Follow-up to Welcome Study C87042 [NCT00308581] Examining Certolizumab Pegol (CDP870) in Subjects With Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Follow-up to Welcome Study C87042 [NCT00308581] Examining Certolizumab Pegol (CDP870) in Subjects With Crohn's Disease (NCT00333788), a non-randomized phase 3 study. The primary outcome is Occurrence of at Least One Study-emergent Adverse Event During the Study (Maximum 164 Weeks).

2. Clinical Question

The study also sought to examine longer-term efficacy, safety, and direct cost parameters. Its secondary outcomes include clinical response, remission, change in the Crohn’s Disease Activity Index, time to loss of response, and hospital stays. The record lists these as outcomes, but the primary question remains a safety question. Because entry followed completion of an earlier study, the findings concern this follow-up population and should not be treated as results from a newly randomized comparison.

3. Trial Design

This was a phase 3, non-randomized, open-label, single-group study of certolizumab pegol in people with Crohn’s disease who had completed study C87042. The registry lists enrollment of 233 and describes one treatment group: certolizumab pegol 400 mg, administered subcutaneously every 2 weeks or every 4 weeks. The study began in 2006-10, had primary completion in 2010-04, and is recorded as completed.

The follow-up was intended to continue assessment of safety and examine the evolution of long-term efficacy. The registry also describes an assessment of the effect of subcutaneous CDP870 400 mg on direct cost parameters. These are stated study aims; they do not establish that the posted results demonstrate a treatment effect. The listed secondary outcomes cover response and remission at the last visit, change in disease activity, time to loss of response, and hospital stays during specified periods.

The primary safety analysis used the Intent to Treat population, which the registry says was identical to the Safety Set. That population included 229 participants, while enrollment was 233. These are different population descriptions, not interchangeable denominators. The record does not explain the reasons for the difference, so no account of the exclusions or analysis-population construction can be inferred.

With no random allocation, masking, or concurrent comparison group, the design can describe events observed during treatment and follow-up but cannot separate treatment-associated changes from the course of Crohn’s disease, other care, or other influences. The registry record does not report the protocol’s sample-size justification, a detailed statistical analysis plan, or interim analyses. The record lists 24 outcome measures and no analysis entries in its structured analysis information; this does not by itself explain how every outcome was analyzed.

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.

Before assignment: The summary of Participant Flow is based on the All Subjects Population.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of the 233 subjects in the study, 229 are in the Intent to Treat (ITT) population and are included in this analysis. Note that the ITT population is the same as the Safety Set (SS) population.

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 Occurrence of at Least One Study-emergent Adverse Event During the Study (Maximum 164 Weeks), measured over Maximum 164 weeks.

The primary endpoint is the occurrence of at least one study-emergent adverse event during the study, expressed as a percentage of participants. The registry gives a maximum timeframe of 164 weeks. It defines an eligible event as a treatment-emergent adverse event with onset on or after the first study-drug administration and no later than 12 weeks (84 days) after the last injection.

This is a participant-level, yes-or-no summary: it asks whether a participant experienced at least one qualifying event, rather than how many separate events occurred or how long they lasted. Such an endpoint is used to summarize how commonly participants experienced events within a defined observation window. It does not, by itself, distinguish mild from severe events, establish that treatment caused an event, or describe the full burden of recurrent events.

The percentage is tied to the analysis population and the event definition. The registry identifies 229 participants in the Intent to Treat population and says this was the same as the Safety Set. The adverse-event summary also gives counts for serious and other adverse events. Those categories should be read according to their labels, not treated as a substitute for the endpoint definition without a direct mapping in the record. The endpoint’s role is to describe safety occurrence during the specified follow-up, not to compare treatment with an untreated counterfactual.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-level event percentage mean?

In general, a participant-level event percentage summarizes the share of an analysis population in which at least one qualifying event was recorded. Each participant contributes to the endpoint according to whether the event occurred, rather than according to the number of separate events. This makes the result relatively direct to interpret as event occurrence during a defined observation period. It does not communicate how often events recurred, their duration, or their severity unless those features are separately summarized.

For this study, the primary endpoint concerns at least one study-emergent adverse event, and the registry specifies the event window and a maximum timeframe. Those definitions matter: changing the onset window, follow-up duration, or analysis population can change the estimated occurrence. The registry identifies the primary analysis population as the Intent to Treat population and says it is the same as the Safety Set. It does not report a confidence interval or a statistical test for this endpoint in the registry record for interpretation.

Why distinguish serious from other adverse events?

In general, a serious adverse event category is a classification based on seriousness criteria, while an adverse event is a broader safety observation. These categories help readers distinguish event types, but they are not necessarily exclusive at the participant level. A participant can have more than one event, and the record does not say that serious events and other events were assigned to wholly separate participants. Therefore, the counts of participants affected in the serious and other categories should be read separately rather than combined.

Term-specific percentages add another layer of categorization. The serious-event terms listed in the registry can each describe events affecting participants, but participants may have multiple terms. A sum across terms would not necessarily represent a participant-level total. The registry’s listed terms and percentages provide descriptive detail; they do not provide a causal assessment or a comparison with an alternative treatment.

What does the single-group design allow?

In general, a single-group study estimates outcomes among participants who receive the studied treatment. It can document what was observed during the study’s follow-up. A randomized control group provides a basis for estimating how outcomes differ under assigned alternatives, because random allocation helps balance other factors on average. That comparison is absent: the registry describes non-randomized allocation, no masking, and a single-group model.

Consequently, an event observed during treatment is not automatically an event caused by treatment. Crohn’s disease, prior health, concurrent care, and other influences can contribute to events. A before-and-after or long-term observation in one group does not, by itself, resolve these competing explanations. This is a design limitation, not a defect that can be repaired by describing the event percentage more precisely.

How should precision be understood?

In general, a confidence interval expresses uncertainty around an estimated quantity under a statistical model. A narrow interval indicates greater statistical precision than a wide interval, but neither width nor location establishes causation. The registry entries for this record do not state a confidence interval or a statistical test for the primary endpoint. The registry record also does not report a statistical analysis plan, so the method used to calculate the endpoint’s uncertainty is not available.

Precision also depends on the population and event definition. The primary safety analysis used 229 participants, while enrollment was 233. The record does not explain why these totals differ. Missing outcome status, differing observation time, and eligibility rules can influence estimates in general, but the record does not report enough information to say which, if any, affected this analysis. No missing-data method should be inferred.

What do the planning illustrations represent?

In general, sample-size planning asks how many participants or events would be needed to detect a specified effect under chosen assumptions. A planning calculation is not an observed result and is not “observed power.” The registry’s stated planning assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detecting a stated fraction of an observed effect. Those assumptions describe an illustration, not the design of this trial: the trial itself was single-group and non-randomized. The record does not provide a trial-specific sample-size justification, and no planning illustration should be read as evidence that the study had a particular power for its actual design.

For time-to-event planning, methods generally use event counts because the number and timing of events carry information about a comparison. For other outcomes, planning may be expressed as participants per arm. Such calculations require a defined comparison and assumptions about the effect and analysis. The present study has no concurrent randomized arm, so two-arm planning assumptions do not turn its descriptive results into a comparative estimate. The registry record does not state that these illustrations formed part of the protocol or its analysis plan.

How do multiple outcomes affect interpretation?

In general, when many outcomes or analyses are examined, the chance of at least one apparently unusual result can increase if each is tested separately without adjustment. Statistical methods may address this with prespecified primary outcomes, hierarchical testing, or multiplicity adjustments. The record lists 24 outcome measures, but the statistical plan for prioritizing or adjusting analyses is not reported in the registry record. The existence of many listed outcomes is not evidence that a particular adjustment was or was not used.

For this reason, the primary safety endpoint should be distinguished from the secondary efficacy, disease-activity, and hospitalization outcomes. Each has its own definition and observation window. Without a reported analysis plan and detailed outcome results, the listed outcomes should not be treated as a unified set of confirmatory tests. The safest interpretation is descriptive and limited to the specific definitions and summaries the registry reports.

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("Certolizumab Pegol 400 mg")
n      <- c(229)
events <- c(212)
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  Certolizumab Pegol 400 mg  229  212  92.6  88.4  95.6  88.4  95.3  88.4  95.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 24 outcome measures, including the primary adverse-event endpoint and secondary outcomes covering response, remission, disease activity, time to loss of response, and hospital stays. In general, examining multiple outcomes creates a multiplicity issue when many statistical tests are used to support confirmatory claims. A prespecified testing hierarchy or adjustment can help control the chance of false-positive findings. The registry record does not report whether such procedures were planned or used, or how the outcomes were prioritized beyond identifying a primary endpoint.

The record identifies 229 participants in the primary Intent to Treat analysis and states that this is the same as the Safety Set. Enrollment is listed as 233. The reasons for the difference between enrollment and the analysis population are not reported in the registry record. No further assumptions about exclusions, eligibility, or participant disposition are warranted.

Missing-data handling is also not reported in the registry record. The secondary outcomes refer to a last visit up to the maximum observed study duration or to a withdrawal visit for premature withdrawals. That wording does not explain whether missing measurements were imputed, excluded, or handled using another approach. The record does not state whether participants with different observation lengths were treated identically in each analysis.

The registry record does not report an interim-analysis plan, sample-size justification, or detailed statistical plan. These absences limit assessment of prespecification, analysis choices, and the effect of missing observations. They do not show that a method was absent from the full study documentation; they mean it cannot be established 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 (9.6%), colonic stenosis (2.2%), abdominal abscess (2.2%), perianal abscess (2.2%), abdominal pain (1.7%).

The safety summary reports 73 participants affected in the serious adverse-event category and 190 affected in the other adverse-event category, with 229 at risk for each category. These are participant counts, not counts of individual events. A participant may have experienced more than one event, and the record does not state that the serious and other categories contain mutually exclusive participants. The counts should therefore be interpreted separately, not added.

The listed serious-event terms and percentages are Crohn’s disease at 9.6%, colonic stenosis at 2.2%, abdominal abscess at 2.2%, perianal abscess at 2.2%, abdominal pain at 1.7%, and chest pain at 1.3%. These term-specific values are not a complete accounting of all event types and need not sum to a total. The record does not report a causal assessment for each listed event.

The primary endpoint has its own defined event window, from first study-drug administration through 12 weeks (84 days) after the last injection, with a maximum timeframe of 164 weeks. The serious and other category summaries provide safety context, but they should not be assumed to equal the primary endpoint unless the registry explicitly links them. Because this was a single-group study, the safety counts describe events observed during follow-up; they do not measure an excess risk relative to a control group.

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

The results describe safety experience during long-term follow-up of people with Crohn’s disease who had completed an earlier study and entered this open-label continuation. The registry reports counts of participants affected in serious and other adverse-event categories, and it lists several serious-event terms with their percentages. The primary endpoint is defined as the occurrence of at least one study-emergent adverse event within a stated window. Together, these details characterize what the registry intended to assess and what its safety summary records.

They do not show that every recorded event was caused by certolizumab pegol. An adverse event is an observation during a study; causal attribution requires more than temporal occurrence. The single-group design has no concurrent control to estimate how event experience might have differed under another treatment or without treatment. The long follow-up also does not remove the possibility that disease course, other care, or participant characteristics influenced what was observed.

The results do not establish comparative efficacy. The record lists secondary outcomes for response, remission, disease activity, loss of response, and hospital stays, but the registry entries available for this interpretation do not include numerical results for those outcomes. Their presence in the registry describes what was to be assessed, not what the results were. The study’s stated aim to examine long-term efficacy or direct cost parameters likewise should not be mistaken for evidence of a particular effect.

Precision and completeness are also limited by the information reported. The record does not state a confidence interval or inferential test for the primary endpoint, explain the difference between enrollment and the analysis population, or describe missing-data handling. Consequently, the reported counts can be described, but a fuller assessment of uncertainty and possible bias is not available. The appropriate reading is a descriptive account of observed safety in this follow-up population, not a causal or comparative conclusion.

14. Why This Trial Matters Statistically

This study is statistically instructive because a long observation period can be valuable for documenting safety experience while still leaving important comparative questions unanswered. The registry describes a maximum follow-up timeframe of 164 weeks for the primary safety endpoint and defines a post-injection event window extending through 12 weeks (84 days) after the last injection. Clear time windows help specify which events qualify, but a longer period alone does not establish the cause of an event.

The record also illustrates why analysis populations matter. Enrollment is listed as 233, while the primary safety analysis includes 229 participants in the Intent to Treat population, which is said to match the Safety Set. The denominator used for a reported endpoint affects its interpretation. Because the reasons for the difference are not reported, readers cannot evaluate the effect of those population decisions from this record alone.

Another statistical lesson is the distinction between a descriptive safety count and a comparative estimate. The study has a single group and no randomized control. Counts and term-specific percentages can describe the recorded experience, but they cannot by themselves answer whether outcomes would have differed under another treatment. This distinction is especially important in chronic disease, where events may reflect both treatment exposure and the underlying condition.

Finally, the registry lists numerous outcomes, while its detailed approach to multiplicity, missing data, and statistical testing is not reported. Readers need those methods to judge how securely results support confirmatory claims. The record therefore demonstrates the value of treating outcome definitions, denominators, follow-up windows, and study design as part of the result—not as technical details separate from interpretation.

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 main trial-specific limitation is the single-group, non-randomized design. Participants received certolizumab pegol without a concurrent control group, and masking was absent. The study can describe events and outcomes among those followed, but cannot provide a randomized estimate of differences against another treatment or no treatment. Confounding by disease course, participant characteristics, and other care remains possible.

Participants entered after completing study C87042. This follow-up population is therefore defined by prior study participation and completion, rather than by a newly randomized enrollment process. The registry record does not describe how prior-study completion or continued participation may have shaped who entered or remained in follow-up. Generalizing the findings beyond this population requires caution.

The record lists enrollment of 233, while the primary safety analysis includes 229 participants. Although it identifies the analysis population as the Intent to Treat population and equates it with the Safety Set, it does not report why these numbers differ. Missing-data methods, event ascertainment procedures beyond the stated timing definition, and participant-level follow-up duration are not reported in the registry record.

The primary safety endpoint has a specified event definition and maximum timeframe, but the reported details do not provide a confidence interval or test result. The adverse-event summary separates serious and other categories, and the record does not establish that the participant groups are mutually exclusive or map either category directly to the primary endpoint. This restricts interpretation of how the category counts relate to the primary outcome.

Finally, the registry record does not report the statistical analysis plan, multiplicity procedures, sample-size justification, or interim analyses. The listed secondary outcomes should not be treated as confirmed findings in the absence of their numerical results and analysis details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Follow-up to Welcome Study C87042 [NCT00308581] Examining Certolizumab Pegol (CDP870) in Subjects With Crohn's Disease — NCT00333788.
• Registry record last updated 2018-08-07; status last verified 2011-08.
• Results first posted 2011-07-12.
• 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

NCT00333788 is a completed phase 3, open-label, non-randomized, single-group follow-up study of certolizumab pegol in people with Crohn’s disease who completed study C87042. The listed regimen was 400 mg by subcutaneous injection every 2 weeks or every 4 weeks. Enrollment was 233; the primary safety analysis included 229 participants in the Intent to Treat population, which the registry identifies as the Safety Set.

The primary endpoint was occurrence of at least one study-emergent adverse event, defined by onset from first administration through 12 weeks (84 days) after the last injection, with a maximum timeframe of 164 weeks. The safety summary records 73 participants affected in the serious category and 190 in the other category. Listed serious-event terms include Crohn’s disease at 9.6% and colonic stenosis and abdominal abscess at 2.2% each.

Because there was no concurrent control group, the findings describe the follow-up population rather than a randomized treatment contrast. The registry record does not report a detailed statistical plan, missing-data methods, or sample-size justification.