Statistical analysis plan for the Stepped-wedge Cluster Randomized trial of Electronic Early Notification of sepsis in hospitalized ward patients (SCREEN)
Authors: Arabi Yaseen M. , Vishwakarma Ramesh Kumar , Al-Dorzi Hasan M. , Al Qasim Eman , Abdukahil Sheryl Ann , Al-Rabeah Fawaz K. , Al Ghamdi Huda , Al Ghamdi Ebtisam ,   the SCREEN Trial Group, Arabi Yaseen M. , Alsaawi Abdulmohsen , Al Khathaami Ali M. , AlHazme Raed H. , Al Mutrafy Abdullah , Al Qasim Eman , Abdukahil Sheryl Ann , Al-Rabeah Fawaz K. , Al Ghamdi Huda , Al Ghamdi Ebtisam , Abuelgasim Khadega A. , Alatassi Abdulaleem , Nammour Georges , Caswell Angela , Alchin John , Al-Dorzi Hasan M. , AlKatheri Mufareh Edah , Alharbi Ahmad , Al Almoodi Raed , Jones Joan , Al-Qahtani Saad , Salih Salih Bin , Alselaim Nahar , Tashkandi Nabiha , Vishwakarma Ramesh Kumar , Alyousef Zeyad , Al Moammary Mohamed S. , Rasheed Soud , Matroud Amal , Al Anazi Rasha Ebeid , Al Shammari Haifa , Alshamrani Majid M. , Qasim Saleh , Obbed Saeed , Al Qarni Mohammed , Jazieh Abdul Rahman , Al Zahrani Mohammed , Al-Hameed Fahad , Munshi Adnan A. , Jastaniah Wasil , AlMarhabi Hassan , AlWafi Emad , Alyami Ali H. , Yamani Arwa O. , Al Tabsh Hadia , Banat Basem R. , Abuskout Omar , Marcelo Anna Liza , Alhabshi Mayadah M. , Al Hamdan Abdullah , Al Qarni Ali , Al Arfaj Ahmed , Mustafa Hani T. , Shahin Mohammad , Ghamdi Abdulaziz A. , Yaakob Jamielah , Chalabi Jamal , Greyvenstein Johanna E. , Al Qasem Abdulaziz , Esilan Hattan , Aliyyen Sami Musalam , Sian Christa Myumi , Alwasaidi Turki , Alhasani Amar M. , Jaber Ibrahim J. , Omaish Noha , Abdrabo Mohammad , Qureshi Ahmad S. , Abdrahim Azura , Almughamisi Naif , Rahim Azurahazri Abd , Al Shouabi Ahmed , Qahtani Shaher , Alansari Mariam , Al Somali Hanan , Masala Clara , Madram Gaber , Nasser Wafa , Talaqof Fatimah , Almulhim Maryam 
Published: November 2021

Background

It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the Stepped-wedge Cluster Randomized Trial of Electronic Early Notification of Sepsis in Hospitalized Ward Patients (SCREEN) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality.

Methods and design

This study is designed as a stepped-wedge cluster randomized trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2 months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). During the study period, some of the hospital wards were allocated to manage patients with COVID-19. The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects: hospitals and COVID-19 ward status in addition to the intervention. Results will be expressed as relative risk with a 95% confidence interval.

Conclusion

The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcome analysis will facilitate unbiased analyses of these important clinical data.

Trial registration

ClinicalTrials.gov NCT04078594. Registered on September 6, 2019