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J Am Heart Assoc. 2019 Nov 5;8(21):e013711. doi: 10.1161/JAHA.119.013711. Epub 2019 Oct 30.

Prevalence and Impact of Treatment Crossover in Cardiac Surgery Randomized Trials: A Meta-Epidemiologic Study.

Author information

1
Department of Cardiothoracic Surgery Weill Cornell Medicine New York NY.
2
Schulich Heart Centre Division of Cardiac Surgery Department of Surgery Sunnybrook Health Sciences Centre University of Toronto Ontario Canada.
3
University of Ottawa Heart Institute University of Ottawa Ontario Canada.
4
Heart Department SS Annunziata Hospital Chieti Italy.
5
Department of Cardiothoracic Surgery Stony Brook School of Medicine New York NY.
6
Department of Cardiothoracic Surgery Mount Sinai Hospital New York NY.
7
Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome Latina Italy.
8
Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed Pozzilli Italy.
9
Nuffield Department of Surgical Sciences University of Oxford United Kingdom.
10
Mediterranea Cardiocentro Napoli Italy.

Abstract

Background Crossover dilutes treatment effect and reduces statistical power of intention-to-treat analysis. We examined incidence and impact on cardiac surgery randomized controlled trial (RCT) outcomes of crossover from experimental to control interventions, or vice versa. Methods and Results MEDLINE, EMBASE, and Cochrane Library were searched, and RCTs (≥100 patients) comparing ≥2 adult cardiac surgical interventions were included. Crossover from the initial treatment assignment and relative risks (RRs) for each trial's primary end point and mortality at longest available follow-up were extracted. All RRs were calculated as >1 favored control group and <1 favored experimental arm. Primary outcome was the effect estimate for primary end point of each RCT, and secondary outcome was all-cause mortality; both were appraised as RR at the longest follow-up available. Sixty articles reporting on 47 RCTs (25 440 patients) were identified. Median crossover rate from experimental to control group was 7.0% (first quartile, 2.0%; third quartile, 9.7%), whereas from control to experimental group, the rate was 1.3% (first quartile, 0%; third quartile, 3.6%). RRs for primary end point and mortality were higher in RCTs with higher crossover rate from experimental to control group (RR, 1.01 [95% CI, 0.94-1.07] versus RR, 0.80 [95% CI, 0.66-0.97] and RR, 1.02 [95% CI, 0.95-1.11] versus RR, 0.94 [95% CI, 0.82-1.07], respectively). Crossover from control to experimental group did not alter effect estimates for primary end point or mortality (RR, 0.82 [95% CI, 0.63-1.05] versus RR, 0.95 [95% CI, 0.86-1.04] and RR, 0.88 [95% CI, 0.73-1.07] versus RR, 1.02 [95% CI, 0.95-1.09], respectively). Conclusions Crossover from experimental to control group is associated with outcomes of cardiac surgery RCTs. Crossover should be minimized at designing stage and carefully appraised after study completion.

KEYWORDS:

cardiac surgery; crossover; meta‐epidemiologic study; randomized controlled trial; surgery

PMID:
31663420
DOI:
10.1161/JAHA.119.013711
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