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 Phase III Study in Refractory Behcet's Disease (NCT00995709), a randomized phase 3 study. The primary outcome is Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00995709 |
| Phase | Phase 3 |
| Condition | Behcet Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 118 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
People with posterior uveitis or panuveitis secondary to Behçet's disease, receiving systemic immunosuppressive therapy. The primary outcome population is identified as the Full Analysis Set.
Intervention
AIN457C 300 mg every 2 weeks or AIN457C 300 mg monthly, given alongside standard-of-care immunosuppressive therapy.
Comparator
Placebo alongside standard-of-care immunosuppressive therapy. The registry describes placebo as two subcutaneous injections every 2 weeks.
Primary question
Over 24 weeks, how did the rate of recurrent ocular exacerbations in the study eye compare between each AIN457 regimen and placebo?
The trial addressed an ocular disease question in people whose posterior segment uveitis was associated with Behçet's disease. Its stated purpose was to assess AIN457 as adjunctive therapy, rather than as a replacement for standard-of-care immunosuppressive therapy. The primary endpoint focused on recurrent exacerbations in the study eye during the treatment period.
The comparison has three treatment groups: an every-2-week AIN457 regimen, a monthly AIN457 regimen, and placebo. Each AIN457 regimen is compared with placebo in the posted primary summaries. The question is therefore about the contrast between each regimen and the comparator, not a direct comparison between the AIN457 schedules.
The registry identifies 118 participants as the enrollment and lists 39 participants in each primary-outcome group. The primary outcome is defined for the Full Analysis Set, but the registry record does not report further details about how that set was defined or how participants were handled in the analyses. The question is clinically specific, but the posted statistical results are limited to group summaries and recalculated, unadjusted comparisons.
3. Trial Design
This was a randomized, parallel-group, placebo-controlled Phase III study. The registry labels masking as triple and describes the study as double-masked in its official title; further details about who was masked are not reported in the registry record. The study status is completed. The registry lists the study start as 2009-10 and primary completion as 2010-07.
The trial evaluated two AIN457C 300 mg schedules: every 2 weeks and monthly. The placebo group received two subcutaneous injections every 2 weeks. The study summary describes AIN457 as subcutaneous therapy given adjunctively with standard-of-care immunosuppressive therapy. The registry's description of the monthly regimen is incomplete, so additional administration details for that regimen are not reported in the registry record.
Registry enrollment was 118. The primary endpoint summaries list 39 participants for each of the three groups, and identify the Full Analysis Set as the population. The registry does not explain the relationship between the enrollment figure and the analysis-group counts, nor does it report the number of participants who completed treatment or contributed endpoint data at week 24.
The planned treatment period was 24 weeks, and the primary outcome timeframe is baseline to week 24. The study also listed secondary outcomes covering immunosuppressive medication score, macular edema and visual acuity, quality of life, and systemic non-ocular manifestations of Behçet's disease. Quantitative summaries are posted for some, but not all, of these outcomes.
The registry record does not report the trial's sample-size justification, allocation concealment procedures, detailed statistical analysis plan, interim analyses, or handling of missing data. These omissions limit how fully the design and analysis can be reconstructed from the 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.
Overall Study
| Stage | AIN457C 300 mg Every 2 Week Dosage Regimen | AIN457C 300 mg Monthly Dosage Regimen | Placebo to AIN457C |
|---|---|---|---|
| STARTED | 39 | 40 | 39 |
| COMPLETED | 32 | 31 | 34 |
| NOT COMPLETED | 7 | 9 | 5 |
Reasons for not completing this period:
| Reason | AIN457C 300 mg Every 2 Week Dosage Regimen | AIN457C 300 mg Monthly Dosage Regimen | Placebo to AIN457C |
|---|---|---|---|
| Adverse Event | 4 | 2 | 0 |
| Lack of Efficacy | 0 | 1 | 4 |
| Withdrawal by Subject | 0 | 4 | 1 |
| Lost to Follow-up | 1 | 0 | 0 |
| Death | 0 | 1 | 0 |
| Protocol Violation | 2 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set
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: a. One patient who screen-failed was inadvertently randomized to the AIN457 300 mg monthly group. This patient did not receive any study medication.
| Characteristic | Unit | AIN457C 300 mg Every 2 Week Dosage Regimen | AIN457C 300 mg Monthly Dosage Regimen (a) | Placebo to AIN457C | Total |
|---|---|---|---|---|---|
| Participants analysed | 39 | 40 | 39 | 118 | |
| Age, Continuous | Years | 36.2 (SD 10.96) | 34.0 (SD 11.86) | 32.5 (SD 10.34) | 34.2 (SD 11.09) |
| Sex: Female, Male: Female | Participants | 12 | 11 | 15 | 38 |
| Sex: Female, Male: Male | Participants | 27 | 29 | 24 | 80 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 39 | 39 | 37 | 115 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 | 2 |
| Region of Enrollment: France | Participants | 1 | 0 | 0 | 1 |
| Region of Enrollment: Turkey | Participants | 19 | 18 | 18 | 55 |
| Region of Enrollment: Germany | Participants | 1 | 1 | 1 | 3 |
| Region of Enrollment: Greece | Participants | 3 | 5 | 4 | 12 |
| Region of Enrollment: Italy | Participants | 3 | 2 | 2 | 7 |
| Region of Enrollment: Spain | Participants | 1 | 0 | 1 | 2 |
| Region of Enrollment: United States | Participants | 0 | 2 | 0 | 2 |
| Region of Enrollment: Egypt | Participants | 1 | 2 | 2 | 5 |
| Region of Enrollment: Israel | Participants | 2 | 0 | 1 | 3 |
| Region of Enrollment: Jordan | Participants | 0 | 2 | 1 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Rate of Recurrent Ocular Exacerbations in the Study Eye During 24 Weeks by Treatment, measured over Baseline to week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Ocular Exacerbations |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is titled the rate of recurrent ocular exacerbations in the study eye during 24 weeks by treatment. It concerns repeated worsening events in the affected eye, rather than a single measurement at the end of follow-up. Recurrent events are relevant to the stated trial question because the study aimed to compare the frequency of exacerbations over the treatment period.
The registry describes the endpoint as a mean, with standard deviation as the measure of spread, and gives a baseline-to-week-24 timeframe. The posted group means are 7.7 for the every-2-week AIN457 group, 11.5 for the monthly AIN457 group, and 7.7 for placebo. The corresponding standard deviations are 22.4, 28.19, and 22.35. The summaries are labelled as belonging to the Full Analysis Set.
A mean can describe the average burden of a continuous or count-like outcome, while the standard deviation describes variability among participants. For an endpoint involving recurrent events, a mean alone does not describe how events were distributed across participants or the timing of each event. The registry does not report further details of the endpoint calculation, such as event-level data, person-time, or a model used to estimate a rate. As a result, the posted summaries support a comparison of group averages, but not a more detailed account of recurrence patterns.
7. Results Posted in the Registry
- AIN457C 300 mg Every 2 Week Dosage Regimen: mean 7.70 versus 7.70 on control; difference 0.00 (95% CI -9.93 to 9.93), standardized effect d = 0.00; z-test p = 1.000.
- AIN457C 300 mg Monthly Dosage Regimen (a): mean 11.50 versus 7.70 on control; difference 3.80 (95% CI -7.49 to 15.09), standardized effect d = 0.15; z-test p = 0.509.
Mean difference: AIN457C 300 mg Every 2 Week Dosage Regimen
95% CI: -9.93 to 9.93
Recalculated from the posted summary statistics
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.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| To Determine the Effect of AIN457 on Macular Edema and Visual Acuity in Patients With Posterior Segment Uveitis Secondary to Behçet's Disease as Determined by Optical Coherence Tomography. | Continuous Endpoint | Mean difference | 22.90 (-45.58 to 91.38) | 713 per arm |
| To Observe the Effect of AIN457 on the Systemic Non-ocular Manifestations of Behçet's Disease in Patients With Posterior Segment Uveitis Requiring Systemic Immunosuppression as Measured by the Bechet's Disease Current Activity Form. | Continuous Endpoint | Mean difference | -0.20 (-1.24 to 0.84) | 904 per arm |
To Determine the Effect of AIN457 on Macular Edema and Visual Acuity in Patients With Posterior Segment Uveitis Secondary to Behçet's Disease as Determined by Optical Coherence Tomography.
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
- Result:
- AIN457C 300 mg Every 2 Week Dosage Regimen: mean -26.50 versus -49.40 on control; difference 22.90 (95% CI -45.58 to 91.38), standardized effect d = 0.15; z-test p = 0.512.
- AIN457C 300 mg Monthly Dosage Regimen (a): mean 3.60 versus -49.40 on control; difference 53.00 (95% CI -6.57 to 112.57), standardized effect d = 0.39; z-test p = 0.081.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AIN457C 300 mg Every 2 Week Dosage Regimen and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AIN457C 300 mg Monthly Dosage Regimen (a) and the control. The interval gives the range of effects that remain compatible with the data.
To Observe the Effect of AIN457 on the Systemic Non-ocular Manifestations of Behçet's Disease in Patients With Posterior Segment Uveitis Requiring Systemic Immunosuppression as Measured by the Bechet's Disease Current Activity Form.
- Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
- Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
- Result:
- AIN457C 300 mg Every 2 Week Dosage Regimen: mean -1.30 versus -1.10 on control; difference -0.20 (95% CI -1.24 to 0.84), standardized effect d = -0.13; z-test p = 0.707.
- AIN457C 300 mg Monthly Dosage Regimen (a): mean -1.70 versus -1.10 on control; difference -0.60 (95% CI -1.50 to 0.30), standardized effect d = -0.44; z-test p = 0.189.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AIN457C 300 mg Every 2 Week Dosage Regimen and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between AIN457C 300 mg Monthly Dosage Regimen (a) and the control. The interval gives the range of effects that remain compatible with the data.
The secondary outcomes cover several distinct domains: immunosuppressive medication use, macular edema and visual acuity, quality of life, and systemic non-ocular Behçet's disease activity. This breadth reflects questions beyond the primary focus on recurrent ocular exacerbations. However, the registry lists four secondary outcomes while quantitative results are posted for only a subset. Results for the medication score and quality-of-life outcomes are not reported in the registry record.
For the outcomes with posted numerical summaries, the recalculated comparisons do not produce a consistently clear separation from placebo. The macular-edema comparisons have intervals that include no difference, and the systemic disease activity comparisons also have intervals that include no difference. These are broad summaries of the pattern, not evidence that the outcomes are equivalent. The estimates are uncertain and based on relatively small groups, and the record does not include sponsor-reported analyses.
Secondary findings do not replace the primary result. They address different measures and timepoints, and they cannot by themselves resolve the uncertainty in recurrent ocular exacerbations. A secondary measure might move in a different direction from the primary outcome without establishing a coherent treatment effect across outcomes.
Unadjusted secondary results also carry less weight when multiple outcomes and comparisons are examined. The more statistical tests considered, the greater the chance that some results may appear notable by chance. The registry record does not report a multiplicity plan or adjusted secondary analyses. The secondary estimates are therefore best read as exploratory descriptions of the posted data, rather than as confirmatory evidence.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Change From Baseline for Composite Immunosuppressive Medication Score at Week 24 by Treatment (Full Analysis Set)
- To Determine the Effect of AIN457 on Macular Edema and Visual Acuity in Patients With Posterior Segment Uveitis Secondary to Behçet's Disease as Determined by Optical Coherence Tomography.
- To Establish the Impact of AIN457 on Quality of Life of Posterior Segment Uveitis Patients Secondary to Behçet's Disease Refractory to Systemic Immunomodulatory Therapy as Measured by National Eye Institute Visual Function Questionaire-25 and Euroqol.
- To Observe the Effect of AIN457 on the Systemic Non-ocular Manifestations of Behçet's Disease in Patients With Posterior Segment Uveitis Requiring Systemic Immunosuppression as Measured by the Bechet's Disease Current Activity Form.
9. Statistical Interpretation
The posted primary summaries show a mean of 7.7 ocular exacerbations in both the every-2-week AIN457 group and the placebo group. The recalculated unadjusted mean difference for that comparison is 0.0, with a 95% confidence interval from -9.931 to 9.931 and p = 1.0. On these summaries, the observed group means are identical, while the interval indicates considerable uncertainty about the underlying difference.
For the monthly AIN457 regimen, the posted mean is 11.5, compared with 7.7 for placebo. The recalculated unadjusted mean difference is 3.8, with a 95% confidence interval from -7.491 to 15.09 and p = 0.509. The observed mean is higher in the monthly group, but the interval includes both negative and positive differences, including no difference. The registry does not report an adjusted sponsor analysis for these comparisons; these are recalculations from the posted group summaries.
Neither comparison yields a precise estimate that clearly distinguishes a difference from no difference. The p-values are unadjusted, and the record does not report whether or how the multiple treatment comparisons were addressed in the trial's analysis plan. They should therefore be read as descriptive recalculations rather than as a substitute for a reported primary analysis.
The standard deviations are large in relation to the group means, indicating substantial participant-to-participant variability in the posted endpoint summaries. That variability contributes to the broad confidence intervals. A group mean does not show whether many participants had similar outcomes or whether the mean was influenced by a smaller number with many recurrences. No distributional summary or event-level account is reported.
These results describe the available registry summaries; they do not establish that either treatment schedule does or does not affect ocular exacerbations. The record does not include a sponsor-reported estimate, test, or analysis details that could clarify the primary endpoint result. The confidence intervals and p-values should be interpreted with that limitation in mind, alongside the modest number of participants listed in each group.
10. Statistical Methods Explained
What does a group mean represent?
A mean is the arithmetic average of the observed outcome values in a group. For recurrent events, it gives a compact summary of the average count or burden across participants over the stated observation period. It does not show the range of individual experiences, the timing of events, or whether outcomes are concentrated among a subset of participants.
The registry reports standard deviations alongside the means. A standard deviation describes how dispersed participant values are around a group mean. It is not the same as a standard error: the standard deviation describes variability among participants, while the standard error describes uncertainty in an estimated mean. In these summaries, the standard deviations are substantial, so the group averages should not be mistaken for typical outcomes shared by all participants.
How are the treatment contrasts read?
A mean difference compares the group averages. The posted recalculations compare each AIN457 group with placebo, rather than comparing the two AIN457 schedules directly. A difference of 0.0 for the every-2-week comparison reflects the identical posted group means. For the monthly comparison, the estimated difference is positive because its posted mean is higher than the placebo mean.
These are simple, unadjusted recalculations from posted summary statistics. They are not reported sponsor analyses. The record lists no reported analyses, and no detailed analysis plan is available. A recalculated contrast cannot account for features of the trial analysis that are not described in the registry record, such as adjustments or modeling choices.
What does a confidence interval convey?
A confidence interval describes the uncertainty around an estimated contrast under the assumptions of the method used. A narrower interval represents greater precision; a wider interval represents less precision. An interval that includes zero is compatible with no difference, as well as with differences in either direction across the values it spans. This does not prove that the groups are identical. It means the data summaries do not locate the contrast precisely enough to exclude those possibilities.
The intervals posted with the primary comparisons are recalculated from group-level information. The registry does not provide the trial's own confidence intervals or statistical test results. Accordingly, the recalculated intervals are useful for understanding scale and precision, but they should not be mistaken for the sponsor's analysis.
Why can variability matter for recurrent outcomes?
Recurrent-event measures may have a distribution in which observations are not evenly spread around the mean. When event counts vary substantially across participants, a mean and standard deviation may not fully capture the distribution. In general, over-dispersion means that the observed variability is greater than a simpler statistical model expects; accounting for it can affect uncertainty estimates. The registry does not report whether over-dispersion was assessed or whether a recurrent-event model was used. This is a general statistical consideration, not a claim about the trial's analysis.
It is also useful to distinguish an event rate from a count summary. A rate ordinarily relates events to time at risk, while the registry's posted primary results are expressed as means with standard deviations. The record does not provide person-time or a model-based rate estimate, so the recalculations compare the reported means rather than reconstructing a rate model.
What do the planning illustrations mean?
The sample-size illustrations are based on observed effects and are planning illustrations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and detection of a specified fraction of the observed effect. For the primary comparison of the monthly regimen with placebo, the illustration gives 704 participants per arm for 80% power and 942 participants per arm for 90% power when planning for 100% of the observed effect. Smaller fractions of that effect require larger illustrated sample sizes.
These figures are not the trial's enrollment target or a reconstruction of its design rationale. The registry's own sample-size justification is not reported. Observed effects can be imprecise, especially in a small study, so using them as planning inputs is only an illustration. The figures do not indicate the probability that the completed trial detected an effect.
11. Confidence Intervals and Precision
The primary comparisons are estimated with broad confidence intervals. For the every-2-week regimen, the recalculated mean difference is 0.0 and its 95% confidence interval runs from -9.931 to 9.931. For the monthly regimen, the recalculated mean difference is 3.8 and its 95% confidence interval runs from -7.491 to 15.09. Both intervals include zero and span differences in either direction.
A confidence interval is a way of expressing statistical uncertainty around an estimate. It is not a range containing a fixed proportion of individual participant outcomes, nor does it show that every value in the interval is equally plausible. In general, the interval is interpreted using the assumptions of the analysis that generated it. Here the intervals are simple unadjusted recalculations from posted summaries, not sponsor-reported results.
The width of the intervals matters because the point estimates alone can give a misleading impression of certainty. The identical means in the every-2-week group and placebo do not imply that the underlying group averages must be identical. Likewise, the positive observed difference for the monthly group does not establish that the underlying difference is positive. The intervals remain compatible with meaningful differences on either side of zero.
Substantial variation in the group summaries and 39 participants listed per primary-outcome group contribute to uncertainty. The registry record does not report a model-based estimate, an adjusted confidence interval, or detail about the distribution of recurrence outcomes. Thus, precision can be assessed only from the posted summaries and recalculations, not from a complete account of the trial's planned analysis.
12. Multiplicity, Missing Data and Analysis Populations
The registry identifies the primary outcome population as the Full Analysis Set, but does not describe the exact membership rules or how participants with incomplete data were treated. The analysis population is important because it defines whose outcomes contribute to an estimate and how departures from the randomized assignment are handled. Further population details are not reported in the registry record.
The record lists no reported analyses. It therefore does not establish how the sponsor analyzed the primary outcome, whether the analysis adjusted for baseline values or other factors, or whether the reported comparisons were the prespecified primary contrasts. The recalculated estimates are simple unadjusted comparisons of posted summaries and cannot fill in those missing methodological details.
Multiplicity is another unresolved issue. The study includes more than one treatment comparison and several secondary outcomes. The registry record does not report whether the testing plan controlled the overall chance of false-positive findings across those comparisons, or whether a hierarchy or other procedure was prespecified. The p-values shown for recalculated comparisons are unadjusted and should be interpreted accordingly.
Missing-data procedures are not reported. This does not establish that data were missing, but it means the record does not explain how incomplete follow-up, withdrawal, or unavailable endpoint measurements would affect the estimates. The numbers contributing to the week 24 outcomes and the reasons for any differences from enrollment are also not reported.
Interim analyses, stopping rules, and the trial's sample-size justification are likewise not reported in the registry record. Those details matter for understanding the design and interpretation of a completed trial. Without them, the public registry summaries support a limited descriptive reading, rather than a full audit of the planned statistical analysis.
13. 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 |
|---|---|---|---|
| AIN457 300mg Every 2 Weeks | 6 | 39 | 15.4% |
| AIN457 300mg Monthly | 8 | 39 | 20.5% |
| Placebo | 5 | 39 | 12.8% |
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 |
|---|---|
| AIN457 300mg Every 2 Weeks | 28 of 39 |
| AIN457 300mg Monthly | 25 of 39 |
| Placebo | 22 of 39 |
Most frequent serious adverse event terms
| Event term | Organ system | AIN457 300mg Every 2 Weeks | AIN457 300mg Monthly | Placebo |
|---|---|---|---|---|
| Uveitis (Fellow eye) | Eye disorders | 1 of 39 | 1 of 39 | 0 of 39 |
| Uveitis (Study eye) | Eye disorders | 0 of 39 | 1 of 39 | 1 of 39 |
| Folliculitis | Infections and infestations | 2 of 39 | 0 of 39 | 0 of 39 |
| Supraventricular tachycardia | Cardiac disorders | 1 of 39 | 0 of 39 | 0 of 39 |
| Vertigo | Ear and labyrinth disorders | 0 of 39 | 1 of 39 | 0 of 39 |
| Cataract cortical (Fellow eye) | Eye disorders | 0 of 39 | 0 of 39 | 1 of 39 |
| Cataract nuclear (Fellow eye) | Eye disorders | 0 of 39 | 0 of 39 | 1 of 39 |
| Cataract subcapsular (Fellow eye) | Eye disorders | 0 of 39 | 0 of 39 | 1 of 39 |
| Choroiditis (Fellow eye) | Eye disorders | 1 of 39 | 0 of 39 | 0 of 39 |
| Glaucoma (Fellow eye) | Eye disorders | 0 of 39 | 0 of 39 | 1 of 39 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AIN457 300mg Every 2 Weeks | AIN457 300mg Monthly | Placebo |
|---|---|---|---|---|
| Headache | Nervous system disorders | 9 of 39 | 6 of 39 | 9 of 39 |
| Pyrexia | General disorders | 6 of 39 | 2 of 39 | 4 of 39 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 4 of 39 | 3 of 39 | 3 of 39 |
| Nausea | Gastrointestinal disorders | 4 of 39 | 3 of 39 | 2 of 39 |
| Fatigue | General disorders | 2 of 39 | 2 of 39 | 4 of 39 |
| Upper respiratory tract infection | Infections and infestations | 3 of 39 | 4 of 39 | 1 of 39 |
| Vision blurred (Fellow eye) | Eye disorders | 0 of 39 | 6 of 39 | 1 of 39 |
| Visual acuity reduced (Study eye) | Eye disorders | 4 of 39 | 2 of 39 | 1 of 39 |
| Influenza | Infections and infestations | 2 of 39 | 4 of 39 | 1 of 39 |
| Cataract subcapsular (Study eye) | Eye disorders | 4 of 39 | 1 of 39 | 0 of 39 |
Serious events with the highest arm-level rate: folliculitis (5.1%), supraventricular tachycardia (2.6%), vertigo (2.6%), cataract cortical (fellow eye) (2.6%), cataract nuclear (fellow eye) (2.6%).
The registry reports serious adverse events for 6 participants in the every-2-week AIN457 group, 8 in the monthly AIN457 group, and 5 in the placebo group. Each group lists 39 participants at risk. These are descriptive counts; they do not, on their own, establish whether an event was caused by treatment or whether groups differed reliably. The record does not report a comparative statistical analysis of these counts.
The listed serious adverse-event terms include folliculitis at 5.1%, supraventricular tachycardia at 2.6%, vertigo at 2.6%, cataract cortical (Fellow eye) at 2.6%, cataract nuclear (Fellow eye) at 2.6%, and cataract subcapsular (Fellow eye) at 2.6%. The registry presents these as the top serious terms; further detail on their timing, duration, severity, or attribution is not reported in the registry record.
Other adverse events affected 28 participants in the every-2-week group, 25 in the monthly group, and 22 in the placebo group, with 39 at risk in each group. Death results are not reported in the registry record. These summaries should be read as event counts within the trial, not as proof of a safety difference or a causal relationship.
14. What the Result Does, and Does Not, Mean
The posted results show similar primary-outcome means for the every-2-week AIN457 regimen and placebo, and a higher mean for the monthly regimen than for placebo. The recalculated unadjusted confidence intervals are broad and include no difference for both comparisons. The data summaries therefore leave substantial uncertainty about the size and direction of the underlying differences.
That uncertainty should not be converted into a claim that the regimens are equivalent to placebo. A result that does not clearly distinguish a difference from no difference is not proof that no difference exists. Conversely, a point estimate alone does not establish a real treatment effect. The registry record does not provide a sponsor-reported analysis that would support a more definitive interpretation.
The endpoint captures recurrent ocular exacerbations over the study period, but the record posts means and standard deviations rather than event-level histories or detailed rate-model estimates. The available summaries do not show how outcomes were distributed across participants or whether the event pattern varied over time. They also do not explain how missing observations were handled.
The secondary summaries cover other clinical domains, but only some have numerical results posted, and the analyses are unadjusted recalculations. They offer context rather than resolving the primary endpoint's uncertainty. Safety counts are also descriptive and do not establish causation or comparative risk.
In short, the registry record documents a completed randomized study and posts useful group summaries. It does not report enough statistical detail to support a definitive account of the primary treatment comparison, multiplicity, missing data, or the planned analysis. These limitations define what can reasonably be concluded from the posted results.
15. Why This Trial Matters Statistically
This trial illustrates why an observed mean difference is only one part of a clinical-trial result. The primary group means are close for one comparison, and the monthly comparison has a positive point estimate, but both recalculated confidence intervals are broad. The intervals show that the estimates are not precise enough to distinguish clearly between no difference and differences in either direction.
The endpoint also raises a useful design and analysis issue. Recurrent exacerbations are not necessarily well described by a single average, especially when participant outcomes vary substantially. A mean and standard deviation provide a starting point, but a fuller statistical account would explain the event definition, follow-up time, distribution of recurrences, and any model used to estimate the rate. Those details are not reported in the registry record.
The study has three randomized groups and several secondary questions, yet the registry reports no analyses and no multiplicity plan. That makes it important to separate recalculated descriptive contrasts from confirmatory sponsor analyses. It also demonstrates why secondary estimates and unadjusted p-values should be interpreted cautiously when many outcomes are under consideration.
Finally, the sample-size illustrations are not evidence of observed power and are not the trial's design justification. They show how planning requirements depend on the assumed effect size and variability, but they cannot recover the original design rationale. For clinical researchers, this record is a useful example of how limited reporting can constrain interpretation even when group summaries are available.
16. 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 provides only group-level summaries for the primary endpoint and does not include participant-level outcomes, event timing, or an account of the recurrence distribution. This prevents assessment of whether a small number of participants contributed disproportionately to the group means, or how exacerbations changed over the 24-week period. The posted primary measure is described as a rate, but no person-time summaries or rate-model estimates are reported.
The record identifies a Full Analysis Set but does not define it or explain how the analysis population was formed. It lists 118 participants as enrollment and 39 in each primary outcome group, but does not explain the relationship between these figures. Completion counts, withdrawals, endpoint availability, and missing-data procedures are not reported. These omissions make it difficult to assess attrition or the effect of incomplete observations.
No sponsor-reported analyses are listed. The comparisons discussed are recalculated from the posted means, standard deviations, and group sizes; they may not reflect the trial's prespecified method. The record also does not report adjustment for multiplicity, interim analyses, the sample-size justification, or the handling of protocol deviations. It describes masking as triple in one field and double-masked in the official title, without clarifying masking roles.
Quantitative secondary results are not available for every secondary outcome, and the posted secondary comparisons are unadjusted. Safety summaries are counts without reported comparative analyses or detailed event-level information. These limitations do not show that a particular design or analysis choice was made; they mark what is not reported in the registry record and narrow the interpretation that can be supported.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: Phase III Study in Refractory Behcet's Disease — NCT00995709.
- Registry record last updated 2015-08-31; status last verified 2015-08.
- Results first posted 2015-08-31.
- 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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20. Record Summary
The registry identifies NCT00995709 as a completed, randomized Phase III, parallel-group study of AIN457 in Behçet's disease. The study compared AIN457C 300 mg every 2 weeks and monthly with placebo, alongside standard-of-care immunosuppressive therapy. Enrollment is listed as 118, and the primary endpoint is the rate of recurrent ocular exacerbations in the study eye from baseline to week 24.
Primary summaries list 39 participants per group. The recalculated, unadjusted comparisons show broad confidence intervals that include no difference. The registry lists secondary outcomes across ocular, medication, quality-of-life, and systemic disease measures, but quantitative summaries are posted for only some. Serious and other adverse-event counts are descriptive; comparative safety analyses are not reported.
The registry record does not list sponsor-reported analyses or key statistical details such as missing-data handling, multiplicity procedures, interim analyses, or sample-size justification. Interpretation is therefore limited to the posted summaries and their recalculations.