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 AIN457 in Noninfectious Uveitis (NCT00685399), a randomized phase 2 study. The primary outcome is Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00685399 |
| Phase | Phase 2 |
| Condition | Non-infectious Uveitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 76 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
People with noninfectious uveitis were studied. The brief summary describes active uveitis requiring systemic immunosuppression. The registry reports enrollment of 76 participants, but the safety outcome applies to a defined Safety Analysis Set rather than automatically to everyone enrolled.
Intervention
AIN457 was administered in different cohorts and regimens. The record describes intravenous doses, a subcutaneous regimen, and an extension period in which dosing could occur after a flare or periodically at the investigator’s discretion. Dose, route, formulation and schedule varied across cohorts.
Comparator
The record describes randomized, double-masked, parallel-group features, including saline infusions or injections to maintain masking in Cohort 6. It does not identify one common comparator for all cohorts or give a single treatment-versus-control comparison for the primary safety outcome.
Primary question
The primary outcome counted participants with adverse events, serious adverse events and deaths from Day 1 to Day 603. The safety results are reported by cohort. They describe event counts in the Safety Analysis Set, but the registry record does not report an inferential comparison between treatment groups.
The trial title and summary frame the study around the safety and efficacy of AIN457 in noninfectious uveitis. However, the designated primary outcome is safety: the number of participants with adverse events, serious adverse events and deaths. Secondary outcomes address response, remission, corticosteroid or other immunosuppressant reduction, and re-induction of remission after a flare. Those are separate questions from the primary safety count.
The multiple cohorts reflect different AIN457 regimens and study periods, including an extension cohort. The record therefore should not be read as if it describes one uniform dose compared with one shared control. Some Cohort 6 arms used saline alongside active treatment to maintain masking, but the registry does not identify a single comparator applicable to all cohorts. The clinical question answered by the posted primary outcome is descriptive: what safety events were recorded among participants assessed in each cohort during the stated timeframe?
3. Trial Design
This was a phase 2 study with randomized allocation, double masking and a parallel-group model. The official title also describes an open-label proof-of-concept study with a double-masked, dose-ranging component. These descriptions indicate that the study included components with different masking arrangements; the registry does not give enough detail to reconstruct the full allocation and masking procedures for every cohort.
The registry reports enrollment of 76 and lists six numbered cohorts, with three arms within Cohort 6. Cohort 1, Cohort 2 and Cohort 3 used intravenous AIN457 regimens, although the doses, formulations and timing varied. Cohort 4 was an extension period, with dosing after a flare or periodically at the investigator’s discretion. Cohort 5 used a single intravenous dose of 30 mg/kg, with a second dose contingent on the stated tolerability and follow-up conditions. Cohort 6 compared three administration regimens, using saline infusions or injections in some arms to maintain masking.
The registry gives a start date of 2008-06, primary completion of 2013-09 and status of completed. The primary safety timeframe is Day 1 to Day 603. The registry does not report a detailed participant flow, the allocation ratio, concealment procedures, or the number randomized to each cohort. Nor does it state how all cohort transitions or extensions were handled in the analysis. Enrollment should therefore not be treated as the denominator for every safety result: the primary outcome defines a Safety Analysis Set consisting of participants who received at least one dose and had at least one post-baseline safety assessment.
The design includes both a broad safety assessment and efficacy-related secondary outcomes. The posted primary results are presented as cohort-specific counts, rather than as one pooled estimate or a direct comparison between assigned regimens. The statistical plan, including any prespecified comparisons, is 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.
Only the first 6 of 8 groups are shown.
Treatment Period 1
| Stage | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 Arm 1 |
|---|---|---|---|---|---|---|
| STARTED | 16 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 10 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 0 | 0 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 Arm 1 |
|---|---|---|---|---|---|---|
| Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 | 0 |
| Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Administrative | 2 | 0 | 0 | 0 | 0 | 0 |
| Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 |
Treatment Period 2
| Stage | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 Arm 1 |
|---|---|---|---|---|---|---|
| STARTED | 0 | 14 | 5 | 0 | 4 | 12 |
| COMPLETED | 0 | 2 | 2 | 0 | 4 | 10 |
| NOT COMPLETED | 0 | 12 | 3 | 0 | 0 | 2 |
Reasons for not completing this period:
| Reason | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 Arm 1 |
|---|---|---|---|---|---|---|
| Administrative Problems | 0 | 2 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 |
| Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Lack of Efficacy | 0 | 10 | 2 | 0 | 0 | 1 |
Extension
| Stage | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 Arm 1 |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 28 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 21 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 7 | 0 | 0 |
Reasons for not completing this period:
| Reason | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 Arm 1 |
|---|---|---|---|---|---|---|
| Administrative Issues | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
| Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 |
| Lack of Efficacy | 0 | 0 | 0 | 2 | 0 | 0 |
| Adverse Event | 0 | 0 | 0 | 2 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set (SAS) consisted of all participants who received at least one dose of study drug and had at least one post-baseline safety assessment. All safety evaluations were carried out on the safety 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.
Only the first 6 of 8 groups are shown.
| Characteristic | Unit | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 5 | Cohort 6 Arm 1 | Cohort 6 Arm 2 |
|---|---|---|---|---|---|---|---|
| Participants analysed | 16 | 14 | 5 | 4 | 12 | 13 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 1 |
| Age, Categorical: Between 18 and 65 years | Participants | 15 | 13 | 5 | 4 | 12 | 11 |
| Age, Categorical: >=65 years | Participants | 1 | 1 | 0 | 0 | 0 | 1 |
| Sex: Female, Male: Female | Participants | 12 | 10 | 3 | 3 | 8 | 9 |
| Sex: Female, Male: Male | Participants | 4 | 4 | 2 | 1 | 4 | 4 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 0 | 1 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 3 | 0 | 0 | 2 | 2 |
| Race (NIH/OMB): White | Participants | 7 | 10 | 4 | 1 | 9 | 9 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 5 | 1 | 1 | 2 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died, measured over Day 1 to Day 603.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with adverse events, serious adverse events and deaths during Day 1 to Day 603. An adverse event is defined in the record as an unfavorable or unintended diagnosis, symptom, sign, syndrome or disease that begins during the study or worsens from baseline. A serious adverse event is classified by consequences such as death, life threat, hospitalization, persistent or significant disability, congenital anomaly or birth defect, or another condition judged by investigators to represent a significant hazard.
Counting participants with at least one event is a way to describe how many people experienced an event in each category. It is different from counting every event: one participant may have more than one event, but the endpoint is framed as a participant count. The record also presents participants with other adverse events separately from those with serious adverse events, and reports deaths.
Safety outcomes are used to characterize harms observed during exposure and follow-up. They are particularly relevant when a trial includes different doses, routes or schedules, since the nature and frequency of observed events may vary across regimens. These counts do not by themselves establish that an event was caused by treatment. The registry record does not report a causal attribution analysis or an adjusted comparison for this endpoint.
The endpoint’s population is the Safety Analysis Set: participants who received at least one dose and had at least one post-baseline safety assessment. This definition is narrower than enrollment as a general study descriptor and determines which participants contribute to the safety summaries.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results show serious adverse events in one participant in Cohort 3, one participant in Cohort 6 - Arm 1, and one participant in Cohort 4 (Extension). The other listed cohorts report zero participants with serious adverse events. No deaths are reported in any listed cohort. These are descriptive counts; the registry record gives no statistical test, confidence interval or adjusted comparison for the primary outcome.
For the separate count of participants with other adverse events, the registry reports 15 of 16 in Cohort 1, 12 of 17 in Cohort 2, 5 of 5 in Cohort 3, 3 of 4 in Cohort 5, 9 of 12 in Cohort 6 - Arm 1, 10 of 13 in Cohort 6 - Arm 2, 12 of 12 in Cohort 6 - Arm 3, and 20 of 28 in Cohort 4 (Extension). These results describe the recorded experience in each cohort; they should not be interpreted as a ranking of regimens. Cohorts differ in size, dose and administration schedule, and the record does not provide a common comparative analysis.
The serious-event counts are small, so the observed counts alone offer limited precision about the underlying frequency of such events. General statistical interpretation: when an outcome is uncommon and the number of people observed is limited, a small change in the count can correspond to a substantial change in an estimated rate. Without reported confidence intervals or a formal model, the precision of an underlying rate cannot be read directly from the count.
The record lists serious-event terms with percentages, including Uterine cancer at 20.0%, Pyelonephritis at 8.3%, Urinary tract infection at 8.3%, Hypokalaemia at 8.3%, and Tibia fracture at 3.6%. The denominators and method used to calculate these term-specific percentages are not reported in the registry record. They should not be treated as directly comparable cohort-specific rates or as evidence of causation.
The primary safety results do not answer the efficacy questions described among the secondary outcomes. Although the record identifies response and remission outcomes, no analyses are recorded for those outcomes in the statistical-analysis listing. The safety counts therefore support a descriptive reading of recorded events, not a conclusion about comparative efficacy or treatment effects.
9. Statistical Methods Explained
The registry classifies the primary outcome as a count of participants, with results organized by cohort. The outcome is not a continuous measurement such as a laboratory value, nor is it reported as a time-to-event estimate. The central quantities are the number of people at risk in each cohort and the number who experienced the specified event category during the stated timeframe.
What does a participant count represent?
General statistical explanation: a participant count answers how many people in an analyzed group had at least one event. This differs from an event count, because one person can experience multiple events. It also differs from a rate per unit of follow-up time, which accounts for how long each person was observed. The registry presents participant counts and cohort denominators; it does not give person-time rates for the primary outcome.
The serious adverse event count, other adverse event count and death count are distinct summaries. They should not be combined into a single measure unless the analysis defines how categories overlap and what combined event means. The registry does not report such a combined endpoint. A participant may also appear in more than one cohort over a study’s course, but the record does not provide enough participant-flow detail to determine how cohort membership was treated for every summary. Consequently, adding cohort denominators or affected-participant counts would not be an appropriate way to produce a new total.
Why is the cohort structure important?
General statistical explanation: a treatment comparison is most interpretable when the groups being compared have clearly defined assignment, follow-up and analysis populations. Here, the listed cohorts include differing doses, routes, schedules and an extension period. Cohort 6 contains multiple arms, while the other cohorts are described separately. The registry does not provide a single, prespecified contrast for the primary safety outcome, so the cohort-specific results should remain descriptive rather than being recast as one treatment effect.
The randomized, double-masked and parallel-group labels are important design features, but they do not fill in missing details about the allocation ratio, concealment, cohort-specific assignment, or the analysis model. The official title additionally describes an open-label proof-of-concept component. The precise relationship between the open-label and masked components is not reported in the registry record. These details matter when assessing how treatment groups were formed and whether a comparison can be interpreted causally.
What can uncertainty measures add?
General statistical explanation: a confidence interval expresses the range of effect estimates compatible with the observed data under a stated statistical method. It conveys precision as well as direction and magnitude. A p-value addresses how unusual the data would be under a specified null model; it does not measure the probability that a treatment works, and it does not substitute for an effect estimate. The registry record reports no confidence intervals or p-values for this primary outcome. Therefore, the counts cannot be used to infer statistical significance or to quantify comparative uncertainty.
For sparse safety outcomes, ordinary large-sample approximations may be unreliable. General explanation: sparse data can yield unstable estimates, and exact or otherwise suitable methods may be needed depending on the comparison and estimand. No inferential method for the primary outcome is reported, so it is not possible to know whether such methods were considered.
How should planning illustrations be understood?
General statistical explanation: a sample-size calculation is a planning exercise based on assumptions about the effect to detect, significance level, allocation and statistical model. It does not describe what the trial observed, and it is not observed power. The registry’s stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect is defined as a fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm. The primary outcome has multiple categories or time points and is not reduced to one comparison in the registry record, so a single primary-outcome comparison cannot be assumed from that description.
No prespecified statistical analysis plan, model, handling of repeated or multiple events, or adjustment strategy is reported in the registry record. The analysis listing records zero analyses. This means the posted information does not document inferential results for the outcomes; it should not be interpreted as proof that no analyses were conducted outside the registry.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies 7 outcome measures and lists secondary outcomes concerning response, complete response, reduction in corticosteroid or other immunosuppressant drugs, induction of remission, remission, and re-induction of remission after a flare. Multiple outcomes create a multiplicity question: if many hypotheses are tested, the chance of at least one apparently unusual result can increase. General statistical explanation: investigators may address this by prespecifying a hierarchy, adjusting significance thresholds, or emphasizing estimation rather than a collection of unadjusted tests. The registry record does not report a multiplicity plan.
No analysis entries are recorded for the outcomes. In particular, the posted primary safety results are counts by cohort, without a reported statistical test, confidence interval or adjusted comparison. The record does not describe interim analyses, an analysis hierarchy, or rules for selecting which outcomes would support a confirmatory conclusion. These elements are not reported in the registry record.
The safety population is defined as participants who received at least one dose and had at least one post-baseline safety assessment. That definition describes the analysis population for safety evaluations. It does not establish how missing safety assessments were handled, whether participants were excluded for other reasons, or how missing efficacy outcomes were treated. Missing-data methods and the analysis populations for the secondary efficacy outcomes are not reported in the registry record.
General statistical explanation: missing-data handling can affect an estimate when participants with incomplete follow-up differ from those with complete data, especially if missingness is related to outcomes or treatment. A transparent report ordinarily describes the amount and pattern of missingness and any assumptions or sensitivity analyses. Those details are not reported for this study’s outcomes in the registry record. Therefore, no conclusion about the effect of missing data on the posted results can be drawn.
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 |
|---|---|---|---|
| Cohort 1 | 0 | 16 | 0.0% |
| Cohort 2 | 0 | 17 | 0.0% |
| Cohort 3 | 1 | 5 | 20.0% |
| Cohort 5 | 0 | 4 | 0.0% |
| Cohort 6 - Arm 1 | 1 | 12 | 8.3% |
| Cohort 6 - Arm 2 | 0 | 13 | 0.0% |
| Cohort 6 - Arm 3 | 0 | 12 | 0.0% |
| Cohort 4 (Extension) | 1 | 28 | 3.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 | 0 of 16 |
| Cohort 2 | 0 of 17 |
| Cohort 3 | 0 of 5 |
| Cohort 5 | 0 of 4 |
| Cohort 6 - Arm 1 | 0 of 12 |
| Cohort 6 - Arm 2 | 0 of 13 |
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 |
|---|---|
| Cohort 1 | 15 of 16 |
| Cohort 2 | 12 of 17 |
| Cohort 3 | 5 of 5 |
| Cohort 5 | 3 of 4 |
| Cohort 6 - Arm 1 | 9 of 12 |
| Cohort 6 - Arm 2 | 10 of 13 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 5 | Cohort 6 - Arm 1 | Cohort 6 - Arm 2 |
|---|---|---|---|---|---|---|---|
| Pyelonephritis | Infections and infestations | 0 of 16 | 0 of 17 | 0 of 5 | 0 of 4 | 1 of 12 | 0 of 13 |
| Urinary tract infection | Infections and infestations | 0 of 16 | 0 of 17 | 0 of 5 | 0 of 4 | 1 of 12 | 0 of 13 |
| Hypokalaemia | Metabolism and nutrition disorders | 0 of 16 | 0 of 17 | 0 of 5 | 0 of 4 | 1 of 12 | 0 of 13 |
| Uterine cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 16 | 0 of 17 | 1 of 5 | 0 of 4 | 0 of 12 | 0 of 13 |
| Tibia fracture | Injury, poisoning and procedural complications | 0 of 16 | 0 of 17 | 0 of 5 | 0 of 4 | 0 of 12 | 0 of 13 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 5 | Cohort 6 - Arm 1 | Cohort 6 - Arm 2 |
|---|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 10 of 16 | 4 of 17 | 3 of 5 | 2 of 4 | 5 of 12 | 3 of 13 |
| Eye pain | Eye disorders | 3 of 16 | 2 of 17 | 1 of 5 | 0 of 4 | 1 of 12 | 1 of 13 |
| Intraocular pressure increased | Investigations | 5 of 16 | 0 of 17 | 0 of 5 | 0 of 4 | 0 of 12 | 1 of 13 |
| Vision blurred | Eye disorders | 3 of 16 | 1 of 17 | 1 of 5 | 0 of 4 | 0 of 12 | 0 of 13 |
| Fatigue | General disorders | 2 of 16 | 0 of 17 | 0 of 5 | 0 of 4 | 1 of 12 | 2 of 13 |
| Nasopharyngitis | Infections and infestations | 1 of 16 | 1 of 17 | 1 of 5 | 0 of 4 | 1 of 12 | 1 of 13 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 2 of 16 | 1 of 17 | 1 of 5 | 0 of 4 | 0 of 12 | 1 of 13 |
| Rash | Skin and subcutaneous tissue disorders | 1 of 16 | 2 of 17 | 1 of 5 | 0 of 4 | 0 of 12 | 1 of 13 |
| Macular oedema | Eye disorders | 1 of 16 | 2 of 17 | 0 of 5 | 1 of 4 | 0 of 12 | 0 of 13 |
| Vitreous floaters | Eye disorders | 1 of 16 | 1 of 17 | 2 of 5 | 0 of 4 | 0 of 12 | 0 of 13 |
Serious events with the highest arm-level rate: uterine cancer (20.0%), pyelonephritis (8.3%), urinary tract infection (8.3%), hypokalaemia (8.3%), tibia fracture (3.6%).
The serious adverse event figures are participant counts within the Safety Analysis Set for each cohort. Cohort 1 reports 0 of 16 participants with a serious adverse event; Cohort 2, 0 of 17; Cohort 3, 1 of 5; Cohort 5, 0 of 4; Cohort 6 - Arm 1, 1 of 12; Cohort 6 - Arm 2, 0 of 13; Cohort 6 - Arm 3, 0 of 12; and Cohort 4 (Extension), 1 of 28. The record reports zero deaths in each listed cohort.
These are observed counts over the primary timeframe of Day 1 to Day 603. They are not rates adjusted for follow-up duration, and a count of zero does not establish that an event is impossible. General statistical explanation: when the number observed is limited, estimates for uncommon outcomes are imprecise even if no event is recorded in a group.
The serious-event terms are listed with percentages, but their denominators are not reported in the registry record. The term list should therefore be read as a separate descriptive summary, not as a set of directly comparable cohort rates. A serious event recorded during a study is not necessarily caused by the study treatment; the registry does not report a causal attribution analysis for these counts.
12. What the Result Does, and Does Not, Mean
The posted results document safety events among participants included in the defined Safety Analysis Set. They show that serious adverse events were recorded in three of the listed cohorts, with one affected participant reported in each of those cohorts, and that no deaths were reported. The separate other-adverse-event counts vary across cohorts. These observations describe what the registry reports for the study timeframe; they do not establish a comparative treatment effect.
The study included different AIN457 doses, routes and schedules, and an extension period. The cohort-specific results are not a substitute for a prespecified comparison. Differences in observed counts may reflect differing group sizes, regimens, follow-up or participant characteristics; the registry record does not provide analyses that separate these possibilities. The results therefore should not be used to rank cohorts or identify a regimen as safer on the basis of these counts alone.
The record’s title and secondary outcomes also concern efficacy, including response and remission. The primary endpoint addressed safety, and no efficacy analyses are recorded in the analysis listing. The safety results do not establish whether AIN457 improves uveitis outcomes or reduces use of other medicines.
General statistical explanation: absence of a reported statistically significant difference is not the same as evidence of equivalence, and no comparison should be inferred when an estimate and uncertainty measure are not reported. Likewise, a safety event occurring during a trial does not by itself show that treatment caused it. Causal assessment requires context and an appropriate analysis, neither of which is provided for these events in the registry record.
The study is best understood as a phase 2 trial with a complex cohort structure and descriptive safety summaries in the registry. Its posted results can inform what events were recorded, but the registry record does not establish the precision of between-group differences, a causal safety effect, or a comparative efficacy conclusion.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way a single study record combines a proof-of-concept description, a dose-ranging component, multiple cohorts and an extension period. That structure makes it important to distinguish the overall study labels from the specific population and comparison used for each outcome. A randomized, double-masked, parallel-group designation does not alone identify the exact contrast behind every cohort-specific safety count.
The primary endpoint is a participant-based safety measure, while secondary outcomes concern response and remission. Those outcome types answer different questions and need not share the same analysis population or statistical method. The safety endpoint is reported as counts, but the registry does not provide an inferential comparison, confidence intervals or a detailed analysis plan. This illustrates why descriptive results and comparative estimates should not be treated as interchangeable.
The small serious-event counts also highlight the distinction between observed frequency and precision. General statistical explanation: a sparse count can be informative as a record of what happened, yet still provide limited information about the range of plausible underlying risks. Without uncertainty estimates and clearly defined comparisons, readers cannot assess the precision of differences between cohorts.
Finally, the record’s statistical-analysis listing contains no analysis entries, while it identifies multiple outcomes and a defined safety population. The absence of documented multiplicity, missing-data and inferential methods limits how far the results can support comparative conclusions. The case underscores the value of reporting prespecified contrasts, analysis populations, denominators, uncertainty intervals and methods alongside outcome counts.
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 a detailed statistical analysis plan, inferential method, confidence intervals, p-values, or adjusted comparisons for the primary safety outcome. The cohort-level counts therefore provide descriptive information but do not quantify comparative effects or their precision. No analysis entries are recorded, and the record does not explain whether analyses were conducted outside the registry.
The design is complex: different cohorts used different doses, formulations, routes and schedules, and Cohort 4 is an extension. The official title describes an open-label proof-of-concept component alongside a double-masked, dose-ranging component, but the registry does not explain how those components relate for all participants. Allocation ratio, concealment procedures, detailed participant flow and cohort-specific assignment are not reported in the registry record.
The safety denominator is defined by the Safety Analysis Set, but participant flow into that set is not fully described. The registry does not report missing-data amounts or methods, the analysis populations for secondary outcomes, or how repeated events were handled. The term-specific serious-event percentages are listed without denominators or a calculation method. These omissions restrict interpretation of the percentages and comparison across groups.
The primary outcome spans Day 1 to Day 603, but the record does not provide cohort-specific follow-up duration or exposure-adjusted rates. The counts do not establish causality, and no causal attribution analysis is reported. The record also does not report a multiplicity plan despite identifying multiple outcome measures. These limitations mean that the posted safety counts should not be used alone to infer comparative safety, efficacy, or a definitive treatment effect.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of AIN457 in Noninfectious Uveitis — NCT00685399.
- Registry record last updated 2017-07-17; status last verified 2017-06.
- Results first posted 2017-07-17.
- 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
NCT00685399 is a completed phase 2 study titled “Safety and Efficacy of AIN457 in Noninfectious Uveitis.” The registry describes randomized allocation, double masking and a parallel model, as well as an open-label proof-of-concept component with a double-masked, dose-ranging component. Enrollment was 76; the recorded start was 2008-06 and primary completion was 2013-09.
The primary outcome counted participants with adverse events, serious adverse events and deaths from Day 1 to Day 603 in the Safety Analysis Set. Results are reported by cohort. Serious adverse events were recorded in Cohort 3, Cohort 6 - Arm 1 and Cohort 4 (Extension); no deaths were reported in the listed cohorts. Other adverse-event counts are also reported by cohort.
The record identifies secondary response and remission outcomes but has no analysis entries. It does not report inferential comparisons, uncertainty estimates, multiplicity methods or missing-data methods. The posted primary results are therefore descriptive safety summaries rather than a comparative treatment-effect analysis.