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On trial: clinical research in the USA
Editorial
A glance at the Aug 5 issue of Nature suggests exciting times in research on cardiovascular disease. A large international consortium, studying cohorts of up to 100 000 people, has unearthed new associations between 59 different genetic loci and plasma lipids, offering possible new therapeutic avenues in coronary artery disease. In a separate study, a genetic variant at the SORT1 locus on chromosome 1p has been shown to alter LDL cholesterol, affecting risk of myocardial infarction. Yet Transforming clinical research in the United States, a workshop report released on Aug 2 by the US Institute of Medicine (IOM), frets that the process of generating actionable medical evidence in the USA is “extraordinarily expensive”, “frequently misunderstood”, and hamstrung by regulatory hurdles and weak infrastructure. Randomised controlled trials are often referred to as the gold standard of clinical research, evoking a long-vanished, unaffordable epoch of financial stolidity. Has the process of clinical research, as currently planned, carried out, and paid for, become a draining and dysfunctional bottleneck between the increasing pace of discovery in basic research, on the one hand, and on the other the growing clinical demands created by ageing populations and chronic diseases in both developed and developing worlds? In fact the numbers suggest that the US clinical research endeavour is in a vibrant state of health. The IOM report was initiated at an open workshop in October, 2009, when there were more than 10 000 ongoing registered clinical trials involving at least one US site, seeking to enrol some 2·8 million patients. About half of all trials fall under the umbrella of oncology, but cardiovascular research contributes in excess of 1000 live trials with the largest total number of participants, 300 000, being sought. It is surely a good thing that clinical trials in China, Brazil and, interestingly, Germany, can cost half as much as they do in the USA, provided that appropriate standards of ethics and scientific scrutiny are maintained, although the IOM’s sphere of interest is restricted to US clinical research. The report makes some striking points about the culture and organisation of US clinical trials. US physicians who participate in clinical research seem to be labouring under conditions of professional apartheid—a select group of successful researchers possess the skills, experience, and infrastructure needed to take on the www.thelancet.com Vol 376 August 14, 2010
complex demands posed in a clinical trial, while most doctors receive only meagre recognition for recruiting patients into a trial, a process likely to bring with it financial disincentives for their everyday clinical practice. There is also the inevitable question of financial support. The findings of industry-sponsored trials might be mistrusted by public and professionals alike, yet public funding is likely to be tightly constrained, inherently conservative, and organised into transient grants which could pose problems of continuity for clinical trialists. In cardiovascular disease, the report cites the Bostonbased TIMI (Thrombolysis in Myocardial Infarction) study group as a paragon of a contemporary academic research organisation, publicly funded at inception in 1984 but now largely doing industry-funded trials. Although highly successful, the TIMI study group is very different from the integrated clinical research enterprise mooted by the 2003 US National Institutes of Health (NIH) roadmap for medical research. Spanning a decade, the NIH plan is to construct a national clinical research network to provide resources and infrastructure for US clinical trialists (similar national clinical research networks already exist in England, for example, to facilitate clinical research in various specialties, including stroke, dementia, and mental health). The paradox of US medicine remains that, although the best health care is available to some, the country lacks a universal health-care system. In clinical research this deficit is likely to perpetuate glaring inequalities, with minorities under-represented in interventional studies. The IOM’s report creates a frustrating sense that in clinical research the USA’s very substantial financial and human resources are being underused in a false economy predicated on commercial gain. The report nonetheless places welcome emphasis on the continuing need for clinical resources to be coordinated nationally—including the organisation of continuous federal funding and of permanent clinical research networks able to provide expertise in data management and biostatistics, for example. Such integration might not please all the stakeholders in clinical research, but it should facilitate selection of those urgent clinical questions needing the highest priority, yield greater value for public investment, and inspire greater confidence in clinical research in the USA. ■ The Lancet
Science Photo Library
On trial: clinical research in the USA
For Transforming clinical research in the United States see http://www.iom.edu/ Reports/2010/TransformingClinical-Research-in-the-UnitedStates.aspx For the NIH roadmap see http:// www.sciencemag.org/feature/ plus/nihroadmap.pdf and Williams RL, Johnson SB, Greene SM, et al. Arch Intern Med 2008; 168: 1919–25.
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A glance at the Aug 5 issue of Nature suggests exciting times in research on cardiovascular disease. A large international consortium, studying cohorts of up to 100 000 people, has unearthed new associations between 59 different genetic loci and plasma lipids, offering possible new therapeutic avenues in coronary artery disease. In a separate study, a genetic variant at the SORT1 locus on chromosome 1p has been shown to alter LDL cholesterol, affecting risk of myocardial infarction. Yet Transforming clinical research in the United States, a workshop report released on Aug 2 by the US Institute of Medicine (IOM), frets that the process of generating actionable medical evidence in the USA is “extraordinarily expensive”, “frequently misunderstood”, and hamstrung by regulatory hurdles and weak infrastructure. Randomised controlled trials are often referred to as the gold standard of clinical research, evoking a long-vanished, unaffordable epoch of financial stolidity. Has the process of clinical research, as currently planned, carried out, and paid for, become a draining and dysfunctional bottleneck between the increasing pace of discovery in basic research, on the one hand, and on the other the growing clinical demands created by ageing populations and chronic diseases in both developed and developing worlds? In fact the numbers suggest that the US clinical research endeavour is in a vibrant state of health. The IOM report was initiated at an open workshop in October, 2009, when there were more than 10 000 ongoing registered clinical trials involving at least one US site, seeking to enrol some 2·8 million patients. About half of all trials fall under the umbrella of oncology, but cardiovascular research contributes in excess of 1000 live trials with the largest total number of participants, 300 000, being sought. It is surely a good thing that clinical trials in China, Brazil and, interestingly, Germany, can cost half as much as they do in the USA, provided that appropriate standards of ethics and scientific scrutiny are maintained, although the IOM’s sphere of interest is restricted to US clinical research. The report makes some striking points about the culture and organisation of US clinical trials. US physicians who participate in clinical research seem to be labouring under conditions of professional apartheid—a select group of successful researchers possess the skills, experience, and infrastructure needed to take on the www.thelancet.com Vol 376 August 14, 2010
complex demands posed in a clinical trial, while most doctors receive only meagre recognition for recruiting patients into a trial, a process likely to bring with it financial disincentives for their everyday clinical practice. There is also the inevitable question of financial support. The findings of industry-sponsored trials might be mistrusted by public and professionals alike, yet public funding is likely to be tightly constrained, inherently conservative, and organised into transient grants which could pose problems of continuity for clinical trialists. In cardiovascular disease, the report cites the Bostonbased TIMI (Thrombolysis in Myocardial Infarction) study group as a paragon of a contemporary academic research organisation, publicly funded at inception in 1984 but now largely doing industry-funded trials. Although highly successful, the TIMI study group is very different from the integrated clinical research enterprise mooted by the 2003 US National Institutes of Health (NIH) roadmap for medical research. Spanning a decade, the NIH plan is to construct a national clinical research network to provide resources and infrastructure for US clinical trialists (similar national clinical research networks already exist in England, for example, to facilitate clinical research in various specialties, including stroke, dementia, and mental health). The paradox of US medicine remains that, although the best health care is available to some, the country lacks a universal health-care system. In clinical research this deficit is likely to perpetuate glaring inequalities, with minorities under-represented in interventional studies. The IOM’s report creates a frustrating sense that in clinical research the USA’s very substantial financial and human resources are being underused in a false economy predicated on commercial gain. The report nonetheless places welcome emphasis on the continuing need for clinical resources to be coordinated nationally—including the organisation of continuous federal funding and of permanent clinical research networks able to provide expertise in data management and biostatistics, for example. Such integration might not please all the stakeholders in clinical research, but it should facilitate selection of those urgent clinical questions needing the highest priority, yield greater value for public investment, and inspire greater confidence in clinical research in the USA. ■ The Lancet
Science Photo Library
On trial: clinical research in the USA
For Transforming clinical research in the United States see http://www.iom.edu/ Reports/2010/TransformingClinical-Research-in-the-UnitedStates.aspx For the NIH roadmap see http:// www.sciencemag.org/feature/ plus/nihroadmap.pdf and Williams RL, Johnson SB, Greene SM, et al. Arch Intern Med 2008; 168: 1919–25.
487