Top Things to Know: Methodological Standards for the Design, Implementation, and Analysis of Randomized Trials in Cardiac Surgery

Published: December 06, 2021

  1. The statement reviews key concepts in cardiac surgery randomized trial design and implementation, and provides suggestions for planning, conducting and interpreting cardiac surgery trials.
  2. Lack of formal training in clinical trials methodology for cardiac surgeons remains a barrier to successful leadership of investigator-initiated clinical trials. This is an area of opportunity for academic cardiac surgical organizations to promote training in clinical trials methodology, facilitate identifying the priority areas for clinical studies and actively supporting key clinical trials in the specialty through strategic funding, advocacy and expertise.
  3. When developing cardiac surgery clinical trials, a first consideration should be evaluating the suitability of the research question, assessment of clinical equipoise, the feasibility of enrolling a representative patient cohort, the impact of practice variation on the safety and efficacy of the study intervention, the likelihood and impact of cross-over, and the duration of follow-up.
  4. The suitability of the study question for a cardiac surgery trial should be determined by a multidisciplinary working group which includes cardiologist, cardiac surgeons, nurses, clinical trialists, other healthcare professionals relevant to the topic and patient representatives.
  5. Cardiac surgery randomized control trials (RCTs) tend to have patient cohorts with an under-representation of women and underserved groups. Diversity in trial leadership, and involvement of patient representatives and care stakeholders are key in addressing healthcare disparities in trial design and conduct.
  6. Clinical equipoise is the crucial measure for determining whether a study should be done. Whether a study can be done depends on individual equipoise. Rigorous assessment of clinical and individual equipoise in the cardiac surgery and cardiology community through surveys, and analysis of registries is an essential early step in the design of cardiac surgery trials.
  7. An essential part of cardiac surgery trial design is ensuring that the tested interventions can consistently and efficiently be performed within the trial setting.
  8. Superiority trials inform health-care decisions in cardiac surgery related to survival and major complications where a treatment effect is the primary reason for a proposed treatment. Non-inferiority designs support comparisons of therapy where potential benefits (cost, convenience, fast recovery) may be acceptable at the expense of pre-specified margin of reduced efficacy or safety.
  9. Leveraging established investigator-led cardiac surgery clinical trials networks may reduce costs, increase methodological quality, maximize feasibility, and enroll a diverse, representative patient population.
  10. Randomized controlled trials (RCTs) are considered the highest quality source of evidence for healthcare decisions; cardiac surgery presents specific methodological challenges in the design, implementation, and analysis of RCTs.


Gaudino M, Chikwe J, Bagiella E, Bhatt DL, Doenst T, Fremes SE, Lawton J, Masterson Creber RM, Sade RM, Zwischenberger BA; on behalf of the American Heart Association Council on Cardiovascular Surgery and Anesthesia. Methodological standards for the design, implementation, and analysis of randomized trials in cardiac surgery: a scientific statement from the American Heart Association [published online ahead of print December 6, 2021]. Circulation. doi: 10.1161/CIR.0000000000001037