Autoimmune Protocol Diet and Inflammatory Bowel Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Autoimmune Protocol Diet and Inflammatory Bowel Disease (NCT03512327), a na na study. The primary outcome is Number of Participants With Clinical Remission for Crohn's Disease.

2. Clinical Question

3. Trial Design

The registry describes a completed, single-group intervention study sponsored by Scripps Health. The listed enrollment is 15. The study start date is 2016-09-01, and the primary completion date is 2016-12-10. The intervention was the autoimmune protocol diet, with the participant description specifying an 11-week dietary intervention. The study included adults with active Crohn disease or ulcerative colitis.

Allocation is listed as not applicable, masking as none, and the model as single group. These design details mean the registry does not describe a randomized comparison or a masked assessment. There is no like-for-like control group in the record. Changes measured during the intervention therefore cannot, by themselves, distinguish an intervention-associated change from changes related to time, other care, participant behavior, or other influences. The registry record does not report additional design features that would address those possibilities.

The primary endpoint is restricted to Crohn disease: the number of participants with clinical remission, assessed at 11 weeks. The record states that 9 participants had Crohn disease and 6 had ulcerative colitis; the ulcerative colitis participants were not included in the Crohn disease subgroup analysis. The registry also lists secondary outcomes concerning mucosal healing, inflammatory biomarkers, gene ontology terms, and fecal microbiome composition. Details of the methods used for those measures are not reported in the registry record.

The record labels the phase as not applicable. It does not report a protocol rationale for the enrollment target, a sample-size justification, an interim-analysis plan, or a statistical analysis plan. Those omissions limit what can be concluded about the design choices and how the investigators intended to interpret the 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: In this study, 9 out of the 15 participants had Crohn's disease. The other 6 participants had ulcerative colitis, so were not included in this subgroup analysis.

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 Number of Participants With Clinical Remission for Crohn's Disease, measured over 11 weeks.

The primary endpoint is the number of participants with Crohn disease who achieved clinical remission by 11 weeks. Remission is defined using the Harvey Bradshaw Index (HBI), with a score below 5 meeting the study definition. The HBI evaluates general well-being, abdominal pain severity, daily stool count, abdominal mass, and complications. Its stated range is 0-16, with lower values representing a better outcome and higher values representing more disease activity.

A remission count is a binary endpoint summarized as the number meeting a defined threshold. In general, such an endpoint can make a clinical state easier to interpret than a score alone, because it distinguishes participants who do and do not meet the specified criterion. The count does not show how far each participant’s score was from the threshold, or how much an individual score changed. Those questions require additional results that are not reported in the registry record.

The primary endpoint applies to the Crohn disease subgroup, not to all participants with inflammatory bowel disease in the study. The registry states that participants with ulcerative colitis were not included in this subgroup analysis. The remission count itself is not reported in the registry record, so the endpoint definition can be described but its observed frequency cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design allow?

The registry identifies this as a single-group study of the autoimmune protocol diet. A single-group design can describe measurements made among participants receiving an intervention, but it does not supply a concurrent comparison group. In general, without such a group, an observed change cannot separate the influence of the intervention from other explanations, including the natural course of disease, changes in other care, or changes in measurement. This is a design limitation, not a statement about whether any individual participant changed.

Allocation is listed as not applicable and masking as none. These entries are consistent with the registry’s single-group description. The record does not report additional procedures for reducing bias in outcome assessment or analysis. It also does not provide enough information to determine how the diet was implemented or how adherence was assessed.

How should the primary endpoint be read?

The primary endpoint is a count of Crohn disease participants meeting the remission definition. The definition is an HBI score below 5 at 11 weeks. Because the endpoint is a count of participants meeting a threshold, it is a binary outcome at the participant level: each participant either meets the stated criterion or does not. The registry record does not report the count of participants in either category.

In general, a count should be interpreted alongside its denominator and an uncertainty estimate. The denominator matters because the same count can imply different levels of evidence in groups of different sizes. An interval estimate helps communicate the uncertainty around the observed result. Neither the primary remission count nor an interval estimate is reported in the registry record. No new estimate can be reconstructed from the endpoint definition alone.

What can a confidence interval communicate?

In general, a confidence interval is a method-based range used to express uncertainty around an estimate. A wider interval indicates less precision than a narrower interval, all else equal. It does not describe the range of individual participant outcomes, and it is not a probability statement that a fixed parameter falls inside a particular calculated interval. The registry record does not report a confidence interval for the primary endpoint, so the precision of the remission estimate cannot be assessed.

What do the planning illustrations mean?

The sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. For time-to-event illustrations, the stated quantity is a total number of events; other illustrations are expressed as participants per arm. These assumptions describe hypothetical planning calculations, not the design of this single-group trial. They are not observed power and do not show that the study had a particular probability of detecting an effect.

The registry record does not report a sample-size justification for the trial itself. It also does not report the method used to estimate the observed effect underlying those illustrations or the result of the primary remission endpoint needed to assess it. Consequently, the illustrations should not be treated as a substitute for the trial’s missing endpoint count, an uncertainty interval, or a prospective design rationale.

What role would a comparison play?

In general, a two-group comparison estimates how outcomes differ between groups under the specified analysis. Its interpretation depends on how participants entered each group, how outcomes were measured, and how uncertainty was quantified. Those principles do not create a comparison where none is recorded. The autoimmune protocol diet study is listed as single group; allocation is not applicable. The record therefore does not support an estimate of a treatment contrast against another diet or usual care.

The registry lists secondary measures involving clinical, biomarker, gene-expression, and microbiome outcomes. Different outcome types can call for different summary measures and statistical models. For example, binary outcomes are often summarized as counts or proportions, whereas continuous measurements may be summarized using measures of location and spread. In general, model choice should reflect the outcome scale, data distribution, and design. The statistical methods for the listed secondary outcomes are not reported in the registry record.

Over-dispersion is a general issue for count data: observed variability can exceed what a simple model assumes, which can make standard errors and uncertainty estimates too small if the model does not account for that extra variability. This concept does not establish that over-dispersion occurred in this study. The registry record does not report a count-data model or a dispersion assessment for the primary endpoint.

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("Participants With Crohn's Disease")
n      <- c(9)
events <- c(6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Participants With Crohn's Disease  9  6  66.7  29.9  92.5  35.4  87.9  34.8  87.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and secondary outcomes concerning mucosal healing, C-reactive protein, fecal calprotectin, gene ontology terms, and fecal microbiome composition. When a study examines multiple outcomes, general statistical practice considers whether the chance of a false-positive finding across the collection of tests should be controlled or otherwise addressed. The registry record does not report a multiplicity strategy, such as a prespecified hierarchy or adjustment method. Without that information, the approach to interpreting multiple statistical tests is not reported in the registry record.

The registry record also does not report how missing outcome measurements were handled, whether all enrolled participants contributed to the primary analysis, or how the analysis population was defined beyond the Crohn disease subgroup description. It states that 9 participants had Crohn disease and that the other 6 participants had ulcerative colitis and were not included in the Crohn disease subgroup analysis. This describes the disease-specific subgroup, but not the handling of missing measurements or exclusions within that subgroup.

Details of the statistical analysis plan, interim analyses, and sample-size justification are not reported in the registry record. Those omissions mean that readers cannot assess whether the endpoint definitions and analysis decisions were fixed in advance, or how deviations and incomplete data were intended to be addressed. The primary remission count is also not reported, so neither the result nor its precision can be evaluated. These are reporting gaps; they do not establish that particular analyses or procedures were or were not performed.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: small bowel obstruction (6.7%).

The registry lists 1 serious adverse event and 1 other adverse event in the autoimmune protocol diet group. Each category lists 15 participants at risk. The record lists 0 deaths. Small bowel obstruction is listed among the serious adverse event terms, with 6.7% shown for that term.

These figures describe the safety entries in the registry and should not be read as establishing whether the diet caused an event. The registry record does not report the investigators’ assessment of causal relationship, event timing, event duration, or clinical outcome. The serious and other adverse event entries are separate categories; the record does not establish from these figures whether they involved the same participant or different participants. They should not be added together to infer a number of affected participants.

In general, adverse-event counts describe reported events within the observation and reporting framework used by a study. They do not, by themselves, establish comparative risk. This single-group study has no like-for-like control group described, so the registry record does not provide a randomized safety comparison. The serious-event term and percentage should therefore be read as registry safety information, not as a causal estimate or a comparison with another intervention.

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

The registry record describes a completed study of an 11-week autoimmune protocol diet intervention in adults with active Crohn disease or ulcerative colitis. Its primary question concerns clinical remission among participants with Crohn disease, using an HBI score below 5 at 11 weeks. The record does not report the number of Crohn disease participants who met that definition. As a result, it does not establish the observed remission frequency or its statistical precision.

The design also limits what an outcome change could mean. The study is listed as single group, with allocation not applicable and no masking. There is no randomized comparison in the record. In general, observations made in one group cannot by themselves show that an intervention caused a change, because other explanations may contribute. The registry record does not report a control group that could support a direct contrast.

The primary endpoint applies to Crohn disease, not to the ulcerative colitis participants. The registry reports that 9 participants had Crohn disease and 6 had ulcerative colitis, and that the ulcerative colitis participants were not included in the Crohn disease subgroup analysis. The endpoint therefore should not be interpreted as a result for ulcerative colitis or for all participants with inflammatory bowel disease.

The record identifies secondary outcome areas, including mucosal healing, inflammatory biomarkers, gene ontology terms, and fecal microbiome composition. Their outcome results and statistical analysis details are not reported in the registry record. Safety entries include a serious adverse event, an other adverse event, and no deaths as listed, but the record does not report causal attribution. These entries do not provide a comparative safety estimate.

Overall, the registry supports a description of the study design, population, endpoint definition, and listed safety events. The missing primary outcome count, uncertainty estimate, comparator, and statistical-plan details prevent a conclusion about the size, precision, or cause of any change. The record does not establish whether the primary remission endpoint was met.

14. Why This Trial Matters Statistically

This study raises a statistical question that is important whenever a clinical intervention is evaluated in a small, single-group setting: what can be learned from measuring participants during an intervention when there is no concurrent comparison? Such a study can describe what was measured in the group, but a causal interpretation requires stronger support than a within-group observation alone. The design context is essential to interpreting any reported change.

The primary outcome is also defined for a specific subgroup. The endpoint concerns remission in Crohn disease, while the enrolled study population includes both Crohn disease and ulcerative colitis. Keeping the endpoint population distinct from the full study population prevents an outcome in one disease subgroup from being generalized to participants with another condition. The registry record explicitly excludes the ulcerative colitis participants from the Crohn disease subgroup analysis.

Statistical precision matters alongside the endpoint definition. A count of participants meeting a threshold would need to be read with its denominator and uncertainty estimate. Neither the remission count nor a confidence interval is reported in the registry record. Without them, readers cannot judge the magnitude or precision of the primary result. In general, a study’s enrollment alone does not reveal whether an estimate is precise or whether a design was adequately powered.

The listed secondary outcome areas illustrate another broader issue: studies may examine outcomes on different scales, and multiple analyses can complicate interpretation. The registry record does not report how multiplicity, missing measurements, or the statistical analysis plan were handled. These details matter for understanding how results were selected, analyzed, and interpreted. The record is therefore informative about the question and design, while leaving central elements of the statistical evidence unreported.

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 primary limitation for interpreting the main question is that the registry record does not report the number of participants with Crohn disease who achieved clinical remission. It also does not report an uncertainty estimate for that endpoint. Consequently, readers cannot evaluate the observed remission frequency or its precision from this record.

The study is described as single group, with no randomized comparator. This prevents a direct controlled comparison and limits causal interpretation. The record lists masking as none. It does not report whether outcomes were assessed using procedures intended to reduce the influence of knowledge of treatment, nor does it describe other safeguards against bias.

The primary endpoint applies only to Crohn disease. The registry states that participants with ulcerative colitis were not included in the Crohn disease subgroup analysis. Any interpretation must therefore keep that distinction clear; the primary endpoint does not represent an outcome estimate for ulcerative colitis. The record does not report further details about participant characteristics or the representativeness of the enrolled group.

The registry lists secondary outcomes, but their results and analysis details are not reported in the registry record. The statistical plan, approach to missing measurements, analysis population, multiplicity strategy, and sample-size justification are also not reported. These gaps limit assessment of how outcomes were handled and how the investigators intended to interpret them. The listed adverse-event figures do not include a reported causal assessment, and the single-group design does not provide a comparative safety estimate.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Autoimmune Protocol Diet and Inflammatory Bowel Disease — NCT03512327.
• Registry record last updated 2025-01-09; status last verified 2024-12.
• Results first posted 2025-01-09.
• 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 registry describes a completed, single-group study sponsored by Scripps Health, evaluating an 11-week autoimmune protocol diet intervention in adults with active Crohn disease or ulcerative colitis. Enrollment is listed as 15, with 9 participants with Crohn disease and 6 with ulcerative colitis. The primary endpoint is the number of Crohn disease participants in clinical remission at 11 weeks, defined as an HBI score below 5.

The registry record does not report the primary remission count or its uncertainty. Allocation is listed as not applicable and masking as none; no randomized comparison is described. Secondary outcomes cover mucosal healing, inflammatory biomarkers, gene ontology terms, and fecal microbiome composition. Safety entries list 1 serious adverse event, 1 other adverse event, and 0 deaths. Small bowel obstruction is listed as a serious adverse event term with 6.7%. Statistical analysis details and causal attribution for adverse events are not reported in the registry record.