Determining the Efficacy and Value of Immunotherapy on the Likelihood of Peanut Tolerance: The DEVIL Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Determining the Efficacy and Value of Immunotherapy on the Likelihood of Peanut Tolerance: The DEVIL Study (NCT00932828), a na phase 2 study. The primary outcome is Determine the Percentage of Subjects Who Demonstrate Sustained Unresponsiveness (SU) by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC)..

2. Clinical Question

In general, sustained unresponsiveness asks whether a response persists after treatment has stopped for a specified period; it is distinct from a challenge performed while dosing continues. This study’s primary question therefore concerns the challenge result after the stated avoidance interval, not simply whether participants tolerated peanut during treatment. The registry describes desensitization as a separate secondary outcome, also assessed by a negative food challenge. The record does not report results for either challenge outcome.

3. Trial Design

The DEVIL Study was a phase 2, single-group study of peanut oral immunotherapy. It enrolled 37 participants and is recorded as completed. The sponsor was the University of North Carolina, Chapel Hill. The registry gives a start date of 2009-06-22 and a primary completion date of 2017-02-01.

All participants were assigned to the peanut oral immunotherapy intervention in the single-group design. Allocation is listed as NA, and the study was unmasked. There was no concurrent control group, so the design does not provide a like-for-like comparison between participants receiving OIT and participants receiving a different intervention or no OIT. The registry does not describe randomization, a comparator arm, or a masking procedure.

The intervention is described as peanut flour used as oral immunotherapy for newly diagnosed allergic children. The primary endpoint timeframe is after 36 months of OIT dosing followed by 1 month of avoidance. The endpoint description also specifies a 4-week avoidance period before the double-blind placebo-controlled food challenge. The record does not explain the relationship between those two phrasings or give further dosing details.

The registry lists three outcome measures: the primary sustained-unresponsiveness outcome and secondary outcomes concerning desensitization and treatment-related adverse effects. It records no analyses. The primary analysis population is described as 37 subjects under an ITT analysis, including 5 withdrawals; how withdrawals were handled in calculating the endpoint is not reported. The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or results for the primary or secondary outcomes.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 37 subjects considered with ITT analysis including 5 withdrawals

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 Determine the Percentage of Subjects Who Demonstrate Sustained Unresponsiveness (SU) by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC)., measured over After 36 months of OIT dosing followed by 1 month of avoidance.

The primary endpoint is the percentage of subjects demonstrating sustained unresponsiveness by a negative double-blind placebo-controlled food challenge. The stated timeframe is after 36 months of OIT dosing followed by 1 month of avoidance. The endpoint description further characterizes the challenge as a negative DBPCFC to 5 grams of peanut after the OIT course and 4 weeks without therapy.

This endpoint is intended to capture whether the challenge result remains negative after a period off treatment. In general, this differs from an endpoint assessing tolerance during ongoing dosing: the latter measures response under treatment, while sustained unresponsiveness concerns response after treatment interruption. The registry also lists desensitization by negative DBPCFC as a secondary outcome, but does not give its result or explain how its challenge timing differs from the primary endpoint.

A percentage endpoint ordinarily requires both a defined denominator and a count meeting the endpoint. The registry identifies 37 subjects in the ITT population, including 5 withdrawals, but does not report the number with a negative challenge, the calculated percentage, or a confidence interval. It also does not state how missing challenge results or withdrawals were handled. Consequently, the recorded endpoint definition can be described, but its observed frequency and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: participants either meet the sustained-unresponsiveness definition or do not, based on the stated challenge. For a binary endpoint, a basic summary is the count meeting the definition and the proportion of the analysis population represented by that count. This is a general description of how such outcomes can be summarized, not a statement that a particular calculation was reported for this study. The registry gives neither the count meeting the endpoint nor a proportion.

What a confidence interval would describe

In general, a confidence interval expresses uncertainty around an estimated quantity. For a proportion, it helps show how much uncertainty remains about the underlying frequency, given the observed participants and the statistical method. An interval is not a guarantee that the true value lies within its endpoints, and its width depends on factors such as the amount of information and the method used. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated.

Why the analysis population matters

The registry describes 37 subjects considered under ITT analysis, including 5 withdrawals. In general, an ITT approach aims to analyze participants according to their assigned study group, but in a single-group study the practical issue is still how all enrolled participants contribute to the endpoint summary. If a participant has no challenge result, the analysis needs a stated rule for that missing outcome. Different missing-data assumptions can produce different summaries. The record does not report the withdrawal handling, missing-data method, or analysis denominator used for the primary endpoint. Therefore, the ITT label alone does not resolve how the endpoint was calculated.

Why a comparator changes interpretation

In general, a control group allows an outcome under one study condition to be compared with an outcome under another condition. Here, the registry records a single-group model, allocation NA, and no masking. There is no concurrent control estimate. A summary of outcomes in this group could describe the participants’ observed experience, but it would not provide a randomized between-group treatment contrast. No adjusted or comparative analysis is listed.

Multiplicity and analysis plans

Multiplicity arises when several outcomes or statistical tests are considered; repeated testing can affect the chance of obtaining apparently notable findings. The registry lists three outcome measures, consisting of the primary outcome and two secondary outcomes, but records no analyses. It does not report a multiplicity adjustment, a hierarchy among tests beyond identifying the primary outcome, or a prespecified statistical plan. These aspects are not reported in the registry record and should not be inferred from the outcome titles.

Planning calculations are not study results

The registry’s sample-size assumptions describe a planning illustration based on an 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 framed as a stated fraction of the observed effect. These assumptions do not describe the enrolled study’s single-group design, and the illustration is not the trial’s own design justification. Such calculations are planning aids rather than evidence of an observed outcome. They are not observed power, and they cannot replace a reported endpoint estimate and its uncertainty. The registry record does not report the study’s own sample-size justification or explain how the illustration relates to this single-group trial.

Finally, the record gives no interim-analysis details, no named statistical procedure for the primary outcome, and no model specification. In general, these choices can affect how estimates and uncertainty are calculated, but no particular method should be attributed to this study without a report. The available record supports a description of the endpoint, population, design, and posted adverse-event counts; it does not support reconstruction of an unreported efficacy analysis.

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("Peanut Oral Immunotherapy")
n      <- c(37)
events <- c(29)
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  Peanut Oral Immunotherapy  37  29  78.4  61.8  90.2  62.8  88.6  62.7  88.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: sustained unresponsiveness as the primary outcome, desensitization as a secondary outcome, and treatment-related adverse effects as a secondary outcome. It records no analyses. Although identifying one outcome as primary distinguishes it from the secondary outcomes, the record does not describe a testing hierarchy, adjustment for multiple comparisons, or another multiplicity strategy. These matters are not reported in the registry record.

The primary analysis population is described as 37 subjects under an ITT analysis, including 5 withdrawals. The record does not state how the withdrawals were handled, whether all subjects had a challenge assessment, or how an absent or uninterpretable challenge result would enter the calculation. It provides no imputation procedure, missing-data assumption, or sensitivity analysis. The stated ITT population therefore does not reveal the endpoint denominator or how missing outcomes were treated.

In general, missing data can affect an outcome estimate when the probability of having an observed result is related to the outcome itself or to participant characteristics. An analysis rule makes those assumptions explicit; a sensitivity analysis can explore how conclusions vary under different plausible rules. Neither approach is described in the registry record. The record also does not report an analysis population separate from the stated ITT population or explain whether any per-protocol analysis was planned or conducted.

Because the registry lists no analyses and no primary outcome result, it is not possible to assess how multiplicity or missingness affected the study’s efficacy findings. The relevant procedures are not reported in the registry record.

12. 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 non-serious adverse event terms

For the listed Peanut Oral Immunotherapy group, the registry records 37 at risk for serious adverse events and 0 affected. It also records 37 at risk under other adverse events and 35 affected. No top serious-event terms are listed. These are the posted safety figures for the group; they are not a measure of the primary sustained-unresponsiveness endpoint.

The count of 0 indicates that no serious adverse events are recorded for this group in the registry entry. It does not, by itself, establish that serious events could not occur or describe the completeness and duration of safety follow-up. The record does not give details about event collection, exposure time, severity categories beyond serious versus other, or the relationship of each event to treatment. Although a secondary outcome is titled as the frequency of treatment-related adverse effects, the posted counts do not specify which of the other adverse events were judged treatment-related.

In general, safety counts should be interpreted in light of how events were defined, collected, and attributed, as well as the number followed. The registry gives the at-risk counts and affected counts but does not report those additional methods. The 35 affected under other adverse events should therefore be read as a registry count, not as proof that every recorded event was caused by OIT or as a severity classification beyond the category shown.

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

The registry record describes a study intended to assess sustained unresponsiveness after peanut OIT and a period of avoidance. It provides the primary endpoint definition, the single-group design, the stated ITT population, and adverse-event counts. It does not report the primary endpoint count or percentage, a confidence interval, a p-value, or analyses. Accordingly, the record does not establish how often participants met the primary endpoint or how precisely that frequency was estimated.

The design information is important for interpreting any outcome that might be reported elsewhere. Because this was a single-group, unmasked study with no concurrent comparator, an observed outcome would describe the enrolled group but would not alone show what would have occurred under a different treatment condition. This is a general limitation of the design, not a conclusion about the intervention’s effects.

The primary endpoint concerns a negative challenge after OIT and avoidance, while desensitization is listed separately as a secondary outcome. Those concepts should not be treated as interchangeable: sustained unresponsiveness is framed around the period after treatment stops, whereas desensitization is another stated study outcome. The registry does not report results for either measure, so neither outcome can be characterized from this record.

The safety entry records 0 serious adverse events and 35 affected under other adverse events among 37 at risk. Those counts provide limited descriptive safety information; the record does not give event details, attribution, or collection methods. Overall, the available registry information supports an account of the study’s aims, design, and posted safety counts, but not a conclusion about the primary efficacy outcome or a comparison with another treatment condition.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between response during treatment and response after treatment has stopped. Its primary endpoint is framed as sustained unresponsiveness assessed by a negative DBPCFC after an OIT course and an avoidance period. The record separately identifies desensitization as a secondary outcome. Keeping those endpoint concepts distinct is important when describing what a trial intends to measure and what its results, if reported, would mean.

The study also illustrates why an endpoint definition is not enough to interpret an outcome. Readers need the observed count, denominator, a clear account of participants without assessments, and an estimate of uncertainty. The registry identifies an ITT population of 37, including 5 withdrawals, but does not report the endpoint count, the calculation denominator, or the handling of missing challenge results. The absence of these details prevents assessment of both the observed frequency and its precision.

Its single-group design makes the distinction between descriptive evidence and comparative evidence especially important. An outcome in one group can describe that group, but the design has no concurrent control group for estimating a between-group contrast. This is a general statistical limitation, rather than a claim about the study’s actual outcomes.

Finally, the record shows why safety summaries require context. It posts serious and other adverse-event counts, but does not provide event-level descriptions or the methods for collection and attribution. A count can be informative while still leaving uncertainty about what was counted and how it relates to treatment. The statistical importance of this trial lies in these interpretive questions; its registry record does not report the primary result needed to answer the stated efficacy question.

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 main trial-specific limitation in interpreting the registry entry is that the primary outcome result is not reported. The record defines sustained unresponsiveness and identifies an ITT population, but provides no count meeting the endpoint, percentage, confidence interval, or analysis. The primary result and its statistical precision therefore cannot be assessed.

The single-group, unmasked design has no concurrent control group. Any reported outcome from such a design would be descriptive of the study group and would not provide a direct randomized comparison. The record does not describe a comparator or allocation process.

Withdrawal and missing-outcome details are also limited. The stated ITT population includes 5 withdrawals, but the registry does not explain how those participants were included in the primary endpoint calculation, how many participants completed the challenge, or what method was used for missing results. The record does not report an analysis plan, multiplicity procedure, interim analyses, or the study’s sample-size justification.

The safety entry is limited to group-level counts: 0 serious adverse events and 35 affected under other adverse events among 37 at risk. Event descriptions, treatment attribution, follow-up duration, and event-collection procedures are not reported in the registry record. The secondary outcome titles also do not substitute for the missing results. These limitations concern what can be concluded from this record; they do not establish that details were absent from other study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Determining the Efficacy and Value of Immunotherapy on the Likelihood of Peanut Tolerance: The DEVIL Study — NCT00932828.
• Registry record last updated 2018-05-24; status last verified 2018-02.
• Results first posted 2018-05-24.
• 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

The DEVIL Study was a completed phase 2, single-group, unmasked study of peanut oral immunotherapy, sponsored by the University of North Carolina, Chapel Hill. It enrolled 37 participants. The registry lists a start date of 2009-06-22 and a primary completion date of 2017-02-01.

The primary outcome was sustained unresponsiveness by negative DBPCFC after 36 months of OIT dosing and an avoidance period. The record describes 37 subjects in the ITT population, including 5 withdrawals, but does not report the primary outcome result or any analyses. Secondary outcomes concerned desensitization and treatment-related adverse effects.

For the intervention group, the registry records 0 serious adverse events among 37 at risk and 35 affected under other adverse events among 37 at risk. Further event and analysis details are not reported in the registry record.