Volume 100: clinical investigations: where next?
In this 100th volume of the British Journal of Anaesthesia, it seems appropriate to consider the role of clinical investigations in contributing to our current clinical practice and how this might change in the future. Ideally, clinical investigations are a scientific assessment of a clinical problem involving direct data collection from patients. This may be either in the form of an experimental study (either randomized or non-randomized) to determine the benefit or safety of an intervention, for example, treatment or prevention of disease, or an observational study, which may be either descriptive (with no comparator group) or analytical (e.g. cohort studies or case–control studies).1 The hope is that high-quality clinical research will provide a basis for evidence-based medical practice and improve the quality of healthcare delivered by our speciality.We need to consider the widely acknowledged challenges facing clinical research which include concerns over maintaining and extending academic anaesthesia, with a pool of appropriately trained clinician scientists who can continue to contribute to evidence-based clinical research in all areas of anaesthesia, critical care, and pain medicine. This will require training and support of medical graduates. It could be argued that within anaesthesia we are well placed to meet this challenge, with an emphasis on the importance of clinical and basic science in our postgraduate training that is not always reflected in other specialities. Other challenges to clinical research include changes in societal expectations, legislation, and models of healthcare delivery.
There is concern that the numbers of clinicians following an academic training route is decreasing, although there is some evidence from the USA that this may not in fact be the case.2 Changes in medical training in the UK have increased the concern that clinical researchers may be discouraged from pursuing an academic career route, although it is recognized at some levels that this problem needs to be addressed.3 4 Within anaesthesia, there is an acknowledgement that developing a recognized and supportive career pathway for future academic anaesthesia is important, with some centres developing their own solutions and also much wider national strategies being considered.5 After a comprehensive report from the Royal College of Anaesthetists, there has been active collaboration between a range of anaesthetic groups, including the British Journal of Anaesthesia, to found a National Institute for Academic Anaesthesia within the UK.6 Work on developing this is ongoing, and will not only support training of future clinical researchers, but may also provide a model that will allow the development of network-based research for large-scale multi-centre trials, using the expensive and expert infrastructure required to conduct such trials.7
Before going on to discuss the future challenges of clinical research, it is worth considering the spectrum of previous clinical research in anaesthesia. The last 100 volumes of the British Journal of Anaesthesia have published many clinical investigations—rather than selecting a few key studies, it is interesting to consider the range of manuscripts published and to see how many of these are directly related to clinical studies. A Pubmed Search of the British Journal of Anaesthesia for ‘clinical trials’ revealed 2741 hits, covering a broad range of clinical issues in anaesthesia, intensive care, pain medicine, and also emergency medicine. The focus, however, was not evenly divided, with 346 trials on propofol anaesthesia, 133 on sevoflurane anaesthesia, 83 on remifentanil, 7 on chronic pain, 62 in intensive care, 32 on chronic pain, and 25 in emergency medicine and pre-hospital treatment. This may not be a reflection of clinical relevance, but rather a number of factors such as ease of conducting the study, sources of funding, competition from other speciality journals, and perceived areas of interest that may affect the focus of manuscripts submitted.
An encouraging finding from a recent review of published research from anaesthesia departments showed a broad diversity of clinical anaesthesia research with nearly 7000 publications in the international literature over a 5 yr period, with nearly 70% of these being randomized controlled trials (RCT). Publication rates were relatively consistent year on year, with 
1100 per year over the period studied up to 2005. European nations had the highest research output per capita, although 20% of the total publications were from the USA. The British Journal of Anaesthesia was the third equal ranking journal in terms of number of publications—464 (6.89%) of the total, with 75% of these being RCTs.8 It is clear that anaesthesia journals in general, and the British Journal of Anaesthesia in particular, are supportive of clinical research, with the majority of publications being RCTs that should contribute to the evidence-base of our speciality.
We do need to consider, however, whether these publications have any impact on clinical care. One of the strengths of clinical research is to answer immediately relevant clinical questions that arise in day-to-day practice and should have an impact on patient care. It is essential therefore that our research agenda is informed by clinicians, rather than driven by basic science. This may require developing an innovative approach in the future, breaking down barriers between clinicians and scientists, and supporting collaborative research in order to achieve clinically relevant research that tries to answer important questions and uncertainties in clinical practice, although rapidly translating important basic science findings to the clinic. Two-way communication between basic science researchers and clinicians is an essential part of this process. We need to consider how we will develop this approach in terms of training future clinicians and clinician scientists and how to provide the essential infrastructure needed to support high-quality clinical research.9 Similar initiatives and approaches are being used elsewhere to foster clinical research programmes, taking account of advances in biomedical sciences, often closely linked to areas of direct relevance to anaesthesia, changes in delivery of healthcare and financing, and the effect of improved information technology.10 11 The wide range of clinical investigations published in the British Journal of Anaesthesia over the course of 100 volumes do display changes in clinical practice arising from clinical investigations. Importantly, this is combined with a critical appraisal of how these changes in clinical practice may impact on patients.12 13
The importance of a translational approach to clinical and biomedical research has been recognized by many countries, with new strategies to support clinical and translational research by the NIH, a need also identified in the Cooksey report.14 15 This report clarified concerns about delays in translating basic science advances into clinical practice. Factors contributing to this included: lack of support from the NHS, barriers within individual institutions, and greater recognition for basic science research than clinical research, including funding distribution. This report has contributed to a resulting shift in the emphasis of research funding by the major public funding bodies in the UK towards translational research.
In addition to closer collaboration with basic science colleagues, there are many changes in policies about the conduct of clinical trials, such that it is important to have a research infrastructure supporting high-quality clinical research rather than discouraging it. Patient recruitment to clinical investigations is fundamental to success, with researchers often overestimating the number of patients available for a research study (Lasagna's law).16 The lack of patients may be due to many factors, including narrow inclusion criteria, unattractive trial interventions, and failure in patient approach, all of which may delay or impede successful conclusion of a trial. Many of these factors would be addressed by having the necessary infrastructure in place to support clinical trials, including expert advice on trial design and analysis. The multiple factors that may affect successful study conduct need to be considered, not only patients and carer-related, but also wider societal changes in healthcare delivery.17 18
In the future, the recognition of end-user involvement as part of the process of clinical trial design may engage patients and society in general more closely to important clinical research and move away from popular concerns voiced in the media about the ethics of clinical research.19 Broad ranging clinical trials may require using novel health and information technology to allow the study of large numbers of patients required for the best possible evidence-base. This may include integration with electronic patient records for clinical research and national and international collaborations to develop widely applicable shared systems and approaches.20 21
The EU Directives on the conduct of clinical trials has had to be considered in new legislation throughout Europe, with changes in the review processes, both scientific and ethical that are required before starting any clinical research.22 23 Although this has necessitated major changes within individual countries in terms of clinical research, it may, in the future, make international collaboration easier, as areas of ethical concern identified by the European Commission are addressed. Another area raised by the EC is the ethical importance of disseminating research findings, an important role for high-quality international journals.24
Critical assessment of clinical investigations is essential for practising clinicians to maintain professional competence throughout their careers. This emphasizes the importance of communicating research findings in a way that is clear and comprehensible to clinicians and allows them to assess relevance to their own clinical practice. Medicine has moved from using expert opinion to a more rigorous evidence-based approach. Although this is important, we do need to consider the limitations of this approach—there are many systematic reviews of the literature within our field where the conclusion is that there is an inadequate evidence-base for common clinical practice.25 It is essential, therefore, that as a speciality we continue to carry out high-quality clinical research, hopefully much of it published in the next 100 volumes of the British Journal of Anaesthesia!
1 Edinburgh, UK
2 Herlev, Denmark
* E-mail: lesley.colvin{at}ed.ac.uk
References
1 Grimes DA, Schulz KF. An overview of clinical research: the lay of the land. Lancet (2002) 359:57–61.[CrossRef][Web of Science][Medline]
2 Ley TJ, Rosenberg LE. The physician–scientist career pipeline in 2005: build it, and they will come. JAMA (2005) 294:1343–51.
3 Tunbridge M. Conference of Postgraduate Medical Deans of the United Kingdom. Monitoring the clinician scientist scheme. Clin Med (2004) 4:141–3.[Web of Science][Medline]
4 Academy of Medical Sciences. Strengthening Clinical Research (2003).
5 Menon DK, Wheeler DW, Wilkins IA, et al. Integrated approaches to academic anaesthesia—the Cambridge experience. Anaesthesia (2004) 59:785–92.[CrossRef][Web of Science][Medline]
6 Pandit JJ. A National Strategy for Academic Anaesthesia (2005) 20. Available from www.rcoa.ac.uk.
7 Pandit JJ. The national strategy for academic anaesthesia. A personal view on its implications for our specialty. Br J Anaesth (2006) 96:411–5.
8 Swaminathan M, Phillips-Bute BG, Grichnik KP. A bibliometric analysis of global clinical research by anesthesia departments. Anesth Analg (2007) 105:1741–6.
9 Murillo H, Reece EA, Snyderman R, et al. Meeting the challenges facing clinical research: solutions proposed by leaders of medical specialty and clinical research societies. Acad Med (2006) 81:107–12.[CrossRef][Web of Science][Medline]
10 Tilghman C, Tilghman J, Johnson RW. Integration of technology in a clinical research setting. ABNF J (2006) 17:112–4.[Medline]
11 Heinig SJ, Quon AS, Meyer RE, et al. The changing landscape for clinical research. Acad Med (1999) 74:726–45.[Web of Science][Medline]
12 Wigmore TJ, Smythe JF, Hacking MB, Raobaikady R, MacCallum NS. Effect of the implementation of NICE guidelines for ultrasound guidance on the complication rates associated with central venous catheter placement in patients presenting for routine surgery in a tertiary referral centre. Br J Anaesth (2007) 99:662–6.
13 Hopkins PM. Editorial: ultrasound guidance as a gold standard in regional anaesthesia. Br J Anaesth (2007) 98:299–302.
14 Zerhouni EA, Zerhouni EA. Clinical research at a crossroads: the NIH roadmap. J Investig Med (2006) 54:171–3.[CrossRef][Web of Science][Medline]
15 Black N. The Cooksey review of UK health research funding. Br Med J (2006) 333:1231–2.
16 van der Wouden JC, Blankenstein AH, Huibers MJ, van der Windt DA, Stalman WA, Verhagen AP. Survey among 78 studies showed that Lasagna's law holds in Dutch primary care research. J Clin Epidemiol (2007) 60::819–24.[CrossRef][Web of Science][Medline]
17 Nosowsky R, Giordano TJ. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) privacy rule: implications for clinical research. Ann Rev Med (2006) 57:575–90.[CrossRef][Web of Science][Medline]
18 Dunlop AL, Graham T, Leroy Z, et al. The impact of HIPAA authorization on willingness to participate in clinical research. Ann Epidemiol (2007) 17:899–905.[CrossRef][Web of Science][Medline]
19 Thornton H. Patients and health professionals working together to improve clinical research: where are we going? Eur J Cancer (2006) 42:2454–8.[CrossRef][Web of Science][Medline]
20 DiLaura RP. Clinical and translational science sustainability: overcoming integration issues between electronic health records (EHR) and clinical research data management systems ‘separate but equal. Medinfo (2007) 12:137–41.[Medline]
21 Riegman PH, Dinjens WN, Oosterhuis JW. Biobanking for interdisciplinary clinical research. Pathobiology (2007) 74:239–44.[CrossRef][Web of Science][Medline]
22 Lemaire F. Patient care versus research: does clinical research provide individual benefit to patients enrolled in trials? Curr Opin Crit Care (2004) 10:565–9.[CrossRef][Medline]
23 Dawson AJ, Yentis SM. Contesting the science/ethics distinction in the review of clinical research. J Med Ethics (2007) 33:165–7.
24 Chaplin C. Ethics of international clinical research collaboration—the experience of AlloStem. Int J Immunogenetics (2006) 33:1–5.[CrossRef]
25 Zlowodzki M, Jonsson A, Bhandari M. Common pitfalls in the conduct of clinical research. Med Princ Pract (2006) 15:1–8.[Web of Science][Medline]
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