Should the two-trial paradigm still be the gold standard in drug assessment?
Should the two-trial paradigm still be the gold standard in drug assessment?
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DOI：
10.1002/pst.2262
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发表时间：
2023-01
影响因子：
1.5
通讯作者：
Stallard, Nigel
中科院分区：
文献类型：
--
作者：
Zhan, Stella Jinran;Kunz, Cornelia Ursula;Stallard, Nigel
新药通常需要两个重要的关键试验才能获得监管机构的批准。这一标准要求被称为两次试验范例。然而，几位作者质疑，我们为什么需要恰好两个关键试验，监管机构试图防止什么统计错误，以及潜在的替代方法。因此，研究这些问题对于更好地理解药物有效性评价中的监管决策具有重要意义。两个设计相同的试验仅仅为了遵守两次试验的规则而进行，这是很常见的。以前的工作表明，将来自两个试验的数据合并到一个单一试验(一个试验范例)中将增加功率，同时确保与两个试验范例相同的I型错误保护水平。然而，只有在特定的场景下才是这样的，并且几乎没有关于整个零区上的类型I错误保护的研究。在本文中，我们通过考虑两个试验在相同或不同的总体以及相同或不同大小的人群中进行的情景来比较这两种范式。在具有相同总体的情况下，结果表明，单次试验提供了更好的I类错误保护和更高的功率。相反，对于不同的人群，尽管一次试验规则在某些情况下更强大，但它并不总是防止I类错误。因此，需要围绕两审模式保持适当的灵活性，并应根据我们感兴趣的问题选择适当的办法。
Two significant pivotal trials are usually required for a new drug approval by a regulatory agency. This standard requirement is known as the two‐trial paradigm. However, several authors have questioned why we need exactly two pivotal trials, what statistical error the regulators are trying to protect against, and potential alternative approaches. Therefore, it is important to investigate these questions to better understand the regulatory decision‐making in the assessment of drugs' effectiveness. It is common that two identically designed trials are run solely to adhere to the two‐trial rule. Previous work showed that combining the data from the two trials into a single trial (one‐trial paradigm) would increase the power while ensuring the same level of type I error protection as the two‐trial paradigm. However, this is true only under a specific scenario and there is little investigation on the type I error protection over the whole null region. In this article, we compare the two paradigms by considering scenarios in which the two trials are conducted in identical or different populations as well as with equal or unequal size. With identical populations, the results show that a single trial provides better type I error protection and higher power. Conversely, with different populations, although the one‐trial rule is more powerful in some cases, it does not always protect against the type I error. Hence, there is the need for appropriate flexibility around the two‐trial paradigm and the appropriate approach should be chosen based on the questions we are interested in.
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DOI：
10.1016/s0140-6736(20)32661-1
发表时间：
2021-01-09
期刊：
Lancet (London, England)
影响因子：
--
作者：
Voysey M;Clemens SAC;Madhi SA;Weckx LY;Folegatti PM;Aley PK;Angus B;Baillie VL;Barnabas SL;Bhorat QE;Bibi S;Briner C;Cicconi P;Collins AM;Colin-Jones R;Cutland CL;Darton TC;Dheda K;Duncan CJA;Emary KRW;Ewer KJ;Fairlie L;Faust SN;Feng S;Ferreira DM;Finn A;Goodman AL;Green CM;Green CA;Heath PT;Hill C;Hill H;Hirsch I;Hodgson SHC;Izu A;Jackson S;Jenkin D;Joe CCD;Kerridge S;Koen A;Kwatra G;Lazarus R;Lawrie AM;Lelliott A;Libri V;Lillie PJ;Mallory R;Mendes AVA;Milan EP;Minassian AM;McGregor A;Morrison H;Mujadidi YF;Nana A;O'Reilly PJ;Padayachee SD;Pittella A;Plested E;Pollock KM;Ramasamy MN;Rhead S;Schwarzbold AV;Singh N;Smith A;Song R;Snape MD;Sprinz E;Sutherland RK;Tarrant R;Thomson EC;Török ME;Toshner M;Turner DPJ;Vekemans J;Villafana TL;Watson MEE;Williams CJ;Douglas AD;Hill AVS;Lambe T;Gilbert SC;Pollard AJ;Oxford COVID Vaccine Trial Group
通讯作者：
Oxford COVID Vaccine Trial Group
BNT162B2 mRNA COVID-19疫苗的安全性和功效。
DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
通讯作者：
C4591001 Clinical Trial Group
影响因子：
2
作者：
Shao, J;Chow, SC
通讯作者：
Chow, SC
影响因子：
--
作者：
Rosenkranz, G
通讯作者：
Rosenkranz, G
DOI：
10.1111/rssa.12493
发表时间：
2019-12-26
影响因子：
2
作者：
Held, Leonhard
通讯作者：
Held, Leonhard