Interactions in clinical trials: Protocol and statistical analysis plan for an explorative study of four randomized ICU trials on use of pantoprazole, oxygenation targets, haloperidol and intravenous fluids
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Interactions in clinical trials : Protocol and statistical analysis plan for an explorative study of four randomized ICU trials on use of pantoprazole, oxygenation targets, haloperidol and intravenous fluids. / Schjørring, Olav L.; Lange, Theis; Krag, Mette; Andersen-Ranberg, Nina Christine; Meyhoff, Tine S.; Marker, Søren; Klitgaard, Thomas L.; Estrup, Stine; Moller, Morten Hylander; Rasmussen, Bodil S.; Poulsen, Lone M.; Perner, Anders.
I: Acta Anaesthesiologica Scandinavica, Bind 66, Nr. 1, 2022, s. 156-162.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Interactions in clinical trials
T2 - Protocol and statistical analysis plan for an explorative study of four randomized ICU trials on use of pantoprazole, oxygenation targets, haloperidol and intravenous fluids
AU - Schjørring, Olav L.
AU - Lange, Theis
AU - Krag, Mette
AU - Andersen-Ranberg, Nina Christine
AU - Meyhoff, Tine S.
AU - Marker, Søren
AU - Klitgaard, Thomas L.
AU - Estrup, Stine
AU - Moller, Morten Hylander
AU - Rasmussen, Bodil S.
AU - Poulsen, Lone M.
AU - Perner, Anders
PY - 2022
Y1 - 2022
N2 - Background Intensive care unit (ICU) patients receive numerous interventions, but knowledge about potential interactions between these interventions is limited. Co-enrolment in randomized clinical trials represents a unique opportunity to investigate any such interactions. We aim to assess interactions in four randomized clinical trials with overlap in inclusion periods and patient populations. Methods This protocol and statistical analysis plan describes a secondary explorative analysis of interactions in four international ICU trials on pantoprazole, oxygenations targets, haloperidol and intravenous fluids, respectively. The primary outcome will be 90-day all-cause mortality. The secondary outcome will be days alive and out of hospital in 90 days after randomization. All patients included in the intention-to-treat populations of the four trials will be included. Four co-primary analyses will be conducted, one with each of the included trials as reference using a logistic regression model adjusted for the reference trial's stratification variables and for the co-interventions with interactions terms. The primary analytical measure of interest will be the analyses' tests of interaction. A p-value below .05 will be considered statically significant. The stratification variable- and co-intervention-adjusted effect estimates will be reported with 95% confidence intervals without adjustments for multiplicity. Conclusion This exploratory analysis will investigate the presence of any interactions between pantoprazole, oxygenation targets, haloperidol and amount of intravenous fluids in four international ICU trials using co-enrolment. Assessment of possible interactions represents valuable information to guide the design, statistical powering and conduct of future trials.
AB - Background Intensive care unit (ICU) patients receive numerous interventions, but knowledge about potential interactions between these interventions is limited. Co-enrolment in randomized clinical trials represents a unique opportunity to investigate any such interactions. We aim to assess interactions in four randomized clinical trials with overlap in inclusion periods and patient populations. Methods This protocol and statistical analysis plan describes a secondary explorative analysis of interactions in four international ICU trials on pantoprazole, oxygenations targets, haloperidol and intravenous fluids, respectively. The primary outcome will be 90-day all-cause mortality. The secondary outcome will be days alive and out of hospital in 90 days after randomization. All patients included in the intention-to-treat populations of the four trials will be included. Four co-primary analyses will be conducted, one with each of the included trials as reference using a logistic regression model adjusted for the reference trial's stratification variables and for the co-interventions with interactions terms. The primary analytical measure of interest will be the analyses' tests of interaction. A p-value below .05 will be considered statically significant. The stratification variable- and co-intervention-adjusted effect estimates will be reported with 95% confidence intervals without adjustments for multiplicity. Conclusion This exploratory analysis will investigate the presence of any interactions between pantoprazole, oxygenation targets, haloperidol and amount of intravenous fluids in four international ICU trials using co-enrolment. Assessment of possible interactions represents valuable information to guide the design, statistical powering and conduct of future trials.
KW - critical illness
KW - drug interactions
KW - haloperidol
KW - infusions
KW - intensive care units
KW - intravenous
KW - oxygen inhalation therapy
KW - pantoprazole
KW - pragmatic clinical trials
KW - randomized controlled trials
KW - DELIRIUM
U2 - 10.1111/aas.13990
DO - 10.1111/aas.13990
M3 - Journal article
C2 - 34606090
VL - 66
SP - 156
EP - 162
JO - Acta Anaesthesiologica Scandinavica
JF - Acta Anaesthesiologica Scandinavica
SN - 0001-5172
IS - 1
ER -
ID: 282106397