Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease (NCT00409682), a randomized phase 3 study. The primary outcome is Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 26.

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase 3, randomized, parallel-group study with quadruple masking. Its official title describes a multicenter, double-blind study evaluating safety, efficacy, and pharmacokinetics of adalimumab in pediatric subjects with moderate to severe Crohn's disease. Abbott is listed as the sponsor. The record gives a start date of 2007-04, a primary completion date of 2010-05, and a completed status.

All subjects received open-label adalimumab induction from Week 0 to Week 4. At baseline, subjects weighing greater than or equal to 40 kg received 160 mg at Week 0 and 80 mg at Week 2; those weighing less than 40 kg received 80 mg at Week 0 and 40mg at Week 2. From Week 4 to Week 52, subjects were randomized to the low-dose or high-dose regimen, with the dose determined by Week 4 body weight. The posted descriptions indicate that dose changes could begin at the Week 12 study visit for subjects experiencing a disease-related change, but the full details of those descriptions are not reported in the registry record.

The primary efficacy comparison is high-dose versus low-dose adalimumab in the stated intent-to-treat analysis set: all randomized subjects who received at least one dose of double-blind study medication. The record lists 95 participants in the low-dose group and 93 in the high-dose group for the primary result. The trial’s original sample-size justification, its detailed randomization procedures, and the procedures used to maintain masking are not reported in the registry record. The comparison therefore concerns two active regimens following a common open-label induction, rather than a treatment-versus-placebo contrast.

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: Enrolled pediatric subjects were given an induction regimen of 160/80 mg adalimumab at Baseline/Week 2 or 80/40 mg at Baseline/Week 2 according to the subjects' Baseline body weight (BW) and were randomized at Week 4 to receive one of two maintenance regimens of adalimumab every other week (eow).

Open-label Induction Period

Reasons for not completing this period:

EOW Double-blind Maintenance Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Comparison of adalimumab High-Dose versus Low-Dose with respect to the primary efficacy endpoint in the intent-to-treat analysis set as all randomized subjects who received at least one dose of double-blind study medication.

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 Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 26, measured over Week 26.

The primary endpoint is the percentage of participants with clinical remission at Week 26, defined as a Pediatric Crohn's Disease Activity Index score of 10 or less. The PCDAI is an index for measuring disease activity in pediatric patients with Crohn's disease. The registry says it assesses abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. Its scale ranges from 0 to 100, with higher scores indicating more active disease.

Using a threshold turns the score into a binary outcome for this endpoint: a participant either meets the remission definition or does not. Reporting the percentage meeting the threshold makes the group results interpretable as the proportion classified as in remission at that assessment. It also means the primary result does not describe the full range of PCDAI scores or the amount of change for each participant. A score just above the threshold and a much higher score both fall outside the endpoint’s remission category.

The registry identifies the Week 26 comparison as high-dose versus low-dose adalimumab. The outcome is a measure of clinical status at that timepoint, not a direct measure of long-term disease course. The registry’s endpoint definition does not by itself establish how missing Week 26 assessments were handled; that information is not reported in the registry record.

7. Results Posted in the Registry

• High-Dose Adalimumab: 40 mg or 20 mg Eow (Week 4 to Week 52): 38.7% (36/93) versus 28.4% (27/95) on control; risk difference 10.3 percentage points (95% CI -3.1 to 23.7), risk ratio 1.36 (0.90–2.05); unadjusted two-proportion z-test p = 0.135.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 52

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • High-Dose Adalimumab: 40 mg or 20 mg Eow (Week 4 to Week 52): 33.3% (31/93) versus 23.2% (22/95) on control; risk difference 10.2 percentage points (95% CI -2.6 to 23.0), risk ratio 1.44 (0.90–2.29); unadjusted two-proportion z-test p = 0.121.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between High-Dose Adalimumab: 40 mg or 20 mg Eow (Week 4 to Week 52) and the control. The interval gives the range of effects that remain compatible with the data.

Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 26

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • High-Dose Adalimumab: 40 mg or 20 mg Eow (Week 4 to Week 52): 59.1% (55/93) versus 48.4% (46/95) on control; risk difference 10.7 percentage points (95% CI -3.5 to 24.9), risk ratio 1.22 (0.93–1.60); unadjusted two-proportion z-test p = 0.141.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between High-Dose Adalimumab: 40 mg or 20 mg Eow (Week 4 to Week 52) and the control. The interval gives the range of effects that remain compatible with the data.

Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • High-Dose Adalimumab: 40 mg or 20 mg Eow (Week 4 to Week 52): 41.9% (39/93) versus 28.4% (27/95) on control; risk difference 13.5 percentage points (95% CI -0.0 to 27.0), risk ratio 1.48 (0.99–2.20); unadjusted two-proportion z-test p = 0.052.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between High-Dose Adalimumab: 40 mg or 20 mg Eow (Week 4 to Week 52) and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover remission at Week 52, clinical response at Week 26 and Week 52, and change in IMPACT III scores at Week 26 and Week 52. For the three secondary outcomes with posted group comparisons, the high-dose group has a higher reported percentage than the low-dose group. This direction is broadly consistent with the primary result, which also has a higher observed remission percentage in the high-dose group. The results nevertheless concern different outcomes or assessment times and do not establish a single consistent effect across all aspects of disease status.

The registry lists five secondary outcomes, but the results for the IMPACT III score changes are not reported in the registry record. The available secondary comparisons have confidence intervals that include zero, including the Week 52 clinical response comparison, whose registry-reported interval extends from -0.01 to 27.04. For that comparison, the registry reports p = 0.038, while the interval includes zero at the stated 95% level. This illustrates why estimates, intervals, methods, and p-values should be considered together, especially when their analytic procedures may differ.

Secondary outcomes are generally less decisive than a prespecified primary outcome because they may be numerous, may be exploratory, and can increase the chance of apparently notable findings when considered together. General statistical context: multiplicity adjustments or a hierarchy of testing can help control interpretation across several outcomes, but the registry’s procedures are not reported. The secondary findings therefore offer supporting context rather than independent confirmation of the primary comparison. They should not be used to override the primary result or to claim that the dose regimens differ conclusively.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 52
• Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 26
• Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52
• Change From Baseline IMPACT III Scores at Week 26 (Observed Case)
• Change From Baseline IMPACT III Scores at Week 52 (Observed Case)

9. Statistical Interpretation

10. Statistical Methods Explained

For the primary outcome, each participant is classified according to whether the PCDAI remission threshold is met at Week 26. A percentage summarizes the share in each group who meet that definition. The principal contrast is between the high-dose and low-dose groups. Because the endpoint is binary, the analysis can describe the difference in proportions, rather than a difference in average PCDAI score.

What does the risk difference describe?

The unadjusted re-calculation reports a risk difference of 0.103 for high-dose relative to low-dose adalimumab. A risk difference is the difference between the outcome proportions in the two groups, expressed on the proportion scale. A value of zero would represent equal proportions; a positive estimate in this comparison indicates a higher observed proportion in the high-dose group. Its confidence interval, -0.031 to 0.237, includes zero, so the data are compatible with no difference as well as with differences in either direction within the interval.

The registry’s own result is reported as a Cochran-Mantel-Haenszel analysis, with a mean difference (net) of 10.29 and a 95% confidence interval from -3.14 to 23.71. The registry does not report further details of the stratification or adjustment used for this analysis. The re-calculation is explicitly unadjusted, so it should be read as a separate summary calculation from posted group counts, not as a replacement for the sponsor’s analysis.

How should the p-values be read?

A p-value describes how incompatible the observed data are with a specified null model, assuming the model and its assumptions apply. It is not the probability that the null hypothesis is true, the probability that the result occurred by chance, or a measure of clinical importance. The registry reports p = 0.075 for its primary analysis; the unadjusted re-calculation reports p = 0.135. Different analysis methods can produce different p-values even when the estimates are similar. The registry’s analysis is the primary reported result, and its method should be kept distinct from the unadjusted calculation.

The posted confidence interval is a range of values generated by an inferential procedure. In repeated applications under the method’s assumptions, intervals constructed in this way have a stated coverage property. For an individual trial, it conveys uncertainty around the estimated contrast; it does not assign probabilities to particular effect values. Because the primary interval crosses zero, it does not rule out equal group proportions at the confidence level stated.

What is the role of the analysis population?

The registry describes the primary analysis set as all randomized subjects who received at least one dose of double-blind study medication. That definition matters because results depend on who is included and how participants with unavailable outcomes are treated. The missing-outcome procedures and any departures from the stated population are not reported in the registry record. The reported group sizes and outcome counts therefore describe the posted analysis, but do not by themselves explain the handling of every randomized participant.

General statistical context: analyses of binary outcomes can be affected by small numbers of events, uneven outcome availability, and choices about adjustment. No claim about a particular adjustment strategy, missing-data method, interim analysis, or multiplicity correction can be made from the registry record unless it is explicitly reported. The record names the Cochran-Mantel-Haenszel method for the sponsor’s primary analysis, but does not provide enough detail to reconstruct every aspect of that analysis.

The registry also lists other outcomes, including remission at Week 52, clinical response at Week 26 and Week 52, and changes in IMPACT III scores at Week 26 and Week 52. These outcomes concern different definitions or timepoints and are not substitutes for the primary Week 26 remission endpoint. General statistical context: when multiple outcomes are examined, the chance of seeing an apparently notable result among them can increase unless the testing strategy accounts for multiplicity. The registry’s multiplicity procedures are not reported, so secondary findings should be interpreted cautiously.

11. Confidence Intervals and Precision

The primary estimate is accompanied by a 95% confidence interval. In the registry’s analysis, the mean difference (net) is 10.29, with limits from -3.14 to 23.71. The interval extends from a value below zero to one above zero, so the reported analysis does not pin down the direction of the underlying difference with high precision. The observed percentages are higher in the high-dose group, but the interval also includes no difference.

The unadjusted re-calculation gives a risk difference of 0.103 and a confidence interval from -0.031 to 0.237. It likewise spans zero. The interval is broad enough to include a small negative contrast as well as a larger positive contrast. This breadth is a reminder that the point estimate alone does not convey the uncertainty in the comparison. The re-calculation and the registry analysis use different methods, so their intervals should be read as method-specific summaries, not combined into a single estimate.

A confidence interval is not a range containing a fixed percentage of individual participant outcomes, and it is not a guarantee about the true effect. In general, a wider interval signals less precision than a narrower one under the same measurement scale and method. Here, the registry’s interval communicates uncertainty around the between-group estimate, while the study’s reported group sizes and event counts provide context for how much information contributes to that estimate. The registry does not report a separate precision measure for the PCDAI scores themselves.

Precision and statistical evidence are related but not identical. A confidence interval crossing zero indicates that the stated interval procedure does not exclude no difference; it does not establish that the regimens are equivalent. Conversely, a point estimate away from zero is not enough to establish a precise or conclusive effect. The result is best described as an observed difference with considerable uncertainty in its size.

12. 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 sample-size table and curve are planning illustrations based on the observed effect, not the trial’s original design assumptions. The figures are participants per arm, not total participants or total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses a stated fraction of the observed effect as the effect to detect. The trial’s own sample-size justification and original planning assumptions are not reported in the registry record.

The 80% power column gives the planned number of participants per arm for a hypothetical study to have an 80% chance of detecting the chosen effect under the stated assumptions, if that effect were the true one. The 90% power column uses the same idea but targets a 90% chance. These are design calculations, not guarantees about the results of a future study and not statements about the chance that the observed finding is true.

The rows for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect illustrate how the planning requirement changes when the target effect is smaller than the observed estimate. The posted calculations show increasing participant requirements as the target shrinks. In general, smaller effects need more participants to distinguish them from random variation under otherwise similar assumptions.

This is not observed power. Observed power is not a measure of how reliable the trial result is; these figures are prospective planning illustrations generated from an effect estimate and stated assumptions. They should not be read as the actual enrollment target or as evidence that the original trial was adequately or inadequately sized. The registry does not report the original sample-size rationale.

13. 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 = 0.284; treatment proportion p₁ = 0.387; average p̄ = 0.336.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6678 = 1.3089.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6638 = 0.5587.
4. n = (1.3089 + 0.5587)² / (0.1029)² = 329.5, rounded up to 330 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 <- 0.284210526315789                          # control proportion
p1 <- 0.387096774193548                          # 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(409682)
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 = 330 (80% power), 441 (90% power)
 75% of observed effect: n per arm = 576 (80% power), 770 (90% power)
 50% of observed effect: n per arm = 1,268 (80% power), 1,697 (90% power)
power.prop.test: 329.5 
Simulated power at n = 330 per arm: 0.811 (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.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison using a Cochran-Mantel-Haenszel analysis. The reported mean difference (net) is 10.29, its 95% confidence interval is -3.14 to 23.71, and p = 0.075. The unadjusted re-calculation from the posted group summary gives a risk difference of 0.103, a confidence interval from -0.031 to 0.237, and p = 0.135.

The estimates are similar in direction and magnitude, but the methods and reported p-values differ. The sponsor’s analysis is the registry’s own analysis and takes precedence as the primary reported result. The re-calculation is a simple unadjusted calculation from posted summary statistics; it does not reproduce the Cochran-Mantel-Haenszel analysis. The registry does not report enough detail about the sponsor’s analysis to reconstruct all its features.

The discrepancy flag is false, meaning the record does not identify a discrepancy between the posted result and its own analysis. That does not make the unadjusted calculation identical to the sponsor’s method. The p-values should therefore be attributed to their respective analyses, rather than selected or compared as though they were competing versions of the same calculation. Neither p-value should be interpreted as the probability that one dose is superior.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary Week 26 remission endpoint and lists secondary remission, response, and IMPACT III outcomes at later or additional timepoints. It does not report whether a multiplicity procedure was used, whether outcomes were tested in a hierarchy, or which secondary analyses were considered confirmatory. Without that information, the extent to which the reported p-values account for testing multiple outcomes cannot be assessed.

Missing-data handling is also not reported in the registry record. The primary analysis population is described as all randomized subjects who received at least one dose of double-blind study medication, but the record does not state how participants without an observed Week 26 outcome were handled, whether any imputation was used, or how missingness was assessed. The posted group sizes and counts do not establish what assumptions underlie unavailable assessments. Missing outcomes can affect binary percentages and the estimated between-group contrast, so this omission limits evaluation of the analysis.

The registry does not report whether interim analyses were conducted or whether any stopping rules were used. The original statistical analysis plan, sample-size justification, and detailed analytic specifications are not reported in the registry record. The sponsor’s primary result names the Cochran-Mantel-Haenszel method, but details sufficient to assess all adjustments and assumptions are not given.

These omissions do not show that a particular procedure was absent; they mean the registry record does not report it. They limit independent assessment of how the full outcome family was handled and how robust the results are to missing data or analytic choices. Interpretation should therefore distinguish the documented outcome estimates from procedures that cannot be confirmed from the record.

16. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: crohn's disease (15.8%), anaemia (4.3%), small intestinal obstruction (1.1%), abdominal abscess (1.1%), anal abscess (1.1%).

The safety record lists serious adverse events for the open-label induction period and for each randomized dose group. During open-label adalimumab from Week 0 to Week 4, 6 of 192 participants are listed as having a serious adverse event. For the Week 4 to Week 52 low-dose group, the figures are 19 of 95; for the high-dose group, they are 22 of 93. These are descriptive counts and denominators as posted, not estimates adjusted for time on treatment.

The record also lists other adverse events for the same groups: 64 of 192 during open-label induction, 62 of 95 in the low-dose group, and 69 of 93 in the high-dose group. Serious and other adverse-event figures are separate registry summaries and should not be added together. The open-label induction period and randomized treatment period differ in timing and group structure, so their figures should not be treated as a direct randomized comparison.

The most frequent serious adverse-event terms listed include Crohn's disease at 15.8% and anaemia at 4.3%; small intestinal obstruction, abdominal abscess, anal abscess, and gastroenteritis are each listed at 1.1%. The registry does not report deaths in the posted safety summary. These figures alone do not establish whether events were caused by treatment, how long participants were exposed, or how event rates compare under another treatment. The safety information should be read as a registry summary, not as individualized medical guidance.

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

The primary result describes the observed proportion meeting the PCDAI remission threshold at Week 26 in two adalimumab dose groups following open-label induction. The high-dose group had a higher posted remission percentage than the low-dose group. The sponsor’s reported estimate has a 95% confidence interval that includes zero, and p = 0.075. The unadjusted re-calculation also has an interval that includes zero. These results leave substantial uncertainty about the size and direction of the underlying difference.

The result does not establish that the dose regimens are equivalent: a confidence interval containing zero is not an equivalence test. Nor does the observed difference establish that the high-dose regimen is superior. Such conclusions depend on the analysis plan, assumptions, precision, and broader evidence, while some relevant details are not reported in the registry record.

The comparison is not against placebo or no treatment. It concerns high-dose versus low-dose adalimumab after all subjects received open-label induction. It does not isolate the contribution of induction, address every possible dose regimen, or establish results for people outside the pediatric subjects with moderate to severe Crohn's disease described in the record. The primary endpoint is a threshold-based remission classification at Week 26, not a complete account of symptoms, quality of life, disease activity over time, or all safety outcomes.

The secondary results show a generally higher observed proportion in the high-dose group for the posted remission and response comparisons, but they do not remove the uncertainty in the primary comparison. Results for the listed IMPACT III changes are not reported in the registry record, and multiplicity and missing-data procedures are also not reported. The findings should therefore be understood as the results of this registered trial comparison, with its specified endpoint and limitations, rather than as a universal conclusion about treatment or a basis for individual medical decisions.

18. Why This Trial Matters Statistically

This trial illustrates why the estimated difference and its uncertainty need to be read together. The high-dose group has a higher observed Week 26 remission percentage, but the sponsor’s confidence interval extends across zero. A point estimate alone would conceal that the registry’s analysis remains compatible with no difference and with a range of other contrasts. The interval makes the uncertainty visible.

It also illustrates that closely related analyses need not produce identical inferential results. The sponsor’s Cochran-Mantel-Haenszel analysis and the unadjusted re-calculation have similar point estimates but different p-values. Understanding which result belongs to which method prevents an unadjusted summary from being mistaken for the trial’s primary analysis. The registry’s own result is the primary reported analysis.

The treatment structure matters to interpretation. Participants received open-label induction before randomization to two active dose regimens, so the randomized contrast concerns dose after induction. It is not a comparison of adalimumab with no treatment. The endpoint also matters: a threshold-based remission outcome at Week 26 answers a narrower question than a continuous score or a longer-term outcome would.

Finally, this record highlights the importance of reporting analysis populations, missing-data procedures, multiplicity handling, and original sample-size assumptions. The registry supplies a stated primary analysis population and names its method, but other key analytic details are not reported in the registry record. Statistical interpretation can be careful about the documented results while remaining clear about what the record does not establish.

19. 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 registry record does not report the original sample-size justification or the assumptions used to plan the trial. The sample-size illustrations based on the observed effect are not a substitute for that information. The detailed statistical analysis plan, handling of missing outcomes, and multiplicity procedures are also not reported, limiting assessment of how the primary and secondary results were specified and analyzed.

The posted primary comparison concerns a binary Week 26 remission threshold. It does not provide the distribution of PCDAI scores or individual changes that would show how participants’ scores varied around the threshold. The endpoint’s clinical meaning is described, but the registry does not report additional information about how outcome assessments were collected or adjudicated.

The comparison is between two active dose regimens after common open-label induction. The registry result therefore cannot answer a treatment-versus-placebo question or separate the effects of induction from the randomized dose comparison. The arm descriptions are incomplete in the record’s displayed text, including truncated details about possible changes beginning at the Week 12 visit; the full rules for those changes are not reported in the registry record.

The safety summary is descriptive. It does not report exposure-adjusted rates, event timing in detail, treatment attribution, or a direct comparative safety analysis. The registry’s death fields do not contain a reported count. Results for the listed IMPACT III score-change outcomes are not reported in the registry record. These gaps constrain interpretation of long-term outcomes, safety comparisons, and the full set of secondary endpoints.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease — NCT00409682.
• Registry record last updated 2011-08-04; status last verified 2011-07.
• Results first posted 2011-08-04.
• 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.

23. Record Summary

The registry describes a completed Phase 3, randomized, parallel-group study with quadruple masking, sponsored by Abbott. Pediatric subjects with moderate to severe Crohn's disease received open-label adalimumab induction from Week 0 to Week 4, then entered high-dose or low-dose adalimumab regimens from Week 4 to Week 52.

The primary endpoint was clinical remission at Week 26, defined as a PCDAI score of 10 or less. The posted percentages were 28.4% in the low-dose group and 38.7% in the high-dose group. The registry’s Cochran-Mantel-Haenszel analysis reported a mean difference (net) of 10.29, a 95% confidence interval from -3.14 to 23.71, and p = 0.075. The interval includes zero, so the estimated difference remains uncertain.

The record lists additional remission, response, and IMPACT III outcomes, as well as descriptive adverse-event figures. Some analysis details, including missing-data and multiplicity procedures and the original sample-size justification, are not reported in the registry record.