Overall Survival and Quality-of-Life Superiority in Modern Phase 3 Oncology Trials
Notice bibliographique
Résumé
Importance: Alternative end points, such as progression-free survival, are increasingly used in phase 3 randomized clinical trials (RCTs). However, alternative end points are often not valid surrogates for overall survival and quality of life (QOL) and may be less relevant to patients. Objective: To determine the proportion of phase 3 RCTs with overall survival or QOL superiority. Design and Setting: Meta-epidemiological study of 2-group, superiority-design, interventional phase 3 oncology RCTs screened from ClinicalTrials.gov and published between 2002 and 2024. Main Outcomes and Measures: Alternative end-point, overall survival, and QOL superiority in the experimental group vs the reference/control group according to prespecified statistical criteria for each RCT. A secondary goal was to evaluate the quality of QOL analyses, since approaches unadjusted for baseline scores may bias results. Results: A total of 791 RCTs representing 555 580 enrolled patients were included. Alternative primary end points were most common (n = 495 [63%]). The primary end point was met in 53% of the RCTs (n = 420); alternative end-point superiority was shown in 55% (n = 434). Overall survival superiority was shown in 28% (n = 221). Patient-reported outcomes were collected in 61% of the RCTs (n = 482), but global QOL results were published in only 34% (n = 271). Most between-group global QOL analyses did not adjust for baseline scores (223 [82%]). Global QOL superiority was shown in 11% (n = 84). Among all RCTs, 32% (n = 257) demonstrated either overall survival or global QOL superiority. Superiority of both overall survival and global QOL was shown in 6% (n = 48). Among 434 RCTs with a positive alternative end point, only a minority showed superiority of either overall survival (185 [43%]) or global QOL (67 [15%]). Conclusions and Relevance: Findings of superiority-design phase 3 oncology RCTs are commonly interpreted as positive. However, this is mostly based on improvements in alternative end points. Gains in either overall survival or QOL are uncommon, even when alternative end-point findings are positive. QOL appears both underevaluated and underreported; furthermore, the majority of phase 3 QOL analyses are unadjusted for baseline scores, which lose efficiency and add bias compared with adjusted analyses. To increase the meaningfulness of late-phase research, future trial designs and regulatory processes should be refocused toward overall survival and QOL improvements.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,006 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,011 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».