Peanut Oral Immunotherapy in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Peanut Oral Immunotherapy in Children (NCT01867671), a randomized phase 2 study. The primary outcome is Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT).

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group Phase 2 study comparing peanut oral immunotherapy with peanut placebo in children with peanut allergy. The registry record identifies the study as multicenter and completed. The recorded enrollment is 146. Its start date is 2013-08-13, and its primary completion date is 2018-07-02.

The registry’s masking field says triple masking, while the brief summary describes the study as double-blind. Both descriptions indicate that masking was part of the study, but the registry record does not explain this difference or specify which roles were masked. It also does not report the randomization procedure or allocation-concealment details.

The two arms followed the same broad schedule: 134 weeks of assigned oral immunotherapy or placebo, then 26 weeks of peanut avoidance. The primary outcome was assessed at Week 134, at the end of the treatment period. A secondary outcome assessed tolerance at Week 160, after the avoidance period. The registry lists liquid extract and peanut flour forms for the active and placebo interventions.

The recorded primary analysis compares the percentage desensitized in the two arms. The arm-level outcome denominators were 96 for oral immunotherapy and 50 for placebo. The registry record does not explain the difference between enrollment and these outcome denominators, or state whether the outcome analysis used an intention-to-treat, per-protocol, or other analysis population. Details of withdrawals and the handling of missing primary outcome data 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: Individuals with a history of severe anaphylaxis (previous hypotension) to peanut were excluded.

Overall Study

Reasons for not completing this period:

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 Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT), measured over Week 134.

The primary endpoint is the percentage of participants desensitized to peanut protein at Week 134. In the registry definition, a participant was desensitized if they passed a masked oral food challenge to 10 grams of peanut flour, equivalent to 5 grams of peanut protein, without significant symptoms. The listed significant symptoms were hives, wheezing, vomiting, or laryngeal edema.

This endpoint turns the challenge result into a binary outcome: each participant either met the registry’s definition or did not. Reporting the percentage in each arm makes the frequency of that outcome visible, while the comparison estimates how much the observed frequency differed between the assigned groups. The arm percentages were 71.0 for oral immunotherapy and 2.0 for placebo.

A masked challenge can help standardize outcome assessment and reduce the influence of expectations on decisions about whether symptoms meet the endpoint definition. The registry record does not report details of challenge administration, adjudication, or whether assessors remained masked throughout outcome assessment. The endpoint measures passing this specified challenge at the stated time point; it is not, by itself, a measure of every aspect of peanut allergy or of outcomes beyond those recorded in the study.

7. Results Posted in the Registry

• Peanut Oral Immune Therapy (OIT): 70.8% (68/96) versus 2.0% (1/50) on control; risk difference 68.8 percentage points (95% CI 58.9 to 78.7), risk ratio 35.42 (5.07–247.57); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Tolerant Participants at Week 160

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Peanut Oral Immune Therapy (OIT): 20.8% (20/96) versus 2.0% (1/50) on control; risk difference 18.8 percentage points (95% CI 9.8 to 27.8), risk ratio 10.42 (1.44–75.37); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Peanut Oral Immune Therapy (OIT) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes address more than the primary Week 134 challenge result. They include tolerance at Week 160, transient desensitization, highest tolerated cumulative dose, and withdrawals. The available numerical secondary comparison concerns the percentage of tolerant participants at Week 160. The other listed secondary outcomes are not reported in the registry record with results in the available outcome information.

The Week 160 outcome is relevant to the study’s schedule because it follows the 26 weeks of peanut avoidance after treatment. It is distinct from desensitization at Week 134: the outcomes have different labels and are assessed at different times. The Week 160 finding therefore adds information about a later outcome, but it should not be read as a repeat measurement of the primary endpoint or as proof that the same participants maintained the primary status.

The reported secondary comparison points in the same broad direction as the primary comparison, with a higher reported percentage in the oral immunotherapy arm than in the placebo arm. Its uncertainty is reflected in the arm confidence intervals and the reported comparison interval. The registry does not report participant-level transitions between the primary and secondary outcomes, so the relationship between individual Week 134 and Week 160 results cannot be assessed from this record.

Secondary endpoints commonly involve additional questions beyond the primary one. When several outcomes are examined, the chance of obtaining at least one apparently notable result can increase unless the analysis accounts for multiplicity. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for secondary outcomes. Consequently, unadjusted secondary results generally carry less confirmatory weight than the designated primary endpoint and should be interpreted as supportive or exploratory evidence, not as independent confirmation of the primary finding.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Tolerant Participants at Week 160
• Count of Participants With Transient Desensitization
• Highest Tolerated Cumulative Dose
• Percentage of Participants That Withdrew From the Study

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary: participants either met the stated challenge-based definition of desensitization or did not. A percentage summarizes the fraction meeting that definition within each arm. Comparing those percentages is one way to describe the size of the observed separation between the assigned groups.

What does the risk difference express?

The posted unadjusted risk difference is 0.688, with a 95% confidence interval from 0.590 to 0.787. A risk difference compares the outcome probabilities directly by subtracting one arm’s probability from the other on the probability scale. It is often easier to relate to absolute outcome frequency than a relative measure, although the estimate still depends on the outcome definition, follow-up, and participants included in the analysis. The reported risk difference is a recalculation from the posted arm-level summary counts, rather than the sponsor’s regression model.

Why is a logistic-regression odds ratio also reported?

Logistic regression models the odds of a binary outcome. The registry reports an odds ratio of 205.45, with a 95% confidence interval from 24.00 to 1758.51 and p < 0.001. An odds ratio compares odds, not probabilities. When the outcome is uncommon in one group or common in another, an odds ratio can be numerically far from a risk difference and can be less intuitive to interpret as a change in probability. The registry record does not state which covariates, if any, were included in the regression, so the model’s adjustment details are not reported in the registry record.

What does a p-value contribute?

The recalculated unadjusted comparison reports p < 0.001, while the sponsor’s logistic-regression analysis reports p < 0.001. A p-value describes how unusual data at least as inconsistent with a null hypothesis would be if that hypothesis and the test assumptions held. It is not the probability that the observed result is due to chance, nor does it measure the size or clinical importance of an effect. Interpretation should consider the effect estimate and its interval as well as the p-value.

Why use an interval as well as a point estimate?

A point estimate gives one summary value for the observed contrast. A confidence interval shows a range of values that are compatible with the data under the interval procedure and its assumptions. Here, the risk-difference interval gives information about the precision of the unadjusted comparison, while the regression interval gives information about the sponsor’s odds-ratio estimate. The regression interval is wide, indicating substantial uncertainty about the magnitude on the odds-ratio scale, even though the interval does not include the null value of one.

What does sparse outcome information mean for interpretation?

The placebo arm had a reported outcome percentage of 2.0, based on an outcome count of 1 among 50 participants. Sparse events can make relative measures such as odds ratios unstable, with intervals extending across a wide range of possible effect sizes. The observed contrast remains clear in the posted percentages, but precise estimation of a very large odds ratio is difficult when the event is rare in one arm. The risk-difference scale gives a more direct description of the absolute contrast, while still carrying sampling uncertainty.

Why can over-dispersion matter in other settings?

As a general statistical point, over-dispersion occurs when variation in the observed data exceeds what a model assumes. If it is ignored in a setting where it is present, standard errors can be too small and confidence intervals too narrow. The primary endpoint is a binary outcome, and the registry does not report an over-dispersion analysis. That concept should not be interpreted as a finding about this trial.

The registry’s randomized parallel-group design supports a comparison between assigned arms, but the validity of any particular estimate also depends on how outcomes were collected and how missing data were handled. Those details, the model specification, and the analysis population are not reported in the registry record. These limits matter when interpreting the precision and generalizability of both the unadjusted and regression estimates.

11. Confidence Intervals and Precision

The primary arm estimates have 95% confidence intervals of 61.7 to 79.9 for oral immunotherapy and 0.0 to 5.9 for placebo. These intervals communicate uncertainty around each arm’s observed percentage. They are not ranges containing a known fixed share of individual participant outcomes, and they do not guarantee that a future study would produce an estimate within the same bounds.

For the unadjusted risk difference, the 95% confidence interval is 0.590 to 0.787. It lies above zero, supporting a positive observed difference on the probability scale under the calculation’s assumptions. The interval also indicates that the exact size of the contrast is uncertain. Its bounds should be read alongside the point estimate, rather than as a substitute for it.

The sponsor’s logistic-regression odds ratio has a 95% confidence interval of 24.00 to 1758.51. This is a very wide interval on the odds-ratio scale. It indicates that the data are compatible with a broad range of relative odds estimates, even though the interval lies above one. Sparse outcome information in the placebo arm is relevant to this imprecision: the posted count meeting the endpoint was 1 among 50 participants.

Confidence intervals address sampling uncertainty under the method used. They do not account automatically for every possible source of uncertainty, such as missing outcomes, deviations from the protocol, or limitations in how broadly the study population represents other groups. The registry record does not report enough detail to assess those issues fully. Precision therefore has to be considered together with the endpoint definition, analysis method, and limitations of the record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect rather than the trial’s own design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planning exercise uses the stated fraction of the observed effect as the effect to detect. The registry record does not report the original design assumptions or sample-size justification.

The 80% power column gives the planned number of participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under those assumptions, if the effect and model assumptions are correct. The 90% power column gives the corresponding planning figure for a higher target chance of detecting that effect. These are design targets, not probabilities that the completed trial’s result is correct.

The planning scenarios use 100%, 75%, and 50% of the observed effect. For the primary comparison, the listed participants per arm for 80% power are 7, 11, and 20, respectively; for 90% power, they are 8, 14, and 26. Smaller effects require more participants to detect under otherwise unchanged assumptions, which is why the planning requirements increase as the assumed effect fraction decreases.

The curve is a visual way to follow the relationship between the assumed effect and the planning requirement; its interpretation should remain tied to the stated assumptions. These values are not observed power: observed power is not an appropriate way to reinterpret the completed trial’s result. The figures do not establish what sample size the investigators planned, because that information is not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.020; treatment proportion p₁ = 0.708; average p̄ = 0.364.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6805 = 1.3338.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4756 = 0.4003.
4. n = (1.3338 + 0.4003)² / (0.6883)² = 6.3, rounded up to 7 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.02                          # control proportion
p1 <- 0.708333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1867671)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 7 (80% power), 8 (90% power)
 75% of observed effect: n per arm = 11 (80% power), 14 (90% power)
 50% of observed effect: n per arm = 20 (80% power), 26 (90% power)
power.prop.test: 6.3 
Simulated power at n = 7 per arm: 0.851 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s reported primary analysis uses logistic regression and presents an odds ratio of 205.45, with a 95% confidence interval from 24.00 to 1758.51 and p < 0.001. This is the analysis reported by the registry for the trial’s primary comparison.

The accompanying recalculation is an unadjusted comparison derived from the posted arm-level counts. It reports a risk difference of 0.688, with a 95% confidence interval from 0.590 to 0.787 and p < 0.001. It also gives an unadjusted odds ratio of 119.0, with a 95% confidence interval from 15.66 to 904.4. The risk difference and odds ratio summarize the contrast on different scales, and the recalculated odds ratio is not the same model estimate as the sponsor’s regression result.

The two analyses point in the same direction: the recorded proportion meeting the endpoint was higher in the oral immunotherapy arm. They are not interchangeable because the regression model specification is not reported in the registry record, and the recalculation does not apply any model adjustment. The registry record does not identify which covariates, if any, were included in the sponsor’s regression. The sponsor’s own analysis remains the study-reported inferential analysis; the unadjusted calculation is a complementary summary of the posted counts.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists secondary outcomes, but it does not report a plan for controlling multiplicity across the analyses. When multiple outcomes or comparisons are examined, the overall chance of false-positive findings can rise. A prespecified testing hierarchy or adjustment can address that issue, but neither is described in the registry record. The posted secondary results should therefore be read with caution and should not be treated as equivalent in evidential status to the primary analysis.

The registry record does not report how missing primary endpoint data were handled, how many participants lacked an evaluable challenge, or whether missingness differed between arms. It also does not describe sensitivity analyses for missing outcomes. Without these details, the effect of missing data on the reported percentages and comparison cannot be evaluated from the registry record.

The outcome denominators are 96 in the oral immunotherapy arm and 50 in the placebo arm, while recorded enrollment is 146. The registry record does not explain the relationship between enrollment and these outcome denominators. It does not report the primary analysis population as intention-to-treat, per-protocol, or another defined set, nor does it explain whether all randomized participants were analyzed according to assigned group.

The record reports a logistic-regression analysis but does not specify the model covariates, handling of sparse data, or other model diagnostics. It also does not report protocol deviations or how they were addressed in the analysis. These omissions do not change the posted estimates, but they limit independent assessment of the analysis choices and their influence on inference. A fuller statistical analysis plan and participant disposition information are not reported in the registry record.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: vomiting (4.0%), anaphylactic reaction (2.0%), vaccination complication (2.0%), asthma (2.0%), pyelonephritis (1.0%).

The registry reports serious adverse events for 3 participants at risk in the oral immunotherapy arm and 4 at risk in the placebo arm. It reports zero deaths in each arm. These counts describe serious adverse events recorded in the study; they do not by themselves establish whether an event was caused by the assigned intervention. The registry record does not provide event-level timing, duration, severity beyond the serious classification, or causal assessments by arm.

The listed serious-event terms include vomiting at 4.0%, anaphylactic reaction at 2.0%, vaccination complication at 2.0%, asthma at 2.0%, pyelonephritis at 1.0%, and respiratory tract infection at 1.0%. The registry’s list does not provide arm-specific counts for each term, so those percentages should not be assigned to one arm or used to compare arms.

Serious adverse event counts are not a complete description of safety. The registry also records other adverse events affecting 96 participants at risk in the oral immunotherapy arm and 50 at risk in the placebo arm, but the summary figures do not describe the individual events or their clinical significance. These summaries should be interpreted as reported event information, not as a complete account of risks or as a causal comparison.

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

The primary result describes a higher observed percentage meeting the registry’s challenge-based definition of desensitization in the oral immunotherapy arm than in the placebo arm at Week 134. The unadjusted risk difference and its confidence interval quantify that contrast, while the sponsor’s logistic-regression analysis gives a separate comparison on the odds scale. Together, the posted estimates show a clear separation in the recorded primary outcome within this trial.

The endpoint has a specific meaning: passing a masked oral food challenge to 10 grams of peanut flour, equivalent to 5 grams of peanut protein, without the listed significant symptoms. The result should not be extended beyond that definition or time point. Desensitization at Week 134 and tolerance at Week 160 are separate outcomes in this record, assessed at different stages of the study schedule.

The findings do not establish the probability of an outcome for every child with peanut allergy, nor do they settle how results would apply to populations not described in the registry. The registry record does not report detailed participant characteristics, the handling of missing data, or the analysis population. Those gaps limit assessment of how representative the analyzed groups were and how robust the estimates are to analysis choices.

The estimates also do not provide a complete safety assessment. Serious adverse event summaries are available, but the record does not report enough detail to attribute individual events or assess all relevant harms. The statistical results should therefore be understood as descriptions of trial outcomes and their precision, not as medical advice or a recommendation about treatment.

18. Why This Trial Matters Statistically

This trial illustrates why endpoint definition is central to statistical interpretation. The primary outcome is not a broad label of improvement; it is a specific pass-or-fail result on a masked oral food challenge at Week 134, using a stated peanut flour dose and symptom criteria. Making that definition explicit helps readers understand what the percentages count and what they do not measure.

It also shows the value of reporting both group percentages and a comparative estimate. Arm-level results communicate the observed frequency in each group, while the risk difference places the contrast on an absolute probability scale. The logistic-regression odds ratio offers another scale but is less directly intuitive, particularly when the event is rare in one arm. Its wide interval underscores that a striking point estimate can coexist with uncertainty about its precise magnitude.

The record further demonstrates why study-reported analyses and recalculations should be distinguished. The sponsor’s regression analysis is the reported inferential analysis, while the unadjusted recalculation provides a transparent comparison from posted summary counts. Their estimands and methods differ, even though their direction is consistent.

Finally, the trial’s later tolerance outcome and listed but unreported secondary measures highlight the importance of time point, multiplicity, and completeness of registry reporting. A positive primary comparison does not answer every secondary question, and uncertainty about missing data and analysis populations remains relevant to how confidently the results can be generalized or independently assessed.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several trial-specific limitations follow from the information available in the registry record. The primary endpoint is based on a challenge result at Week 134, while the study schedule continued through a peanut-avoidance period to Week 160. The record does not provide participant-level data linking the primary and later outcomes, so it is not possible to assess individual changes over that interval from the posted summaries.

The outcome denominators are 96 for oral immunotherapy and 50 for placebo, and the record does not explain how these relate to the enrolled population of 146. The analysis population, missing outcome handling, and participant disposition are not reported in the registry record. These omissions limit evaluation of potential attrition or selection effects.

The sponsor reports logistic regression, but the model covariates and other specification details are not reported. The wide confidence interval around the odds ratio also reflects limited precision in the relative estimate, in the context of the low placebo outcome count. The unadjusted recalculation is useful as a simple summary but cannot substitute for an undocumented model specification.

The registry’s masking descriptions differ: the masking field says triple masking, while the brief summary says double-blind. The record does not resolve that difference or describe the roles masked. It also does not report multiplicity procedures for secondary outcomes or results for several listed secondary measures. Finally, serious adverse event summaries lack arm-specific details for the listed terms and do not establish causality. These limitations constrain interpretation without negating the reported outcome comparisons.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Peanut Oral Immunotherapy in Children — NCT01867671.
• Registry record last updated 2020-03-16; status last verified 2020-02.
• Results first posted 2020-01-22.
• 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.

23. Record Summary

The registry record describes a completed, randomized, parallel-group Phase 2 study of peanut oral immunotherapy versus peanut placebo in children with peanut allergy. Treatment or placebo was given for 134 weeks, followed by peanut avoidance for 26 weeks. The primary endpoint was the percentage desensitized at Week 134, defined by passing a masked oral food challenge without specified significant symptoms.

The reported primary percentages were 71.0 for oral immunotherapy and 2.0 for placebo. The unadjusted risk difference was 0.688, with a 95% confidence interval from 0.590 to 0.787. The sponsor’s logistic-regression analysis reported an odds ratio of 205.45, with a 95% confidence interval from 24.00 to 1758.51.

The registry also reports a Week 160 tolerance outcome and serious adverse event summaries. Details of missing-data handling, analysis populations, regression specification, and multiplicity procedures are not reported in the registry record.