Pivotal studies of pharmacotherapies approved by the United States Food and Drug Administration for the treatment of cancer: A systematic review.
Notice bibliographique
Résumé
e23125 Background: The development of pharmacotherapies for cancer treatment has increased significantly. However, an assessment of approvals by the US Food and Drug Administration (FDA) and sample sizes for pivotal studies leading to approval has not yet been conducted. Our aim was to determine the number of pharmacotherapies approved by the FDA for people with cancer and assess the characteristics of studies, including sample size. Methods: We developed a web scraper to collect approved pharmacotherapies for cancer treatments from the FDA website until December 31, 2024. Pharmacotherapies with different routes of administration (i.e., intravenous or a previously approved oral formulation of the same pharmacotherapy) and combinations of previously approved pharmacotherapies were excluded. For each pharmacotherapy, we noted: the pivotal study as per the product monograph; the proposed sample size from the study protocol; and the final sample size of the completed study. We recorded the type of pharmacotherapy (chemotherapy, hormonal therapy, immunotherapy, or targeted therapy) and study design (phase 1, 2, or 3). Regression analyses and data discretisation were conducted to identify trends in sample size. Type I error was set at 0.05. Quality assessment was conducted. OSF Registration DOI: 10.17605/OSF.IO/KVA23. Results: We identified 255 pharmacotherapies: 49.0% were targeted therapies, 23.9% chemotherapies, and 18.4% immunotherapies. A larger proportion of recent novel pharmacotherapies were targeted therapies, compared to previous decades (59.7% in 2020 to 2024 vs 12.0% in 1990 to 1999). The mean and median sample size were 386 (SD 361) and 290 (IQR 427). Three-quarters (75.3%) of studies were at low risk of bias. Table 1 shows that sample sizes were larger in studies since 1990, but no difference from 1990 onwards. Stratified analysis by study design reports phase 2 studies between 1970 and 1979 had smaller median sample sizes than those since 1990; there was no difference among phase 3 studies. For 165 studies reporting proposed sample sizes, these were lower from 2020 to 2024 than from 2010 to 2019. Conclusions: There was a substantial increase in sample size in the 1990s, likely driven by new policies and legislation. There has since been no significant increase, likely due to increasing proportion of novel pharmacotherapies being targeted therapies, employing biomarker-defined subpopulations and modern trial designs such as basket and umbrella studies that require smaller proposed samples. Year Median IQR Q1, Q3 Mean SD 1950-1959 (n = 6) 61 86 21, 107 66.3 52.6 1960-1969 (n = 9) 40 37 33, 70 54.4 36.8 1970-1979 (n = 9) 48 29 46, 75 104.9 157.6 1980-1989 (n = 8) 169 421 74, 495 290.6 318.2 1990-1999 (n = 25) 407 561 222, 764 510.5 398.9 2000-2009 (n = 39) 329 344 153, 497 398.4 343.3 2010-2019 (n = 92) 350 460 190, 650 461.5 403.1 2020-2024 (n = 67) 290 386 126, 512 350.9 292.6
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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 | 0,029 | 0,092 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,008 | 0,009 |
| Bibliométrie | 0,009 | 0,011 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,002 | 0,003 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,009 | 0,001 |
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 ».