Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols

被引:242
作者
Park, Jay J. H. [1 ,2 ]
Siden, Ellie [2 ]
Zoratti, Michael J. [3 ]
Dron, Louis [2 ]
Harari, Ofir [2 ]
Singer, Joel [4 ,5 ]
Lester, Richard T. [1 ]
Thorlund, Kristian [2 ,3 ,6 ]
Mills, Edward J. [2 ,3 ,6 ]
机构
[1] Dept Med, Expt Med, 10th Floor,2775 Laurel St, Vancouver, BC V5Z 1M9, Canada
[2] MTEK Sci, 802-777 West Broadway, Vancouver, BC V5Z 1J5, Canada
[3] McMaster Univ, Med Ctr, Dept Hlth Res Methods Evidence & Impact, 1280 Main St West,2C Area, Hamilton, ON L8S 4K1, Canada
[4] Univ British Columbia, Sch Populat & Publ Hlth, 2206 E Mall, Vancouver, BC V6T 1Z3, Canada
[5] CIHR Canadian HIV Trials Network, Data & Methodol Program, 588-1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada
[6] Bill & Melinda Gates Fdn, Knowledge Integrat, 500 5th Ave N, Seattle, WA 98109 USA
关键词
Master protocols; Basket trials; Umbrella trials; Platform trials; Multi-arm; multi-stage design; PLUS HORMONE-THERAPY; OPEN-LABEL; PHASE-II; ADAPTIVE RANDOMIZATION; TARGETED THERAPY; MULTIARM; MULTISTAGE; STAMPEDE; CELECOXIB; DISEASE;
D O I
10.1186/s13063-019-3664-1
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background Master protocols, classified as basket trials, umbrella trials, and platform trials, are novel designs that investigate multiple hypotheses through concurrent sub-studies (e.g., multiple treatments or populations or that allow adding/removing arms during the trial), offering enhanced efficiency and a more ethical approach to trial evaluation. Despite the many advantages of these designs, they are infrequently used. Methods We conducted a landscape analysis of master protocols using a systematic literature search to determine what trials have been conducted and proposed for an overall goal of improving the literacy in this emerging concept. On July 8, 2019, English-language studies were identified from MEDLINE, EMBASE, and CENTRAL databases and hand searches of published reviews and registries. Results We identified 83 master protocols (49 basket, 18 umbrella, and 16 platform trials). The number of master protocols has increased rapidly over the last five years. Most have been conducted in the US (n = 44/83) and investigated experimental drugs (n = 82/83) in the field of oncology (n = 76/83). The majority of basket trials were exploratory (i.e., phase I/II; n = 47/49) and not randomized (n = 44/49), and more than half (n = 28/48) investigated only a single intervention. The median sample size of basket trials was 205 participants (interquartile range, Q3-Q1 [IQR]: 500-90 = 410), and the median study duration was 22.3 (IQR: 74.1-42.9 = 31.1) months. Similar to basket trials, most umbrella trials were exploratory (n = 16/18), but the use of randomization was more common (n = 8/18). The median sample size of umbrella trials was 346 participants (IQR: 565-252 = 313), and the median study duration was 60.9 (IQR: 81.3-46.9 = 34.4) months. The median number of interventions investigated in umbrella trials was 5 (IQR: 6-4 = 2). The majority of platform trials were randomized (n = 15/16), and phase III investigation (n = 7/15; one did not report information on phase) was more common in platform trials with four of them using seamless II/III design. The median sample size was 892 (IQR: 1835-255 = 1580), and the median study duration was 58.9 (IQR: 101.3-36.9 = 64.4) months. Conclusions We anticipate that the number of master protocols will continue to increase at a rapid pace over the upcoming decades. More efforts to improve awareness and training are needed to apply these innovative trial design methods to fields outside of oncology.
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