Clinical Trials Streamline Research in Perioperative Medicine

Clinical trials provide the strongest evidence for improving patient care and health outcomes. However, they are limited by barriers including the high cost of patient recruitment, logistical issues, and ethical considerations. Recent innovations in clinical trial design have helped researchers make the most of available resources and streamline their investigations. Sunday’s panel discussion at Euroanaesthesia 2025 brings a fresh perspective on novel research methods, their advantages, and their potential impact on clinical practice.   

Study design has evolved in a medical research landscape that is constantly reshaped by the understanding that large patient cohorts are necessary to produce robust trial results, according to Daniel I. Sessler, MD, professor and vice president for clinical research at the McGovern Medical School at the University of Texas, Houston, in the United States. “There is increasing recognition that small trials overestimate treatment effect, often by a lot, or identify treatment effects that are simply not there,” Sessler explained. “Trial size really matters.”  

Comparative effectiveness studies designed to compare the benefits and risks associated with different healthcare interventions are increasingly common. Sessler was the first perioperative investigator to use a type of comparative effectiveness trial known as a cluster crossover trial. In one such study, his team randomised patients having nearly 8,500 intubations for cardiac surgery at the Cleveland Clinic. The team showed that failed intubations were four times more likely with conventional than with hyper-angulated video laryngoscopy.¹ 

“Virtually all cluster trials are done with waived consent,” Sessler said. “That means researchers need to compare [interventions] that are already in routine use, that people think are generally safe, and that are likely to be beneficial.” Cluster trials can incorporate crossover designs, which are ideal for testing the efficacy of complex or bundled interventions in real-world settings. In this type of study, patients within a cluster are assigned to an intervention for a designated period, after which they switch to a different intervention. Clusters can be entire hospitals, units within a hospital, or patients under the care of a single clinician. Instead of randomising individual participants to specific treatment arms, all patients in the cluster receive the same treatment.  

While cluster trials can enroll large numbers of patients quickly and are much less expensive than conventional randomised trials, they require waived consent, which depends on local regulations. In the United States, federal law allows institutional review boards to waive or modify participant consent in clinical trials investigating treatments that are already in use and considered safe. Research ethics committees across the European Union may benefit from less regulatory guidance when it comes to consent. Moreover, cluster trials require the participation of every clinician involved in the care of the patients in the cluster, including attending physicians, residents, and nurses. “An important caveat is that cluster trials require full collaboration among relevant clinicians, as every member of the clinical team must be willing to comply with the protocol,” Sessler added.  

Cluster randomized trials represent just one of several trends that are increasingly used in medical research. Platform trials have recently gained momentum in response to the need for fast and efficient clinical trials that can adapt to evolving circumstances. “Platform trials assess multiple interventions simultaneously rather than sequentially, so results are available a lot sooner,” said Kate Leslie, MD, the head of research in the department of anaesthesia and pain management at the Royal Melbourne Hospital in Australia. “Ethics and governance are streamlined because the platform has a master protocol, with each intervention described in an appendix. If the platform trial has adaptive features, then interventions that are not promising or are harmful at interim analyses can be dropped, and interventions that look promising can be enriched with more patients. Changes to drug doses or administration and changes to the study population are also possible. If Bayesian methods are used, sample size calculations can be updated during the trial so that enough patients are recruited to prove effectiveness of promising interventions.”   

Nevertheless, researchers must carefully navigate the methodological, ethical, and regulatory issues tied to the specificity of platform trials. “Strong centralized leadership, regulation, operations, and statistics are required,” Leslie said. “Platform trials are not suitable or possible for testing all hypotheses and prior beliefs. A variety of clinical research methodologies will still be required.”  

This type of design can easily be adapted to test various interventions in anesthesiology and intensive care, including drugs, devices, and clinical workflows. Moreover, platform trials represent an effective method for evaluating patient outcomes, including death, cardiovascular complications, acute renal injury, cognitive decline, sepsis, and surgical site infection. “Platform trials are a powerful way to rapidly test multiple interventions and, if implemented in perioperative medicine, will provide stronger evidence about preventing or treating complications,” Leslie added.   

References: 

1. Ruetzler K, Bustamante S, Schmidt MT, et al. Video Laryngoscopy vs Direct Laryngoscopy for Endotracheal Intubation in the Operating Room: A Cluster Randomized Clinical Trial. JAMA. 2024;331(15):1279–1286.