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.     

Review article: A primer for clinical researchers in the emergency department: Part X. Understanding economic evaluation alongside emergency medicine research

In this series we address research topics in emergency medicine. While traditionally there was an almost exclusive focus on the efficacy and effectiveness of interventions in emergency research, analysis of the costs and the societal impact of different approaches and pathways have become increasingly important. In this paper we will address what health economics means and discuss the different types and key features of economic evaluation relevant for clinical researchers.     

CTSA Consortium Consensus Scientific Review Committee (SRC) Working Group Report on the SRC Processes

Human research projects must have a scientifically valid study design, analytic plan, and be operationally feasible in order to be successfully completed and thus to have translational impact. To ensure this, institutions that conduct clinical research should have a scientific review process prior to submission to the Institutional Review Committee (IRB). This paper reports the Clinical and Translational Science Award (CTSA) Consortium Scientific Review Committee (SRC) Consensus Working Group''s proposed framework for a SRC process. Recommendations are provided for institutional support and roles of CTSAs, multisite research, criteria for selection of protocols that should be reviewed, roles of committee members, application process, and committee process. Additionally, to support the SCR process effectively, and to ensure efficiency, the Working Group recommends information technology infrastructures and evaluation metrics to determine outcomes are provided.     

Clinical trials in the 21st century: the case for participant-centered research.

Informed consumers of the 21st century increasingly will be hesitant to enroll in randomized clinical trials (RCTs) because they will be unwilling to (a) submit to random assignment; (b) complete assessments that are too lengthy, intrusive, or irrelevant; or (c) comply with protocols that do not meet their needs. Research centered on the needs and interests of participants is likely to engender greater participation and commitment than are traditional RCTs. Recommendations for making clinical trials more participant centered include: (a) expanding our conceptualizations of study validity, (b) involving consumers as advisers in the development and execution of clinical trials, and (c) offering participants reasonable alternatives to random assignment.     

Clinical research in traditional medicine: priorities and methods

This paper explores the challenges and opportunities associated with the evaluation of treatments arising from traditional medical systems (TMS). Globalization and popular consumer-and industry-driven market forces contribute to the spread of traditional treatments, techniques and technologies, but do not necessarily ensure their usefulness or safety. The international scientific community is obliged to evaluate the safety and efficacy of these treatments because of their potential impact on global public health. Clinical evaluations of traditional treatments, however, have complex methodological and practical challenges, depending on the goals of the research and the audience for the results (country of origin; or new host countries and new patient populations). To address these challenges, the authors offer the following recommendations to identify and prioritize treatments to study and how to design study protocols. Evaluations of traditional treatments are best addressed first by collaborative, international, pragmatic studies. Protocols for observational, prospective, pragmatic pilot study (randomized and controlled, when feasible) should be designed collaboratively and executed simultaneously in the culture of origin and in new contexts. This, in turn, could determine the acceptability, usefulness and feasibility of larger randomized controlled trials (RCTs). International multicentre RCTs would have the potential benefits of evaluating safety and effectiveness and also assessing the transferability of a traditional treatment across social and cultural contexts.     

Introduction of emergency medicine in China

Over the past 20 years, emergency medicine (EM) in China has been through a period of rapid development. This included the formal establishment of professional association of EM in 1986 and the establishment of ED in all county‐level hospitals across the country in the late 1990s. In line with the rapid economic development of China, ED have been equipped with appropriate ‘hardware’ equipment, but the ‘software’ part of the ED system remains underdeveloped. Doctors do not usually work exclusively in ED, but on a rotational basis, while also working as specialists in their own departments, such as medicine and surgery. EM in China remains underdeveloped, at least partly, for two main reasons: the current financial status of the health‐care system and lack of sufficient numbers of qualified EM specialists. Chinese education and training systems are now beginning to produce high‐quality emergency specialists, although there is not yet consistency across all courses. In Australia, the specialty of EM is well developed and, as such, this country is well placed to contribute to the development of ED in China.     

Research Fundamentals: III. Elements of a Research Protocol for Clinical Trials

Abstract. A clinical trial is a powerful technique for evaluating the effectiveness of an experimental intervention. The initial stages of planning a clinical trial involve choosing and refining a research question, selecting a study design, and deciding on appropriate statistical tests and sample sizes. The success of the study depends upon how well these issues are thought out in advance, and how they can be put into practice. The protocol is the written document that allows the investigator to communicate details of how the research question will be answered. In the following article, the basic components of the research protocol are described. Issues related to quality control, data entry, and pilot testing are discussed. This is the third in a series of research fundamental concept papers, written by members of the SAEM Research Committee.     

The future of clinical research: from megatrials towards methodological rigour and representative sampling

A powerful impetus behind the rise of the 'megatrial' (a large, simple, usually multi-centred randomized controlled trial analysed by 'intention to treat') has been the desire for ever-increasing precision in the measurement of therapeutic effectiveness. However, the demand for precision has been allowed to override other and more important methodological considerations. Megatrials have progressively abandoned the pursuit of scientifically rigorous experimentation, valid measurement and optimal epidemiological sampling in favour of recruiting and processing large numbers of subjects. This is a mistaken strategy which leads inevitably to error, because investigators are seeking a primarily statistical, rather than clinically or scientifically relevant, notion of exactness. We are now in a position to describe a clinical research strategy which offers many advantages over a megatrial-led approach. Research should be planned with an awareness that the validity and applicability of estimates is more important than their numerical precision, and that this requires both an unselected denominator population database of all incident cases, and maximally controlled randomized trials and other studies. The Population-Adjusted Clinical Epidemiology (PACE) strategy is suggested as exemplifying the twin principles of clinically useful research: rigorous science and representative epidemiology.     

Evaluating Various Areas of Process Improvement in an Effort to Improve Clinical Research: Discussions from the 2012 Clinical Translational Science Award (CTSA) Clinical Research Management Workshop

Emphasis has been placed on assessing the efficiency of clinical and translational research as part of the National Institutes of Health (NIH) goal to “improve human health.” Improvements identified and implemented by individual organizations cannot address the research infrastructure needs of all clinical and translational research conducted. NIH''s National Center for Advancing Translational Sciences (NCATS) has brought together 61 Clinical and Translational Science Award (CTSA) sites creating a virtual national laboratory that reflects the diversity and breadth of academic medical centers to collectively improve clinical and translational science. The annual Clinical Research Management workshop is organized by the CTSA consortium with participation from CTSA awardees, NIH, and others with an interest in clinical research management. The primary objective of the workshop is to disseminate information that improves clinical research management although the specific objectives of each workshop evolve within the consortium. The fifth annual workshop entitled “Learning by doing; applying evidence‐based tools to re‐engineer clinical research management” took place in June 2012. The primary objective of the 2012 workshop was to utilize data to evaluate, modify, and improve clinical research management. This report provides a brief summary of the workshop proceedings and the major themes discussed among the participants.     

The placebo-controlled trial as a test of complementary and alternative medicine: observations from research experience of individualised homeopathic treatment

The authors' experience of conducting clinical trials in homeopathy and analysing data from these has drawn attention to a fundamental problem with the interpretation of results from placebo controlled trials in homeopathy: It is not reasonable to assume that the specific effects of homeopathic medicine and the non-specific effects of consultations are independent of each other-specific effects of the medicine (as manifested by patients' reactions) may influence the nature of subsequent consultations and the non-specific effects of the consultation may enhance or diminish the effects of the medicine. For clinical trials of homeopathy to be accurate representations of practice, we need modified designs that take into account the complexity of the homeopathic intervention. Only with such trials will the results be generalisable to homeopathic practice in the real world. The authors propose that comparative trials are a meaningful way of evaluating the effectiveness of homeopathic treatment.     

Evidence-based research in complementary and alternative medicine II: the process of evidence-based research

It is a common practice in contemporary medicine to follow stringently the scientific method in the process of validating efficacy and effectiveness of new or improved modes of treatment intervention. It follows that these complementary or alternative interventions must be validated by stringent research before they can be reliably integrated into Western medicine. The next decades will witness an increasing number of evidence-based research directed at establishing the best available evidence in complementary and alternative medicine (CAM). This second paper in this lecture series examines the process of evidence-based research (EBR) in the context of CAM. We outline the fundamental principles, process and relevance of EBR, and its implication to CAM. We underscore areas of future development in EBR. We note that the main problem of applying EBR to CAM at present has to do with the fact that the contribution of EBR can be significant only to the extent to which studies used in the process of EBR are of good quality. All too often CAM research is not of sufficient quality to warrant the generation of a consensus statement. EBR, nevertheless, can contribute to CAM by identifying current weaknesses of CAM research. We present a revised instrument to assess quality of the literature.     

Bias in recruitment to cluster randomized trials: a review of recent publications

Objectives To assess recruitment bias and the techniques employed to counter this problem in a recent selection of published cluster randomized trials. Design Review of 24 cluster trials published in 2008 in four leading medical journals. Data extraction Studies were assessed by four reviewers to identify if an alternative design could have been employed using individual randomization. Data were also extracted on the randomization procedure and the likelihood of this introducing bias to the selection of participants into the study. Results Of the 24 trials, eight could have used individual randomization as an alternative to cluster allocation. Seven studies could have recruited participants prior to cluster randomization but did not. In eight studies where recruitment bias was possible, more than half (five) demonstrated some evidence of differential recruitment rates. Conclusions Many cluster trials published in leading medical journals are not clear in their justification for the design. We also found significant proportions of cluster trials used suboptimal designs that increase their risk of introducing selection bias. Better design of cluster trials is possible and should be adopted.