Tang Albert
Curr Ther Res Clin Exp. 2022 Jul 1;97:100680. doi: 10.1016/j.curtheres.2022.100680. eCollection 2022.
During 2020, the Food and Drug Administration approved 53 novel drugs.
Biomarkers, surrogate endpoints and dosing regimens used in early and pivotal clinical stages are evaluated.
Information on various efficacy end points of 2020 Food and Drug Administration approved novel drugs was gathered from the Drug Approvals and Databases page of the Food and Drug Administration website. Endpoint data from efficacy end points for the 2019 approved novel drugs by Tong and Wang are used as a comparison.
Among the 53 drugs approved during 2020, 49 were for treatment of various diseases and 4 were for diagnostics. Twenty-five drug approvals (51%, relative to 49 drugs for treatment of diseases) were based on surrogate end points, consisting of 12 accelerated approvals and 13 regular approvals. There were 19 drug approvals for cancer treatments (39%, relative to 49 drugs for treatment of diseases). During 2019, there were 48 drugs approved. Forty-four were for treatment of various diseases and 4 were for diagnostics. Fourteen drug approvals (32%, relative to 44 drugs for treatment of diseases) were based on surrogate end points, consisting of 9 accelerated approvals and 5 regular approvals. There were 10 drug approvals for cancer treatments (23%, relative to 44 drugs for treatment of diseases).The approved doses were usually much closer to the highest dose tested in clinical trials (about 2-fold lower) compared with the lower dose tested in clinical trials (about 11-fold higher). Large and variable distances between the starting low dose in humans and the final approved doses indicate that finding the optimal dose in clinical trials is still a time-consuming and costly process. Further dose analysis for cancer drugs approved during 2020 showed that the distances between the starting dose in human beings and the final approved doses of cancer drugs were still large and variable, similar to distances in noncancer drugs. Stratification of drugs approved in 2020 by molecular weights shows that small molecular weights (<1000 Daltons) appeared to be smaller and less variable than those for drugs with large molecules (>1000 Daltons). (. 2022; 83:XXX-XXX).
Surrogate end points with accelerated approval have been widely used for approvals, with an increasing trend from 2019 to 2020 (32% vs. 51%). The approved doses usually were much higher (10-fold) than the lowest tested dose in first-in-human trials, while much closer (2-fold lower) to the highest dose tested in clinical trials.
2020年期间，美国食品药品监督管理局批准了53种新药。
对早期和关键临床阶段使用的生物标志物、替代终点和给药方案进行评估。
从美国食品药品监督管理局网站的药品批准和数据库页面收集了2020年美国食品药品监督管理局批准的新药的各种疗效终点信息。将童和王2019年批准的新药疗效终点的终点数据用作对照。
在2020年批准的53种药物中，49种用于治疗各种疾病，4种用于诊断。25项药物批准（相对于49种治疗疾病的药物，占51%）基于替代终点，包括12项加速批准和13项常规批准。有19项癌症治疗药物批准（相对于49种治疗疾病的药物，占39%）。2019年，有48种药物获批。44种用于治疗各种疾病，4种用于诊断。14项药物批准（相对于44种治疗疾病的药物，占32%）基于替代终点，包括9项加速批准和5项常规批准。有10项癌症治疗药物批准（相对于44种治疗疾病的药物，占23%）。与临床试验中测试的较低剂量相比，获批剂量通常更接近临床试验中测试的最高剂量（约低2倍），而与临床试验中测试的最低剂量相比则高得多（约高11倍）。人体起始低剂量与最终获批剂量之间存在较大且可变的差距，这表明在临床试验中找到最佳剂量仍然是一个耗时且成本高昂的过程。对2020年批准的癌症药物进行的进一步剂量分析表明，人体起始剂量与癌症药物最终获批剂量之间的差距仍然很大且可变，与非癌症药物的差距相似。按分子量对2020年批准的药物进行分层显示，小分子药物（<1000道尔顿）的差距似乎比大分子药物（>1000道尔顿）更小且变化更小。（. 2022；83：XXX - XXX）
加速批准的替代终点已广泛用于批准，从2019年到2020年呈上升趋势（32%对51%）。获批剂量通常比首次人体试验中测试的最低剂量高得多（10倍），而比临床试验中测试的最高剂量更接近（低2倍）。
