Subgroup and Sensitivity Analyses of the Primary Endpoint from the Peginterferon Beta-1a ADVANCE Study: A Pivotal Phase 3 Study in Patients with Relapsing-Remitting Multiple Sclerosis (P3.169)
Bibliographic record
Abstract
OBJECTIVE: To describe subgroup and sensitivity analyses of the ADVANCE study primary endpoint. BACKGROUND: Peginterferon beta-1a is being developed for the treatment of multiple sclerosis (MS). Year 1 findings from the pivotal, Phase 3 ADVANCE trial in patients with relapsing-remitting MS (RRMS) demonstrated that peginterferon beta-1a 125 µg administered subcutaneously every 2 (Q2W) or 4 (Q4W) weeks led to significant reductions in the primary endpoint of annualized relapse rate (ARR) compared with placebo. METHODS: Pre-specified subgroup analyses were conducted by demographics (age, gender, weight, and geographical region) and baseline disease characteristics (prior relapses, McDonald criteria, prior MS treatment, Expanded Disability Status Scale, volume of T2 hyperintense lesions, and presence of gadolinium-enhancing lesions). Five sensitivity analyses were conducted for the primary endpoint: 3 pre-specified (per protocol population, all relapses, and Poisson regression model), and 2 post-hoc (protocol-defined relapses, and adjusting for baseline gadolinium-enhancing lesions). RESULTS: ARR was similar across the demographic and baseline disease characteristic subgroups for both peginterferon beta-1a Q2W and Q4W. Although some differences in the point estimates for the ARR versus placebo were noted among the subgroups, there was considerable overlap in the confidence intervals, suggesting that the efficacy of peginterferon beta-1a is similar in all patients irrespective of gender, age, body weight, geographical region and disease status at initiation of treatment. Results of all 5 sensitivity analyses were consistent with the primary analysis, with significant reductions in ARR versus placebo for both peginterferon beta-1a dosing regimens (Q2W 34-38%; Q4W 27-31%). CONCLUSION: Peginterferon beta-1a Q2W and Q4W demonstrated consistent reductions in ARR versus placebo. Multiple sensitivity analyses corroborated the robustness of the primary endpoint in the ADVANCE study. Study Sponsored by: Biogen Idec Inc.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.070 | 0.074 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.028 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".