TY - JOUR

T1 - Interactions in the 2x2x2 factorial randomised clinical STEPCARE trial and the potential effects on conclusions

T2 - a protocol for a simulation study

AU - Olsen, Markus Harboe

AU - Jensen, Aksel Karl Georg

AU - Dankiewicz, Josef

AU - Skrifvars, Markus B.

AU - Reinikainen, Matti

AU - Tiainen, Marjaana

AU - Saxena, Manoj

AU - Aneman, Anders

AU - Gluud, Christian

AU - Ullen, Susann

AU - Nielsen, Niklas

AU - Jakobsen, Janus Christian

PY - 2022

Y1 - 2022

N2 - Background: Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2x2x2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest.Methods: By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all- cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errorsDiscussion: This protocol for a simulation study will inform the design of a 2x2x2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results.

AB - Background: Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2x2x2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest.Methods: By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all- cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errorsDiscussion: This protocol for a simulation study will inform the design of a 2x2x2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results.

KW - Simulation study

KW - Protocol

KW - Interactions

KW - Factorial design

KW - Randomised clinical trial

KW - Statistical analysis plan

U2 - 10.1186/s13063-022-06796-7

DO - 10.1186/s13063-022-06796-7

M3 - Journal article

C2 - 36273179

VL - 23

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 889

ER -