Extended Access Program of Vedolizumab IV in Ulcerative Colitis and Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extended Access Program of Vedolizumab IV in Ulcerative Colitis and Crohn's Disease (NCT02743806), a na phase 4 study. The primary outcome is Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a Phase 4 extended access program of intravenous vedolizumab in ulcerative colitis and Crohn’s disease. The registry lists Takeda as sponsor, enrollment of 331, and a single-group model with no masking. Allocation is recorded as not applicable. These design features mean the study was not set up as a randomized comparison between treatment groups.

Participants received vedolizumab 300 mg by intravenous infusion, normally once every 8 weeks. The interval could be reduced to once every 4 weeks at the investigator’s judgment of the participant’s clinical status, with acknowledgment by the medical monitor. Treatment was described as lasting up to 6 years. This was an access program for qualifying participants whom the investigator considered to continue deriving benefit and for whom continued treatment was desired; it was not described as a trial assigning participants to different regimens.

The registry gives the study start as 2016-08-01 and primary completion as 2023-01-03, and lists the status as terminated. The reason for termination is not reported in the registry record. The primary endpoint was the percentage of participants with adverse events and serious adverse events, assessed from the first study dose through 18 weeks after the last dose. The maximum stated timeframe was up to 6.3 years.

The registry describes the analysis population as all participants enrolled in the program who received at least one dose of study drug, including the dose at T0, which it identifies as the last vedolizumab dose in the qualifying study. Additional details about eligibility criteria, treatment exposure by participant, follow-up completeness, and the reasons individual participants stopped treatment 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.

Before assignment: A total of 331 participants with a diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) who have successfully completed the participation in qualifying vedolizumab clinical studies (C13008 \[NCT00790933\] and MLN0002-3028 \[NCT02425111\]) were enrolled in this extended access program (XAP) study to receive vedolizumab 300 mg.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS consisted of all participants enrolled in the XAP study, who received at least 1 dose of study drug (i.e., vedolizumab IV treatment), including the dose given at T0 (last vedolizumab dose in the qualifying study).

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: Full Analysis Set (FAS) consisted of all participants enrolled in the XAP study, who received at least 1 dose of study drug (i.e., vedolizumab IV treatment), including the dose given at T0 (last vedolizumab dose in the qualifying study).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over From first dose of study drug in this XAP study through 18 weeks after the last dose of study drug (up to 6.3 years).

The primary endpoint is the percentage of participants with adverse events and serious adverse events. An adverse event is any unfavorable or unintended medical occurrence temporally associated with use of a drug; it need not be judged causally related to treatment. A serious adverse event is an event that, at any dose, results in death, is life-threatening, requires or prolongs hospitalization, causes persistent or significant disability or incapacity, leads to a congenital anomaly or birth defect, or is otherwise considered an important medical event.

The observation window began with the first study dose and continued through 18 weeks after the last dose, with a maximum stated timeframe of up to 6.3 years. Counting participants who experienced events gives a safety summary across the treatment and follow-up period. General statistical context: a participant-level percentage describes how common an event was in the defined population during the stated observation window; it does not by itself describe when an event occurred, how long it lasted, or whether treatment caused it. The registry rounds percentages to the nearest decimal point. Details of the endpoint’s calculation beyond its stated population and event definitions are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is being counted?

The primary endpoint is binary at the participant level: a participant either experienced an adverse event or did not, within the stated observation window. The registry reports the endpoint as a percentage of participants. The safety summary also presents counts of participants with serious events and other adverse events. This kind of summary is useful for describing how many participants had at least one event, but it does not preserve all event-level detail. For example, it does not indicate how many events each participant experienced or how long each event lasted.

General statistical context: a participant-level percentage uses the number of participants in the defined population as its denominator. The registry identifies the safety population as participants who enrolled and received at least one dose, including the qualifying-study dose at T0. The adverse-event summary lists 331 at risk. A percentage alone does not show the number of repeated events, the timing of events, or how observation time varied across participants. Those details require additional event and follow-up information.

What does the single-group design allow?

The study model is single group, with allocation not applicable and no masking. There is no concurrent control arm. The posted counts therefore describe the experience of participants enrolled in this extended access program; they do not estimate a difference between treatment groups. General statistical context: randomization can help balance measured and unmeasured factors across groups, while a concurrent comparator provides a reference for interpreting outcome frequencies. Neither feature is present as a randomized comparison in this record. Without that comparison, observed events cannot be attributed to treatment solely from their occurrence during treatment.

The program’s stated purpose was to monitor ongoing safety and provide access to qualifying participants whom investigators considered to continue deriving benefit. This access context differs from a trial designed to assign treatment and compare outcomes under a prespecified controlled protocol. The registry record does not report a statistical plan for causal comparisons or an adjustment strategy for differences in participant characteristics.

How should the observation window be understood?

The primary safety timeframe runs from the first study dose through 18 weeks after the last dose, and is described as up to 6.3 years. Treatment could continue for up to 6 years. A long observation period can capture events occurring over extended follow-up, but a cumulative participant count does not account for variation in time observed. General statistical context: time-to-event methods or incidence rates can incorporate follow-up time, but they require information about event timing and participants’ time at risk. Such analyses are not listed in the registry record.

It is also important to distinguish a participant count from an event count. The summary reports participants with events, not the total number of episodes. If an individual had repeated events, a participant-level measure may count that individual once for a particular outcome. The registry does not report the event-level structure needed to determine recurrence or the extent to which event categories overlap.

What does uncertainty mean for these results?

General statistical context: an estimate based on a finite group has sampling uncertainty. A confidence interval expresses a range of values compatible with the data under a specified statistical method and assumptions. The registry record does not report confidence intervals for the primary endpoint. Without them, readers cannot use the posted summary to assess the statistical precision of the participant-level event frequency. The absence of an interval does not mean the estimate has no uncertainty; it means that uncertainty is not quantified in the registry summary.

No hypothesis test or treatment-group comparison is reported. The registry lists no analyses. Thus, no p-value or adjusted estimate is available for the primary endpoint in this record. The counts remain descriptive and should not be interpreted as evidence of a statistically established difference or causal effect.

What analysis details are unavailable?

The registry identifies the analysis population but does not report how missing safety follow-up was handled, whether every participant completed the observation period, or how participants who discontinued were followed. It also does not report a detailed statistical analysis plan, methods for calculating uncertainty, or rules for handling participants with incomplete records. Those details matter because incomplete follow-up can affect how fully events are captured.

The registry includes two outcome measures, but the details of the other outcome and any multiplicity strategy are not reported in the registry record. General statistical context: when multiple outcomes are tested, multiplicity can increase the chance of at least one false-positive result if each is assessed separately. That issue cannot be evaluated from this record because no analysis results or adjustment plan are listed. No planning sample-size justification or interim-analysis plan is reported in the registry record. The enrollment count should therefore be read as the reported enrollment, not as evidence of a particular power or design rationale.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures, but the details of the other outcome measure and the relationship between outcomes are not reported in the registry record. It lists no analyses, and no multiplicity strategy is reported. As a result, it is not possible to determine whether outcomes were treated as separate descriptive measures, whether any formal hypotheses were planned, or whether any adjustment for multiple testing was intended. General statistical context: multiplicity matters when several statistical hypotheses are tested because repeated testing can raise the chance of a false-positive finding. That concern cannot be quantified for this program from the registry entry.

The stated analysis population consists of all enrolled participants who received at least one dose, including the dose at T0. The adverse-event summary lists 331 participants at risk. The record does not describe how missing safety information was handled, whether participants with incomplete follow-up remained under observation, or whether the event assessment was complete for every participant through the end of the stated window. It also does not report withdrawals or reasons for loss to follow-up. These omissions limit assessment of whether event capture differed according to follow-up completeness.

The registry record does not report an analysis plan, a missing-data method, or sensitivity analyses for incomplete records. No interim analyses are listed. The endpoint is a safety measure based on events during follow-up, but the record does not explain how event reports were reviewed or classified beyond the stated definitions of adverse and serious adverse events. Therefore, the posted summaries can be described, but the robustness of the results to missingness or alternative analysis decisions cannot be evaluated.

11. Safety Results

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

Deaths

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: colitis ulcerative (2.8%), crohn's disease (2.6%), joint dislocation (0.6%), myocardial infarction (0.6%), osteoarthritis (0.6%).

The adverse-event summary lists 50 participants with serious adverse events and 100 participants in the other adverse-event category, with 331 at risk. It also lists one death. These are counts in the registry’s single-group safety summary. The event terms listed as serious include colitis ulcerative at 2.8%, Crohn’s disease at 2.6%, and joint dislocation, myocardial infarction, osteoarthritis, and subileus at 0.6% each.

The listed terms describe events recorded in the program; their appearance in the summary does not establish that vedolizumab caused them. The endpoint definition says adverse events need not have a causal relationship with treatment. The registry record does not report the treatment relationship, onset, course, or outcome for each event term. It also does not report whether participants experienced multiple listed events, so term percentages should not be added or treated as separate, non-overlapping groups.

The death count is reported in the adverse-event summary, but its cause and relationship to treatment are not reported in the registry record. The observation window could extend through 18 weeks after the final dose, for up to 6.3 years. The summary does not provide exposure-adjusted rates or timing, and participants may have had different follow-up durations. Accordingly, these figures are descriptive participant counts rather than a controlled comparison or a measure of event risk per unit of time.

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

The registry results describe safety events reported among participants in an extended access program for intravenous vedolizumab. They include 50 participants with serious adverse events, 100 in the other adverse-event category, and one death in the adverse-event summary. The serious-event terms listed include colitis ulcerative, Crohn’s disease, joint dislocation, myocardial infarction, osteoarthritis, and subileus, with the percentages reported in the registry. The stated safety window extends from the first study dose through 18 weeks after the last dose.

These observations do not establish that the study drug caused the events. An adverse event is defined as a medical occurrence temporally associated with drug use, whether or not considered related. The registry does not provide event-level causality assessments, the cause of the listed death, or the timing and course of the events. The listed terms therefore describe what was recorded, not a causal explanation.

The results also do not show how safety compares with another treatment or with no treatment. The study had a single group and no randomized comparator. Differences in disease status, prior treatment, or follow-up cannot be separated from treatment exposure using these counts alone. The registry does not provide confidence intervals or comparative analyses, so the precision of the reported event frequencies is not quantified in the record.

Finally, the findings are specific to the participants enrolled in this access program and the observation period described. They do not answer questions about event timing, recurrence, event rates adjusted for exposure, or outcomes in populations not represented in the program. They are descriptive safety information, not proof of benefit, harm, or comparative safety.

13. Why This Trial Matters Statistically

Extended access programs present a different statistical question from randomized efficacy trials. Their purpose may include continued access for selected participants and ongoing safety monitoring, as stated for this program. The results therefore need to be read as observations from a treatment-exposed group, not as estimates of a randomized treatment contrast. Recognizing that distinction prevents descriptive counts from being mistaken for evidence of a causal difference.

This record also illustrates why endpoint definitions and observation windows matter. An adverse event includes a broad range of medical occurrences and need not be attributed to treatment. A serious adverse event is defined by specified outcomes or clinical importance. The observation window extends beyond the last dose, and participants could be followed for different lengths of time. A count of participants with events gives a cumulative description, while timing and exposure-adjusted summaries would answer different questions. Those additional details are not reported in the registry record.

The registry reports event counts and selected serious-event terms, but no confidence intervals or analyses. Statistical interpretation should therefore focus on what the counts document and on the uncertainty that remains unquantified. The absence of a comparator also makes it impossible to distinguish the event experience of the program participants from what might have occurred under another treatment or in the absence of treatment.

For clinical researchers and biostatisticians, the record is a useful example of the limits and value of descriptive safety reporting. Counts can document events observed in a defined program population and help frame further questions. They do not, on their own, resolve causality, comparative safety, or the effect of differing follow-up. Keeping these distinctions explicit supports a careful reading of registry results.

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.

The single-group design has no randomized comparator, so the program cannot provide a controlled estimate of how event experience differs under another treatment or no treatment. The registry lists allocation as not applicable and masking as none. The event counts are therefore descriptive of the enrolled participants rather than comparative evidence.

The observation window is broad, extending from the first dose through 18 weeks after the last dose, with a maximum timeframe of up to 6.3 years. Treatment could continue for up to 6 years. The registry does not report individual follow-up duration, time at risk, event timing, or exposure-adjusted rates. This limits interpretation when participants may have had different observation periods.

The safety summary lists participant counts and selected serious-event terms, but does not report event-level detail such as recurrence, duration, resolution, or participant overlap across terms. The cause and treatment relationship of the death are not reported in the registry record. The record also does not report confidence intervals, statistical tests, or comparative analyses, so precision is not quantified.

The registry does not describe missing-data handling, follow-up completeness, participant withdrawals, or sensitivity analyses. The reason the study was terminated is not reported in the registry record. Details of the second outcome measure, the statistical analysis plan, multiplicity handling, and sample-size justification are also not reported. These gaps limit evaluation of completeness, analysis choices, and the broader interpretation of the posted safety summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Extended Access Program of Vedolizumab IV in Ulcerative Colitis and Crohn's Disease — NCT02743806.
• Registry record last updated 2023-11-18; status last verified 2023-11.
• Results first posted 2023-11-18.
• 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

NCT02743806 is a Phase 4, single-group extended access program of vedolizumab IV in ulcerative colitis and Crohn’s disease, sponsored by Takeda. The registry reports enrollment of 331 and lists the study status as terminated. Participants received vedolizumab 300 mg by intravenous infusion, usually once every 8 weeks, with possible reduction of the interval to once every 4 weeks based on investigator judgment and medical-monitor acknowledgment.

The primary endpoint was the percentage of participants with adverse events and serious adverse events, assessed from the first study dose through 18 weeks after the last dose, up to 6.3 years. The adverse-event summary lists 50 participants with serious events, 100 in the other adverse-event category, and one death. No randomized comparator or analyses are listed. The registry record does not report the reason for termination, confidence intervals, missing-data methods, or detailed statistical analysis plan.