Adverse Events During Dosing of Delayed-release/Extended-release Methylphenidate: Learnings From the Open-label Phase of a Registration Trial and a Real-world Postmarketing Surveillance Program
Bibliographic record
Abstract
PURPOSE: Delayed-release/extended-release methylphenidate (DR/ER-MPH) (formerly HLD200) is an evening-dosed agent used for the treatment of attention-deficit/hyperactivity disorder. Postmarketing surveillance data from approximately 74,000 patients exposed to DR/ER-MPH (up to June 17, 2022) were reported and compared with the open-label, treatment-optimization phase of a Phase III clinical trial to derive possible learnings on how to approach adverse events (AEs) that emerge during dose titration. METHODS: An analysis of AEs spontaneously reported to Ironshore in postmarketing surveillance included, where available, age, dose, timing, and discontinuations. Data were summarized using descriptive statistics. FINDINGS: A total of 395 children, adolescents, and adults reported 601 AEs in postmarketing surveillance. Five AEs were classified as serious. AEs preceded drug use discontinuation in 172 patients. Many AEs occurred early (52% were reported within 30 days) and at lower doses (54% were reported at 20 to 40 mg), similar to the trial data. Reported AEs included those similar in type but orders of magnitude lower in number than those from the clinical trial. IMPLICATIONS: No new safety concerns were revealed in this real-world setting compared with the safety profile identified in DR/ER-MPH trial data. In real-world practices, clinicians tended to discontinue DR/ER-MPH treatment after AE onset, whereas trial investigators continued to optimize treatment and found that AEs were generally tolerable, suggesting that health care practitioners may consider developing strategies to manage tolerability issues with DR/ER-MPH treatment on AE emergence rather than immediately discontinuing use of the drug to provide optimal therapeutic benefit. CLINICALTRIALS: gov identifier: NCT02493777.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".