Clinical Trials In Emergency Medicine Research Articles

Regulations and ethics surrounding cluster randomized controlled trials and other clinical trials in emergency medicine

Introduction: A cluster randomized controlled trial is performed as an intervention in a group of subjects (collectively labeled as a “cluster”), rather than for an individual. Despite practical challenges and ethical issues inherent in obtaining informed consent for patient participation in cluster randomized controlled trials, many countries and regions have aggressively pursued these trials to increase the quality of medical evidence. However, Japan has yet to create an established protocol for obtaining informed consent for clinical trials in emergency medicine, including resuscitation science, and cluster randomized controlled trials. The aim of this study was to develop a method for obtaining informed consent in cluster randomized controlled trials of resuscitation science in Japan and other regions.

Clinical trials in emergency medicine: Comparison among European countries, United States and Japan

Clinical trials in emergency medicine: Comparison among European countries, United States and Japan

Influence of Adaptive Analysis on Unnecessary Patient Recruitment: Reanalysis of the RATPAC Trial

Recruitment to clinical trials is a challenging but essential activity in emergency medicine. Conventional fixed-sample trials may continue to recruit patients after efficacy has been demonstrated or when further recruitment is futile. Adaptive trials make use of emerging information to modify aspects of a trial or terminate it prematurely, potentially resulting in savings in terms of sample size, time, and cost. We aim to use sequential testing procedures to reanalyze data from a fixed-sample trial, the Randomised Assessment of Treatment Using Panel Assay of Cardiac Markers (RATPAC) trial, and investigate the potential for adaptive designs to reduce unnecessary recruitment. The trial was reanalyzed with a triangular group sequential design, with interim analyses planned every 3 months. Patients were analyzed in the order in which they entered the original trial. We found that the RATPAC trial could potentially have stopped 1 year earlier, with 722 patients enrolled compared with 2,243 patients in the original trial, making a potential saving of approximately $390,000. Estimates of effect were similar, and the qualitative conclusions of the original and group sequential RATPAC trials were in agreement. However, the group sequential approach is not without limitations and would have resulted in less precise estimates of effect and less information available for the subsequent evaluation of secondary endpoints. Sequential designs are well suited in emergency medicine because of the rapidly obtained outcomes and the need to avoid unnecessary recruitment. We recommend that group sequential designs be considered for clinical trials in emergency medicine.

Informed consent for clinical trials in acute coronary syndromes and stroke following the European Clinical Trials Directive: investigators' experiences and attitudes.

BackgroundDuring clinical trials in emergency medicine, providing appropriate oral and written information to a patient is usually a challenge. There is little published information regarding patients' opinions and competence to provide informed consent, nor on physicians' attitudes towards the process. We have investigated the problem of obtaining consent from patients in emergency-setting clinical trials (such as acute coronary syndromes (ACS) and stroke) from a physicians' perspective.MethodsA standardised anonymous 14-item questionnaire was distributed to Polish cardiac and stroke centres.ResultsTwo hundred and fourteen informative investigator responses were received. Of these investigators, 73.8% had experience with ACS and 25.2% had experience with acute stroke trials (and 1% with both fields). The complete model of informed consent (embracing all aspects required by Good Clinical Practice (GCP) and law) was used in 53.3% of cases in emergency settings, whereas the legal option of proxy consent was not used at all. While less than 15% of respondents considered written information to have been fully read by patients, 80.4% thought that the amount of information being given to emergency patients is too lengthy. Although there is no legal obligation, more than half of the investigators sought parallel consent (assent) from patients' relatives. Most investigators confirmed that they would adopt the model proposed by the GCP guidelines: abbreviated verbal and written consent in emergency conditions with obligatory "all-embracing" deferred consent to continue the trial once the patient is able to provide it. However, this model would not follow current Polish and European legislation.ConclusionAn update of national and European regulations is required to enable implementation of the emergency trial consent model referred to in GCP guidelines.

Sequential clinical trials in emergency medicine

In a traditional clinical trial, a fixed number of patients are evaluated before the data are analyzed. This has the disadvantage that more patients may be enrolled than are necessary to achieve a statistically significant result. Sequential statistical techniques provide a method for the analysis of clinical trials so that a reliable result is obtained with a minimum number of patients. In a sequential trial, the data are analyzed after each patient's outcome is known, and the trial is halted as soon as treatment efficacy or lack thereof is demonstrated. This study was undertaken to confirm the advantages of sequential statistical techniques over conventional fixed-sample-size statistical techniques for the analysis of clinical trials. Using sequential techniques, we conducted computer simulations of two fixed-sample-size clinical studies from the literature - a trial of hepatitis B vaccine in homosexual men (N Engl J Med 1980;303:833-841) and a trial of the pneumatic antishock garment in hypotensive patients with penetrating abdominal trauma (Ann Emerg Med 1987;16:653-658). In the trial simulations, patients were randomly assigned to the control and test groups, their outcomes were determined randomly according to the frequency of outcomes observed in the actual studies, and the simulated sequential studies were continued until conclusions were reached. Thousands of possible realizations of each trial were simulated; thus, the distribution of required patient numbers was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential clinical trials in emergency medicine

Sequential clinical trials in emergency medicine

The beta error and sample size determination in clinical trials in emergency medicine

In the analysis of a clinical trial an investigator may fail to discern a statistically significant difference in outcome between control and experimental groups, when in fact one exists. Failure to demonstrate such a difference when it actually exists is known as "type II" error, and its probability of occurring is termed "beta." The purpose of our study was to determine the distribution of beta errors in negative trials in the Journal of the American College of Emergency Physicians (JACEP) (1972-1979) and Annals of Emergency Medicine (1980-1984). All negative comparative clinical trials appearing in JACEP and Annals from volume 1 (1972) to volume 13 (1984) were surveyed and were eligible for inclusion in the study. A trial was defined as negative if the investigator specifically stated that there was no significant difference in outcome between the experimental and control groups. For each negative trial the following parameters were calculated: beta error, based on the sample size used and the difference determined to be important to detect clinically; sample size required to detect a clinically meaningful difference as determined by the authors of this study; and minimum true difference that had to be detected in the trial at a beta equal to 0.20, to discern a statistically significant result. For the 13 years surveyed, we found 21 endpoints in 14 negative trials that were analyzable. Only one of the trials (7.1%) addressed the issues of beta errors and sample size determination. In the remaining 13 negative trials, the calculated beta error ranged from .60 to .97. For the endpoints analyzed, a sample size of up to 450 times larger than that used would have been required to detect a clinically important difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Methods of randomization in controlled clinical trials.

In this second article of a series that explores design and analysis issues in controlled clinical trials in emergency medicine, we have discussed the case for randomization, reviewed the methods involved in simple randomization, highlighted some of the practical problems involved with randomization, and presented some modified randomization schemes intended to remedy these problems.

Beta error and sample size determination in clinical trials in emergency medicine

Beta error and sample size determination in clinical trials in emergency medicine

Controlled clinical trials in emergency medicine

In this first article of a series on controlled clinical trials in emergency medicine, an overview of the structure of such studies and the relevant issues related to study design, data generation, statistical analysis, and reporting are presented. The importance of precise patient selection, randomization and stratification, blinding, and equivalent therapeutic intervention in study design has been discussed. In addition, precise outcome and measurement criteria, assessor qualifications, deficiencies in data, appropriate sample-size selection, and reporting are also presented. Although an idealized framework for the conduct and analysis of a controlled clinical trial is provided, it should be appreciated that design and analytical compromises may at times be difficult to avoid in clinical research. Future articles in this series will discuss randomization in clinical trials, alternatives to randomization, beta error and sample-size determination, the statistical and analytical issues related to imperfections in the execution of a trial, and issues related to the reporting of clinical trials.