Postmarketing Safety Surveillance European Registry of Crohn's Disease Patients Treated With Remicade or Standard Therapy (MK-2155-035): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Postmarketing Safety Surveillance European Registry of Crohn's Disease Patients Treated With Remicade or Standard Therapy (MK-2155-035) (NCT00705614), a registered phase not stated study. The primary outcome is Number of Participants With Serious Infections.

2. Clinical Question

The question is about safety surveillance in people treated in clinical practice, not a randomized test of whether one treatment is better than another. The registry also tracked health status, Crohn's disease activity, work and daily activity, fistulas, hospital stays, and surgery. Participants who began in the standard therapy group and later switched to Remicade were assessed in the standard therapy group until the switch and in the switched group afterward. That definition makes treatment history and assessment period important when interpreting any group figures.

3. Trial Design

This was a prospective, observational, parallel-group, postmarketing safety surveillance registry in Europe. Its stated focus was participants with active or fistulizing Crohn's disease treated with Remicade or standard therapy. The registry was completed; its recorded start was 2003-07 and its primary completion was 2013-02. Enrollment was 2662, and follow-up was described as up to 5 years.

Participants were not described as randomly assigned. The registry record does not state how allocation to the initial groups was determined. The Remicade group included participants without prior Remicade exposure who were scheduled to receive Remicade within 30 days of baseline. They remained evaluated in that group even if they discontinued Remicade or switched treatment. The standard therapy group included participants treated with standard therapy who had not previously received Remicade and were to be offered an alternative treatment that did not include Remicade. Standard therapy participants could switch to Remicade during follow-up.

Switching was handled by changing the evaluation group at the time of the switch: participants were assessed as standard therapy participants before switching and as switched participants afterward. This is a time-dependent grouping rule, not an assignment to a fixed treatment group for the whole follow-up period. The groups therefore do not represent a randomized, like-for-like comparison.

The primary endpoint was the number of participants with serious infections. The registry also listed secondary outcomes concerning overall health status, Crohn's disease activity, work and daily activity, draining fistulas, hospital stays, and surgical procedures. The detailed protocol, allocation process, and statistical analysis plan 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.

Initial Intervention

Reasons for not completing this period:

Switch to Remicade

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The population consisted of all enrolled participants. The Standard Therapy group was assessed only as long as they were on Standard Therapy without Remicade and the Switched group was assessed starting at the time of the switch to Remicade.

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: 298 of the 1121 participants enrolled in the Standard Therapy Group switched to Remicade during follow-up. They are included in both the Standard Therapy and Switched to Remicade treatment groups, but baseline measures (obtained at the time of their switch to Remicade) are shown as separate rows in the Baseline Measures table.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Serious Infections, measured over Up to 5 Years.

The primary endpoint counts participants who experienced serious infections during follow-up of up to 5 years. The registry's description includes tuberculosis, opportunistic infections such as Pneumocystis carinii pneumonia, listeriosis, atypical mycobacteria, and histoplasmosis, as well as salmonellosis and serious viral infections. The listed examples are not an exhaustive definition.

A participant count is a measure of how many people met the endpoint, not a count of infection episodes. It does not by itself describe when infections occurred, how long participants were observed, or how frequently events occurred relative to time at risk. Those distinctions matter when follow-up varies or when participants change treatment groups. The endpoint population was all enrolled participants, but the registry specifies that standard therapy participants were assessed only while receiving standard therapy without Remicade, and switched participants were assessed from the time they switched to Remicade.

Serious infection surveillance is used to describe an important safety outcome in a postmarketing setting. It can identify the number of affected participants recorded under the registry's definitions. A count alone does not establish that treatment caused an infection, and it cannot show comparative risk without an appropriate comparison, clear exposure-time information, and an analysis that addresses differences between groups. The serious infection outcome count by group is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpretation starts with the design. This was a prospective observational registry, not a randomized trial. In general, observational groups can differ because treatment choices and clinical circumstances are not assigned by chance. Those differences can affect outcome counts. Here, the method of allocation is not stated, and the record does not provide a like-for-like control comparison. The descriptive group figures should therefore be treated as surveillance summaries rather than causal estimates.

What does a participant count tell us?

A count reports how many participants met an outcome definition. For the serious adverse event summaries, the record also reports how many participants were at risk. Such counts are useful for describing the scale of recorded events, but they do not fully describe event timing or duration of observation. A participant count is also different from an event count: one participant may experience more than one event, while a count of affected participants ordinarily records people who experienced at least one qualifying event. The primary endpoint is explicitly a number of participants, and the posted serious adverse event figures are also presented as affected participants.

In general, rates account for the amount of time participants are observed or exposed. The registry's follow-up was up to 5 years, but group-specific person-time and time-to-event results are not reported in the registry record. The posted counts should not be converted into rates or interpreted as if every participant had identical observation time. No additional rate or comparison has been calculated for this explanation.

Why does switching matter?

Switching makes treatment group a time-dependent feature of the registry. A participant who started in standard therapy contributed to that group's assessment until switching, and then to the switched group afterward. This rule reflects the registry's stated evaluation approach, but it means that the groups represent different periods of treatment and follow-up. General statistical methods for changing exposure over time require information about dates, exposure duration, outcome timing, and potential confounders. Those details and any analysis using them are not reported in the registry record.

The Remicade group is defined by starting Remicade near baseline, regardless of whether the participant later continued it or changed treatment. This is not equivalent to classifying everyone by the treatment they received throughout follow-up. The precise effects of that grouping choice cannot be assessed from the posted counts alone. The registry's group definitions should be kept in view whenever the figures are compared.

What would uncertainty measures add?

In general, a confidence interval describes a range of values compatible with data and a statistical model, and conveys precision as well as the estimated quantity. A p-value, when used, describes how compatible data are with a specified null model; it is not a measure of clinical importance or proof of causation. Neither a confidence interval nor a p-value for the primary serious infection outcome is reported in the registry record. The record also lists 0 analyses, so there is no reported inferential comparison to interpret. The precision of any difference between groups cannot be established from the available results.

How should planning illustrations be read?

Any sample-size figures accompanying the registry results are planning illustrations, not observed power and not the registry's original design justification. The 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 described as a stated fraction of the observed effect. For time-to-event planning, the stated method uses the total number of events with the Schoenfeld approach; other planning displays are expressed as participants per arm for 80% power or another stated power level. Such calculations depend on assumptions and do not retrospectively demonstrate that a study had a particular probability of detecting an effect. The trial's own sample-size justification is not reported in the registry record.

The record does not report the statistical model, covariate adjustment, handling of repeated measures, or a formal analysis plan. No adjusted treatment effect or uncertainty estimate should be inferred from the descriptive safety counts. General statistical concepts can explain what such analyses would address, but they do not establish that those methods were used in this registry.

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("Remicade", "Standard Therapy", "Switched to Remicade")
n      <- c(1541, 1121, 298)
events <- c(132, 47, 18)
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  Remicade  1541  132  8.6  7.2  10.1  7.3  10.1  7.3  10.1
ARM  Standard Therapy  1121  47  4.2  3.1  5.5  3.2  5.5  3.2  5.5
ARM  Switched to Remicade  298  18  6.0  3.6  9.4  3.9  9.3  3.9  9.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures and 0 analyses. It does not report how multiplicity across outcomes or study visits was addressed. In general, assessing many outcomes can increase the chance of finding an apparently notable result by chance, especially when formal testing is conducted. Without reported tests or a stated multiplicity strategy, the outcome list alone does not indicate which findings were prespecified for inferential emphasis or how any testing was controlled.

Missing-data handling is not reported in the registry record. The record does not describe the amount or pattern of missing outcome information, the reasons for missingness, or any imputation or sensitivity analysis. Follow-up was up to 5 years, but the number of participants with complete follow-up at each assessment is not reported. Consequently, the available counts cannot show whether missing observations differed across groups or affected the descriptive results.

The primary endpoint population is described as all enrolled participants, with standard therapy participants assessed only while on standard therapy without Remicade and switched participants assessed beginning at the switch. The record does not report a broader analysis-population definition, an intention-to-treat analysis, or a separate per-protocol analysis. Allocation was not stated. These omissions limit evaluation of how the analyzed population was assembled and whether outcome ascertainment differed across treatment histories.

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 (19.3%), anal abscess (4.0%), anal fistula (3.0%), abdominal pain (3.0%), ileal stenosis (3.0%).

The serious adverse event summaries report both participants at risk and participants affected: Standard Therapy, 1121 at risk and 391 affected; Remicade, 1541 at risk and 792 affected; Switched to Remicade, 298 at risk and 136 affected. These are group-specific participant counts. They are not the number of serious infections, and they should not be treated as a direct randomized comparison. The registry's primary outcome is serious infections, whereas the adverse event summaries cover serious adverse events more broadly.

The record also lists serious adverse event terms and percentages: CROHN'S DISEASE, 19.3%; ANAL ABSCESS, 4.0%; ANAL FISTULA, 3.0%; ABDOMINAL PAIN, 3.0%; ILEAL STENOSIS, 3.0%; and INTESTINAL OBSTRUCTION, 2.3%. The denominator and method used for these percentages are not reported in the registry record. They are not identified as percentages of all enrolled participants or as serious infection rates, so those interpretations should not be assumed.

In general, adverse event counts describe recorded safety experience, not causation. Differences in group membership, treatment switching, follow-up, and time at risk complicate comparisons. The available summaries do not report event timing or person-time.

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

The registry contributes descriptive safety information about participants with Crohn's disease treated with Remicade or standard therapy in a postmarketing setting. It records 2662 enrolled participants and defines a primary question about the number experiencing serious infections during follow-up of up to 5 years. It also provides serious adverse event counts for the standard therapy, Remicade, and switched to Remicade groups. Those counts can describe the recorded experience within the registry's group definitions.

The available record does not report the primary serious infection count by group, or a statistical comparison of that endpoint. It therefore does not quantify a difference in serious infection occurrence between groups. The serious adverse event counts are broader than the primary infection outcome, and the listed event-term percentages have no reported denominator or calculation details. These results should not be used as a substitute for an infection-specific analysis.

The registry was observational and did not report allocation. Participants could switch from standard therapy to Remicade, and group membership changed at the switch for evaluation. As a result, the groups do not form a randomized comparison, and the posted figures cannot establish that treatment caused an outcome or changed its likelihood. Differences in group counts could reflect group size, treatment history, follow-up, underlying clinical differences, or other factors that the record does not characterize.

The results also do not establish the absence of events. A count is limited to the events captured and defined in the registry, and missing-data procedures are not reported. The registry's safety surveillance purpose is distinct from a controlled estimate of treatment effect. The figures describe what is recorded; they do not establish that either treatment is safer or less safe, and they do not support medical advice.

14. Why This Trial Matters Statistically

Postmarketing registries can describe treatment experience among participants followed in routine clinical settings. This registry is statistically notable for tracking a treatment-switching pathway: participants could begin in standard therapy and later be evaluated in a switched group. That feature makes the definition of exposure and follow-up central to interpretation, rather than a minor detail.

The registry also illustrates why descriptive counts need context. The serious adverse event summaries include affected participants and participants at risk, while the primary endpoint concerns serious infections specifically. Those are distinct outcomes. The record's list of serious event terms adds another layer of safety description, but without a reported denominator for the term percentages, their scale cannot be compared directly with the group counts.

For biostatistical interpretation, the key issue is the boundary between surveillance and comparative inference. A registry can record outcomes and characterize who was followed, but a causal comparison requires a design and analysis that address how treatment groups were formed, how follow-up differed, and how switching was handled. The registry record does not report allocation, a statistical analysis plan, or inferential results for the primary endpoint. Recognizing these limits prevents raw counts from being mistaken for treatment effects.

The record's 14 outcome measures and 0 analyses also make reporting scope important. The endpoint definitions and group rules provide useful context, while missing details about multiplicity, missing data, and analysis populations constrain how much can be inferred. The study is therefore useful as an example of how registry design choices shape the meaning of safety summaries, without converting those summaries into a randomized treatment comparison.

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.

This registry's observational design is the central limitation for comparative interpretation. Allocation was not stated, and the record explicitly cautions that the arms are not a like-for-like control comparison. The registry does not report baseline balance or adjustment for differences between participants, so the posted group counts cannot isolate a treatment effect.

Group membership also reflects treatment changes. Standard therapy participants could switch to Remicade at any time during follow-up; their evaluation moved to the switched group at that point. The record does not provide the timing or duration details needed to assess how switching affected exposure and outcome summaries. Remicade group membership was based on starting Remicade near baseline, even if treatment later changed.

Follow-up was described as up to 5 years, but group-specific follow-up duration and person-time are not reported. The serious adverse event counts are not the primary serious infection endpoint, and the infection counts by group are not reported in the registry record. The denominators and calculation basis for the listed event-term percentages are also not reported. The record does not describe missing-data handling, outcome ascertainment completeness, multiplicity procedures, or the statistical analysis plan. These limits constrain both the precision of interpretation and the extent to which the safety summaries can support comparisons.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Postmarketing Safety Surveillance European Registry of Crohn's Disease Patients Treated With Remicade or Standard Therapy (MK-2155-035) — NCT00705614.
• Registry record last updated 2017-03-22; status last verified 2017-02.
• Results first posted 2014-08-26.
• 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

NCT00705614 is a completed prospective, observational, parallel-group, postmarketing safety surveillance registry of participants with Crohn's disease treated with Remicade or standard therapy. Enrollment was 2662, and follow-up was up to 5 years. The registry recorded its start as 2003-07 and primary completion as 2013-02.

The primary outcome was the number of participants with serious infections. Participants in standard therapy were assessed while on standard therapy without Remicade; participants who switched were assessed in the switched group from the time of switching. The record lists secondary outcomes concerning health status, Crohn's disease activity, work and daily activity, fistulas, hospital stays, and surgery.

Serious adverse event counts are reported for the standard therapy, Remicade, and switched to Remicade groups, but the primary serious infection result by group and formal analyses are not reported in the registry record. The registry does not state allocation or provide a like-for-like control comparison.