Effectiveness and Safety in Patients With Crohn´s Disease in Clinical Routine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness and Safety in Patients With Crohn´s Disease in Clinical Routine (NCT01083680), a registered phase not stated study. The primary outcome is Mean Change From Baseline in Crohn's Disease Activity Index (CDAI) at Each Visit.

2. Clinical Question

The study concerns treatment in daily clinical practice rather than a randomized treatment contrast. Its primary question is consequently descriptive: the record identifies a measure of disease activity and planned follow-up visits, but does not provide the numerical estimates needed to describe the size or precision of change. The results cannot establish what would have happened to comparable participants under a different treatment or no treatment. Without a comparison group, changes over time could reflect several influences, including the course of disease and care received in routine practice; the registry record does not quantify those influences.

3. Trial Design

This was a post-marketing observational study of adalimumab for moderate to severe Crohn's disease in daily clinical practice. The record lists the study as completed, with enrollment of 4107. The study start is recorded as 2007-05 and primary completion as 2015-12. AbbVie (prior sponsor, Abbott) is listed as sponsor. The stated purpose was to evaluate long-term safety and effectiveness among participants treated as recommended in the product label.

The arm description identifies participants with Crohn's disease treated with adalimumab (HUMIRA®) in routine clinical practice. The registry does not describe a randomized allocation or a separate control arm; allocation is not stated. The record specifically indicates that this is not a randomized comparison and that the arms are not a like-for-like control comparison. A treatment contrast against another therapy or usual care is therefore not available from the design described.

The primary endpoint is mean change from baseline in CDAI at visits listed for months 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60. The record identifies the outcome as continuous, with a mean and standard deviation. Effectiveness analyses included all participants with evaluable data. The registry also lists mean Harvey Bradshaw Index over time and compliance with self-injection via the Humira®-PEN among secondary outcomes. It lists 6 outcome measures and 0 analyses. The numerical primary endpoint results and details of analysis procedures are not reported in the registry record.

The observational setting is relevant to interpretation: treatment took place in clinical routine, not under a randomized allocation described in the record. This can make results informative about recorded experience in that setting, but does not by itself isolate a causal effect of adalimumab. The record does not report specific recruitment procedures, visit completion, or the reasons participants might have missing assessments.

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:

Analysis population for the primary outcome, as defined in the registry: Effectiveness analyses included all participants with evaluable data.

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: Baseline analyses accounts for safety analysis set population (all participants who received at least 1 dose of study drug).

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Crohn's Disease Activity Index (CDAI) at Each Visit, measured over Months 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60.

The primary endpoint is mean change from baseline in the Crohn's Disease Activity Index (CDAI) at each listed visit. CDAI is a clinical activity measure developed for use in clinical trials. It combines eight variables, including patient-reported symptoms and general well-being, along with objective information such as medication use, laboratory variables, abdominal mass or complications, and weight. Symptom information is recorded daily and summed for the week; weighted values for the items are combined to produce the CDAI score.

Higher CDAI scores indicate greater disease activity. The record describes scores below 150 as indicating remission, 150 to 219 as mildly active disease, 220 to 450 as moderately active disease, and scores above 450 as severely active disease. Negative changes indicate reductions in disease activity. These ranges help give clinical context to a score, while the endpoint itself summarizes the average change from baseline across participants with evaluable data.

A mean is useful for describing the average direction and magnitude of change in a continuous measure. It does not show how individual participants changed, whether changes were similar across participants, or how many crossed a particular CDAI threshold. The standard deviation describes spread around the mean and helps distinguish a tightly clustered set of values from more variable individual responses. The registry identifies mean and standard deviation as the summary statistics, but numerical CDAI estimates are not reported in the registry record. As a result, the direction, size, and variability of observed change cannot be assessed from the available endpoint results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous, and the registry specifies reporting a mean and standard deviation. The record gives the endpoint definition and visit schedule, but not the numerical outcome estimates, inferential tests, or uncertainty intervals. The explanations below describe general statistical principles rather than methods confirmed as used in this study.

What does a mean change describe?

A mean change summarizes the average difference between a participant's follow-up score and baseline score among the observations included in the calculation. It provides a compact description of the center of the observed changes. A mean can be influenced by values far from the rest of the data, and different individual patterns can produce the same average. For that reason, a mean is most informative when read alongside a measure of spread and information about the participants contributing data.

For this endpoint, negative changes are defined as reductions in disease activity. A numerical mean change would therefore indicate the average direction and size of change in the analyzed observations. It would not, on its own, indicate that every participant improved, that all participants reached a remission threshold, or that treatment caused the change. The registry record does not report the actual mean changes for the listed visits.

What does the standard deviation add?

In general, the standard deviation describes how dispersed individual observations are around their mean. A smaller standard deviation indicates that values are more closely grouped around the mean, while a larger one indicates greater spread. It is not the same as the standard error, which describes uncertainty in an estimated mean. Standard deviation is mainly about variation among observations; standard error and confidence intervals concern the precision of an estimate.

A confidence interval is, in general, a range calculated by a statistical procedure to express uncertainty around an estimate. Its width depends on features such as the amount of information and variability in the data, as well as the chosen method. No confidence interval for the primary CDAI outcome is reported in the registry record. It is therefore not possible to assess the precision of a mean change from the posted endpoint information.

Why does the visit schedule matter?

The primary endpoint is evaluated at months 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54 and 60. Repeated observations can describe how an outcome develops over time, but the observations from the same participant are generally related rather than independent. A statistical method for repeated measurements may account for that relationship and for differences in the amount of data available at different visits. The registry record does not report the method used to model repeated measurements, if any, or how incomplete follow-up was handled.

Visit-specific means can also be affected by changes in who contributes data over time. If participants with available observations at later visits differ from those with earlier observations, the apparent pattern in averages may partly reflect a change in the analyzed group. This is a general concern in longitudinal data. The record identifies the effectiveness population as participants with evaluable data but does not provide visit-specific counts or a description of how evaluability was determined.

Why consider multiplicity?

In general, testing or estimating results at multiple visits raises a multiplicity issue. When many statistical comparisons are made, the chance of at least one apparently notable result can increase if each is assessed separately. Researchers may define a primary time point, adjust inference across comparisons, or focus on estimation rather than repeated significance tests. The registry lists multiple primary endpoint visits, but the analysis plan, any multiplicity procedure, and any inferential results are not reported in the registry record. It would not be appropriate to assume a particular approach.

What can an observational mean establish?

An observed mean change describes what happened in the analyzed observations, subject to the data and methods used. It does not automatically estimate what would have happened without treatment. In a randomized comparison, allocation can support an interpretable contrast between groups under the design and analysis assumptions. Here, no randomized control group is described, and allocation is not stated. The record's own caution is that this is not a randomized comparison and that arms are not a like-for-like control comparison. A within-group change must therefore be distinguished from a controlled treatment effect.

Adjustment for measured characteristics can sometimes address observed differences in nonrandomized data, but it cannot guarantee removal of bias from unmeasured factors. No adjusted analysis is reported in the registry record. This is a general explanation of the limitation, not a claim about an analysis undertaken in this study.

How should planning illustrations be read?

Sample-size illustrations are planning calculations, not observed study findings and not evidence of power achieved by the completed study. The described planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The record says time-to-event illustrations use a total number of events and other illustrations use participants per arm. Those assumptions are not a description of this observational study's design: a like-for-like two-arm comparison is not described, and the numerical effect and illustration results are not reported in the registry record.

In general, a planning calculation estimates the amount of information needed to detect a specified effect under stated assumptions. Its result depends on the selected effect, variability, allocation, and statistical procedure. It should not be read as a count of participants who were observed to experience an outcome, nor as proof that a study had a particular probability of detecting an effect. No numerical planning outputs or sample-size justification are reported in the registry record.

Finally, the registry lists 0 analyses. This absence of analysis entries means that the record does not supply a numerical analysis result to interpret for the primary endpoint. It does not establish which computations may or may not have been performed outside the registry; such details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is listed at multiple visits, from month 3 through month 60. When results are assessed repeatedly across visits, the interpretation of statistical tests can depend on whether the analysis accounts for multiple comparisons or identifies a primary time point in advance. The registry record does not report a multiplicity plan, a primary visit selected for inference, or statistical test results. No particular testing strategy should be inferred.

The effectiveness population is described as all participants with evaluable data. The record does not define evaluability, give the number analyzed at each visit, or explain whether participants with missing visits were excluded, imputed, or handled by another approach. The missing-data method is not reported in the registry record. This matters because the people contributing data may vary across visits, and the pattern and reasons for missingness can affect interpretation of longitudinal averages.

The registry lists 0 analyses and provides no numerical primary outcome estimates. It therefore does not report an analysis population count for CDAI at each time point, a strategy for missing data, or uncertainty estimates for the mean changes. Enrollment of 4107 should not be treated as the denominator for every effectiveness estimate: the record says analyses included participants with evaluable data, without specifying visit-level denominators.

These omissions constrain interpretation but do not establish that a particular approach was or was not used outside the registry record. They mean that the record does not provide the information needed to assess the handling of missing outcomes or multiplicity for the primary endpoint.

11. 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

Serious events with the highest arm-level rate: crohn's disease (1.4%), intestinal resection (1.2%), intestinal stenosis (0.8%), ileal stenosis (0.6%), anal abscess (0.6%).

The adverse-event summary lists 4107 participants at risk for serious adverse events and 548 affected. It also lists 4107 at risk and 0 affected in the other adverse-event category. These are the counts entered in the registry record; they should be read as recorded summaries, not as a comparison of treatment groups. The record does not report deaths.

The listed serious-event terms and recorded percentages are Crohn's disease (1.4%), intestinal resection (1.2%), intestinal stenosis (0.8%), ileal stenosis (0.6%), anal abscess (0.6%), and anal fistula (0.5%). These entries identify events recorded under those terms. They do not establish that each event was caused by adalimumab, and the listed terms should not be summed to infer a total because the record does not state whether categories overlap.

In general, a count of participants affected is not necessarily the same as a count of all event episodes: one participant may have more than one event. The registry summary does not provide further detail on event timing, duration, attribution, or overlap among terms. The safety figures are descriptive and do not provide a controlled estimate of risk relative to an alternative treatment.

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

The study is relevant as a post-marketing observational evaluation of adalimumab in routine clinical practice for Crohn's disease. The registry describes a substantial enrollment, a long-term intent, and repeated assessment of disease activity with CDAI. It also records serious adverse events and identifies terms appearing in the safety summary. These details show what the study set out to evaluate and what kinds of outcomes the record contains.

The posted primary outcome information does not include numerical CDAI changes or standard deviations. Consequently, it does not show whether the mean score rose or fell, the size of any change, or how much individual scores varied. The scale definitions explain how to interpret a score if reported; they do not establish an observed improvement or response. A definition of negative change as improvement is not itself a result.

The design does not include a described randomized comparator. Therefore, even a reported within-group change would not alone show how outcomes would compare under another treatment or no treatment. Observational results can describe experience in the treated population, but causal interpretation requires assumptions and analyses beyond a simple before-and-after summary. The record does not report an adjusted comparative analysis.

The safety summary is also descriptive. It records 548 affected by serious adverse events among 4107 at risk and gives percentages for selected serious-event terms. These observations are not evidence on their own that the treatment caused the events, nor do they establish comparative safety. Deaths are not reported in the registry record.

Thus, the record supports a description of study purpose, setting, endpoint, and selected safety entries, but not a conclusion about the magnitude or precision of CDAI change or a causal treatment effect. The absence of numerical primary results is a central constraint on what can be inferred.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a treatment's evaluation in routine practice and a randomized comparison. Post-marketing observational studies can describe outcomes and safety events recorded among people treated in clinical settings. That perspective is useful for understanding what was monitored outside a described randomized allocation. At the same time, observed changes in a treated group do not isolate the effect of treatment from the many other influences that may shape outcomes over time.

The primary endpoint also illustrates why definitions and results are both essential. CDAI combines patient-reported and objective components, and the record explains the direction of its scale and the meaning of score ranges. Those details allow a reader to understand what a reported change would represent. Without numerical mean changes, standard deviations, and visit-level information, however, the endpoint definition cannot show the observed pattern or its precision.

The repeated visits make the analysis population and missing-data approach especially important. A trajectory across time is interpretable only with attention to who contributes observations at each visit and how incomplete data are treated. The registry record identifies an evaluable-data population but does not report visit-specific counts or methods for missing data. It also does not report a multiplicity plan for results across the listed visits.

Finally, the safety summary demonstrates the need to distinguish event counts from causal conclusions. A registry entry can document events and their recorded frequency, but a nonrandomized summary without a like-for-like comparator cannot establish whether observed events are more or less frequent because of treatment. These statistical distinctions apply broadly to clinical research and are particularly relevant when interpreting post-marketing observational evidence.

14. 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.

Several trial-specific limitations follow from the registry record. First, the study is observational, with no randomized comparison described and allocation not stated. The record explicitly cautions that this is not a randomized comparison and that arms are not a like-for-like control comparison. The design therefore does not provide a direct randomized estimate of treatment effect relative to a comparator.

Second, numerical results for the primary endpoint are not reported in the registry record. Although the endpoint, scale interpretation, summary statistics, and planned visits are identified, no mean change or standard deviation is available for interpretation. The record lists 0 analyses, so there is no numerical analysis result for CDAI in the registry entry.

Third, the effectiveness population consists of participants with evaluable data, but the record does not report visit-specific denominators, define evaluability, or describe missing-data handling. This makes it difficult to assess how much information contributed to the longitudinal endpoint or whether the analyzed population changed across visits.

Fourth, the analysis plan is not described. Multiplicity handling across repeated visits, inferential methods, uncertainty intervals, and any adjustment for confounding are not reported in the registry record. The sample-size assumptions describe planning illustrations rather than a reported design justification or observed power; numerical illustration results are not available.

Finally, safety information is presented as a descriptive summary. The record does not provide further detail about timing, attribution, or possible overlap among serious-event terms. Deaths are not reported in the registry record. These limitations restrict comparative and causal interpretation and leave important details of endpoint precision and safety context unresolved.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness and Safety in Patients With Crohn´s Disease in Clinical Routine — NCT01083680.
• Registry record last updated 2017-04-04; status last verified 2017-03.
• Results first posted 2017-04-04.
• 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.

18. Record Summary

The registry record describes a completed post-marketing observational study of adalimumab (HUMIRA®) in routine clinical practice for Crohn's disease. Enrollment was 4107. The study was intended to evaluate long-term safety and effectiveness among participants treated as recommended in the product label. The listed primary endpoint is mean change from baseline in CDAI at visits from month 3 through month 60.

Effectiveness analyses included participants with evaluable data. The record lists 6 outcome measures and 0 analyses, but does not report numerical CDAI results, visit-specific analysis counts, uncertainty intervals, or methods for missing data and multiplicity. It does not describe a randomized comparator.

The safety summary records 548 participants affected by serious adverse events among 4107 at risk and 0 affected in the other adverse-event category among 4107 at risk. Selected serious-event terms and percentages are recorded; deaths are not reported in the registry record. The available information supports description of the study and its recorded outcomes, but not a numerical interpretation of CDAI change or a causal comparison.