A Study of Adalimumab After Dose Escalation in Japanese Subjects With Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Adalimumab After Dose Escalation in Japanese Subjects With Crohn's Disease (NCT01958827), a na phase 3 study. The primary outcome is Percentage of Participants Who Achieved Clinical Response 50 (CR50; Crohn's Disease Activity Index [CDAI] Decrease ≥ 50 From Week 0) at Week 8.

2. Clinical Question

In statistical terms, the primary question is descriptive for this treated group: how often was the stated response observed under the study’s endpoint definition? It is not a randomized comparison of adalimumab with placebo, usual care, or another regimen. The study also lists secondary outcomes covering clinical remission, other CDAI response thresholds, C-reactive protein, laboratory parameters, and blood pressure. The existence of those outcomes does not supply their results, which are not reported in the registry record.

3. Trial Design

The registry identifies NCT01958827 as a Phase 3, completed, multicenter, open-label, single-group study of adalimumab in Japanese participants with Crohn’s disease. The recorded start is 2013-09 and the primary completion is 2015-03. Enrollment was 28. These design details establish the setting and scale of the study, but they do not establish how many participants contributed to each endpoint analysis.

All participants were to receive open-label adalimumab 80 mg by subcutaneous injection every other week from Week 0 to Week 50. Because the study had one group and no masking, participants and investigators were not blinded to the assigned treatment, and there was no randomized allocation between competing regimens. The registry does not report a control condition or a treatment contrast. Consequently, the central statistical description is the response observed among participants receiving the stated regimen, not an estimated difference between treatment groups.

The primary assessment was at Week 8. It was the percentage achieving CR50, defined by a CDAI decrease of at least 50 from Week 0. The registry also names repeated assessments of remission and CR50, CR70, and CR100 through Week 52, along with several laboratory and blood-pressure outcomes. The treatment schedule ends at Week 50, while some listed assessments extend to Week 52; the record does not explain the visit schedule or the reason for that timing.

The listed primary analysis population is the Full Analysis Set, consisting of enrolled participants who received at least one dose and had at least one post-treatment efficacy assessment. Missing CDAI observations for the primary endpoint were handled using non-responder imputation. The record does not report participant flow, the number included in the primary analysis, or counts of missing observations. It also does not report the statistical plan beyond the endpoint description and this missing-data rule. Details such as the dose-escalation history, eligibility criteria, interim analyses, or sample-size justification 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: This study included a 21-day screening period.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): All enrolled participants who received at least one dose of study drug and had at least one post-treatment efficacy assessment.

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 Percentage of Participants Who Achieved Clinical Response 50 (CR50; Crohn's Disease Activity Index [CDAI] Decrease ≥ 50 From Week 0) at Week 8, measured over Week 8.

The primary endpoint is the percentage of participants who achieved Clinical Response 50 at Week 8. The CDAI is used to quantify signs and symptoms of Crohn’s disease. For this endpoint, a participant is classified as a responder when the CDAI has decreased by at least 50 from Week 0 to the Week 8 assessment. The outcome is therefore a proportion of participants meeting a specified threshold, rather than a mean change in CDAI.

A threshold-based response is useful because it translates a continuous score into an outcome that can be counted: participants either meet the prespecified response definition or do not. The registry also explains that a CDAI score below 150 indicates remission and a score above 450 indicates severe disease. Those reference points give context to the index, but they are not the definition of the primary endpoint. The primary endpoint is a decrease from baseline, not a requirement to reach remission.

The registry specifies non-responder imputation for missing CDAI observations. Under that approach, a missing assessment is treated as failure to meet the response criterion in the primary analysis. This makes the endpoint definition depend not only on observed CDAI scores but also on the stated rule for missing observations. The primary result itself—the percentage classified as responders and its 95% confidence interval—is not reported in the registry record. Without those estimates, the endpoint’s observed frequency and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary endpoint as a percentage, with a 95% confidence interval, and specifies non-responder imputation for missing CDAI observations. It does not describe the precise confidence-interval method, any covariate adjustment, or a broader statistical analysis plan. The following concepts explain how these methods are generally read; they should not be taken as a claim that an unreported method was used.

What does a response percentage represent?

A binary endpoint divides participants into two categories according to a stated rule. For CR50, the rule is whether CDAI decreased by at least 50 from Week 0 at Week 8. The percentage is the share of analyzed participants classified as responders. It is not a measure of average CDAI change, and it does not indicate how far an individual participant’s score changed once the response threshold was reached.

Thresholds simplify reporting, but they discard information about the size of changes within each category. Participants with decreases just short of the threshold and participants with no decrease are both classified as non-responders under the rule. Responders may also have different magnitudes of improvement despite sharing the same classification. A response percentage is therefore best read alongside other relevant outcomes when those outcomes are reported. The registry lists several other CDAI-based outcomes, but their results are not reported in the registry record.

What does a confidence interval convey?

In general, a confidence interval expresses statistical uncertainty around an estimate. For a response percentage, the interval gives a range of values compatible with the data under the interval’s method and assumptions. It is not a guarantee that the true value lies within the particular interval, and it does not measure every source of uncertainty. In a single-group study, it addresses uncertainty in the group’s estimated response proportion; it does not create a comparison with an unobserved control group.

The record specifies a 95% confidence interval for the primary endpoint but does not report its limits or the method used to calculate it. Without the estimate and interval, neither the response frequency nor its precision can be assessed. General statistical interpretation also distinguishes precision from causal evidence: a precise estimate in an uncontrolled group would still not establish how the outcome compares with another treatment.

How should non-responder imputation be understood?

Non-responder imputation classifies participants with missing CDAI observations as not having achieved the response. It is a conservative convention in the sense that missing assessments do not count as successes. It also makes assumptions: a participant whose outcome is missing is treated as a non-responder regardless of the unobserved score. This rule can affect the reported response proportion, particularly when missingness is substantial or differs across participants. The registry does not report the number or reasons for missing assessments, so the impact of the rule cannot be quantified.

The analysis population is defined as enrolled participants who received at least one dose and had at least one post-treatment efficacy assessment. This is not necessarily identical to all enrolled participants. Because the record does not report the population count or participant flow, readers cannot determine how many participants were excluded from the Full Analysis Set, whether every included participant had a Week 8 assessment, or how missing observations were distributed over time.

Why does the single-group design matter?

A single-group study estimates outcomes among participants receiving the study regimen, subject to its population, assessments, and analysis rules. A randomized comparison instead assigns participants to different conditions, allowing the between-group contrast to support a causal interpretation under appropriate assumptions. No such contrast is available in this study: allocation is listed as not applicable, masking as none, and the model as single group.

As a general matter, outcomes in an uncontrolled group may reflect treatment, natural changes in the condition, concurrent care, measurement variability, or other factors. An open-label design can also influence subjective reporting or assessment. These are potential interpretive limitations of the design, not proof that any particular bias occurred. The registry record does not report procedures that would allow these influences to be evaluated.

What do the planning assumptions mean?

The planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are assumptions for a hypothetical sample-size calculation, not a description of the actual trial design. This study is single-group, not an equal-allocation, two-arm comparison. The illustration is not observed power and should not be read as evidence about the probability that the study detected an effect.

The record does not report the study’s own sample-size justification. Nor does it report the observed primary effect needed to interpret a calculation based on a fraction of that effect. No sample-size illustration can replace the actual endpoint estimate, its confidence interval, or a clearly described comparison. In this record, the primary result and its interval are not reported.

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("Adalimumab 80 mg")
n      <- c(28)
events <- c(21)
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  Adalimumab 80 mg  28  21  75.0  55.1  89.3  56.6  87.3  56.5  87.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary CR50 response at Week 8 and multiple secondary outcomes. Several secondary outcomes involve repeated assessments through Week 52, and the list includes more than one CDAI response threshold. When many outcomes or time points are examined, the chance of at least one apparently notable result can increase. As a general statistical practice, multiplicity procedures or a prespecified hierarchy may be used to manage interpretation across multiple tests. Whether such procedures or a hierarchy were specified for this study is not reported in the registry record.

The record lists zero analyses and does not report outcome estimates or hypothesis-test results. It therefore does not permit assessment of how multiple endpoints were analyzed, whether results were adjusted for multiplicity, or whether any particular outcome was designated for confirmatory inference beyond the stated primary endpoint. A list of endpoints alone does not establish which analyses were performed or how their results should be interpreted.

Missing CDAI observations for the primary endpoint were handled using non-responder imputation. Under this rule, participants with missing CDAI observations are counted as non-responders. The record does not report how many observations were missing, the reasons for missingness, or whether missingness occurred at particular visits. It also does not describe sensitivity analyses using alternative assumptions. As a result, the robustness of the primary estimate to missing-data assumptions cannot be evaluated.

The Full Analysis Set includes enrolled participants who received at least one dose and had at least one post-treatment efficacy assessment. The number meeting that definition is not reported in the registry record. Participant flow, the number contributing to each endpoint, and details of any exclusions are also not reported. These gaps limit evaluation of both the analysis denominator and the potential effects of missing data.

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 0% 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 (14.3%), ileus (3.6%), intestinal obstruction (3.6%), small intestinal ulcer haemorrhage (3.6%), subileus (3.6%).

The registry reports 28 participants at risk for both serious and other adverse events. It records 8 participants affected by serious adverse events and 21 affected by other adverse events. These are participant counts in the single study group. The record does not report a comparison group, so the counts cannot be interpreted as comparative rates between treatments.

The listed serious-event terms and percentages are Crohn’s disease, 14.3%; ileus, 3.6%; intestinal obstruction, 3.6%; small intestinal ulcer haemorrhage, 3.6%; subileus, 3.6%; and anal abscess, 3.6%. These terms describe the registry’s coded event categories. The record does not provide event narratives or explain whether one participant could contribute to more than one listed term, so the entries should not be assumed to represent mutually exclusive groups.

The number of deaths is not reported in the registry record. The event counts also do not establish causation: the record does not give enough information to determine whether an event was attributed to adalimumab, when it occurred, or how it related to participants’ underlying disease. These figures describe reported safety information in this study, not a comparative estimate of treatment risk.

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

The registry record establishes that the study investigated adalimumab after dose escalation in Japanese participants with Crohn’s disease and identifies CR50 at Week 8 as the primary endpoint. It also describes the regimen, analysis population, and non-responder imputation rule. Those details explain what the study set out to measure and how missing primary endpoint observations were to be classified.

The record does not report the primary response percentage or its 95% confidence interval. It also does not report results for the listed secondary outcomes. Consequently, the posted information does not establish how many participants met the primary response definition, how precise an estimate would be, or whether outcomes changed across the listed assessments. The endpoint definition alone is not a result.

Even if an observed response estimate were available, the study design would remain important to its interpretation. As a single-group, open-label study without a concurrent control, it can describe outcomes among participants receiving the stated regimen but cannot, by itself, show how those outcomes compare with an alternative. General influences such as natural changes over time, other care, or assessment effects cannot be separated from treatment effects by a randomized contrast in this design.

The safety counts show that serious and other adverse events were recorded among participants in the study group, and the registry lists several serious-event terms. These observations do not establish that treatment caused the events or quantify risk relative to another condition. The record also does not report the number of deaths. Any broader judgment about benefits, harms, or treatment choice would go beyond the reported statistical information.

In short, the registry describes the trial’s question and design, but does not post the outcome estimates needed to answer the primary efficacy question statistically. The absence of a reported result should not be mistaken for evidence of no response or for evidence of a particular response. It means that the response frequency and its precision are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a study question, a design, and a result. The record clearly defines a threshold-based primary endpoint and a population for analysis, and it states how missing CDAI observations were handled. These details matter because a response estimate is meaningful only when readers know what counts as a response, which participants are included, and how missing outcomes affect classification.

The design also matters. A single-group study can describe the observed experience of participants receiving a regimen, but it does not provide a randomized estimate of the difference between that regimen and a comparator. This distinction is central when interpreting an endpoint that might otherwise be mistaken for proof of a treatment effect. The open-label nature of the study is another relevant feature when considering outcomes based on clinical assessment.

Several recurring issues in clinical statistics are visible in the record: a binary endpoint derived from a clinical index, imputation for missing observations, multiple listed outcomes, and a planning illustration based on a two-arm assumption despite the study’s single-group model. Understanding those elements helps readers distinguish endpoint definitions from endpoint findings, and planning assumptions from the design actually conducted.

The record’s limitations are equally instructive. Although it specifies the primary endpoint and its confidence-interval type, it does not report the estimate or interval. It lists outcomes without posted analyses, and it does not give the analysis count, missing-data counts, or the study’s own sample-size justification. Statistical transparency requires both methods and results: a clear definition of what was measured cannot substitute for the numerical findings needed to assess magnitude and precision.

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 most important limitation for statistical interpretation is that the registry record does not report the primary endpoint result or its 95% confidence interval. Without these, the response percentage and its precision cannot be assessed. The record also does not report results for the listed secondary outcomes, despite listing 15 outcome measures and zero analyses.

The enrollment was 28, but the number in the Full Analysis Set is not reported. The registry defines that set as enrolled participants who received at least one dose and had at least one post-treatment efficacy assessment. Participant flow, analysis denominators by outcome, and the number with Week 8 data are not reported. This prevents assessment of how the analysis population relates to total enrollment.

Non-responder imputation was used for missing CDAI observations, but the amount and pattern of missingness and reasons for missing assessments are not reported. No sensitivity analyses are described in the registry record. The effect of the imputation rule on the primary estimate therefore cannot be examined.

The single-group, open-label design has no randomized comparator. It can describe outcomes in the treated group, but it cannot isolate a treatment contrast from other changes over time or influences on assessment. The record does not report details that would allow those potential influences to be assessed. Multiple outcomes and repeated time points are listed, but multiplicity procedures or an analysis hierarchy are not reported.

Finally, the registry does not report the study’s own sample-size justification, the precise confidence-interval method, or details such as the dose-escalation history. Safety reporting includes participant counts and event terms, but not timing, attribution, or event narratives; deaths are not reported. These omissions limit interpretation without establishing that any particular event or bias occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Adalimumab After Dose Escalation in Japanese Subjects With Crohn's Disease — NCT01958827.
• Registry record last updated 2016-04-12; status last verified 2016-03.
• Results first posted 2016-04-12.
• 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

NCT01958827 is a completed Phase 3, multicenter, open-label, single-group study of adalimumab in Japanese participants with Crohn’s disease. Enrollment was 28. Participants were to receive adalimumab 80 mg by subcutaneous injection every other week from Week 0 to Week 50.

The primary endpoint was the percentage achieving CR50 at Week 8, defined as a CDAI decrease of at least 50 from Week 0. The Full Analysis Set required at least one dose and at least one post-treatment efficacy assessment; non-responder imputation was used for missing CDAI observations. The primary result and its 95% confidence interval are not reported in the registry record.

The record lists 15 outcome measures and zero analyses. It reports 8 participants affected by serious adverse events and 21 affected by other adverse events, among 28 at risk. The number of deaths is not reported. No randomized comparator is described.