This paper proposes randomized controlled clinical trial design to evaluate external cooling as a means to control fever and thereby reduce mortality in patients with septic shock. The trial will include concurrent external cooling and control arms while adaptively incorporating historical control arm data. Bayesian group sequential monitoring will be done using a posterior comparative test based on the 60-day survival distribution in each concurrent arm. Posterior inference will follow from a Bayesian discrete time survival model that facilitates adaptive incorporation of the historical control data through an innovative regression framework with a multivariate spike-and-slab prior distribution on the historical bias parameters. For each interim test, the amount of information borrowed from the historical control data will be determined adaptively in a manner that reflects the degree of agreement between historical and concurrent control arm data. Guidance is provided for selecting Bayesian posterior probability group-sequential monitoring boundaries. Simulation results elucidating how the proposed method borrows strength from the historical control data are reported. In the absence of historical control arm bias, the proposed design controls the type I error rate and provides substantially larger power than reasonable comparators, whereas in the presence bias of varying magnitude, type I error rate inflation is curbed.
Bibliographical noteFunding Information:
∗Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA, firstname.lastname@example.org †Department of Biostatistics, M. D. Anderson Cancer Center, Houston, TX, USA ‡Service of Intensive Care Unit, Hôspital Intercommunal de Créteil, Créteil, France §Service of medical Intensive care and hyperbaric oxygen therapy unit, Centre Hospitalier Univer-sitaire Angers, Angers, France ¶Laboratoire de Biologie Neurovasculaire et Mitochondriale Intégrée, CNRS UMR 6214 - Inserm U1083, UniversitéAngers, UBL, Angers, France ‖Inserm, Centre de Recherche des Cordeliers, Sorbonne Université, Universitéde Paris, Paris, France ∗∗CIC-EC 1418 Inserm, Hôpital Européen Georges-Pompidou, Paris, France ††Funded in part by NIH/NCI Grant P30-CA077598. Thanks to Medtronic Inc. for their support in the form of a Faculty Fellowship. ‡‡Funded in part by NIH/NCI Grant 5-R01-CA083932. §§Katsahian S. and Zohar S. have equally contributed to this paper.
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- commensurate prior
- conditional autoregressive model
- evidence synthesis
- intensive care unit
- non-proportional hazards
- restricted mean survival