Interpretation of active-control randomised trials: the case for a new analytical perspective involving averted events.
Interpretation of active-control randomised trials: the case for a new analytical perspective involving averted events.
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DOI：
10.1186/s12874-023-01970-0
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发表时间：
2023-06-26
影响因子：
4
通讯作者：
Glidden, David V.
中科院分区：
文献类型：
--
作者：
Dunn, David T.;Stirrup, Oliver T.;McCormack, Sheena;Glidden, David V.
当纳入安慰剂对照组被认为是不道德的时，就会进行主动对照试验，即试验性治疗与已建立的治疗进行比较。对于时间到事件的结果，主要估计通常是比率比率，或密切相关的风险比率，比较实验组和对照组。在这篇文章中，我们使用新冠肺炎疫苗和艾滋病毒暴露前预防试验的例子，描述了解释这一估计的主要问题。特别是，当对照治疗非常有效时，比率可能表明，即使从公共卫生的角度来看，实验治疗在统计上显然是次要的。我们认为，在解释主动对照试验时，考虑避免事件和观察到的事件是至关重要的。提出了一个包含这一信息的替代度量--避免事件比率，并举例说明。它的解释很简单，在概念上很吸引人，即通过使用实验治疗而不是对照治疗可以避免的事件的比例。避免事件比率不能从主动对照试验中直接估计，并且需要关于以下两个方面的附加假设：(A)在假想的安慰剂组中观察到的发生率(反事实发生率)或(B)与主动对照试验有关的对照治疗(相对于不治疗)的疗效。尽管对这些参数的估计并不直接，但必须尝试这样做才能得出合理的推论。到目前为止，这种方法只应用于艾滋病毒预防研究，但在治疗试验和其他疾病领域具有更广泛的适用性。
Active-control trials, where an experimental treatment is compared with an established treatment, are performed when the inclusion of a placebo control group is deemed to be unethical. For time-to-event outcomes, the primary estimand is usually the rate ratio, or the closely-related hazard ratio, comparing the experimental group with the control group. In this article we describe major problems in the interpretation of this estimand, using examples from COVID-19 vaccine and HIV pre-exposure prophylaxis trials. In particular, when the control treatment is highly effective, the rate ratio may indicate that the experimental treatment is clearly statistically inferior even when it is worthwhile from a public health perspective. We argue that it is crucially important to consider averted events as well as observed events in the interpretation of active-control trials. An alternative metric that incorporates this information, the averted events ratio, is proposed and exemplified. Its interpretation is simple and conceptually appealing, namely the proportion of events that would be averted by using the experimental treatment rather than the control treatment. The averted events ratio cannot be directly estimated from the active-control trial, and requires an additional assumption about either: (a) the incidence that would have been observed in a hypothetical placebo arm (the counterfactual incidence) or (b) the efficacy of the control treatment (relative to no treatment) that pertained in the active-control trial. Although estimation of these parameters is not straightforward, this must be attempted in order to draw rational inferences. To date, this method has been applied only within HIV prevention research, but has wider applicability to treatment trials and other disease areas.
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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
DOI：
10.1016/s0140-6736(21)00432-3
发表时间：
2021-03-06
期刊：
Lancet (London, England)
影响因子：
--
作者：
Voysey M;Costa Clemens SA;Madhi SA;Weckx LY;Folegatti PM;Aley PK;Angus B;Baillie VL;Barnabas SL;Bhorat QE;Bibi S;Briner C;Cicconi P;Clutterbuck EA;Collins AM;Cutland CL;Darton TC;Dheda K;Dold C;Duncan CJA;Emary KRW;Ewer KJ;Flaxman A;Fairlie L;Faust SN;Feng S;Ferreira DM;Finn A;Galiza E;Goodman AL;Green CM;Green CA;Greenland M;Hill C;Hill HC;Hirsch I;Izu A;Jenkin D;Joe CCD;Kerridge S;Koen A;Kwatra G;Lazarus R;Libri V;Lillie PJ;Marchevsky NG;Marshall RP;Mendes AVA;Milan EP;Minassian AM;McGregor A;Mujadidi YF;Nana A;Padayachee SD;Phillips DJ;Pittella A;Plested E;Pollock KM;Ramasamy MN;Ritchie AJ;Robinson H;Schwarzbold AV;Smith A;Song R;Snape MD;Sprinz E;Sutherland RK;Thomson EC;Török ME;Toshner M;Turner DPJ;Vekemans J;Villafana TL;White T;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
影响因子：
6
作者：
Glidden DV;Das M;Dunn DT;Ebrahimi R;Zhao Y;Stirrup OT;Baeten JM;Anderson PL
通讯作者：
Anderson PL
影响因子：
2
作者：
Potter, Gail E.
通讯作者：
Potter, Gail E.
影响因子：
2
作者：
Snapinn, Steven;Jiang, Qi
通讯作者：
Jiang, Qi