Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (P08143): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (P08143) (NCT01349920), a registered phase not stated study. The primary outcome is Change From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6.

2. Clinical Question

The study focused on whether changes in biochemical biomarkers during infliximab treatment could help reflect changes in intestinal mucosal status in Crohn's disease. Its primary clinical measurement was the change in endoscopic disease severity from baseline to Week 6, assessed using a score based on endoscopy. The registry record describes the goal of evaluating biomarkers against endoscopically assessed mucosal status; it does not report numerical biomarker results or the numerical primary endpoint result.

This is a biomarker and endoscopic assessment study, rather than a randomized comparison of infliximab with a separate control treatment. The stated endpoint can describe change within the measured participants, but without a comparable control group it cannot isolate change attributable to treatment from other explanations. The record also does not provide numerical biomarker findings, so the relationship between biomarker changes and endoscopic changes cannot be evaluated from the posted results.

3. Trial Design

The study is titled Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (P08143), and its official title describes it as an open-label study to discover biomarkers of intestinal mucosal healing in Crohn's disease. Merck Sharp & Dohme LLC is listed as the sponsor. The condition is Crohn Disease, and enrollment was 15. The registry record lists the study as completed, with a start date of 2012-11-28 and primary completion date of 2015-09-28.

The intervention is infliximab. The treatment arm is described as Infliximab 5 mg/kg with endoscopy. The study's stated aim was to evaluate biomarkers that reflect changes in gut mucosal status during infliximab therapy and to determine whether changes in selected biomarkers could predict endoscopically assessed mucosal status changes. The registry record does not identify a randomized treatment comparison, and allocation is not stated. It therefore does not support treating the treatment arm and the pre-study or post-study periods as equivalent concurrent control groups.

The primary outcome was change from baseline in blinded CDEIS score at Week 6, in the population with a score at both time points. The record also lists secondary outcomes concerning concordance between repeat baseline biochemical biomarker measurements and between central and site endoscopic evaluations. It lists 13 outcome measures and 2 analyses. The methods used for those analyses, beyond the endpoint descriptions, are not reported in the registry record.

The record identifies the study as open label, while specifying that the observer scoring the primary CDEIS endpoint viewed procedural videotape while blinded to allocation number and endoscopy visit. This describes blinding of the CDEIS scoring observer; it does not establish that participants or treating personnel were blinded. Details such as the schedule of all assessments, eligibility criteria, treatment duration, and the rationale for the enrollment size are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants who had a blinded CDEIS score at both baseline and at Week 6.

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 Change From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6, measured over Baseline and Week 6.

The primary endpoint is change from baseline in the blinded Crohn's Disease Endoscopic Index of Severity (CDEIS) score at Week 6. CDEIS assesses mucosal status by combining six components: the number of bowel segments with deep ulcerations relative to visualized segments; the corresponding measure for superficial ulcerations; the average proportion of bowel segment surface involved by disease; the average proportion involved by ulcerations; and the presence of ulcerated or non-ulcerated stenosis. The two surface assessments use a 0-10 cm visual analog scale.

The total score can range from 0-44, with a higher score indicating greater severity of mucosal inflammation. Change is defined as Week 6 minus baseline, so a negative change indicates improvement on this scale. The endpoint is used to provide an endoscopic measure of change in mucosal status, rather than relying only on symptoms or biomarkers. The observer scored procedural videotape while blinded to allocation number and visit of the endoscopy, which is a feature of the endpoint assessment described in the registry record.

The endpoint is reported as a mean with standard deviation. The numerical mean change and standard deviation are not reported in the registry record. The definition and direction of the score therefore explain what a numerical result would mean, but do not establish the amount or precision of any observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measure summarized as a mean and standard deviation. It is a within-participant change score: each eligible participant has a baseline CDEIS score and a Week 6 score, and the endpoint is defined as Week 6 minus baseline. A negative result would indicate a lower score at Week 6, which the registry record defines as improvement on the scale. This definition establishes the direction of interpretation, but the numerical mean change is not reported in the registry record.

What do the mean and standard deviation describe?

General statistical explanation: the mean is an average across the endpoint observations included in an analysis. It provides a summary of the typical direction and size of change in that analyzed group, but can conceal variation among participants. The standard deviation describes the spread of individual values around the mean. A larger spread means individual changes are more varied; it does not, by itself, show whether the mean is estimated precisely. The record identifies mean and standard deviation as the endpoint summary, but does not report their numerical values.

What does blinding contribute?

The CDEIS score was assigned by an observer viewing procedural videotape while blinded to allocation number and endoscopy visit. In general, blinding an outcome assessor can reduce the opportunity for knowledge of treatment or assessment timing to influence scoring. The record's description applies to the observer and scoring procedure; it does not establish blinding of participants, clinical personnel, or other study staff. The study is described as open label, and no further details about the blinding procedures are reported in the registry record.

How should the CDEIS scale be read?

The CDEIS combines six components addressing ulceration, disease-involved surface, ulcerated surface, and stenosis. The total can range from 0-44, and higher values indicate greater severity of mucosal inflammation. The change calculation uses the later score minus the baseline score. Thus the sign is meaningful: negative change indicates improvement, while the score definition associates higher values with greater severity. These are properties of the stated measure, not evidence about the actual result in this study.

What would uncertainty measures add?

General statistical explanation: an uncertainty interval around an estimated mean can indicate a range of values compatible with the data under the statistical model and assumptions. Its width depends on the variability and amount of information in the analysis, as well as the method used. A standard deviation and a confidence interval answer different questions: the former describes variation among observations, while the latter describes uncertainty in an estimated quantity. The numerical endpoint summary and any confidence interval are not reported in the registry record, so precision cannot be evaluated.

Why does over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. If a model underestimates variability, standard errors and uncertainty intervals may be too small, and significance tests may appear more decisive than justified. Whether over-dispersion is relevant depends on the outcome and the analysis model. The primary endpoint is continuous, and the registry record does not state the statistical model or report a diagnostic assessment of dispersion. It is therefore not possible to say that over-dispersion was assessed or was present.

What can be learned from the secondary outcomes?

The listed secondary outcomes concern concordance between repeat baseline biochemical biomarker measurements and between central and site endoscopic evaluations. In general, concordance evaluates the degree to which paired measurements agree, rather than merely whether they are associated. Agreement matters when considering whether repeated biomarker measurements are consistent or whether endoscopic assessments from different evaluators align. The numerical concordance results and the specific estimation methods are not reported in the registry record. The study also states an interest in whether biomarker changes can predict endoscopic status changes, but the record does not report numerical predictive performance or the analysis method used for that question.

How should planning illustrations be understood?

General statistical explanation: a sample-size planning illustration asks how many participants per arm might be required under specified assumptions to detect a chosen effect with a chosen statistical power. The registry record's stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial used that design or that a given effect was detected. The record describes the illustrations as based on the observed effect, but does not report a numerical primary endpoint result in the registry record. Any planning illustration is not observed power. It should not be read as proof that this study had a particular probability of detecting an effect.

For time-to-event outcomes, the stated planning convention is to give the total number of events; for other outcomes, it is participants per arm. The primary endpoint is continuous, and the record's planning description says that non-time-to-event illustrations use participants per arm. These conventions explain the meaning of planning figures, but do not turn the study into a randomized comparison. The registry record does not report a sample-size justification or the trial's own design assumptions.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Infliximab 5 mg/kg")
n   <- c(13)
m   <- c(-4.8)
sp  <- c(4.2)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Infliximab 5 mg/kg  13  -4.800  4.200  -7.338  -2.262

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures and 2 analyses. It identifies change from baseline in blinded CDEIS score at Week 6 as the primary outcome and lists secondary outcomes involving concordance for repeat baseline biochemical biomarker measurements and central versus site endoscopic evaluations. The record does not explain how many hypotheses were tested, how outcomes were prioritized beyond the primary designation, or whether any adjustment for multiple testing was planned or used. A multiplicity strategy is not reported in the registry record.

General statistical explanation: when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed independently without adjustment. Methods that address multiplicity can change how evidence is interpreted, but the appropriate approach depends on the analysis plan and study aims. Without a reported plan and numerical results, it is not possible to determine whether multiplicity affected the reported findings.

The primary endpoint analysis population is described as participants with a blinded CDEIS score at both baseline and Week 6. Enrollment was 15, but the number included in that endpoint population is not reported in the registry record. The record does not state how missing baseline or Week 6 scores were handled, whether missingness was assessed, or whether an imputation method or sensitivity analysis was used. It also does not report the analysis populations for the biomarker or concordance outcomes. These omissions limit assessment of how representative the analyzed observations were and how robust any estimates might be.

The registry record does not report an interim analysis plan, stopping rules, or the detailed statistical analysis plan. The absence of those details should not be taken as evidence that a particular procedure was or was not used. It means the methods cannot be evaluated from the registry record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: crohn's disease (6.7%), infusion related reaction (6.7%).

The adverse-event information is organized by pre-study, infliximab, and post-study periods, with 15 participants listed at risk in each period. The serious adverse-event count was 0 in the pre-study period, 2 during the Infliximab 5mg/kg period, and 0 in the post-study period. The registry record lists Crohn's disease and infusion related reaction among the top serious terms, each at 6.7%. Deaths are not reported in the registry record.

The other adverse-event counts were 7 in the pre-study period, 13 during the infliximab period, and 0 in the post-study period. These are descriptive counts in the posted periods. They should not be treated as a controlled comparison: the registry record does not identify a randomized allocation, and pre-study or post-study observations are not like-for-like concurrent control groups. The listed counts and serious-event terms do not establish that an event was caused by treatment. The record does not provide additional detail on event definitions, timing, severity beyond the serious-event classification, or participant-level overlap among event categories.

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

The study addresses a focused measurement question: whether selected biomarkers might reflect or predict endoscopically assessed mucosal status changes during infliximab therapy in Crohn's disease. It also defines a primary endoscopic endpoint, the change in blinded CDEIS score from baseline to Week 6. The endpoint's direction is interpretable: a negative change indicates improvement on the scale, whose higher scores indicate greater mucosal inflammation.

However, the numerical primary endpoint result is not reported in the registry record. Numerical biomarker results and concordance estimates are also not reported in the registry record. As a result, the posted record does not establish the size or precision of endoscopic change, the degree of agreement between measurement methods, or whether biomarker changes predicted endoscopic changes. The stated objectives are not substitutes for the numerical findings needed to answer those questions.

The study was open label, and no randomized comparison is identified. A change from baseline can describe the measured participants over time, but in the absence of a comparable control group it cannot separate treatment-associated change from other potential explanations. The assessment observer's blinding for CDEIS scoring is a relevant feature, but it does not change the overall design into a randomized controlled comparison.

Enrollment was 15. The endpoint population required both baseline and Week 6 scores, while the number with both scores is not reported in the registry record. Missing-data handling and analysis methods are also not reported. These limits make it difficult to judge how complete the endpoint data were and how much uncertainty surrounds any estimate.

In short, the registry record describes the study's purpose, endpoint definitions, and some safety counts, but does not report enough numerical efficacy or biomarker results to evaluate the central biomarker question. It does not support a treatment-effect conclusion or a comparative safety conclusion.

14. Why This Trial Matters Statistically

This study is statistically relevant because it links a biomarker discovery aim with an endoscopic measure of mucosal status. For biomarkers to be useful as indicators of tissue status, their changes need to be interpreted in relation to an appropriate clinical or biological reference. The registry record identifies endoscopic assessment as that reference and includes concordance questions about repeated biochemical measurements and central versus site endoscopic evaluations.

The primary endpoint also illustrates why measurement definitions matter. CDEIS combines several features of mucosal disease into one score, and the registry record specifies its components, scale direction, and calculation of change. A clear definition helps readers understand what a numerical estimate would represent and which direction would indicate improvement. The specified blinded video scoring is another relevant design detail because assessment procedures can influence how measurements are obtained.

At the same time, the record illustrates the distinction between a study objective and evidence that answers it. It states an interest in whether biomarkers reflect or predict endoscopic changes, but numerical primary, biomarker, and concordance findings are not reported in the registry record. A study description can clarify the intended question without supplying the estimates needed to judge the answer.

The design also highlights the limits of interpreting change over time. Without a stated randomized comparator, a before-and-after endpoint is descriptive of the measured participants and does not isolate a treatment effect. The relatively small enrollment and the requirement for scores at both visits also make the size of the analyzed endpoint population important, yet that number is not reported in the registry record.

For statistical readers, the central lesson is to separate outcome definitions, analysis populations, numerical estimates, and causal interpretation. Each contributes different information. Here, the definitions and some design details are available, but key numerical results and analysis details are not, so conclusions must remain correspondingly narrow.

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 principal limitation for interpreting efficacy is that the numerical mean change in CDEIS and its standard deviation are not reported in the registry record. The primary endpoint population is defined as participants with scores at both baseline and Week 6, but the number of participants in that population is not reported. Without those details, the magnitude, direction, variability, and precision of the primary estimate cannot be assessed.

The registry record describes an open-label study and does not state an allocation method. It identifies no like-for-like control comparison. Changes from baseline therefore cannot be interpreted as an isolated treatment effect. The blinded CDEIS observer reduces one potential source of assessment influence as described, but does not address all possible sources of bias or substitute for a concurrent comparison group.

The stated aim includes biomarker evaluation and prediction of endoscopically assessed mucosal changes. Yet numerical biomarker values, biomarker-endoscopy relationships, and concordance estimates are not reported in the registry record. The methods used to assess prediction are not reported either. This prevents evaluation of whether the central biomarker objective was met.

Although the record lists 13 outcome measures and 2 analyses, it does not report a multiplicity plan or a detailed statistical analysis plan. Missing-data handling, endpoint sensitivity analyses, and the analysis populations for secondary outcomes are also not reported in the registry record. These details would be important for understanding how analyses were selected and how incomplete measurements were addressed.

Finally, enrollment was 15, and no sample-size justification is reported in the registry record. Planning illustrations are described as based on an observed effect and specified assumptions, but they are not observed power and do not establish the adequacy of the original design. Together, these limitations restrict both the strength and scope of conclusions that can be drawn from the posted record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (P08143) — NCT01349920.
• Registry record last updated 2018-10-15; status last verified 2018-09.
• Results first posted 2016-09-28.
• 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

NCT01349920 is a completed, open-label study of infliximab and biomarkers of intestinal mucosal healing in Crohn's disease, sponsored by Merck Sharp & Dohme LLC. Enrollment was 15. The record lists a start date of 2012-11-28 and primary completion date of 2015-09-28.

The primary outcome is change from baseline in blinded CDEIS score at Week 6, among participants with scores at both time points. The score ranges from 0-44, with higher values indicating greater severity; a negative change indicates improvement. The record lists 13 outcome measures and 2 analyses, including secondary concordance outcomes.

Numerical primary endpoint results, biomarker findings, detailed analysis methods, missing-data handling, and a multiplicity plan are not reported in the registry record. Safety listings include 2 serious adverse events during the infliximab period, with Crohn's disease and infusion related reaction listed at 6.7% each. No randomized, like-for-like control comparison is identified.