Rapidity of Response to Adalimumab Treatment in Patients With Crohn´s Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rapidity of Response to Adalimumab Treatment in Patients With Crohn´s Disease (NCT02148718), a na phase 4 study. The primary outcome is Percentage of Participants With Clinical Response at Day 4.

2. Clinical Question

In practical terms, the study was organized to describe the timing of an early clinical response after treatment began. It was not designed, as recorded, to estimate a randomized treatment difference. Without a posted endpoint estimate and its uncertainty interval, the registry information does not establish how often the defined response occurred at Day 4 or how precisely that percentage was estimated.

3. Trial Design

RAPIDA is a Phase 4, completed, single-group study sponsored by AbbVie. The registry lists enrollment of 100 participants and identifies moderate to severe Crohn’s disease as the condition. The study began in 2014-06 and had primary completion in 2016-08. These registry dates describe the study record; they do not by themselves give the timing of individual participant follow-up or analysis.

All participants were assigned to the adalimumab group in the recorded design. Treatment was planned for 12 weeks, with an initial 160 mg dose at Week 0, 80 mg at week 2, and then 40 mg every other week starting at Week 4. Masking is recorded as none. The registry does not identify a control group, and the allocation field is not applicable. This is therefore a descriptive study of outcomes during treatment rather than a randomized comparison between treatment strategies.

The primary outcome was clinical response at Day 4, defined using change in HBI score. Listed secondary outcomes include clinical response at Week 1; clinical remission at Weeks 2 and 4; changes in quality-of-life scores, fatigue score, hemoglobin, and hematocrit from baseline to Week 12. The record lists 18 outcome measures, but it does not report the primary response result in the registry record for this analysis. It also does not provide a complete account of how each listed outcome was analyzed or how missing measurements were handled.

The primary endpoint population is defined as enrolled participants who received at least one dose of study drug. Although the registry lists enrollment of 100, the number actually included in the primary endpoint analysis is not reported in the registry record. The record also does not report the study’s sample-size justification, the intended handling of withdrawals, or whether any protocol changes affected the analysis.

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 100 participants were enrolled in the study; 14 participants did not receive study drug and are excluded from the analyses.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT) population: all enrolled participants who received at least 1 dose of study drug

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: Intent to Treat (ITT) population: all enrolled participants who received at least 1 dose of study drug

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Clinical Response at Day 4, measured over Day 4.

The primary endpoint is the percentage of participants with clinical response at Day 4. Clinical response is defined as a decrease of at least 3 points in the Harvey-Bradshaw Index (HBI) score. The HBI combines clinical features: general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications. The record notes that the first 3 items are scored for the previous day. It also describes HBI scores of 3 or less as strongly associated with remission and scores of 8 to 9 or higher as indicating severe disease.

A percentage is a way to express how common a defined event was among the participants assessed. For this endpoint, the event is meeting the specified decrease in HBI score by Day 4. The endpoint focuses on early change, which fits the stated study purpose of evaluating the rapidity of clinical response. It does not, on its own, describe the size of improvement among participants who did not meet the response threshold, or whether a response was sustained after the assessment.

The registry specifies a 95% confidence interval for the primary percentage. A confidence interval communicates uncertainty around an estimate: a narrower interval indicates greater precision, while a wider interval indicates less precision. However, the primary response percentage, the number of responders, the analyzed denominator, and the confidence interval are not reported in the registry record. The endpoint definition is available, but its observed value and precision cannot be interpreted from the available results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary event summarized as a percentage: a participant either meets the registry’s response definition at the assessment or does not. Here, response is a decrease of at least 3 points in HBI score at Day 4. A percentage is useful because it translates the event count into a proportion of the assessed population. To interpret that proportion, the numerator and denominator are both important. The registry record does not report either count for the primary analysis, nor does it report the calculated percentage.

The planned uncertainty summary is a 95% confidence interval. In general, a confidence interval describes the range of values compatible with the observed data under the method’s assumptions. It is not a guarantee that a particular interval contains the underlying value, and it does not repair limitations in the design or data. The interval’s width depends in part on the number of observations and the event frequency. Because the primary estimate and interval are not reported in the registry record, their precision cannot be assessed.

The endpoint is based on change in an index, rather than a laboratory measurement alone. The HBI includes general well-being, abdominal pain, liquid stools per day, abdominal mass, and complications. The record specifies that the first 3 items are scored for the previous day. Applying a threshold to change in a score turns a continuous or multi-point measure into a binary response classification. Such thresholds can make an endpoint easier to interpret, but they also mean that participants with similar score changes may be classified differently if they fall on opposite sides of the threshold. This is a general feature of threshold-based outcomes.

The primary population is described as the intent-to-treat population, defined in this record as all enrolled participants who received at least one dose of study drug. That definition should not be confused with the enrollment total. The record lists 100 enrolled, but does not state how many participants received treatment, had a Day 4 HBI assessment, or contributed to the primary estimate. It also does not specify whether participants without an assessment were excluded, counted as nonresponders, or handled by another method. Those details are not reported in the registry record.

For a single-group study, the primary percentage is descriptive. There is no randomized between-group contrast to estimate, and no treatment comparison test is identified in the posted information. General statistical methods for a single proportion can quantify uncertainty around the observed percentage, but the registry record does not report which specific interval method was used. It would be inappropriate to assume a particular method or reconstruct an estimate without the underlying counts.

The registry lists 18 outcome measures and 0 analyses. This does not establish that no analyses were conducted; it means that analyses are not listed in the registry record used for this account. The information does not describe the statistical analysis plan, model specifications, test procedures, interim analyses, or prespecified hierarchy among outcomes. These items are not reported in the registry record.

Multiplicity arises when several outcomes or comparisons are assessed. In general, testing many hypotheses can increase the chance of at least one apparently unusual result if each is interpreted without regard to the others. A study may address this through a hierarchy, adjusted significance thresholds, or other prespecified procedures. The registry record lists multiple outcome measures but does not describe any multiplicity strategy. Since the primary numerical result is also absent, no claim about a significant or nonsignificant finding can be made from the posted record.

A separate planning illustration is described using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of an observed effect. Those assumptions describe hypothetical planning calculations; they do not describe the RAPIDA design, which is single-group. The illustration is not observed power and is not evidence that a particular sample size was justified for this study. The actual sample-size justification and any planning effect are not reported in the registry record. The illustration’s numerical results are also not reported in the registry information used.

In general, over-dispersion means that observed variability is greater than a statistical model expects. This can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variability. The endpoint in this study is a participant-level binary response, but the registry record does not identify a model that would require an over-dispersion assessment. It would therefore be speculative to say whether over-dispersion was relevant to the sponsor’s analysis.

The distinction between the registry’s stated endpoint and the analysis actually performed is important. The record provides the outcome definition and the intended summary scale, but does not report the primary estimate, its interval, the analyzed denominator, or the analysis method. Without those details, statistical interpretation must remain focused on the design and the limits of what is documented.

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")
n      <- c(86)
events <- c(53)
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  86  53  61.6  50.5  71.9  51.1  71.2  51.0  71.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 18 outcome measures, including the primary Day 4 response endpoint and secondary measures of response, remission, quality of life, fatigue, hemoglobin, and hematocrit. It does not report a multiplicity plan, such as a prespecified testing hierarchy or an adjustment for assessing multiple outcomes. In general, multiplicity matters when several statistical tests are interpreted together because the chance of at least one apparently notable result can rise as more tests are considered. No claim about how this issue was handled in RAPIDA can be made from the record.

The record lists 0 analyses, but that should be read as an absence of analyses in the registry listing, not as proof that no statistical work took place. The analysis plan, interim-analysis procedures, and model details are not reported in the registry record. The registry identifies a 95% confidence interval for the primary percentage, but does not state the interval method.

The primary population is defined as enrolled participants who received at least one dose of study drug. The number in that population and the number with an observed Day 4 assessment are not reported. The approach to missing HBI assessments, withdrawals, or other unavailable outcome data is also not reported in the registry record. This matters because excluding participants with missing measurements, treating them as nonresponders, or using another approach can lead to different estimates. The posted record does not support choosing among those possibilities.

Enrollment of 100 is reported, but it should not be taken as the endpoint denominator. The registry does not provide the responder count or the count analyzed for the primary endpoint. Therefore, neither the primary percentage nor its precision can be reconstructed from the 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 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 (1.2%), pyrexia (1.2%), pneumonia (1.2%).

The safety summary records 86 participants at risk in the adalimumab group for serious adverse events and 86 at risk for other adverse events. It reports 2 participants affected by serious events and 35 affected by other events. These are counts in separate safety summaries; they are not the primary endpoint population or a control-group comparison. The registry does not report the primary endpoint denominator, and the enrollment figure of 100 should not be substituted for the safety denominator.

The most frequent serious-event terms listed are Crohn’s disease, pyrexia, and pneumonia, each reported at 1.2%. These are registry-listed event terms, not a causal assessment. The information does not establish whether an event was caused by adalimumab, whether participants experienced more than one event, or how event timing related to treatment. Further details of event definitions and case-level summaries are not reported in the registry record.

Because the study has a single group and no comparator, these safety counts do not provide a direct comparison of event occurrence under different treatments. They describe what the registry reports for participants in the adalimumab group. The figures should be read alongside the limits of the recorded denominator and available event detail, not as evidence for a treatment effect on safety.

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

The record establishes that RAPIDA was designed to examine the rapidity of clinical response to adalimumab in luminal Crohn’s disease. Its primary endpoint was the percentage of participants meeting a defined HBI response threshold at Day 4, with a 95% confidence interval intended as the measure of precision. The registry record does not report the observed percentage, the responder count, the analyzed denominator, or the interval. As a result, the primary statistical question cannot be answered quantitatively from the posted information.

The study’s single-group structure is central to interpretation. A percentage among treated participants can describe the response frequency in that group, but it cannot establish how that frequency compares with an untreated or differently treated group. Without a concurrent comparator, the design cannot isolate the effect of treatment from other possible influences on observed change. This is a general limitation of a single-group design, not a claim about the cause of any participant’s outcome.

The response definition also sets the scope of the endpoint. It classifies participants according to whether their HBI score decreased by at least 3 points by Day 4. It does not, by itself, tell how much scores changed beyond that threshold, how long any response lasted, or how participants experienced other outcomes. The listed secondary outcomes cover some additional domains, but their numerical results are not reported in the registry information available for this account.

The listed safety counts and serious-event terms offer a limited description of events recorded for the adalimumab group. They do not demonstrate causation or establish comparative safety. The registry does not provide enough detail to resolve those questions.

Accordingly, the posted record supports understanding the study’s purpose, regimen, endpoint definition, and broad design. It does not support a conclusion about the frequency or precision of the primary clinical response result, a randomized treatment difference, or the causal relationship between treatment and safety events. Those conclusions would require results and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between an early-response question and a comparative treatment question. RAPIDA focused on the timing of clinical response, with a Day 4 endpoint defined by change in HBI score. That makes the endpoint conceptually aligned with the stated purpose of assessing how rapidly response was observed. The record, however, does not report the endpoint estimate needed to quantify that timing question.

The single-group design clarifies the kind of evidence the registry can describe. It can report outcomes observed among participants receiving adalimumab, but it does not create a randomized contrast with another treatment or control condition. This distinction is important whenever a result is expressed as a response percentage: a descriptive rate and a treatment effect are different statistical quantities. No comparative effect is reported for this study.

The confidence interval matters as much as the point estimate when interpreting a percentage, because it conveys the estimate’s precision. In this record, the endpoint’s intended confidence level is identified, but the estimate and interval are not reported. The denominator is also absent, so readers cannot assess how many participants contributed to the result or how missing assessments might affect interpretation.

The registry lists numerous outcome measures and selected safety information, while offering little analysis detail. That makes transparency about prespecification, multiplicity, missing data, and analysis populations especially relevant. These matters are not reported in the registry record. The study is therefore a useful example of why endpoint definitions and design descriptions are not substitutes for complete outcome reporting: both are needed to evaluate what the observed data show and how precisely they do so.

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 primary limitation for interpreting the study is that the registry record does not report the Day 4 response estimate or its 95% confidence interval. It also does not report the primary analysis numerator or denominator. Although enrollment of 100 is listed, the endpoint population is restricted to enrolled participants who received at least one dose, and the number meeting that definition is not stated. The enrollment total cannot be assumed to equal the number analyzed.

The single-group design has no comparator, so the posted design cannot estimate a randomized difference between adalimumab and another intervention. It also cannot rule out alternative explanations for change over time. This limitation applies to causal interpretation and does not imply that a particular alternative explanation occurred.

The endpoint depends on an HBI threshold at Day 4. The record gives the definition and the index components, but does not report the underlying score distributions, the frequency of missing assessments, or the method used when measurements were unavailable. It is therefore not possible to evaluate how the threshold classified participants in the observed data or how missingness may have affected the estimate.

The registry lists multiple outcome measures, but does not report a multiplicity strategy, detailed analysis methods, interim analyses, or a complete statistical plan. Numerical results for the listed secondary outcomes are not reported in the registry information used. The safety summaries provide selected counts and event terms, but do not establish causality or provide a control-group comparison. The study’s sample-size justification is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rapidity of Response to Adalimumab Treatment in Patients With Crohn´s Disease — NCT02148718.
• Registry record last updated 2018-03-01; status last verified 2018-02.
• Results first posted 2017-08-29.
• 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

RAPIDA is a completed Phase 4, single-group study of adalimumab in participants with moderate to severe Crohn’s disease, with enrollment of 100. The regimen lasted 12 weeks: 160 mg at Week 0, 80 mg at week 2, then 40 mg every other week starting at Week 4. The primary endpoint was the percentage with clinical response at Day 4, defined as a decrease of at least 3 points in HBI score.

The registry specifies a 95% confidence interval but does not report the primary estimate, interval, responder count, or analysis denominator. Listed secondary outcomes include response and remission assessments, quality-of-life and fatigue measures, and changes in hemoglobin and hematocrit. The safety summary reports 2 participants with serious adverse events and 35 with other adverse events among 86 at risk in each summary; the most frequent serious-event terms are listed at 1.2% each. The design has no comparator, and the registry does not report the analysis plan, missing-data approach, or sample-size justification.