Gulf War Digestive Health Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gulf War Digestive Health Study (NCT00680836), a randomized na study. The primary outcome is Global Improvement Scale.

2. Clinical Question

The registry’s stated purposes were broader than this randomized comparison: estimating chronic gastrointestinal illness burden among Persian Gulf veterans, examining whether small bowel bacterial overgrowth was associated with chronic diarrhea, and assessing whether eradication of that overgrowth reduced diarrhea, abdominal pain, and bloating. The posted randomized treatment results address the comparison of rifaximin and placebo on the listed symptom outcomes. The registry record does not report a primary outcome analysis of disease burden or an association analysis of bacterial overgrowth.

The primary score is an average over seven daily ratings, not a change from baseline. A group difference therefore describes the recorded end-of-treatment scores between groups; it does not directly describe change within each participant from pretreatment status. The scale’s interpretation is directional: lower values correspond to symptoms getting worse, the middle value to no change, and higher values to improvement. The registry record does not report a minimum difference considered clinically important.

3. Trial Design

This was a randomized, triple-masked, parallel-group study of rifaximin and placebo. The registry lists the study as completed and records enrollment of 54. Its start was recorded as 2007-10, and primary completion as 2008-10. The phase is listed as NA. The sponsor was the US Department of Veterans Affairs.

The arm descriptions identify the treatment group as participants with IBS receiving rifaximin and the placebo group as participants with IBS receiving placebo. The posted primary outcome summaries include 25 participants in the active group and 19 in the placebo group. Those outcome counts do not equal the registry’s overall enrollment. The registry record does not report participant disposition or explain the difference between enrollment and the primary outcome counts, so the reason should not be inferred from these figures alone.

Triple masking indicates that the registry classifies the study as masked at three levels, but the identities of the masked parties are not reported in the registry record. Details of the randomization sequence, allocation concealment, treatment dose and duration beyond the two-week outcome timeframe, and adherence procedures are also not reported in the registry record.

The primary outcome is a continuous score summarized with a mean and standard deviation. The registry lists six outcome measures and six analyses, and also names stool frequency among the secondary outcomes. However, only five secondary outcome records are posted. The registry record does not explain the difference or identify the missing outcome record. No further assumptions about the protocol or analysis plan can be established from the posted design information.

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

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.

Population: A total of 54 patients were randomized. Of that 54 patients,10 patients were excluded from the analyses. Reasons included, patient withdrawal, physician decision, and loss to follow up.Total of 44 patients were analysed. All data presented here, includes the 44 patients only.

6. Primary Endpoint

The registry lists the primary outcome as Global Improvement Scale, measured over Measured for seven days at the end of 2 weeks treatment and average score is calculated.

The primary endpoint was the Global Improvement Scale, measured after two weeks of treatment. Participants rated whether their IBS symptoms had improved or worsened over seven days; the average of those daily ratings was used. The scale ranges from 1 to 7: scores from 1 to 3 indicate worsening, 4 indicates no change, and scores from 5 to 7 indicate improvement. The endpoint is expressed in scale units and summarized as a mean and standard deviation.

This outcome is intended to capture participants’ overall assessment of symptom change rather than a single symptom such as stool frequency or abdominal pain. Averaging ratings across seven days can represent the reported experience over that measurement period, rather than relying on a single daily score. That is a general property of repeated ratings; it does not establish how the registry handled incomplete daily responses, which is not reported in the registry record.

The endpoint was not measured at baseline. Consequently, the posted primary outcome is a comparison of the groups’ end-of-treatment average scores, not a baseline-to-follow-up change score. The registry record does not report a threshold for interpreting the size of a difference as clinically important, or explain how the scale was validated for this study. Interpretation should therefore stay close to the stated score anchors and the observed group comparison.

7. Results Posted in the Registry

• Active Group: mean 4.30 versus 4.30 on control; difference 0.00 (95% CI -0.57 to 0.57), standardized effect d = 0.00; z-test p = 1.000.

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.

Change in Stool Consistency

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Active Group: mean -0.30 versus -0.40 on control; difference 0.10 (95% CI -0.54 to 0.74), standardized effect d = 0.09; z-test p = 0.760.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Active Group and the control. The interval gives the range of effects that remain compatible with the data.

Change in Bowel Urgency

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Active Group: mean -0.10 versus 0.00 on control; difference -0.10 (95% CI -0.38 to 0.18), standardized effect d = -0.21; z-test p = 0.488.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Active Group and the control. The interval gives the range of effects that remain compatible with the data.

Change in Abdominal Pain With Bowel Movement

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Active Group: mean -0.20 versus -0.30 on control; difference 0.10 (95% CI -0.62 to 0.82), standardized effect d = 0.09; z-test p = 0.786.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Active Group and the control. The interval gives the range of effects that remain compatible with the data.

Across the posted secondary outcomes, the group summaries and reported tests do not present a consistent, clearly separated pattern favoring one group. The comparisons are generally small relative to the uncertainty reported or implied by the available summaries, and the reported tests do not provide strong evidence against their respective null comparisons. The secondary results therefore sit broadly alongside the primary result, which also does not show a clear between-group separation in the posted summaries.

That overall pattern should not be taken to mean that every symptom changed in the same way or that all outcomes have been ruled out. Each secondary measure has its own scale and interpretation, and the registry record does not provide a common clinical-importance threshold for comparing effects across them. Detailed endpoint estimates and analyses should be interpreted on their own terms rather than combined into a single overall effect.

Secondary outcomes are ordinarily supportive or exploratory unless a prespecified analysis plan gives them a confirmatory role. The registry record does not report a hierarchy, multiplicity adjustment, or the planned status of each secondary test. When several outcomes are tested, unadjusted p-values can overstate the strength of evidence from an isolated result because multiple opportunities for a notable result have been examined. This general concern makes the secondary findings carry less weight than a clearly prespecified primary analysis, particularly when the analysis plan and handling of missing outcomes are not reported.

The record lists six outcome measures, but only five secondary outcome records are posted. The missing record and the absence of information about outcome selection make it difficult to establish whether the posted set captures all planned secondary findings. The secondary results are best treated as descriptive context for the primary comparison, not as independent proof of a treatment effect or its absence.

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

• Change in Stool Frequency (Number of Bowel Movements Per Day)
• Change in Stool Consistency
• Change in Bowel Urgency
• Change in Abdominal Pain With Bowel Movement
• Change in Bloating

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean difference represent?

A mean difference compares the average outcome in one group with the average in the other. Here, the outcome is the Global Improvement Scale average after treatment, and the group means are both 4.3. Using these displayed means, the unadjusted difference is 0.0. This is a descriptive comparison of the posted group summaries. It is not a comparison of individual changes because baseline scores were not collected for this endpoint.

Standard deviation describes how dispersed individual scores are around a group mean. The posted standard deviations are 1.0 in the placebo group and 0.9 in the active group. A standard deviation is not the same as the uncertainty in the mean: uncertainty in a group mean also depends on how many observations contribute to it. The registry’s comparison calculation uses the displayed group sizes and variability to estimate uncertainty in the difference.

How should the t-test and p-value be read?

The sponsor’s reported primary analysis is a two-sided t-test of the mean difference in final values. In general, a t-test evaluates whether an observed difference in means is unusual under a model in which the population means are equal, accounting for sampling variability. A two-sided test considers departures in either direction. The reported p-value is 0.26. It should be read as a measure of compatibility with the null model under the test’s assumptions, not as a measure of the size or importance of an effect.

The unadjusted recalculation from the posted primary group summaries gives p = 1.0. This is a simple calculation from summary statistics, not a replacement for an analysis using participant-level data. The sponsor’s reported estimate and test are distinct posted results, and the registry record does not explain their difference from the summary-based recalculation. The underlying participant-level values, model details beyond the test label, and any adjustments are not reported in the registry record.

What does a confidence interval add?

A confidence interval expresses uncertainty around an estimate. In general, a 95% confidence procedure is designed so that intervals constructed repeatedly under its assumptions would cover the target parameter at the stated rate. It does not mean there is a 95% probability that this particular fixed interval contains the true effect. The sponsor-reported primary interval is -1.0 to 0.3. Since it contains 0, the data do not exclude no difference under that reported interval. Its width also signals that the estimate is not precise enough to pin down a narrow range of possible differences.

Confidence intervals rely on assumptions of the analysis, such as how observations are sampled and how variability is modeled. The registry reports the test label and interval but does not give enough detail to assess all assumptions or reproduce the sponsor’s analysis. The recalculated summary-based comparison is also an approximation from aggregated information and cannot recover features of participant-level data.

What do the sample-size illustrations mean?

The posted planning illustrations concern secondary outcomes, not the trial’s original design. They express participants per arm for 80% or 90% power under stated assumptions, using the observed effect or a stated fraction of it, equal allocation, a two-sided significance level of 0.05, and a normal approximation. These are planning illustrations, not observed power and not evidence that the original study was designed with those sample sizes. The registry record does not report the trial’s own sample-size justification or design assumptions.

General statistical interpretation: planning from an observed effect can be unstable when the observed groups are small, because the effect estimate itself is uncertain. A smaller target effect generally requires more participants to detect under otherwise comparable assumptions. The illustrations should therefore be read as conditional scenarios, not as forecasts of a future study’s actual results or requirements.

Why do unadjusted secondary tests need caution?

When several outcomes are tested, the chance of at least one apparently notable result can increase if each test is interpreted separately without accounting for multiplicity. Adjustment methods or a prespecified hierarchy can address that issue, but neither is reported in the registry record. Secondary analyses can help describe the pattern of measured symptoms, but they are less persuasive as isolated confirmatory findings when the analysis plan and multiplicity handling are unknown.

The registry lists six outcome measures and six analyses, while five secondary outcome records are posted. It does not report the analysis population for each outcome, how missing values were handled, or whether all analyses followed a prespecified plan. These gaps limit independent assessment of the statistical methods and the strength of conclusions drawn from individual secondary tests.

11. Confidence Intervals and Precision

The sponsor-reported primary estimate is a mean difference of -0.3, with a 95% confidence interval from -1.0 to 0.3. The interval includes 0, so the reported results are compatible with no difference. They are also compatible with effects on either side of 0 within the interval. Because the scale’s direction is defined by its anchors, a value below 0 would indicate a lower average score for the group represented by the reported difference, but the registry does not explain the sign convention for the reported comparison.

The interval’s breadth is important alongside its center. An estimate near 0 does not by itself show that the true difference is very small; the interval describes uncertainty and includes a range of possible values. The registry does not report a threshold for a clinically important difference, so the interval cannot be classified against such a threshold.

The summary-based recalculation uses the displayed means, standard deviations, and group sizes and produces a difference of 0.0 with p = 1.0. It should not be treated as a participant-level reconstruction of the sponsor’s result. The registry record does not provide a confidence interval for that recalculation in the reported analysis, and the sponsor’s own confidence interval remains a separate posted result.

In general, confidence intervals are more informative than a threshold-only decision because they show both the estimate and its uncertainty. Here, both the sponsor’s interval and the identical displayed means place the comparison near no difference, but the record does not establish equivalence or rule out all potentially important effects. The relatively limited outcome group counts, together with the absence of participant-level data and a stated importance threshold, constrain how finely the result can be interpreted.

12. Analyses Reported by the Sponsor

The sponsor reports a two-sided t-test for the mean difference in final values. Its estimate is -0.3, with a 95% confidence interval from -1.0 to 0.3 and p = 0.26. The interval includes 0. The posted arm summaries, by contrast, give a mean of 4.3 in both groups, and a simple unadjusted recalculation from those means gives a difference of 0.0 and p = 1.0.

These are not numerically identical results. The registry record does not explain why the sponsor-reported estimate differs from the recalculation based on the displayed summaries. It does not provide participant-level observations or further analysis details that would resolve the difference. The discrepancy indicator in the record is false; therefore, the special circumstance in which a flagged discrepancy would require the sponsor’s analysis to take precedence does not apply. The sponsor’s analysis should still be described as the analysis reported by the registry, while the summary-based result should be identified as a recalculation rather than substituted for it.

Both presentations are centered close to no difference, but they do not supply the same estimate or test result. The sponsor’s confidence interval is the available reported uncertainty interval for the primary analysis. The recalculation is limited to the rounded group summaries and cannot reproduce analyses that depend on information not contained in those summaries.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and six analyses, but it does not report a multiplicity strategy. When a study examines several outcomes, repeated testing can increase the chance of at least one result appearing notable by chance. General approaches include adjusting the testing threshold or specifying a hierarchy in which outcomes are assessed in a planned order. Neither approach is reported in the registry record, so the secondary p-values should be read as unadjusted evidence unless otherwise specified in the posted results.

The registry record does not report how missing observations were handled, whether the primary analysis followed an intention-to-treat principle, or how participants were included in each outcome analysis. The primary endpoint summaries include 19 participants in the placebo group and 25 in the active group, whereas overall enrollment is 54. These counts alone do not identify why fewer participants appear in the outcome summaries, whether observations were missing, or whether the analysis used a particular population definition. Participant disposition is not reported in the registry record.

The Global Improvement Scale was not measured at baseline, so baseline adjustment or within-participant change analysis for that endpoint is not reported. The registry does not say whether daily ratings were complete for all participants or how an average was calculated if some daily ratings were unavailable. These details matter because missingness and analysis choices can affect the estimate and its uncertainty.

The record also lists six outcome measures but posts five secondary outcome records. It does not explain the unposted outcome or whether its absence reflects missing reporting, a change in analysis, or another reason. The original protocol, statistical analysis plan, interim analysis procedures, and sample-size justification are not reported in the registry record. Without these details, it is not possible to verify which analyses were prespecified or how selection and missing data may have shaped the posted results.

14. Safety Results

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

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

The registry reports no serious adverse events among 27 participants at risk in the placebo group and 27 at risk in the active group. It also reports 10 other adverse events in the placebo group and 14 in the active group, with 27 at risk in each group. These are event counts as recorded; the registry record does not describe event severity beyond the serious-versus-other classification, event types, timing, or whether participants could contribute more than one event.

Deaths are not reported in the registry record. No serious adverse event terms are listed. A zero count in the posted serious-event summaries means none were recorded in these groups during the reported period; it does not establish that the risk of a serious event is absent. The registry record does not report the safety observation period or provide enough detail to assess completeness of adverse-event collection.

The adverse-event figures should be interpreted descriptively. They do not by themselves establish a causal difference between treatments, and the group counts and missing details limit comparisons. Safety conclusions require context about event definitions, exposure, follow-up, and participant-level events, which is not reported in the registry record.

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

The primary result describes average Global Improvement Scale ratings at the end of two weeks of treatment. The two displayed group means are 4.3, and the sponsor’s reported estimate has a confidence interval that includes 0. Taken together, the posted results do not show a clear difference between the groups on this endpoint. They do not establish that the treatments are equivalent, nor do they prove that no difference exists.

The score’s anchor of 4 means no change, but the endpoint was not measured at baseline. The group mean therefore cannot be read as a measured change from pretreatment status. Nor does an average reveal how many participants improved, worsened, or reported no change. The registry record does not provide the distribution of individual scores or a clinically important difference threshold.

The result applies to the posted primary comparison and the outcome participants recorded over seven days at the end of treatment. It does not directly answer every broader objective in the study description, including disease burden or the association between bacterial overgrowth and chronic diarrhea. The secondary outcomes add symptom-specific information, but their unadjusted analyses and incompletely reported plan warrant caution.

General statistical interpretation: failure to find strong evidence of a difference is not the same as evidence that two treatments have the same effect. A claim of equivalence or non-inferiority ordinarily requires a specific design, margin, and analysis. These are not reported in the registry record. The result is consequently best understood as an uncertain comparison that is centered near no difference in the posted summaries, not as a definitive statement about treatment effects beyond this study’s measurements and analysis.

16. Why This Trial Matters Statistically

This trial illustrates why a p-value should not be read alone. The posted primary group means are identical at the displayed precision, the summary-based recalculation is centered at 0.0, and the sponsor-reported interval includes 0. The estimate and interval convey the location and uncertainty of the comparison, while the p-value addresses compatibility with a null model under specific assumptions. Neither the p-value nor the near-zero estimate answers whether any difference would matter clinically.

It also shows the limits of aggregated results. The sponsor’s reported estimate differs from the recalculation based on the displayed group means, and the registry record does not explain why. Without participant-level data and fuller analysis details, the recalculation cannot reproduce or diagnose the sponsor analysis. Keeping those results distinct is important for transparent interpretation.

The trial record also demonstrates why endpoint definitions matter. The primary measure is an end-of-treatment average on a scale with explicit anchors, but it was not collected at baseline. Its mean therefore answers a different question from a change score. The secondary outcomes use other measures, and multiple unadjusted tests require more caution than a single prespecified primary comparison.

Finally, planning illustrations based on observed secondary effects are not observed power and do not reveal how the original study was designed. The registry does not report the original sample-size justification, analysis populations, missing-data procedures, or multiplicity plan. These absences limit how confidently readers can move from posted statistics to broader conclusions, and underscore the importance of complete registry reporting.

17. 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 has no baseline measurement, so the posted result cannot describe within-participant change from baseline. The registry does not state a clinically important difference for the scale, nor does it provide participant-level scores or a distribution of responses. The group means and standard deviations cannot show how many individuals improved, worsened, or reported no change.

The primary outcome summaries include 19 placebo participants and 25 active participants, compared with enrollment of 54. The record does not report participant flow, reasons for exclusion or missing outcomes, or the analysis population. It therefore does not establish whether the difference in counts reflects missing outcome data or another analysis decision. The posted adverse-event risk sets are 27 in each group, and the record does not explain how those counts relate to enrollment or outcome analyses.

The sponsor-reported primary estimate differs from the simple recalculation using the displayed group means. The registry record does not explain this difference, provide participant-level data, or give additional analysis detail sufficient to reconcile the results. The recalculation is limited by reliance on rounded summary statistics, while the sponsor’s reported confidence interval and test are not accompanied by a full analysis plan.

Other limitations include the absence of reported details on randomization implementation, masking roles, missing-data handling, analysis populations, sample-size justification, interim analyses, and multiplicity control. Only five secondary outcome records are posted despite six listed outcome measures. The safety record does not provide event types, follow-up duration, or deaths. These reporting limitations constrain assessment of both the statistical methods and the completeness of the evidence.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Gulf War Digestive Health Study — NCT00680836.
• Registry record last updated 2014-08-29; status last verified 2014-08.
• Results first posted 2014-08-29.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The Gulf War Digestive Health Study was a completed, randomized, triple-masked, parallel-group comparison of rifaximin and placebo, with enrollment of 54. Its primary outcome was the Global Improvement Scale average after two weeks of treatment, based on daily ratings over seven days. The endpoint was not measured at baseline.

The posted primary means are 4.3 in both groups. The sponsor reports a mean difference of -0.3, with a 95% confidence interval from -1.0 to 0.3 and p = 0.26. A simple unadjusted recalculation from the posted group summaries gives a difference of 0.0 and p = 1.0; the registry record does not explain the difference between these results. The record does not report a clinical-importance threshold, missing-data methods, multiplicity handling, or the original sample-size justification.