A matching-adjusted indirect comparison of centanafadine versus lisdexamfetamine, methylphenidate and atomoxetine in adults with attention-deficit/hyperactivity disorder: long-term safety and efficacy
Bibliographic record
Abstract
Aim: To compare long-term safety and efficacy outcomes of centanafadine versus lisdexamfetamine dimesylate (lisdexamfetamine), methylphenidate hydrochloride (methylphenidate) and atomoxetine hydrochloride (atomoxetine), respectively, in adults with attention-deficit/hyperactivity disorder (ADHD) using matching-adjusted indirect comparisons (MAICs). Patients & methods: Patient-level data from a centanafadine trial (NCT03605849) and published aggregate data from a lisdexamfetamine trial (NCT00337285), a methylphenidate trial (NCT00326300) and an atomoxetine trial (NCT00190736) were used. Patient characteristics were matched in each comparison using propensity score weighting. Study outcomes were assessed up to 52 weeks and included safety (rates of adverse events [AEs]) and efficacy (mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale [AISRS] or ADHD Rating Scale [ADHD-RS] score). Results: In all comparisons of matched populations, risks of AEs were statistically significantly lower with centanafadine or non-different between centanafadine and comparator; the largest differences in AE rates included upper respiratory tract infection (risk difference in percentage points: 18.75), insomnia (12.47) and dry mouth (12.33) versus lisdexamfetamine; decreased appetite (20.25), headache (18.53) and insomnia (12.65) versus methylphenidate; and nausea (26.18), dry mouth (25.07) and fatigue (13.95) versus atomoxetine (all p < 0.05). Centanafadine had a smaller reduction in the AISRS/ADHD-RS score versus lisdexamfetamine (6.15-point difference; p < 0.05) and no statistically significant difference in the change in AISRS score versus methylphenidate (1.75-point difference; p = 0.13) and versus atomoxetine (1.60-point difference; p = 0.21). Conclusion: At up to 52 weeks, centanafadine showed significantly lower incidence of several AEs than lisdexamfetamine, methylphenidate and atomoxetine; efficacy was lower than lisdexamfetamine and non-different from methylphenidate and atomoxetine.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".