Efficacy and Long Term Safety of Adalimumab in Pediatric Subjects Who Have Demonstrated Clinical Response in M06-806: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Long Term Safety of Adalimumab in Pediatric Subjects Who Have Demonstrated Clinical Response in M06-806 (NCT00686374), a na phase 3 study. The primary outcome is Number of Participants Who Achieved Pediatric Crohn's Disease Activity Index (PCDAI) Clinical Remission Over Time.

2. Clinical Question

The study was intended to evaluate maintenance of clinical response and collect long-term safety and tolerability information in pediatric participants who had already responded in the preceding study. That entry condition matters to interpretation: this was not a study of all pediatric patients with Crohn's disease, nor was it designed as a randomized comparison of adalimumab with another treatment or with no treatment. Its primary question is therefore about the observed remission counts over time in this selected, continuing-treatment group, rather than a comparative treatment effect.

3. Trial Design

This was a Phase 3, multicenter, open-label, single-group study of adalimumab. The registry lists enrollment of 100 participants, no masking, and allocation as not applicable. The study is marked completed. Its recorded start date is 2008-05-01, and its primary completion date is 2017-04-04. The sponsor is AbbVie (prior sponsor, Abbott).

Participants could enroll after participating in and successfully completing Study M06-806 through Week 52. The study description says it evaluated adalimumab for maintaining clinical response and collected long-term safety and tolerability data. Adalimumab was administered by subcutaneous injection, with dose based on body weight and clinical status. The listed regimens ranged from 10, 20, or 40 mg every other week to 20 or 40 mg every week. The registry does not report how many participants received each regimen or how dosing changed over time.

The primary endpoint was assessed at Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, and 408. Secondary outcomes included CDAI clinical remission and response, steroid-free PCDAI and CDAI remission, and mean changes in PCDAI and CDAI over time. The record lists eight outcome measures but no analyses. The protocol's sample-size justification, detailed statistical analysis plan, interim-analysis plans, and handling of treatment changes 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: 36 participants discontinued study drug when adalimumab became commercially available (received regulatory approval for pediatric Crohn's disease) in their country. These participants were considered to have completed the study, and are included as study completers in the subject disposition.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population: all participants who received ≥ 1 dose of adalimumab in Study M06-807 and also had ≥ 1 non-missing efficacy measurement during the study.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: ITT Population: all participants who received ≥ 1 dose of adalimumab in Study M06-807 and also had ≥ 1 non-missing efficacy measurement during the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Achieved Pediatric Crohn's Disease Activity Index (PCDAI) Clinical Remission Over Time, measured over Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408.

The primary endpoint is the number of participants who achieved clinical remission according to the Pediatric Crohn's Disease Activity Index (PCDAI) at scheduled assessments. The PCDAI assesses abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdominal findings, perirectal disease, and extraintestinal manifestations. Its range is 0 to 100, with higher scores indicating more active disease. The registry defines clinical remission as a PCDAI score at or below 10.

A count of participants in remission gives an understandable description of how many people in the defined study population met the stated threshold at each assessment. Repeated assessments can describe the course of this outcome over time, but interpretation of each count depends on knowing how many participants were assessed at that time and how missing measurements were handled. Those visit-specific counts and denominators are not reported in the registry record.

The registry specifies assessments from Week 0 through Week 408, but does not report the primary endpoint values. Consequently, the endpoint definition and schedule can be described, but the record does not support a numerical account of remission at any visit or of change in remission over time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a single-group study with an endpoint expressed as a count of participants meeting a clinical threshold. It does not report the statistical methods used to analyze that endpoint. The explanations below are general statistical context, not a claim about methods applied in this trial.

What does a count endpoint describe?

A count reports how many participants met a defined condition. For this endpoint, the condition is PCDAI clinical remission, defined as a score at or below 10. A count is easiest to interpret alongside the number of participants assessed at the same visit. Without that denominator, a count alone cannot show what share of the assessed group met the endpoint. The registry record gives overall enrollment of 100 and defines the primary endpoint population, but does not give the number assessed at each scheduled visit or the remission count at any visit.

Counts at repeated visits can describe how an outcome is distributed over follow-up. They do not automatically show individual trajectories: the people contributing data may differ from one visit to another. A longitudinal analysis may account for repeated observations within participants, but the choice of model and the handling of incomplete follow-up must be specified. Those methods are not reported in the registry record.

What would an estimate and confidence interval add?

General explanation: an estimate describes a quantity calculated from observed data, while a confidence interval conveys its statistical uncertainty under the assumptions of the analysis. A narrower interval generally indicates greater precision than a wider interval, but an interval does not remove design limitations, missing-data concerns, or bias. No estimate or confidence interval for the primary endpoint is reported in the registry record, so precision cannot be assessed.

For a proportion or count-based outcome, a statistical analysis would need to specify the analysis population and the denominator used at each assessment. It would also need to state whether results are descriptive or adjusted, and which model or interval method was used. None of these detailed analysis choices is reported. It would be inappropriate to infer a particular test or model from the endpoint description alone.

Why does the single-group design matter?

General explanation: a concurrent comparator helps distinguish outcomes associated with an intervention from changes that might have occurred over time for other reasons. In a single-group study, observed outcomes can be described, but the absence of a concurrent control prevents a like-for-like estimate of the difference between treatment strategies. Prior response-based eligibility further means the enrolled group is selected by its history in the preceding study. The record does not report an adjustment strategy that would change these design features.

How should repeated assessment and multiplicity be considered?

The primary endpoint has assessments at many timepoints, and the record also lists secondary outcomes. General explanation: examining multiple outcomes or timepoints can raise multiplicity concerns when statistical claims are made, because the chance of at least one seemingly notable finding can depend on how many comparisons are considered. Prespecified outcome hierarchies, adjustment procedures, or a clearly descriptive interpretation can address different parts of this issue. The registry record does not report a multiplicity strategy, a testing hierarchy, or inferential analyses. It therefore does not establish how any potential multiplicity was handled.

What do the planning assumptions mean?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. These are planning assumptions, not a description of this trial's design: this study is listed as single-group, not as a two-arm randomized comparison. No calculated planning sample-size values are reported in the record, and the assumptions should not be read as evidence of the study's original sample-size justification or as observed power.

General explanation: a sample-size illustration estimates the number of participants that a hypothetical design might require under stated assumptions. Such an illustration is not a measure of how likely a completed study was to detect an effect, and it cannot substitute for an effect estimate with uncertainty. The protocol's own sample-size justification is not reported in the registry record. More broadly, the record does not report a detailed statistical analysis plan, interim analyses, model specifications, or methods for missing data; none should be inferred from the outcome labels or planning assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome assessed repeatedly over time and several secondary outcomes: CDAI clinical remission and response, steroid-free PCDAI and CDAI remission, and mean changes in PCDAI and CDAI. It reports eight outcome measures overall, but lists no analyses. The statistical plan, including any outcome hierarchy or adjustment for multiple comparisons, is not reported in the registry record. Without reported analysis results or a stated multiplicity approach, no claim about statistical significance across outcomes or visits can be evaluated.

The primary endpoint population is described as participants who received at least one dose of adalimumab in Study M06-807 and had at least one non-missing efficacy measurement during the study. This definition does not itself explain how missing measurements were handled in the analysis, whether participants with incomplete follow-up contributed to all available visits, or whether any imputation was used. Those methods are not reported in the registry record.

The registry gives enrollment of 100, but not the number contributing endpoint data at each scheduled assessment. It is therefore not possible to tell from the record whether denominators changed over time or to assess the extent and pattern of missing measurements. The protocol's analysis population definitions beyond the stated primary endpoint population, sensitivity analyses, and handling of withdrawal or discontinuation are also not reported in the registry record. These omissions limit interpretation of longitudinal outcome counts, even apart from the absence of the counts themselves.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: crohn's disease (25.0%), anal abscess (3.0%), anaemia (2.0%), gastritis (2.0%), gastroenteritis (2.0%).

The registry lists 100 participants at risk for serious adverse events and 48 affected by serious adverse events. It also lists 100 at risk for other adverse events and 98 affected. Deaths are listed as 0. These are safety counts for the Any Adalimumab group; they are not comparisons with an untreated or alternative-treatment group. The registry record does not provide further detail in this summary about event timing, duration, severity beyond the serious classification, or participant-level overlap between event categories.

The listed serious adverse-event terms include Crohn's disease at 25.0%, anal abscess at 3.0%, and anaemia, gastritis, gastroenteritis, and pneumonia at 2.0% each. These are the reported percentages for the listed terms. The record does not state in this summary whether participants could contribute to more than one term, so the terms should not be added or treated as mutually exclusive categories. Nor do the listed terms establish that an event was caused by adalimumab. The data describe reported safety events during the study, without a concurrent control to support comparative risk estimates.

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

The trial record establishes that a completed Phase 3, open-label, single-group study enrolled 100 pediatric participants with Crohn's disease who had previously demonstrated a clinical response in Study M06-806. It specifies the PCDAI remission definition, the scheduled assessment weeks, the broad dose regimens, and summary safety counts. Those details describe what the study set out to observe and what safety events were listed.

The primary endpoint result itself is not reported in the registry record. No remission counts, visit-specific denominators, estimates, confidence intervals, or inferential results are listed. Consequently, the record cannot establish the observed level or pattern of PCDAI remission over time, or the precision of any such pattern. The secondary outcome names likewise do not substitute for reported results.

Even if outcome counts were available, this design would not provide a concurrent treatment comparison. Because participants were selected after prior successful completion of a study in which they had demonstrated response, the findings would pertain to that selected group, not automatically to all pediatric participants with Crohn's disease. A single-group observation also cannot isolate the effect of treatment from other explanations for outcomes during follow-up. The open-label design and the unreported details of outcome assessment and missing-data handling add further uncertainty.

The safety counts are descriptive. Without a comparator and additional event-level context, they cannot quantify how safety outcomes would differ under another treatment strategy or establish that a listed event was caused by the study intervention. The most defensible reading is therefore narrow: the registry provides study-design information and selected safety summaries, while the primary efficacy results and the statistical analyses needed to interpret them are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable for its long repeated-assessment schedule and for the population from which participants were drawn. The primary endpoint was assessed from Week 0 through Week 408, and enrollment was limited to participants who had successfully completed the preceding study through Week 52. These features make the definition of the analysis population, follow-up patterns, and time-specific denominators important to understanding any reported remission trajectory.

A count at each assessment can be informative descriptively, but longitudinal data need careful interpretation when not all participants contribute observations at every visit. The registry record does not report visit-level denominators, missing-data methods, or primary endpoint results. It is therefore not possible to assess how much the observed population might have changed over time or how that could affect the interpretation of the outcome.

The single-group, open-label design also marks a clear boundary on statistical inference. It can describe outcomes and safety events in the enrolled group, but it does not furnish a concurrent comparison for estimating a difference between treatment strategies. Prior response-based entry further narrows the population to which any results would apply. Those design properties are distinct from statistical precision: even a precisely estimated single-group outcome would not, by itself, resolve the absence of a control group.

Finally, the registry names multiple secondary outcomes alongside repeated primary assessments, while reporting no analyses or multiplicity approach. This makes transparent reporting of prespecified analyses especially relevant. The record's absence of endpoint values and analytical detail prevents readers from evaluating effect estimates, uncertainty, or the relationship among outcomes. Statistically, the key contribution of the record is thus the design and endpoint description, together with a reminder that reported outcome values and analysis methods are essential for evaluating longitudinal clinical evidence.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the primary endpoint counts or denominators at any scheduled visit. It also does not report estimates, confidence intervals, or inferential analyses for the primary or secondary outcomes. As a result, the efficacy findings cannot be quantified or assessed for precision from this record.

The single-group, open-label design has no concurrent comparator, and participants entered after successful completion of the preceding study through Week 52. This selected population limits generalization beyond participants with that prior study history and response. The record does not describe whether outcome assessors were independent or whether any measures were used to reduce potential bias in an open-label setting.

Important operational details are also absent: visit-specific numbers assessed, participant flow over follow-up, reasons for missing assessments or discontinuation, methods for handling missing data, and whether the stated dosing regimens changed for particular participants. The statistical analysis plan, sample-size justification, interim analyses, model specifications, and multiplicity methods are not reported in the registry record. These omissions preclude evaluation of how analyses were planned or how incomplete follow-up was addressed.

The safety summary gives affected counts and selected serious-adverse-event terms, but does not provide event timing or other detail needed for a fuller comparative safety assessment. Since no concurrent control group is reported, the safety figures are descriptive rather than comparative. The record does not establish causal attribution for the listed events.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Long Term Safety of Adalimumab in Pediatric Subjects Who Have Demonstrated Clinical Response in M06-806 — NCT00686374.
• Registry record last updated 2018-07-02; status last verified 2018-03.
• Results first posted 2018-04-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00686374 is a completed Phase 3, multicenter, open-label, single-group study of adalimumab in pediatric participants with Crohn's disease who had demonstrated clinical response in Study M06-806. Enrollment was 100. Adalimumab was given by subcutaneous injection, with dosing based on body weight and clinical status.

The primary endpoint counted participants meeting PCDAI clinical remission criteria over assessments from Week 0 through Week 408. Remission was defined as a PCDAI score at or below 10. The registry record does not report primary endpoint values, visit-specific denominators, or analyses. It lists serious adverse events in 48 of 100 participants at risk, other adverse events in 98 of 100 at risk, and 0 deaths. The single-group design does not provide a concurrent treatment comparison.