Oral Immunotherapy for Wheat Allergy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral Immunotherapy for Wheat Allergy (NCT01980992), a randomized phase 1, phase 2 study. The primary outcome is The Percentage of Desensitized Participants as Measured by the Ability to Consume at Least 4443 mg of Wheat Protein During a 7443 mg Wheat Protein Oral Food Challenge (OFC) Performed 1 Year After Initiating Treatment..

2. Clinical Question

The endpoint is a challenge-based measure of desensitization: it asks whether participants could consume a specified amount of wheat protein during an oral food challenge without dose-limiting symptoms. It is not a general measure of everyday wheat consumption, and the registry's stated goal also refers to the ability to eat wheat regularly without allergic symptoms after stopping treatment. Those are related but distinct questions. The primary endpoint described in the record is assessed one year after initiating treatment; the record does not identify it as an assessment after treatment cessation.

The posted primary results show 12 participants in the Wheat OIT arm meeting the endpoint and 0 in the placebo arm. The risk difference estimate is 0.522, with a confidence interval from 0.318 to 0.726 and p < 0.001. These results describe the randomized comparison at the stated assessment. They do not establish what happens after treatment stops, or how participants fare with unrestricted wheat intake beyond the challenge setting.

3. Trial Design

The registry identifies this as a randomized, triple-masked, crossover trial in Phase 1 and Phase 2. The enrollment was 46, and the record gives 23 participants in each of the two primary arms. The study status is completed. The start was 2013-10 and primary completion was 2015-11.

The active intervention was Wheat OIT, described as Vital Wheat Gluten. The placebo arm received placebo for Vital Wheat Gluten followed by crossover to open-label active therapy. The registry describes oral food challenges in both arm descriptions, with up to four challenges for the active-treatment participants and up to three for the placebo group. The specific challenge schedule, sequence details, and timing of the crossover are not reported in the registry record.

The primary outcome was assessed one year after initiating treatment and was defined by the ability to consume at least 4443 mg of wheat protein during a 7443 mg wheat protein oral food challenge, without dose-limiting symptoms. The registry says all randomized participants were included in the primary outcome population. It does not report the handling of missing primary endpoint observations or further details of the analysis population.

The crossover structure matters when interpreting the comparison. The primary result contrasts the active-treatment and placebo arms at the stated one-year assessment; placebo participants later crossed over to open-label active therapy. The later crossover experience is not the same randomized comparison as the initial placebo-controlled period. The record does not report enough detail to assess whether, or how, crossover data contributed to any analysis of the primary endpoint. No reported analyses are listed in the registry record.

The registered study goal included medical, safety, and immunologic effects, and whether participants could eat wheat regularly without allergic symptoms after stopping treatment. The posted primary endpoint addresses challenge-based desensitization at one year. A post-treatment persistence endpoint is 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.

52 Weeks Blinded Study Treatment

Reasons for not completing this period:

52 Weeks Open Label Active Wheat OIT

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants were included.

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 The Percentage of Desensitized Participants as Measured by the Ability to Consume at Least 4443 mg of Wheat Protein During a 7443 mg Wheat Protein Oral Food Challenge (OFC) Performed 1 Year After Initiating Treatment., measured over 1 Year.

The primary endpoint is the percentage of desensitized participants, operationalized as the ability to consume at least 4443 mg of wheat protein during a 7443 mg wheat protein oral food challenge performed one year after treatment initiation. The description specifies consumption without dose-limiting symptoms. The posted results are presented as participant counts: 12 in the Wheat OIT arm and 0 in the placebo arm.

A challenge endpoint provides a defined test condition for comparing groups. Rather than relying only on a broad report of symptoms or ordinary food exposure, it specifies the amount of wheat protein and a clinical response threshold. That makes the outcome interpretable as a protocol-based measure of desensitization under the challenge conditions. In general, a binary endpoint records whether each participant meets a stated criterion; it does not capture the full range of individual responses or indicate how participants would respond under every real-world circumstance.

The endpoint is useful for the registered comparative question because it assesses whether participants in the active-treatment arm reached the defined challenge threshold relative to placebo at the stated time. Its scope is limited, however. It does not by itself measure sustained tolerance after treatment has stopped, unrestricted wheat intake, or outcomes at times beyond the specified assessment. Those questions are not answered by the posted primary endpoint result.

7. Results Posted in the Registry

• Wheat OIT: 52.2% (12/23) versus 0.0% (0/23) on control; risk difference 52.2 percentage points (95% CI 31.8 to 72.6); 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.

Number of Subjects Who Achieve the Targeted Maintenance Dose of Wheat OIT

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Wheat OIT: 82.6% (19/23) versus 91.3% (21/23) on control; risk difference -8.7 percentage points (95% CI -28.0 to 10.6), risk ratio 0.90 (0.72–1.13); unadjusted two-proportion z-test p = 0.381.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Wheat OIT and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address related but distinct aspects of the study: consuming a wheat protein oral food challenge, achieving a targeted maintenance dose, desensitization in the placebo crossover group, and serious adverse events. They broaden the context for the primary result but are not substitutes for the randomized primary comparison. The registry's listed outcome titles alone do not establish that each outcome has a posted numerical result.

The maintenance-dose outcome is the secondary comparison with numerical results reported in the registry record. Its risk difference estimate is -0.087, and its confidence interval includes zero; the posted p-value is 0.381. This result concerns reaching the targeted maintenance dose by the stated timeframe, rather than meeting the primary challenge-based desensitization criterion. A maintenance-dose measure and a challenge response answer different questions, so their estimates need not have the same direction or strength.

The primary result shows a clear difference in the challenge endpoint at one year, while the secondary maintenance-dose comparison is uncertain and does not show a statistically clear difference on its reported test. This contrast does not invalidate either result: a participant's ability to reach a target dose is not identical to the ability to meet a challenge threshold, and the outcomes may capture different parts of the treatment process.

The registry lists four secondary outcomes, but full numerical results for all of them are not reported in the registry record. The result for desensitization in the placebo crossover group is particularly distinct from the initial randomized comparison because crossover changes the treatment exposure. Its interpretation cannot be equated with a concurrent placebo-controlled contrast.

Secondary tests carry less evidential weight when they are not protected by a reported multiplicity plan. Testing multiple outcomes without adjustment can increase the chance of apparently notable findings arising by chance. The registry does not report a multiplicity strategy, and the posted secondary comparison is unadjusted. These results are therefore best read as additional context rather than as independent confirmation of the primary finding.

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

• Number of Subjects Who Successfully Consume a Wheat Protein Oral Food Challenge
• Number of Subjects Who Achieve the Targeted Maintenance Dose of Wheat OIT
• Number of Subjects That Achieve Desensitization in the Placebo Cross Over Group
• Incidence of All Serious Adverse Events During the Study.

9. Statistical Interpretation

10. Statistical Methods Explained

Randomization assigns participants to treatment groups by a chance-based process. In general, this helps make groups comparable at the start with respect to measured and unmeasured characteristics, though randomization does not guarantee perfect balance in a particular trial. The registry identifies the study as randomized but does not report the allocation procedure or any stratification factors.

Masking means that some people involved in a trial do not know which intervention a participant received. The record labels the trial triple-masked, but it does not specify which parties were masked or how masking was maintained. In general, masking can limit the influence of expectations on treatment delivery, outcome assessment, or reporting. The registry label alone does not establish how well masking worked.

The crossover design means that participants in an arm may receive more than one intervention across different study periods. In this trial, the placebo arm description says that participants crossed over to open-label active therapy. A crossover can allow observation of participants under more than one treatment condition, but interpretation depends on timing, sequence, carryover, and the analysis approach. The registry record does not report the detailed sequence or a statistical method addressing these issues. For the primary result, the reported contrast is between Wheat OIT and placebo at the one-year assessment.

The primary endpoint is binary: participants either meet the defined oral food challenge criterion or they do not. For a binary outcome, a group proportion describes the share of participants meeting the criterion. The risk difference compares those proportions by subtraction; positive estimates favor a higher observed proportion in the arm named in the comparison, while negative estimates indicate a lower one. The registry reports a risk difference estimate of 0.522 for Wheat OIT relative to placebo. This is the posted estimate, not a recalculation.

A confidence interval gives a range of values that are reasonably compatible with the observed data under the statistical method and its assumptions. It conveys uncertainty in the estimated group contrast. In general, a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. The interval does not show the range of individual participant responses, and it is not a guarantee that the true effect lies within its endpoints.

A p-value assesses how unusual the observed data, or data more extreme, would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, and it does not quantify clinical importance. The primary comparison reports p < 0.001. The registry record does not describe the test used to obtain this p-value, so its precise model and assumptions are not reported in the registry record.

For the secondary maintenance-dose outcome, the posted comparison is a risk difference of -0.087, with a confidence interval from -0.28 to 0.106 and p = 0.381. The registry also includes risk ratio and odds ratio estimates for this comparison. These are alternative ways to express a binary group contrast: a risk ratio compares proportions as a ratio, while an odds ratio compares the odds of the outcome. They are not interchangeable with the risk difference, and each has a different scale. Because this is a secondary result and the record does not report a multiplicity adjustment, its p-value should be treated as unadjusted.

The record lists a sample-size planning illustration for the maintenance-dose comparison. It assumes a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The entries are planning illustrations, not observed power and not evidence that the trial was designed to have a particular power. The registry does not report the trial's own sample-size justification or design assumptions. In general, planning calculations depend on assumptions about the effect size, outcome frequency, analysis method, and desired error rates; changing those assumptions changes the required sample size.

For a binary outcome, the variability depends on the underlying event probability. General statistical methods may require adjustments when data are more variable than a model expects; this is often described as over-dispersion. Over-dispersion is especially relevant to count or clustered data, where events may not behave as independent observations. The primary outcome is posted as participant counts, and the registry does not describe an over-dispersion adjustment or a model requiring one. It would be inappropriate to infer an analysis method from the outcome type alone.

The record states that all randomized participants were included in the primary outcome population. In general, an intention-to-treat analysis retains participants in their randomized groups regardless of treatment adherence, but the registry does not explicitly name the primary analysis as intention-to-treat or describe how missing endpoint measurements were handled. The stated population alone is not enough to reconstruct every analysis detail.

The secondary p-value is described as unadjusted. When several outcomes are tested, the chance of at least one small p-value can increase if each is evaluated separately without adjustment. This is why secondary results, especially when numerous outcomes are registered, are generally interpreted as supportive or exploratory unless a prespecified multiplicity strategy is reported. The registry record lists four secondary outcomes but does not report a multiplicity plan or the full set of secondary numerical results.

11. Confidence Intervals and Precision

The primary risk difference estimate is 0.522, with a confidence interval from 0.318 to 0.726. The entire reported interval is above zero, the value corresponding to no difference on the risk-difference scale. This indicates that the primary estimate is not only positive at its center; the interval also remains positive under the reported uncertainty range. The reported p-value is p < 0.001.

Precision concerns how narrowly the data locate the effect estimate. The confidence interval is the main posted measure of uncertainty for the primary contrast. Its span indicates that the estimated contrast is not a single known quantity: a range of positive values is compatible with the data under the interval method. The interval does not tell whether every value within it is equally plausible, nor does it account for sources of uncertainty not represented by the statistical model.

For the secondary maintenance-dose comparison, the confidence interval ranges from -0.28 to 0.106 around a risk difference estimate of -0.087. It includes zero and extends in both directions, so the posted estimate is compatible with a range that includes no difference as well as effects in either direction. The reported p-value is 0.381. This should not be interpreted as proof that the groups are equivalent; the interval reflects uncertainty, and the registry does not report an equivalence or non-inferiority framework.

Confidence intervals depend on analysis assumptions, including how the outcome and study design are modeled. Since the registry does not report the detailed methods used for the primary interval, its construction cannot be independently assessed from the record. Precision also does not establish clinical importance. The endpoint's challenge threshold and the treatment context must be considered alongside the statistical estimate, while recognizing that the posted endpoint is limited to the stated assessment.

12. Multiplicity, Missing Data and Analysis Populations

The registry identifies all randomized participants as the primary outcome population. It does not state how missing primary endpoint measurements were handled, whether any participants lacked an assessment, or whether a particular imputation method was used. Those details are not reported in the registry record. As a result, the record does not permit a complete assessment of missing-data assumptions or their potential influence on the estimated contrast.

The record also does not explicitly name the primary analysis as intention-to-treat, although it says all randomized participants were included. In general, intention-to-treat analysis preserves randomized group assignment for analysis, while missing outcome data still require a stated approach. The available population statement should not be taken as a substitute for an analysis description.

Multiplicity concerns arise when multiple hypotheses or endpoints are tested. If each test is assessed separately at a nominal threshold without adjustment, the overall chance of a false-positive finding can rise. This general concern is relevant because the registry lists four secondary outcomes, in addition to the primary endpoint. The record does not report a prespecified hierarchy, family-wise error control, or another multiplicity procedure. The secondary comparison with numerical results is marked by an unadjusted p-value and should be interpreted accordingly.

The record's sample-size illustration is associated with the maintenance-dose comparison and uses the observed effect as its planning basis, with stated assumptions. It is not a report of the trial's original design justification. The sample-size justification for the trial, any interim analyses, stopping rules, and the complete statistical analysis plan are not reported in the registry record.

The record says all randomized participants were included in the primary population, but does not provide a detailed accounting of exclusions, withdrawals, crossover handling, or the number with outcome measurements at each assessment. These omissions limit assessment of how closely the analysis followed the randomized design and how sensitive the results might be to missingness or post-randomization events.

13. 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: asthma (8.7%), gastroenteritis (4.8%), anaphylactic reaction (4.5%), status asthmaticus (4.3%), pneumonia (4.3%).

The registry reports serious adverse event counts separately for Wheat OIT before one year, placebo before one year, Wheat OIT after one year, and placebo crossover. Serious adverse events affected 0 participants in Wheat OIT before one year, 3 in placebo before one year, 1 in Wheat OIT after one year, and 1 in placebo crossover. Deaths were reported as 0 for each listed period.

Other adverse events affected 23 participants in Wheat OIT before one year, 21 in placebo before one year, 18 in Wheat OIT after one year, and 21 in placebo crossover. These are period-specific participant counts. The same participant may contribute to more than one period, so the counts should not be added to create a unique-participant total. The registry also lists serious-event terms with percentages, including Asthma, Gastroenteritis, Anaphylactic Reaction, Status asthmaticus, and Pneumonia. These entries do not by themselves establish that an event was caused by treatment.

Safety counts should be interpreted in light of exposure period and the crossover design. The placebo crossover period followed a change in treatment, so it is not a continued placebo-only comparison. The registry does not report detailed attribution, event-level timing, severity beyond the serious-event designation, or a statistical comparison of adverse event rates. These figures describe reported events and affected participants; they do not establish comparative safety or causation.

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

The primary result means that, in this randomized trial, more participants in the Wheat OIT arm than in the placebo arm met the defined oral food challenge criterion at the one-year assessment. The posted counts were 12 and 0, respectively, and the estimated risk difference was 0.522, with a confidence interval from 0.318 to 0.726. The reported p-value was p < 0.001. This is evidence about a specific challenge-based endpoint under the study conditions.

It does not mean that every participant receiving Wheat OIT became desensitized, or that an individual participant's response can be predicted from the group estimate. It also does not establish the ability to eat any amount of wheat, eat wheat regularly without symptoms, or remain desensitized after treatment has stopped. Those broader claims go beyond the endpoint reported at one year.

The result also does not answer every question about safety. The registry reports serious and other adverse event counts by treatment period, but it does not provide enough detail to determine causality or to make a complete comparative safety assessment. Nor does the primary endpoint answer questions about longer-term outcomes, which are not reported in the registry record.

Statistical significance is not the same as clinical importance, and neither alone is a treatment recommendation. The estimate, confidence interval, endpoint definition, trial design, missing-data details, and limitations of the registry reporting all matter to interpretation. The result should be understood as a group-level finding in a completed Phase 1 and Phase 2 randomized crossover study, not as a guarantee for any person or as evidence about settings not evaluated by the posted endpoint.

15. Why This Trial Matters Statistically

This trial is statistically informative because it reports a randomized comparison on a clearly defined binary endpoint. The challenge threshold specifies what counted as desensitization, while the risk difference places the between-arm contrast on an interpretable probability scale. The accompanying confidence interval communicates uncertainty rather than presenting the estimate as exact.

The posted primary result also illustrates why an endpoint's operational definition matters. Ability to consume a specified amount during an oral food challenge is a measurable study outcome, but it is not interchangeable with everyday eating or sustained tolerance after treatment cessation. Keeping the statistical result tied to its actual measure prevents conclusions from extending beyond the data.

The crossover design adds an important interpretive distinction: the initial placebo comparison and later open-label active treatment are different treatment periods. Later outcomes after crossover cannot automatically be read as if placebo exposure continued. The record does not report the detailed analysis plan needed to assess how crossover was handled beyond the primary comparison.

Finally, the registry's incomplete reporting of secondary numerical results, missing-data procedures, multiplicity handling, and original sample-size justification shows why a striking primary result is only one part of evidence assessment. The primary estimate is clear on the posted endpoint, while unadjusted secondary comparisons and period-specific safety counts need more cautious interpretation. Statistical reasoning helps separate what the reported data support from what remains unknown.

16. 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 primary outcome is a challenge-based measure at one year after treatment initiation. The registry's broader study goal refers to eating wheat regularly without symptoms after stopping treatment, but a result for that post-treatment question is not reported in the registry record. The posted endpoint therefore does not establish persistence after treatment cessation or ordinary dietary experience.

The registry does not report the detailed statistical analysis plan, the method used to construct the primary confidence interval, the handling of missing outcome data, or the original sample-size justification. It states that all randomized participants were included in the primary population, but gives no further account of missing assessments or exclusions. These gaps limit independent evaluation of the analysis and its assumptions.

The trial used a crossover design, and the placebo group later received open-label active therapy. The available record does not describe the timing and sequence details or provide a separate numerical primary result after crossover. This limits interpretation of later-period outcomes as evidence comparable to the initial randomized contrast.

Although four secondary outcomes are listed, numerical results are not reported in the registry record for all of them. The numerical maintenance-dose result is unadjusted, and a multiplicity plan is not reported. This makes the secondary evidence less conclusive than a prespecified and multiplicity-controlled analysis would be.

Safety reporting is presented by treatment period and does not include enough detail to establish attribution or provide a complete comparative analysis. These limitations do not negate the posted primary result, but they constrain the conclusions that can be drawn from the registry record.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Oral Immunotherapy for Wheat Allergy — NCT01980992.
• Registry record last updated 2020-08-14; status last verified 2020-08.
• Results first posted 2017-03-31.
• 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.

20. Record Summary

The registry record describes NCT01980992, Oral Immunotherapy for Wheat Allergy, as a completed Phase 1 and Phase 2 randomized, triple-masked crossover trial. Enrollment was 46. The active intervention was Wheat OIT using Vital Wheat Gluten, with placebo followed by crossover to open-label active therapy.

The primary endpoint assessed challenge-based desensitization one year after treatment initiation. The posted counts were 12 participants meeting the endpoint in Wheat OIT and 0 in placebo. The estimated risk difference was 0.522, with a confidence interval from 0.318 to 0.726 and p < 0.001.

The record lists four secondary outcomes, but full numerical results are not reported in the registry record. A maintenance-dose comparison is posted, with an unadjusted p-value of 0.381. Serious adverse event counts are reported separately across treatment periods. Details about missing-data methods, multiplicity, and the trial's own sample-size justification are not reported in the registry record.