This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Efficacy of Adalimumab in Patients With Active Ankylosing Spondylitis (NCT00195819), a randomized phase 3 study. The primary outcome is Number of Subjects With a Reduction in Signs and Symptoms as Measured by Assessments of Ankylosing Spondylitis (ASAS) 20 Response at Week 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00195819 |
| Phase | Phase 3 |
| Condition | Ankylosing Spondylitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 82 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Abbott |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with active ankylosing spondylitis. The registry reports enrollment of 82. For the primary endpoint, the stated full analysis set included randomized participants who received at least one injection of study medication, analyzed by treatment group. The record does not report how many enrolled participants met that endpoint population definition or how many contributed to the Week 12 result.
Intervention
The intervention was adalimumab, also identified as D2E7 in the intervention listing. The stated study purpose was to assess its safety and clinical efficacy in people with active ankylosing spondylitis. The registry describes the trial as Phase 3, randomized, double-masked, and parallel. Those design features describe how the comparison was organized; they do not, on their own, establish the size or precision of any treatment effect.
Comparator
The listed comparator was placebo. The registry record does not provide arm descriptions beyond the treatment names, and the primary outcome entry does not report the Week 12 responder counts for either group. The posted safety information is listed under Adalimumab, so it does not supply a corresponding placebo safety summary for a between-group comparison.
Primary question
The primary endpoint asked how many participants met the ASAS 20 response definition at Week 12. Response required improvement of at least 20% and an absolute improvement of at least 10 units from baseline in at least 3 of 4 domains, with no deterioration in the potential remaining domain. The registry record does not report the arm-specific responder counts or a single comparison for this endpoint. Consequently, the clinical question is identifiable, but its estimated answer and precision are not reported in the registry record.
3. Trial Design
The registry describes a Phase 3, multicenter study of adalimumab in people with active ankylosing spondylitis. It was randomized, double-masked, and parallel, with adalimumab and placebo listed as the interventions. The record reports enrollment of 82 and marks the study as completed. Its start is recorded as 2003-12, with primary completion in 2004-10. These dates describe the registry timeline; they do not provide details about follow-up for every participant or the timing of any later analysis.
A randomized design assigns participants to treatment groups by chance, in principle helping make the groups comparable at the start. Double masking indicates that masking was part of the design, but the registry record does not specify which people were masked or how masking was maintained. A parallel design means the listed groups are compared as separate treatment paths; the record does not describe the allocation ratio or provide fuller arm-specific procedures.
The primary outcome was the number of participants with an ASAS 20 response at Week 12. The record defines the primary analysis population as the full analysis set: randomized participants who received at least one injection of study medication, analyzed by treatment group. It does not report how many participants were included in that set, whether any were excluded from an analysis, or how missing Week 12 assessments were handled.
The registry also lists secondary outcomes involving ASAS response thresholds, patient global assessment, BASFI, and back pain, with some outcomes described through Week 260 of adalimumab exposure. Those long-term listings do not establish that every participant contributed data at every listed time point. The registry reports 44 outcome measures and 2 analyses, but a detailed analysis plan, allocation procedure, and protocol 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.
Double-Blind
| Stage | Placebo 40 mg Every Other Week (Eow), Subcutaneous (SC) | Any Adalimumab |
|---|---|---|
| STARTED | 44 | 38 |
| COMPLETED | 42 | 38 |
| NOT COMPLETED | 2 | 0 |
Reasons for not completing this period:
| Reason | Placebo 40 mg Every Other Week (Eow), Subcutaneous (SC) | Any Adalimumab |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Moved | 1 | 0 |
Open-label
| Stage | Placebo 40 mg Every Other Week (Eow), Subcutaneous (SC) | Any Adalimumab |
|---|---|---|
| STARTED | 0 | 82 |
| COMPLETED | 0 | 62 |
| NOT COMPLETED | 0 | 20 |
Reasons for not completing this period:
| Reason | Placebo 40 mg Every Other Week (Eow), Subcutaneous (SC) | Any Adalimumab |
|---|---|---|
| Adverse Event | 0 | 9 |
| Lack of Efficacy | 0 | 2 |
| Pregnancy | 0 | 1 |
| Protocol Violation | 0 | 2 |
| Moved | 0 | 1 |
| Withdrawal by Subject | 0 | 5 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set - includes all subjects who were randomized and received at least one injection of study medication. The full analysis set was analyzed by treatment group.
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.
| Characteristic | Unit | Adalimumab |
|---|---|---|
| Participants analysed | 82 | |
| Age Continuous: <=40 years | participants | 35 |
| Age Continuous: Between 40 and 65 years | participants | 45 |
| Age Continuous: >=65 years | participants | 2 |
| Age Continuous | years | 40.9 (SD 10.97) |
| Sex: Female, Male: Female | Participants | 17 |
| Sex: Female, Male: Male | Participants | 65 |
| Region of Enrollment: Canada | participants | 82 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects With a Reduction in Signs and Symptoms as Measured by Assessments of Ankylosing Spondylitis (ASAS) 20 Response at Week 12, measured over Week 12.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a count: the number of participants meeting the ASAS 20 response definition at Week 12. It is not a mean change in one scale. The definition combines improvement across disease-activity domains, so a participant must meet both a relative improvement threshold of at least 20% and an absolute improvement threshold of at least 10 units from baseline in at least 3 of 4 domains. The definition also requires no deterioration in the potential remaining domain.
The domains listed in the registry include the patient’s global assessment of disease activity, total back pain, the Bath Ankylosing Spondylitis Functional Index (BASFI), and inflammation. The description gives visual analog scales and their stated endpoints, including scales running from 0 to 100 for several assessments and an inflammation scale from 1 to 10. It emphasizes that the criteria apply to each scale rather than to an overall global scale.
A composite response endpoint can summarize whether several aspects of a condition improved together, rather than treating any one measure as sufficient. The threshold also gives the outcome an interpretable responder definition. However, a count alone does not convey the size of change among responders, the distribution of changes among nonresponders, or the precision of a treatment comparison. The registry record does not report the Week 12 arm-specific counts or a single treatment-effect estimate, so the endpoint definition can be explained but its comparative result cannot be assessed from the recorded primary outcome information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary question and its assessment time: the number of ASAS 20 responders at Week 12. It does not report arm-specific responder counts, a difference between groups, a confidence interval, or a p-value for one primary comparison. The primary outcome is also flagged as having several categories or time points and not being reduced to one comparison. That means the posted information does not support a numerical estimate of the primary treatment contrast or a judgment about its statistical precision.
This distinction matters because a response definition is not itself a result. The thresholds specify how the outcome was classified, but they do not say how many participants met the definition in either group. Without those counts or a comparison estimate, the direction and size of the Week 12 contrast are not reported in the registry record. It would be inappropriate to infer them from the study title, purpose, design, or other listed outcomes.
The record describes 44 outcome measures and 2 analyses. This indicates that many outcome entries appear in the registry, but does not establish which analyses were prespecified, which were confirmatory, or how multiplicity was handled. The record does not report adjustment for multiple comparisons, a hierarchy among outcomes, an analysis plan, or interim analyses. The available information also does not explain how missing measurements or participants who discontinued were handled. These omissions limit interpretation of any collection of outcome results and make it difficult to distinguish primary confirmatory evidence from exploratory analyses.
For safety, the registry lists an Adalimumab group with 82 at risk for serious adverse events and 20 affected, and 82 at risk for other adverse events and 78 affected. The serious adverse event terms listed include diverticular perforation and osteoarthritis at 2.4% each, and diplopia, peritonitis, umbilical hernia, and appendicitis at 1.2% each. These entries describe recorded events, not a comparison with placebo. The record does not establish whether an event was caused by treatment, and the listed terms need not represent mutually exclusive participants.
Overall, the registry makes the study question, design, endpoint definition, and selected safety counts identifiable. It does not give the primary Week 12 comparison in a form that allows its magnitude or uncertainty to be evaluated. Statistical interpretation should therefore separate what is described—the planned comparison and response criteria—from what is not reported: the primary arm-level result, its uncertainty, and the analysis procedures needed to contextualize it.
9. Statistical Methods Explained
The record describes a randomized, double-masked, parallel Phase 3 study, but it does not report the statistical methods used for the primary comparison. The distinction between a design description and an analysis description is important. Randomization concerns assignment to groups; it does not specify whether the outcome was analyzed with a particular test, regression model, adjustment set, or missing-data method. None of those details is reported in the registry record.
What does a binary endpoint represent?
The primary outcome is a count of participants who met a defined responder criterion. At the participant level, the endpoint classifies each eligible person as meeting or not meeting ASAS 20 at Week 12. A group count is useful for describing how often the defined response occurred, but a count needs its denominator to show the proportion meeting the criterion. A comparison between groups can then be expressed using a suitable effect measure, such as a difference in response proportions or a relative measure. The registry record does not report the primary group counts or such an effect estimate, so no particular comparative value can be interpreted.
Binary outcomes simplify a complex set of measurements into a response category. That makes the criterion easier to communicate, but it discards information about how far participants changed beyond the threshold. Two people with different amounts of improvement may receive the same responder classification. Conversely, small changes around a cutoff can change classification even when the underlying measurements are similar. These are general properties of threshold-based outcomes, not additional findings about this trial.
Why does precision matter?
A confidence interval is a range of values compatible with the observed data and the assumptions of the analysis. It conveys uncertainty around an estimate: a narrower interval indicates greater precision, while a wider interval indicates less precision. A point estimate alone does not show how much uncertainty remains. The registry record does not report a confidence interval for the primary comparison, and there is no single primary comparison available in the posted results to which such an interval could be attached.
A p-value, when reported, measures how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the analysis assumptions. It is not the probability that the null hypothesis is true, nor does it describe the size or clinical importance of an effect. No p-value for a single primary Week 12 comparison is reported in the registry record. The absence of such a value is not evidence of either a positive or a negative result.
How should multiple outcomes be considered?
The registry lists 44 outcome measures and 2 analyses. When many outcomes, time points, or comparisons are examined, the chance of obtaining apparently notable results by chance can increase. Multiplicity methods address that issue through approaches such as prespecified outcome hierarchies or statistical adjustment. This is a general explanation; the registry record does not report which, if any, methods were used, whether the listed outcomes were all tested, or which were intended to support confirmatory conclusions. The primary outcome entry itself notes that it has several categories or time points and is not reduced to one comparison.
Reading multiple outcome entries as though they were a single prespecified test would require information not reported in the registry record. A clear statistical interpretation would ordinarily distinguish the primary endpoint from secondary outcomes, identify the comparisons and time points, and explain any multiplicity strategy. The record’s outcome inventory alone does not resolve those questions.
What do the sample-size illustrations mean?
The record describes planning illustrations computed from an observed effect, rather than the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such illustrations ask how much information a future study might need under specified assumptions. They are planning calculations, not observed power and not evidence that the completed study had a particular probability of detecting an effect.
For outcomes other than time-to-event outcomes, the stated illustrations are in participants per arm; time-to-event illustrations use a total number of events. No illustration values are included in the registry record summarized for this study. The sample-size assumptions do not explain the actual enrollment target, and the trial’s own sample-size justification is not reported in the registry record. Because the primary endpoint has no single posted comparison, the stated observed-effect basis cannot be used to infer the missing primary result.
What can the design tell us about analysis?
Randomization can support an unbiased comparison when the assigned groups are analyzed appropriately, but it does not guarantee that every analysis is unbiased. The primary population definition specifies randomized participants who received at least one injection, analyzed by treatment group. The registry does not report the number meeting this definition, the handling of participants without a Week 12 assessment, or whether sensitivity analyses were performed. A full statistical account would need those details, together with the analysis method and estimate uncertainty.
Over-dispersion is a general concern when counts vary more than a model assumes, but the primary endpoint is a participant-level binary response rather than a count of repeated events. The registry does not report a model for this endpoint, so there is no basis to say whether over-dispersion was assessed or relevant to the actual analysis. More broadly, statistical methods should follow the outcome structure and prespecified question; the available record does not contain enough detail to identify the procedure used for the primary result.
10. Multiplicity, Missing Data and Analysis Populations
The registry reports 44 outcome measures and 2 analyses. The primary outcome is an ASAS 20 response count at Week 12, while listed secondary outcomes include ASAS response thresholds and individual assessments of disease activity, function, and pain. Some secondary outcomes are described through Week 260 of adalimumab exposure. A broad set of outcomes and time points raises questions about multiplicity, but the registry record does not report a testing hierarchy, adjustment procedure, or designation of which comparisons were confirmatory.
The primary outcome entry notes that it has several categories or time points and is not reduced to one comparison. The record therefore does not offer a single primary estimate that can be interpreted alongside a confidence interval or p-value. It also does not report a statistical analysis plan, interim analyses, or the method used to control false-positive findings across outcomes. These details are not reported in the registry record; no particular approach should be assumed.
The stated full analysis set includes randomized participants who received at least one injection of study medication, with analysis by treatment group. The record does not report the number included in this population, whether all such participants had Week 12 data, or how missing outcomes, withdrawal, or protocol deviations were handled. It does not describe imputation, sensitivity analyses, or an alternative analysis population. These omissions matter because missing endpoint measurements can affect both the estimated response frequency and the confidence placed in a comparison.
The registry’s stated population definition is informative, but it is not a complete account of the analysis. Enrollment, randomization, receipt of treatment, inclusion in an endpoint analysis, and availability of an outcome are distinct stages. Their counts and handling are not reported in enough detail to reconstruct participant flow or assess the consequences of missing data. The record also does not report whether the analyses followed the original plan or whether any changes were made.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Adalimumab | 20 | 82 | 24.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Adalimumab | 78 of 82 |
Most frequent serious adverse event terms
| Event term | Organ system | Adalimumab |
|---|---|---|
| Diverticular perforation | Gastrointestinal disorders | 2 of 82 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 2 of 82 |
| Diplopia | Eye disorders | 1 of 82 |
| Peritonitis | Gastrointestinal disorders | 1 of 82 |
| Umbilical hernia | Gastrointestinal disorders | 1 of 82 |
| Appendicitis | Infections and infestations | 1 of 82 |
| Escherichia sepsis | Infections and infestations | 1 of 82 |
| Gastroenteritis | Infections and infestations | 1 of 82 |
| Pneumonia | Infections and infestations | 1 of 82 |
| Pyelonephritis | Infections and infestations | 1 of 82 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Adalimumab |
|---|---|---|
| Nasopharyngitis | Infections and infestations | 38 of 82 |
| Upper Respiratory Tract Infection | Infections and infestations | 33 of 82 |
| Ankylosing Spondylitis | Musculoskeletal and connective tissue disorders | 20 of 82 |
| Headache | Nervous system disorders | 20 of 82 |
| Influenza | Infections and infestations | 14 of 82 |
| Fatigue | General disorders | 13 of 82 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 12 of 82 |
| Back Pain | Musculoskeletal and connective tissue disorders | 11 of 82 |
| Nausea | Gastrointestinal disorders | 10 of 82 |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | 10 of 82 |
Serious events with the highest arm-level rate: diverticular perforation (2.4%), osteoarthritis (2.4%), diplopia (1.2%), peritonitis (1.2%), umbilical hernia (1.2%).
The registry lists safety information under the Adalimumab group. It records 82 at risk for serious adverse events and 20 affected, and 82 at risk for other adverse events and 78 affected. These are counts attached to separate categories in the record. They should not be added together: a participant may have experienced events in both categories, and the record does not provide the overlap.
The listed serious adverse event terms include diverticular perforation and osteoarthritis at 2.4% each. Diplopia, peritonitis, umbilical hernia, and appendicitis are each listed at 1.2%. These percentages are registry entries for the terms; the record does not provide term-specific counts or explain whether a participant could contribute to more than one term. They should not be interpreted as percentages of treatment-caused events.
The posted safety information does not provide a corresponding placebo summary for comparison. It also does not report the relationship between each event and treatment, the duration of observation for each participant, or the criteria used for seriousness. A serious adverse event is a safety classification, not proof that the intervention caused the event. These entries can describe what the registry recorded, but cannot establish comparative risk or causality on their own.
12. What the Result Does, and Does Not, Mean
The registry record supports a clear description of the study question: a randomized, double-masked, parallel Phase 3 comparison of adalimumab and placebo in people with active ankylosing spondylitis, with ASAS 20 response at Week 12 as the primary endpoint. It also gives a detailed responder definition and identifies the full analysis set as randomized participants who received at least one injection of study medication, analyzed by treatment group.
What the record does not provide is the primary result in a single interpretable comparison. There are no reported arm-specific responder counts, effect estimate, confidence interval, or p-value for that endpoint. The absence of those results means the size, direction, and precision of the primary contrast cannot be determined from the registry record. It does not establish that the intervention did or did not produce a difference.
The listed secondary outcomes and safety entries add descriptive context but do not fill that gap. Secondary outcome titles describe measurements across different domains and time points, including outcomes through Week 260 of adalimumab exposure. The titles alone do not give numerical results or show how multiple comparisons were handled. Likewise, the safety counts and listed adverse-event terms describe the Adalimumab group but do not provide a placebo comparison or establish causation.
The study’s completed status and enrollment information describe the trial record, not the strength of its evidence. A statistical conclusion about treatment effects would require the observed data, an appropriate comparison, and an account of uncertainty and missing information. Those elements are not reported for the primary Week 12 comparison. The most accurate reading is therefore limited: the registry identifies what the trial set out to assess, how it defined response, and selected safety counts, while leaving the principal comparative efficacy result and important analysis details unreported.
13. Why This Trial Matters Statistically
This trial illustrates why a well-defined clinical endpoint and a reported treatment-effect estimate are separate parts of statistical evidence. ASAS 20 specifies a structured response rule across disease-related domains, including thresholds for improvement and a requirement against deterioration in the remaining potential domain. That definition tells readers what counted as a response, but it does not indicate how often response occurred in either group or how precisely the groups differed.
The record also shows why registry outcome inventories need careful interpretation. It lists 44 outcome measures and 2 analyses, including several secondary assessments and extended time points. Such breadth can be useful for documenting what was considered, but interpretation depends on knowing which comparisons were prespecified and how multiplicity was addressed. Those details are not reported in the registry record, so the number of listed outcomes cannot be treated as evidence that any particular statistical strategy was used.
Participant definitions are another important part of the evidence. The primary analysis population is described as randomized participants who received at least one injection, analyzed by treatment group. Without the number included, the completeness of Week 12 measurements, and the missing-data approach, readers cannot fully assess how the analysis population relates to enrollment or how missing outcomes may affect results.
Finally, the safety entries demonstrate the difference between event reporting and comparative safety inference. Counts and serious-event terms can identify what the registry recorded in the Adalimumab group, but without a corresponding comparator summary and fuller context they do not establish relative risk or causation. Statistically, the trial matters as an example of how design, endpoint definition, analysis population, missing-data handling, multiplicity, and transparent result reporting all contribute to interpreting a clinical comparison.
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 most important trial-specific limitation for interpreting the primary question is that the registry does not report a single Week 12 ASAS 20 comparison. Arm-specific responder counts, a treatment-effect estimate, a confidence interval, and a p-value are not reported in the registry record. The endpoint definition is detailed, but the comparative result cannot be reconstructed from the information recorded.
The primary outcome entry notes several categories or time points and is not reduced to one comparison. The record does not clarify how those categories or time points relate to the primary analysis or identify a prespecified analysis hierarchy. Although 44 outcome measures and 2 analyses are listed, a detailed statistical plan and any multiplicity procedure are not reported. This limits the ability to distinguish confirmatory findings from other analyses.
The population definition identifies randomized participants who received at least one injection as the full analysis set, analyzed by treatment group. The record does not provide the number in that set, the number with an observed Week 12 assessment, participant flow by arm, or a missing-data strategy. It also does not report sensitivity analyses or the handling of withdrawals. The effect of incomplete endpoint data therefore cannot be evaluated from the registry information.
Safety interpretation is limited because the reported safety group is Adalimumab and no corresponding placebo figures are given in the record. The relationship of events to treatment and the observation time for each participant are also not reported. Event terms and counts should not be read as evidence of causation or as a comparative safety estimate.
Finally, the registry record does not report the trial’s own sample-size justification, a detailed analysis plan, or interim analyses. The planning assumptions described for sample-size illustrations are not substitutes for those trial-specific methods. These limitations concern what is recorded and do not, by themselves, establish how the full study was conducted or what its unreported results might have been.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Adalimumab in Patients With Active Ankylosing Spondylitis — NCT00195819.
- Registry record last updated 2011-06-28; status last verified 2011-06.
- Results first posted 2010-04-28.
- 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.
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18. Record Summary
The registry describes a completed Phase 3, randomized, double-masked, parallel study of adalimumab and placebo in people with active ankylosing spondylitis. Enrollment was 82; the recorded start was 2003-12 and primary completion was 2004-10.
The primary endpoint was the number of participants meeting the ASAS 20 response definition at Week 12. The full analysis set was defined as randomized participants who received at least one injection of study medication, analyzed by treatment group. The record lists 44 outcome measures and 2 analyses, including secondary outcomes across several disease-related assessments and time points.
The registry does not report the primary endpoint as a single comparison, nor does it provide arm-specific responder counts, an effect estimate, confidence interval, or p-value. It lists Adalimumab safety counts and selected serious adverse event terms, without a corresponding placebo safety summary. The primary comparative result, missing-data methods, multiplicity strategy, and detailed statistical plan are not reported in the registry record.