A Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis (NCT00853099), a randomized phase 3 study. The primary outcome is Percentage of Participants With Clinical Remission at 8 Weeks.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, double-blind, parallel-group, placebo-controlled study of adalimumab in Japanese participants with moderately to severely active ulcerative colitis. The registry record lists an enrollment of 274 and a completed study. The study start is recorded as 2009-02, and primary completion as 2011-05. The sponsor is listed as AbbVie (prior sponsor, Abbott).

Participants were assigned to placebo or one of two adalimumab regimens. The 80 mg/40 mg regimen started with 80 mg on Day 1, followed by 40 mg at Week 2 and 40 mg every other week from Week 4 to Week 50. The 160 mg/80 mg regimen started with 160 mg on Day 1, followed by 80 mg at Week 2 and 40 mg every other week from Week 4 to Week 50. Both active-regimen descriptions specify subcutaneous injection. The placebo group was scheduled to receive injections every 2 weeks for 52 weeks.

The primary outcome was clinical remission at Week 8. The registry record also lists secondary outcomes relating to remission at other time points, clinical response, mucosal healing, symptom subscores, quality of life, and adverse events. The record lists 12 outcome measures and 10 posted secondary outcomes. The original protocol's detailed allocation procedures, the rationale for the planned sample size, and the full statistical analysis plan are not reported in the registry record.

The arm descriptions mention rescue therapy from Week 8 for participants with an inadequate response, but the descriptions are truncated. The full rules for switching, subsequent treatment, and how rescue therapy was handled in every analysis are not reported in the registry record. These details matter when interpreting outcomes over longer follow-up, but should not be reconstructed from the partial descriptions.

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.

Double-blind Period

Reasons for not completing this period:

Double-blind + Open-label Periods

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set includes all patients who received at least 1 dose of study drug any time during the first 52 weeks and with at least 1 efficacy measurement after the first dose of study medication. Non-responder imputation (NRI) was used, where all missing values and values after the start of rescue treatment were considered non-remission.

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: 1 participant in the adalimumab 160 mg/80 mg arm was incorrectly treated with open-label (rescue) study drug at Week 0, and was not included in Baseline Characteristics.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Clinical Remission at 8 Weeks, measured over Week 8.

The primary endpoint was the percentage of participants with clinical remission at Week 8. Remission was defined as a total Mayo score of 2 or less, with no individual subscore greater than 1. The Mayo score combines four assessments: stool frequency, rectal bleeding, endoscopic findings, and the physician's global assessment. Each subscore ranges from 0 to 3, and the total score ranges from 0 to 12; higher totals represent more severe disease.

This endpoint combines reported symptoms, endoscopic assessment, and the physician's assessment into a single classification. It therefore represents a broader measure of disease activity than any one subscore alone. The registry record defines the remission threshold, but does not report further information about assessment procedures, assessor training, or how disagreements between assessments were managed.

The endpoint is binary at the participant level: each participant is classified as meeting or not meeting the remission definition for the analysis. The posted result is the percentage meeting that definition in each group. This makes the group summaries readily interpretable as the frequency of the defined outcome, while reducing the detail contained in the underlying continuous Mayo score and its component subscores. The endpoint concerns the Week 8 assessment; it should not be read as a statement about remission at later times or about outcomes not included in this definition.

7. Results Posted in the Registry

• Adalimumab 80 mg/40 mg: 13.8% (12/87) versus 11.5% (11/96) on control; risk difference 2.3 percentage points (95% CI -7.3 to 12.0), risk ratio 1.20 (0.56–2.59); unadjusted two-proportion z-test p = 0.634.
• Adalimumab 160 mg/80 mg: 10.0% (9/90) versus 11.5% (11/96) on control; risk difference -1.5 percentage points (95% CI -10.3 to 7.4), risk ratio 0.87 (0.38–2.01); unadjusted two-proportion z-test p = 0.748.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: a participant either met the specified clinical-remission definition at Week 8 or did not. For each group, the registry results give the percentage meeting the definition, along with the number of participants and outcome events used in the posted comparison. This kind of outcome is often summarized as a proportion or percentage because the event is a classification rather than a continuous measurement.

The comparisons use the risk difference. In general, a risk difference is the outcome proportion in one group minus the outcome proportion in the reference group. A value above zero indicates a larger observed proportion in the first group under the comparison's direction; a value below zero indicates a smaller one. A value of zero corresponds to equal proportions. The posted estimates are 0.023 for adalimumab 80 mg/40 mg versus placebo and -0.015 for adalimumab 160 mg/80 mg versus placebo. These are unadjusted contrasts and should be read together with their confidence intervals, rather than as precise statements about the underlying effect.

The registry record also provides risk ratios and odds ratios for the two comparisons. In general, a risk ratio compares the outcome proportions as a ratio, while an odds ratio compares the outcome odds. These measures express relative rather than absolute differences, and their numerical interpretation differs from that of a risk difference. The posted risk-ratio and odds-ratio estimates have intervals that include the no-association value of 1. The risk-difference intervals include the no-difference value of zero. No single effect measure captures every aspect of the comparison, so the chosen scale should be kept in view when interpreting estimates.

The p-values are unadjusted: 0.634 for the 80 mg/40 mg comparison and 0.748 for the 160 mg/80 mg comparison. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not quantify the size or clinical importance of an effect. Here, the p-values should be considered alongside the observed percentages and confidence intervals. The registry record lists no posted analysis entries beyond these comparisons, and it does not report the complete original statistical procedure.

The registry description identifies a full analysis set consisting of participants who received at least one dose of study drug during the first 52 weeks and had at least one efficacy measurement after the first dose. It also states that non-responder imputation, or NRI, was used. In general, non-responder imputation treats specified missing observations as failures to meet the outcome. This can make the analysis conservative under some conditions, but it does not eliminate uncertainty or bias: the implications depend on why observations are missing and how the rule is applied. The registry description says that all missing values and values after the start of a subsequent circumstance were handled under NRI, but its text is truncated at that point. The full rule and the treatment of rescue therapy in the primary analysis are therefore not reported in the registry record.

Confidence intervals give a range of values reasonably compatible with the data and the method's assumptions. In general, a wider interval indicates less precision, while an interval that crosses the null value permits effects in both directions as well as no difference. The two risk-difference intervals are -0.073 to 0.120 and -0.103 to 0.074. Both cross zero, and both cover a range extending to effects in either direction. These intervals do not mean that every value inside them is equally likely, nor do they guarantee that the true effect lies within them.

Multiplicity arises when several outcomes, comparisons, or analysis choices are examined. In general, making multiple statistical tests can increase the chance of at least one apparently unusual result if each test is treated as though it were the only one. The registry record lists 12 outcome measures, 10 posted secondary outcomes, and two active-regimen comparisons for the primary endpoint. Whether the original protocol specified a testing hierarchy, a multiplicity adjustment, or another control strategy is not reported in the registry record. The posted p-values are explicitly unadjusted and should not be mistaken for multiplicity-adjusted results.

Finally, the registry record does not report enough information to reconstruct every analytic choice. Details such as the original sample-size justification, interim analyses, the complete prespecified analysis plan, and the full missing-data rules are not reported in the registry record. General statistical explanations can clarify what the posted measures mean, but they cannot fill those study-specific gaps.

10. Confidence Intervals and Precision

The risk-difference estimate for adalimumab 80 mg/40 mg versus placebo was 0.023, with a 95% confidence interval from -0.073 to 0.120. For adalimumab 160 mg/80 mg versus placebo, the estimate was -0.015, with a 95% confidence interval from -0.103 to 0.074. Both intervals include zero, the value corresponding to no difference on the risk-difference scale.

In general, a confidence interval communicates uncertainty around an estimate under the analysis method and its assumptions. An interval that includes zero means the data do not pin down the direction of the risk difference: values on either side of zero are compatible with the interval. The intervals also extend across a range of possible differences, so the point estimates should not be read as exact descriptions of the underlying effect. A confidence interval is not a guarantee that the true value lies within its bounds, and values within the interval are not necessarily equally plausible.

The reported group percentages were 11.5% for placebo, 13.8% for adalimumab 80 mg/40 mg, and 10.0% for adalimumab 160 mg/80 mg. Those estimates are based on the group sizes used for the primary outcome analysis: 96, 87, and 90 participants, respectively. The observed event counts were 11, 12, and 9, respectively. The confidence intervals reflect uncertainty in the comparative estimates; they do not capture every possible source of uncertainty, such as incomplete reporting of the full analysis plan or missing-data rules.

Precision and the direction of a point estimate are different issues. A point estimate can be positive or negative while its interval remains compatible with either direction. The posted intervals therefore warrant a cautious reading of the magnitude and direction of the comparisons. They do not, by themselves, establish equivalence or prove that an effect is absent.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are expressed as participants per arm for 80% power and participants per arm for 90% power. They are planning illustrations based on the observed risk difference, not the number of participants enrolled or analyzed in the trial. The rows consider planning for 100% of the observed effect, planning for 75% of the observed effect, and planning for 50% of the observed effect. Smaller effects require more participants to detect under the stated assumptions, so the lower-effect rows have larger planning figures.

The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For this binary outcome, the figures refer to participants per arm, not total events. The registry record does not report the trial's original design assumptions or sample-size justification, so these illustrations should not be treated as a reconstruction of the original planning.

In general, 80% power means that, if the assumed effect and other calculation assumptions held, the design would have an 80% chance of detecting an effect at the specified significance level. The 90% column uses a higher target chance of detection under those same assumptions. These are conditional planning concepts, not guarantees for a particular study. The displayed figures are not observed power.

The figures are calculated separately for each active-regimen comparison with placebo, so the assumed observed effects differ between the two comparisons. They illustrate how much the planning requirement can change when the target effect is made smaller. They do not show that a future study would necessarily achieve the assumed effect or that any particular sample size would resolve all concerns about bias, missing outcomes, multiplicity, or generalizability.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.115; treatment proportion p₁ = 0.138; average p̄ = 0.126.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4697 = 0.9206.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4694 = 0.3951.
4. n = (0.9206 + 0.3951)² / (0.0233)² = 3,175.6, rounded up to 3,176 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.114583333333333                          # control proportion
p1 <- 0.137931034482759                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(853099)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 3,176 (80% power), 4,251 (90% power)
 75% of observed effect: n per arm = 5,535 (80% power), 7,409 (90% power)
 50% of observed effect: n per arm = 12,200 (80% power), 16,332 (90% power)
power.prop.test: 3175.6 
Simulated power at n = 3,176 per arm: 0.798 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The primary endpoint was clinical remission at Week 8, but the registry record also lists multiple secondary outcomes, including remission at other time points, clinical response, mucosal healing, symptom subscores, IBDQ response, and adverse events. It lists 12 outcome measures and 10 posted secondary outcomes. In addition, the primary endpoint has two active-regimen comparisons against placebo. Considering several outcomes and comparisons raises the issue of multiplicity: if many tests are conducted, interpreting each result as though it were the sole test can overstate the evidence from an isolated finding.

The posted p-values for the primary comparisons are unadjusted. Whether the original protocol specified an adjustment, testing hierarchy, or other strategy for controlling multiplicity is not reported in the registry record. The absence of that information means the posted p-values cannot be assumed to account for all outcomes or comparisons. The registry record also lists no posted analysis entries, so the complete original analysis plan cannot be recovered from the record.

For the primary endpoint, the stated analysis population includes participants who received at least one dose during the first 52 weeks and had at least one efficacy measurement after the first dose. The record states that non-responder imputation was used, including for missing values. In general, this approach classifies designated missing observations as not meeting the outcome. The record's description is truncated after mentioning values following the start of a further event or circumstance; the full rule is not reported in the registry record.

Consequently, the exact handling of missing Week 8 assessments, treatment discontinuation, and rescue therapy cannot be fully established from the description. The arm descriptions mention rescue therapy from Week 8 for inadequate response, but do not provide complete details. Whether the original analysis used additional sensitivity analyses or how those analyses were defined is not reported in the registry record. These gaps limit the ability to assess the robustness of the primary result to alternative assumptions about missing outcomes and subsequent treatment.

14. 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: colitis ulcerative (14.3%), colonic polyp (1.1%), adverse drug reaction (1.1%), bronchitis (1.1%), pneumonia bacterial (1.1%).

The registry record reports serious adverse-event counts by group. The counts were 13 among 96 participants in the placebo group, 14 among 87 participants in the adalimumab 80 mg/40 mg group, and 10 among 90 participants in the adalimumab 160 mg/80 mg group. The combined “All Adalimumab” group lists 90 among 266 participants. These are reported counts of participants affected, not counts of every event, and the combined category should be read as its own registry grouping.

Reported serious-event terms include ulcerative colitis at 14.3%, followed by colonic polyp, adverse drug reaction, bronchitis, bacterial pneumonia, and acute pyelonephritis at 1.1% each. The registry record does not make the denominator or detailed coding context for these listed terms clear in the information, so the percentages should be read as reported rather than used to make unreported comparisons.

These figures are descriptive safety summaries. They do not, on their own, establish whether an event was caused by a study treatment or whether groups differed reliably. The death fields are not populated; deaths are therefore not reported in the registry record. The registry record also gives counts for other adverse events, but those are distinct from the serious-event counts and should not be conflated with them.

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

The posted results describe clinical remission at Week 8 in this randomized, double-blind comparison involving Japanese participants with moderately to severely active ulcerative colitis. Remission was defined using the total Mayo score and its component subscores. The reported percentages were 11.5% with placebo, 13.8% with adalimumab 80 mg/40 mg, and 10.0% with adalimumab 160 mg/80 mg. The risk-difference estimates and their confidence intervals express uncertainty around each comparison with placebo.

The results do not establish that either regimen produced a clear difference in the primary outcome: both confidence intervals include zero, and the posted p-values are unadjusted. At the same time, these findings do not prove that the true differences are exactly zero. The intervals permit effects in either direction, and the analysis has the limitations of the available reporting, including incomplete detail about missing-data handling and multiplicity.

The result applies to the defined Week 8 endpoint and analysis population, not automatically to later remission, other secondary outcomes, other populations, or other treatment schedules. The trial's rescue-therapy descriptions are incomplete, and the registry record does not report the full rules for how rescue therapy affected the primary analysis. Interpretation of outcomes beyond the primary time point therefore requires the relevant outcome-specific results and complete analysis details.

Nor should the remission result be treated as a complete account of safety. Serious adverse events are separately listed, but descriptive counts do not show causation and do not answer every safety question. Taken together, the posted outcomes support a careful description of the measured results and their uncertainty; they do not provide a basis for medical advice or a universal conclusion about treatment effects.

16. Why This Trial Matters Statistically

This trial illustrates why a clinical result should be read through both its endpoint definition and its statistical uncertainty. “Clinical remission” is not an unspecified judgment: the registry record defines it using a total Mayo score of 2 or less and requires that no individual subscore exceed 1. That definition combines several components of disease activity, while the reported percentage reduces those details to whether each participant met the threshold.

The trial also compares two active regimens separately with placebo. Their Week 8 remission percentages and risk-difference estimates do not point in the same direction, and both confidence intervals include zero. Looking only at a group percentage or a point estimate would miss how much uncertainty remains around the comparative results. Reading the estimates with their intervals gives a more complete account of what the data can and cannot distinguish.

Multiplicity is another statistical issue made visible by the record. There are two primary comparisons and numerous listed outcomes. The reported p-values are unadjusted, while the original plan for handling multiple comparisons is not reported in the registry record. That distinction matters when judging how much weight to place on individual statistical tests.

Finally, the registry record identifies a full analysis set and non-responder imputation, but does not provide the complete missing-data rule. This illustrates how transparent endpoint definitions and headline estimates can coexist with gaps that limit reproducibility. The study is statistically informative as a case in interpreting binary outcomes, confidence intervals, analysis populations, multiplicity, and registry reporting without overstating what an estimate alone can establish.

17. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The posted primary results concern Week 8 clinical remission, and the available record does not provide the full prespecified analysis plan. It lists 12 outcome measures and 10 posted secondary outcomes, but does not report whether or how the original analysis controlled for multiplicity. The unadjusted p-values should therefore not be presumed to reflect adjustment across the trial's outcomes or comparisons.

The record identifies a full analysis set and says that non-responder imputation was used, but the description of how missing observations and values after the start of a further circumstance were handled is truncated. The full missing-data rules, sensitivity analyses, and treatment of rescue therapy in the primary analysis are not reported in the registry record. The arm descriptions also end before all details are available.

The primary outcome analysis groups participants according to a binary remission threshold. The summary therefore does not convey the full distribution of Mayo scores or how each individual subscore changed. Those details are not reported in the primary result. The listed outcome results do not substitute for a complete account of all outcome-specific methods and estimates.

Although the record gives enrollment as 274, the primary outcome analysis groups list 96, 87, and 90 participants. The record defines the analysis population by treatment received and availability of an efficacy measurement, but does not fully explain the relationship between enrollment and the analysis groups in the information available. The original sample-size justification, interim analyses, and further protocol-level design assumptions are not reported in the registry record. These reporting limits should be kept in mind when assessing precision, reproducibility, and the scope of conclusions.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis — NCT00853099.
• Registry record last updated 2014-09-05; status last verified 2014-09.
• Results first posted 2012-11-27.
• 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.

21. Record Summary

NCT00853099 is a completed, randomized, double-blind, parallel-group, placebo-controlled phase 3 study of adalimumab in Japanese participants with moderately to severely active ulcerative colitis. The registry record lists 274 enrolled participants, a study start of 2009-02, and primary completion in 2011-05.

The primary outcome was the percentage meeting the clinical-remission definition at Week 8. Reported percentages were 11.5% for placebo, 13.8% for adalimumab 80 mg/40 mg, and 10.0% for adalimumab 160 mg/80 mg. The risk-difference confidence intervals for both comparisons with placebo include zero. The registry record also reports serious adverse-event counts and lists multiple secondary outcomes.

The record identifies the primary analysis population and non-responder imputation, but does not fully report the missing-data rules, multiplicity strategy, original sample-size justification, or complete analysis plan. Those limitations qualify interpretation of the posted estimates.