Pilot/Feasibility Metrics, Real-Time Remote Monitoring, and Inter-Observer Agreement on Veno-Occlusion in a National Multicenter Randomized Controlled Trial of Pediatric Venous Thromboembolism: Findings from the Pilot/Feasibility Phase of the Kids-DOTT Trial
Notice bibliographique
Résumé
Abstract BACKGROUND: Successful completion of investigator-initiated pediatric venous thromboembolism (VTE) trials has been hampered when key assumptions in trial design have often not been met during trial execution. Unfortunately, pilot/feasibility (P/F) studies have rarely been conducted and reported prior to implementation of the definitive trials. METHODS: The Kids-DOTT trial is a multicenter, parallel-cohort randomized controlled trial (RCT) evaluating efficacy and safety of shortened (6 weeks) versus conventional (3 months) duration of anticoagulation in pediatric provoked VTE. The Kids-DOTT design included a pre-specified P/F phase consisting of the first 100 subjects enrolled. Quality assurance methods included real-time remote monitoring of patient eligibility criteria immediately prior to enrollment, as well as measurement of inter-observer agreement of mutually-blinded, central versus local radiologic assessments of complete thrombus veno-occlusion (yes/no) at 6 weeks post-diagnosis (a key randomization criterion in the trial). P/F metrics included: screened:enrolled ratio; radiologic inter-observer agreement (measured by percent agreement and kappa statistic); frequency of protocol violations pertaining to eligibility criteria and randomization procedures; proportion of the enrolled population comprising the non-randomized parallel cohorts; and rates of withdrawal/loss to follow-up. The blind was maintained for all P/F analyses. RESULTS: Screened:enrolled ratio was approximately 6:1, of which 4% was due to declined consent. During the last 6 months of the P/F phase, with an average of 15 open centers, 24 subjects were enrolled. Protocol violations due to missed randomization occurred in 3% of subjects (3/92) who have reached the 6-week (randomization) visit. There were no eligibility violations and no improper randomizations. During the two most recent years of the trial, 14% of subjects were allocated to the observational, parallel cohorts on completely veno-occlusive thrombosis or persistent antiphospholipid antibody positivity; remaining subjects comprised the RCT population. Inter-observer agreement in the determination of complete veno-occlusion at 6-week imaging (n=71 adjudicated to date) was 97% (95% confidence interval, 89-100%) with Κ=0.79 (95% CI, 0.50-1.0), indicating “substantial agreement” (Landis-Koch criteria). Complete veno-occlusion, as defined by absence of flow throughout a venous segment (e.g. femoral vein; subclavian vein), was observed at 6 weeks in 6% of adjudicated patients (4/71). Rate of withdrawal/loss-to-follow-up prior to primary endpoint assessment was 10% (10/97). CONCLUSIONS: The P/F phase of the Kids-DOTT trial has provided novel multicenter feasibility data demonstrating substantial inter-observer agreement in radiologic determination of complete thrombus veno-occlusion, and a rate of completely veno-occlusive thrombosis of 6% at 6 weeks following diagnosis of provoked venous thrombosis. In addition, it has defined recruitment and retention rates on the trial that have facilitated determination of the required number of participating sites (40) to complete timely accrual. Kids-DOTT is now continuing toward completion of the definitive RCT, targeted for 2018. Disclosures Goldenberg: Eisai Inc: Research Funding. Off Label Use: Anticoagulants for pediatric venous thrombosis, all of which are off-label for this (pediatric) indication despite their use in the pediatric standard of care. .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,159 | 0,203 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,003 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,002 |
| Communication savante | 0,002 | 0,002 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».