116:
discontinuation of the entire trial. Platform designs allow for addition and/or discontinuation of therapy arms. Importantly, the addition or discontinuation of an arm must follow pre-set protocols such as reaching a certain demonstrated efficacy or being recommended by a set panel of experts. There are frequently caps to the number of arms that can be active at once which are pre-determined by the research team. The number of possible arms is influenced by considerations of cost, time available for the trial, operational feasibility, complications with organization large quantities of patient data and the number of total patients available for enrollment. While an arm most frequently represents a single therapy, advanced designs may have multiple therapies in a single arm. When this is the case, one arm may have different therapies in different therapy classes (i.e. one
64:
found use in oncology, alzheimer's disease and pneumonia research. Platform trials can be a superior design compared to simple 2-arm clinical trials when multiple therapies need investigation, because it only requires a single control group. This means that platform trials can be conducted with fewer enrolled patients than a set of potentially redundant control groups in a series of separate 2-arm trials. This in turn allows for results to be published sooner for time-sensitive diseases, and for fewer patients to be exposed to the risks of a clinical trial. Platform trials may be appropriate for phase II-IV trails.
151:
not yet been completed, as shared data in the trial may still need to remain blinded. Additionally, the complexity of platform designs—often involving multiple sponsors and funding sources as well as changing treatment arms—can make them difficult to register in standardized databases. Platform trials require long planning times, making them unsuitable for therapies needing immediate investigation. Funding can be complicated when different pharmaceutical companies are involved, and the ill-defined trial lengths make them less appealing to federal funding agencies.
137:
outcomes compared to other arms after an interim analysis. Allocation ratios can therefor be adjusted to put more patients into more successful arms; however the ratio of patients randomized to the control group does not change. Allocation ratios are determined through a mix of empirical interim evidence and simulation modeling. Care must be taken, especially early in the trial when limited sample sizes are available, to avoid extreme swings in allocation ratios as such swings could cause early biasing of data.
103:, suggests that n√t patients should be allocated to the control group; where "n" is the sample size for each of the arms and "√t" is the number of active arms. As the number of arms increase, the ratio of patients allocated to control also increases. This results in the control group having a higher proportion of allocated patients than any one arm though platform trials still allow for more total patients to be in intervention arms than multiple 2-arm RCTs.
124:). Another advanced strategy is for each arm to utilize the same treatments, but with each arm representing a different sequence of intervention administration. Advance trials may also be designed such that some arms are only activated depending on the results of other arms. For example, a higher-dose arm may only be activated if a lower-dose arm shows few side effects but also low efficacy.
78:
of platform trials described in the master protocol include: qualified trial staff members, trial sites, recruitment criteria, enrollment procedures, pre-set criteria for adding/discontinuing new therapies, adverse event reporting, communication plans, and statistical analysis plans. The master protocol is submitted to the
150:
in the control group, complicating analysis. Further, care must be taken to ensure that the data from arms added later are compared to appropriate sub-sections of the control group, increasing statistical complexity. Publishing results of terminated arms can also be complicated if the whole trial has
136:
Response-adaptive randomization is not a necessary component of platform trials but unique aspects of platforms allow for this feature to be incorporated. Response-adaptive randomization refers to the capability of redistributing the patient allocation ratio when one arm is showing superior/inferior
77:
Platform trials, like any clinical trial, have many elements that must be established before starting enrollment. While platform trials have the ability to alter their therapies of interest there are still many elements of these trials that remain constant and regulated. Such common, stable elements
63:
began, researchers predicted that there would eventually be multiple different therapies that could be investigated, but that these therapies would be discovered at different times in the pandemic timeline, therefore making a platform trial a useful design. Similar to COVID-19, platform trials have
89:
Platform trials are often large, multi-site investigations and as a result, master protocols frequently try to identify common human and physical infrastructure to maximize resource availability and efficiency. Examples of this include identifying/creating a single IRB to review the trial for all
145:
While platform trials offer many advantages for investigating a single disease, their adaptive nature and potential for numerous and complicated arms may limit their applicability and feasibility. Platforms require a large number of experts for trial design, Data
Monitoring and Safety Boards and
127:
Unlike conventional RCTs, intervention arms do not necessarily need to start at the same time chronologically. This feature is particularly useful when investigating diseases that have new therapies being discovered regularly since these new therapies can be added to the trial without needing to
115:
The second defining aspect of a platform is that the therapies under investigation can change during the active enrollment phase of a trial. By comparison, conventional RCTs must specify the therapies under investigation before active enrollment and then discontinuation of a therapy results in
106:
While the control group is not necessarily designed to change in the way that the treatment arms are, because platform trials can run for long periods of time, control groups may have to evolve to stay current with standard of care. When this is the case, or if there is a change to patient
98:
One of the defining aspects of a platform trial is the shared control group that all interventional arms are compared to. Whereas a conventional RCT would generally have half of all enrolled patients in the control group; platform trials have a higher total number of patients in various
35:. As a disease-focused trial design (compared to an intervention-focused), platform trials attempt to answer the question "which therapy will best treat this disease". Platform trials are unique in their utilization of both: a common
319:
Angus, Derek C.; Alexander, Brian M.; Berry, Scott; Buxton, Meredith; Lewis, Roger; Paoloni, Melissa; Webb, Steven A. R.; Arnold, Steven; Barker, Anna; Berry, Donald A.; Bonten, Marc J. M. (October 2019).
59:
Platform trials can be a particularly useful design when researchers predict that multiple therapies that would become available at different times require investigation. For example, when the
99:
interventional groups. This allows for fewer patients to be enrolled which saves money and accelerates completion time. A common statistical tool for determining allocation ratios,
86:(IRB) approval in the event of changes to the trial arms. Establishing a stable master protocol with adaptive therapy arms allows for faster, more efficient trial execution.
107:
demographics with time, later analysis of the trial must be careful to consider comparing investigational patients to only the appropriate subset of control patients.
382:
Park JJ, Detry MA, Murthy S, Guyatt G, Mills EJ (January 2022). "How to Use and
Interpret the Results of a Platform Trial: Users' Guide to the Medical Literature".
482:
39:
and their opportunity to alter the therapies it investigates during its active enrollment phase. Platform trials commonly take advantage of
774:
770:
263:"The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design"
146:
operations leading to high cost and communication complexity. The long duration of platform trials may necessitate updates to the
820:
778:
766:
90:
sites, creating a single database for collecting data, and creating a single randomization mechanism for all enrolled patients.
475:
941:
857:
722:
692:
468:
979:
31:(RCT) that compares multiple, simultaneous and possibly differently-timed interventions against a single, constant
786:
824:
546:
972:
657:
951:
175:
36:
32:
915:
887:
816:
570:
965:
641:
83:
79:
760:
426:
1001:
698:
646:
526:
744:
614:
592:
561:
536:
519:
165:
24:
895:
732:
653:
261:
Angus DC, Berry S, Lewis RJ, Al-Beidh F, Arabi Y, van Bentum-Puijk W, et al. (July 2020).
736:
623:
531:
495:
170:
44:
460:
702:
8:
609:
541:
862:
812:
627:
556:
514:
407:
357:
287:
262:
238:
40:
936:
900:
867:
792:
714:
491:
446:
411:
399:
361:
349:
341:
292:
242:
230:
100:
60:
322:"Adaptive platform trials: definition, design, conduct and reporting considerations"
321:
710:
631:
585:
580:
442:
438:
391:
333:
282:
278:
274:
225:
220:
208:
147:
48:
905:
728:
683:
427:"A Multiple Comparison Procedure for Comparing Several Treatments with a Control"
931:
852:
804:
509:
160:
28:
337:
995:
910:
877:
872:
450:
345:
207:
Park JJ, Harari O, Dron L, Lester RT, Thorlund K, Mills EJ (September 2020).
121:
395:
752:
636:
403:
353:
296:
234:
946:
800:
673:
663:
82:
and once approved, only arm-specific appendices need to be submitted for
748:
740:
706:
668:
575:
117:
209:"An overview of platform trials with a checklist for clinical readers"
808:
796:
842:
847:
490:
180:
318:
260:
381:
128:
start a new trial each time a therapy is discovered.
206:
131:
993:
431:Journal of the American Statistical Association
110:
476:
256:
254:
252:
377:
375:
373:
371:
202:
200:
198:
196:
23:is a type of prospective, disease-focused,
483:
469:
286:
249:
224:
775:Preventable fraction among the unexposed
771:Attributable fraction for the population
368:
193:
779:Preventable fraction for the population
767:Attributable fraction among the exposed
424:
267:Annals of the American Thoracic Society
93:
994:
464:
425:Dunnett, Charles W. (December 1955).
942:Correlation does not imply causation
858:Animal testing on non-human primates
314:
312:
310:
308:
306:
13:
72:
67:
43:, but may incorporate elements of
14:
1013:
303:
213:Journal of Clinical Epidemiology
132:Response-adaptive randomization
825:Pre- and post-test probability
547:Patient and public involvement
443:10.1080/01621459.1955.10501294
418:
279:10.1513/AnnalsATS.202003-192SD
226:10.1016/j.jclinepi.2020.04.025
140:
1:
326:Nature Reviews Drug Discovery
186:
952:Sex as a biological variable
176:Bayesian Experimental Design
111:Adaptive intervention groups
7:
916:Intention-to-treat analysis
888:Analysis of clinical trials
817:Specificity and sensitivity
571:Randomized controlled trial
154:
10:
1018:
84:Institutional Review Board
54:
960:
925:Interpretation of results
924:
886:
835:
785:
759:
721:
691:
682:
658:Nested case–control study
608:
555:
502:
338:10.1038/s41573-019-0034-3
29:randomized clinical trial
527:Academic clinical trials
745:Relative risk reduction
593:Adaptive clinical trial
537:Evidence-based medicine
520:Adaptive clinical trial
396:10.1001/jama.2021.22507
166:Adaptive Clinical Trial
733:Number needed to treat
45:frequentist statistics
16:Type of clinical trial
737:Number needed to harm
624:Cross-sectional study
576:Scientific experiment
532:Clinical study design
171:Clinical Study Design
703:Cumulative incidence
94:Common control group
610:Observational study
542:Real world evidence
496:experimental design
41:Bayesian statistics
896:Risk–benefit ratio
863:First-in-man study
813:Case fatality rate
654:Case–control study
628:Longitudinal study
437:(272): 1096–1121.
989:
988:
937:Survivorship bias
901:Systematic review
868:Multicenter trial
831:
830:
821:Likelihood-ratios
793:Clinical endpoint
761:Population impact
715:Period prevalence
492:Clinical research
61:COVID-19 pandemic
1009:
836:Trial/test types
711:Point prevalence
689:
688:
632:Ecological study
615:EBM II-2 to II-3
586:Open-label trial
581:Blind experiment
557:Controlled study
485:
478:
471:
462:
461:
455:
454:
422:
416:
415:
379:
366:
365:
316:
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258:
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228:
204:
148:standard of care
49:machine learning
1017:
1016:
1012:
1011:
1010:
1008:
1007:
1006:
1002:Clinical trials
992:
991:
990:
985:
956:
920:
882:
827:
781:
755:
729:Risk difference
717:
678:
612:
604:
559:
551:
515:Trial protocols
498:
489:
459:
458:
423:
419:
380:
369:
332:(10): 797–807.
317:
304:
259:
250:
205:
194:
189:
157:
143:
134:
122:immunomodulator
113:
96:
75:
73:Master protocol
70:
68:Design elements
57:
17:
12:
11:
5:
1015:
1005:
1004:
987:
986:
984:
983:
980:List of topics
976:
969:
961:
958:
957:
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954:
949:
944:
939:
934:
932:Selection bias
928:
926:
922:
921:
919:
918:
913:
908:
903:
898:
892:
890:
884:
883:
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880:
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870:
865:
860:
855:
853:Animal testing
850:
845:
839:
837:
833:
832:
829:
828:
805:Mortality rate
791:
789:
783:
782:
765:
763:
757:
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727:
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719:
718:
697:
695:
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661:
651:
650:
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634:
620:
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602:
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598:Platform trial
590:
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583:
578:
567:
565:
553:
552:
550:
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544:
539:
534:
529:
524:
523:
522:
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510:Clinical trial
506:
504:
500:
499:
488:
487:
480:
473:
465:
457:
456:
417:
367:
302:
273:(7): 879–891.
248:
191:
190:
188:
185:
184:
183:
178:
173:
168:
163:
161:Clinical Trial
156:
153:
142:
139:
133:
130:
112:
109:
101:Dunnett's test
95:
92:
74:
71:
69:
66:
56:
53:
21:platform trial
15:
9:
6:
4:
3:
2:
1014:
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982:
981:
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948:
945:
943:
940:
938:
935:
933:
930:
929:
927:
923:
917:
914:
912:
911:Meta-analysis
909:
907:
904:
902:
899:
897:
894:
893:
891:
889:
885:
879:
878:Vaccine trial
876:
874:
873:Seeding trial
871:
869:
866:
864:
861:
859:
856:
854:
851:
849:
846:
844:
841:
840:
838:
834:
826:
822:
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790:
788:
784:
780:
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772:
768:
764:
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750:
746:
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738:
734:
730:
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690:
687:
685:
681:
675:
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659:
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648:
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642:Retrospective
640:
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638:
635:
633:
629:
625:
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621:
619:
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611:
607:
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591:
587:
584:
582:
579:
577:
574:
573:
572:
569:
568:
566:
563:
562:EBM I to II-1
558:
554:
548:
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543:
540:
538:
535:
533:
530:
528:
525:
521:
518:
516:
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52:
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46:
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37:control group
34:
33:control group
30:
26:
22:
978:
971:
964:
753:Hazard ratio
637:Cohort study
597:
434:
430:
420:
390:(1): 67–74.
387:
383:
329:
325:
270:
266:
216:
212:
144:
135:
126:
114:
105:
97:
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20:
18:
947:Null result
906:Replication
801:Infectivity
723:Association
674:Case report
664:Case series
647:Prospective
141:Limitations
749:Odds ratio
741:Risk ratio
707:Prevalence
693:Occurrence
669:Case study
187:References
118:antibiotic
809:Morbidity
797:Virulence
699:Incidence
451:0162-1459
412:245670604
362:201652338
346:1474-1784
243:218670123
996:Category
973:Glossary
966:Category
843:In vitro
684:Measures
503:Overview
404:34982138
354:31462747
297:32267771
235:32416336
155:See also
120:and one
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848:In vivo
288:7328186
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408:S2CID
358:S2CID
239:S2CID
181:AGILE
626:vs.
494:and
447:ISSN
400:PMID
384:JAMA
350:PMID
342:ISSN
293:PMID
231:PMID
439:doi
392:doi
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283:PMC
275:doi
221:doi
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