LEAP Participants classified as having peanut allergy at Visit 144. This is a binary outcome for each participant: the classification is either peanut allergy or not peanut allergy under the stated criteria. Describing the outcome as a percentage communicates the proportion in the assessed population, but the result cannot be interpreted without knowing the number assessed and the number classified as having allergy. Those endpoint results are not reported in the registry record.

How should a percentage be interpreted?

In general, a percentage is calculated using the number of participants meeting an outcome definition relative to the participants included in that analysis. The numerator and denominator determine what the percentage represents. If different groups have different amounts of missing information, or if eligibility for analysis differs across groups, their percentages may not represent comparable populations. The registry record defines the primary population as LEAP Trio participants in the LEAP Participant cohort with data available to determine allergy status at Visit 144. It does not report the endpoint-specific denominator or explain how unavailable assessments were handled.

For this endpoint, the outcome is not based on a single measurement alone. The record says peanut challenge determined status where possible. It also defines circumstances in which a participant was not considered peanut allergic, including meeting criteria for peanut oral allergy syndrome in the absence of primary peanut allergy and meeting the stated criterion for peanut tolerance through reported consumption without reaction. When challenge was not possible and the tolerance criterion was not met, a prediction model based on listed allergy measurements was used. This rule-based classification can make the endpoint operationally specific, but interpretation also depends on how often each route to classification was used. That information is not reported in the registry record.

What would uncertainty measures add?

As a general statistical explanation, an estimate describes the observed data, while an uncertainty measure describes how much the estimate might vary under the analysis model and sampling process. A confidence interval is one common way to express this uncertainty. It gives a range of values compatible with the data and specified method, rather than a guarantee that the true value lies within that range. A percentage without an interval can be hard to judge: the same observed percentage may be estimated with different precision in different populations. The registry record does not report a confidence interval for the primary endpoint.

A p-value, when used, addresses how compatible the data are with a specified null model under the analysis assumptions. It does not measure the size or importance of an effect, and it does not establish causality. No p-value or primary comparison result is reported in the registry record. Consequently, the primary finding cannot be assessed for statistical significance, and there is no basis to describe an estimated effect as large, small, or precise.

Why does the original assignment need context?

LEAP Participants were originally randomized to Peanut Avoidance or Peanut Consumption in the earlier LEAP study. LEAP Trio groups participants and relatives using that historical assignment. The registry record says that allocation in LEAP Trio was not stated and that the arms are not a like-for-like control comparison. In general, randomization can make treatment groups comparable at the time of assignment, but later follow-up can be affected by participation, missing outcomes, family relationships, and other differences. A historical randomized assignment does not automatically make every later subgroup contrast a randomized comparison. The record does not report methods used to address such issues.

What does over-dispersion mean in general?

For outcomes that count events, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion occurs when the observed variation is greater than that assumption allows. If it is ignored, standard errors and uncertainty intervals can be too small, making results appear more precise than they are. This is a general statistical consideration, not a reported feature of the primary endpoint: the primary outcome is a percentage, and the registry record does not state that an over-dispersion model was used for any analysis.

What is the status of planning calculations?

The record describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total event count; for other outcomes, it expresses participants per arm. Such calculations are planning illustrations, not observed power and not evidence that a study was designed around those assumptions. The numerical planning results are not reported in the registry record, and the record does not establish that these assumptions were the trial’s own design choices.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and 39 analyses. It includes a primary endpoint alongside outcomes involving peanut consumption, allergy-related tests, eczema, asthma, and rhinitis. When many outcomes or analyses are examined, the chance of finding an apparently notable result by chance can increase. As a general statistical matter, multiplicity can be addressed by defining a hierarchy of primary and secondary questions, adjusting significance thresholds, or emphasizing estimation and uncertainty rather than isolated p-values. The registry record does not report whether any multiplicity adjustment or outcome hierarchy was used beyond identifying the primary endpoint.

The record defines the primary analysis population as LEAP Trio participants in the LEAP Participant cohort with data available to determine peanut allergy status at Visit 144. It does not report the number contributing to that analysis or the corresponding analysis populations for the other outcomes. The enrollment of 1868 is not an endpoint-specific denominator. The registry record also does not report how missing assessments were handled, whether participants with partial information were included, or whether any sensitivity analyses were performed.

Missingness can affect both precision and interpretation. In general, if participants without an assessment differ from those assessed in ways related to the outcome, the observed percentage may not represent the full group of interest. The direction and size of any such effect cannot be determined without information about missing data and the analysis. Likewise, the record does not report how the prediction model was applied when some component measurements were unavailable, beyond describing its role when oral challenge was not possible and tolerance criteria were not met.

Analysis plans, including multiplicity control, missing-data procedures, prespecified subgroup analyses, and the definition of each analysis population, are not reported in the registry record. Their absence prevents assessment of whether the posted findings, if reported elsewhere in the record, follow a prespecified statistical approach.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% 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 (0.5%), food allergy (0.5%), vomiting (0.4%).

The registry record lists serious adverse events and other adverse events for the LEAP Participant, sibling, and parent groups. For serious events, the listed counts affected were 1 in LEAP Participants: Peanut Avoidance and 0 in LEAP Participants: Peanut Consumption. Among younger siblings, the corresponding counts were 2 for Peanut Avoidance and 0 for Peanut Consumption. The listed serious-event counts were 0 for both older-sibling groups and both parent groups. The record lists 0 deaths for every group.

For other adverse events, the counts listed were 20 for LEAP Participants: Peanut Avoidance, 6 for LEAP Participants: Peanut Consumption, 3 for Younger Siblings: Peanut Avoidance, and 5 for Younger Siblings: Peanut Consumption. The counts were 0 in both older-sibling groups and both parent groups. These are registry counts, not comparative estimates adjusted for differences between groups. The record also lists Anaphylactic reaction and Food allergy at 0.5% each, and Vomiting at 0.4%, among the top serious terms. It does not give group-specific percentages for those terms.

These counts should be read in light of the listed numbers at risk for each group, not as proof of a causal effect. The registry record does not report the detailed event collection period, adjudication procedures, or exposure-adjusted analyses. Zero recorded events in a group does not establish that an event is impossible or that risk is absent.

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

The record establishes that LEAP Trio was a completed prospective, cross-sectional follow-up with a stated focus on early-life peanut introduction, maintenance of tolerance in adolescence, and additional safety evaluation of the original nutritional intervention. It also describes how peanut allergy status was determined at Visit 144, including the use of challenge where possible and specified criteria or a prediction model in other circumstances. These design and endpoint details clarify what the study set out to assess.

The registry record does not report the primary endpoint result. It therefore does not show the percentage of LEAP Participants classified as having peanut allergy, nor does it report a comparative estimate or uncertainty interval for groups defined by original LEAP assignment. The record cannot establish whether an observed group difference exists, how large it might be, or how precisely it was estimated. It also does not report the analysis population size for this endpoint.

The original Peanut Avoidance and Peanut Consumption labels reflect assignment in the earlier LEAP study. LEAP Trio itself does not have a stated allocation in the registry record, which cautions that these groups are not a like-for-like control comparison. Family members are grouped according to the original assignment of a LEAP Participant. Those labels alone do not establish that later differences are caused by the original nutritional intervention.

As a general statistical matter, an outcome estimate describes the observed analysis population; causal interpretation additionally depends on study design, follow-up, missing data, and the adequacy of the analysis. The record does not report enough information to assess these factors for the primary endpoint. The adverse-event counts are descriptive registry information and do not replace the missing endpoint result or provide a causal comparison.

Accordingly, the defensible reading is limited: the registry record specifies the study purpose, population structure, outcome definition, and some safety counts, but not the primary result or its precision. A conclusion about the frequency of peanut allergy at follow-up, or about differences by historical assignment, would require outcome estimates and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study raises statistical questions that are important in long-term follow-up. The original LEAP assignment provides a meaningful organizing feature, but the follow-up includes relatives and uses groups linked to that earlier assignment. The registry record explicitly notes that LEAP Trio allocation was not stated and that the arms are not a like-for-like control comparison. This distinction matters because labels inherited from an earlier randomized study do not automatically make every follow-up comparison randomized or directly causal.

The endpoint also depends on a structured classification process rather than one uniform test for every participant. Challenge was used where possible; specified criteria addressed peanut oral allergy syndrome and reported tolerance; and a prediction model was used in certain cases when challenge was not possible. Statistically, transparent reporting of how participants were classified, how many contributed data, and how uncertainty was estimated is important when combining different assessment routes. The registry record describes the rules but does not report the resulting endpoint estimates or the number assessed.

The breadth of outcomes is another statistical consideration. The record lists 12 outcome measures and 39 analyses, spanning clinical outcomes and measurements related to allergy. Multiple analyses can help characterize a study, but they also make it important to distinguish primary questions from exploratory ones and to explain how multiplicity was handled. That information is not reported in the registry record.

Finally, the stated safety purpose makes clear reporting of adverse events relevant, but sparse event counts need cautious interpretation. Counts and percentages are informative descriptions, yet they do not by themselves establish comparative risk or causation. Taken together, the study highlights the need for endpoint-specific denominators, uncertainty estimates, missing-data methods, and clear separation of historical assignment from the follow-up design when presenting long-term clinical research.

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 most consequential limitation for interpretation is that the primary endpoint result is not reported in the registry record. There is no endpoint percentage, comparison estimate, confidence interval, or p-value available to describe. The record also does not report how many LEAP Participants had data available to determine status at Visit 144, so the endpoint denominator and its precision cannot be evaluated. The enrollment figure does not resolve this because enrollment is not an endpoint-specific analysis population.

The study is described as prospective and cross-sectional, and allocation for LEAP Trio is not stated. Its groups are defined using the original LEAP assignment, with family members grouped according to a LEAP Participant’s assignment. The registry record warns that these groups are not a like-for-like control comparison. This limits causal interpretation of any contrast based on those labels, even though the original LEAP participants had been randomized in the earlier study.

The endpoint may be determined through different routes: challenge where possible, stated tolerance and oral allergy syndrome criteria, or a prediction model in specified circumstances. The registry record does not report how many participants were assessed by each route, how missing test information was handled, or how the classification process affected uncertainty. Such information would help readers judge comparability and possible misclassification.

The record lists multiple outcomes and analyses, but does not report the statistical analysis plan, multiplicity procedures, missing-data methods, or analysis populations for each outcome. It also does not report detailed safety ascertainment procedures or a comparative safety analysis. These limitations do not negate the study’s stated purpose; they constrain what can be concluded from the registry information available.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Follow up of LEAP Participants and Their Families — NCT03546413.
• Registry record last updated 2024-03-29; status last verified 2024-03.
• Results first posted 2024-03-29.
• 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

NCT03546413, Follow up of LEAP Participants and Their Families, is a completed prospective, cross-sectional study with enrollment of 1868. It began on 2018-07-05 and reached primary completion on 2022-08-31. The study was designed to examine how early-life peanut introduction may relate to maintenance of tolerance in adolescence and to provide an additional safety evaluation of the original nutritional intervention.

The primary outcome is the percentage of LEAP Participants with peanut allergy at Visit 144, assessed using challenge where possible and other stated criteria in specified circumstances. The registry record does not report the primary outcome result, its denominator, or its uncertainty. Groups are labelled according to the LEAP Participant’s original Peanut Avoidance or Peanut Consumption assignment; the record cautions that LEAP Trio allocation was not stated and the arms are not a like-for-like control comparison.

The record also lists outcomes involving peanut consumption, allergy-related tests, eczema, asthma, and rhinitis, as well as adverse-event counts. Analysis methods for multiplicity and missing data are not reported in the registry record. Interpretation is therefore limited to the study design, endpoint definition, group structure, and listed safety information.