We must assume that the researchers, the hospitals and clinics where the research is done, the regulatory bodies and funders are all uniformly in favour of a system of clinical research that will improve health care to the greatest possible extent, in a cost-effective, sustainable and equitable manner.
In this report we have identified six principal components that make up a common, productive ‘culture’ that is highly promotive of research that is high quality, wide and relevant in scope, beneficial to translational outcomes, and sustainable in the clinical sector. These are:
1. The acceptance of the principle that ‘the proper study of humankind is humans themselves’;
2. The understanding that sustainable health care systems require guidance by a critical mass of research-experienced clinicians and the continuous training of new generations of research-informed clinical care givers;
3. Recognition of the complex, multi-dimensional, and challenging nature of clinical research;
4. An appropriate balance between risks and benefits;
5. An appropriate balance between curiosity-driven and problem-directed research;
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6. A clear emphasis on public service and public benefit;
7. Protection and development of new intellectual property.
We start by returning to the first, narrowly-focused question posed above. In words that are slightly altered from the cited original propositions, is the ‘proper science and study of humankind, humans themselves’? (Pope, 1733.) Many years of reductionism in health sciences have revealed countless instances where assumptions of equivalence between humans and laboratory mammals such as rats, mice and primates of various kinds have proved to be incorrect (Casanova and Abel, 2007). A good example is in the complex field of clinical immunology, where detailed studies of genetic immunopathies in human participants have consistently shown the risks of assuming that information gleaned from mice is necessarily applicable to humans (Schnabel, 2008).
Some models of human diseases have been deliberately engineered in laboratory animals (Peh et al., 2002; Wine et al., 2002; Itoh and Narushima, 2005; Aliev and Burnstock, 1998; Lieschke and Currie, 2007), and much drug testing is conducted on selected animal species. In most cases, the validity of the reductionistic or comparative models has proved problematic, even if much useful knowledge has been generated that has made the design of human studies simpler, less open-ended and more focused. It seems, nevertheless, that in general only studies of humans can yield a true picture of human disorders, especially because this generalisation is in any case itself subject to the enormous genotypic and phenotypic variation that is present in the human species itself.
A second aspect of the sectoral ‘culture’ is the belief that a cadre of research-experienced clinicians is essential in the health care system for well-informed, direct health care provision, for the teaching and training of succeeding generations of practitioners, and for the design of health care systems that provide best-possible preventive and therapeutic health care to both individuals and populations (this applies to the deeply established health
‘cultures’ in India and China as much as it applies to the prevailing and much more recent ‘Western’ model).
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A third, narrowly focused ‘cultural’ issue concerning clinical research is its cost and multi-dimensional complexity compared with studies that are purely laboratory based, which is the main reason why animal and in vitro studies still vastly predominate in the broad health research area. Clinical researchers have to provide clinical service in order to underpin their investigative skills. Their involvement in patient care and also frequently in the training of new clinicians makes heavy time demands. The research itself requires theoretical and conceptual knowledge that is difficult to acquire, and even more difficult to maintain. The costs of subject hospitalisation or recruitment, frequently repeated special investigations, multiple subject work-up and skilled monitoring are often so high that grants have to be much larger than for other types of research. Meeting regulatory requirements makes demands on time and patience not found in other areas. Teams of diversely skilled researchers have often to be put together and managed in order to address different dimensions of clinical problems, with appropriate risk management.
Simply put, clinical researchers, who must frequently also have access to the same kind of expensive equipment and consumables used by laboratory- based researchers, require a great deal of courage, resilience and energy, and must make a considerable, concerted effort on a variety of fronts. It is part of a certain ‘culture’ in which this kind of uphill research activity is valued, supported and deliberately fostered; it is easy to regard it in another ‘culture’
as ‘causing too much trouble and cost’.
The fourth important ‘cultural’ issue in the sector is the balance of risks and benefits. Clinical research is unique in its interfaces, firstly with human rights and secondly with risk analysis. In both areas, certain kinds of ‘cultures’ can create significant impediments to the conception and execution of research projects and programmes, while others can have facilitatory and enhancing effects. Because of the element of novelty and uncertainty, there is a popular perception that clinical trials are more risky than everyday activities, while in fact this is not the case. A more precise adjustment of risks to benefits can bring about a prevailing ‘culture’ that promotes both clinical research and its positive impacts on the health of the population.
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The fifth, often controversial consideration is context and relevance, which amounts in practice to translational purpose. It is possible in a particular culture to consider clinical science to be part of the ‘blue sky’ search for knowledge which sometimes ‘spins off’ benefits as serendipitous outcomes. An alternative culture seeks out topics that are obviously related to major health problems, and addresses them according to deliberate project designs, usually with carefully assembled multidisciplinary teams, to maximise the probability of beneficial public outcomes, and to underpin the attainment of those benefits in evidence-based ways. A balance between these polar opposites must be found in a resource-constrained system.
An overridingly important ‘cultural’ issue that directly affects the sector is motivation in respect of private as opposed to public benefit. Compared with a systemic prevalence of public-sector clinical research projects which are initiated and funded only in support of profits by pharmaceutical companies, and/or one where researchers are mainly hunting for personal glory and/or tangible benefits such as salary supplements, conference travel and other perks, the widespread existence of an ethos of public service and public benefit undoubtedly represents a desirable and necessary ‘cultural’ polarisation.
The last, but by no means least, of the dominant issues in a national culture supporting good clinical research concerns the imperative to protect and develop new discoveries in an efficient and effective intellectual property rights regimen that can bring benefits to both the health care practice and economic development of the country. This implies careful construction of partnerships, adequate funding of patent registration applications, and a tax system that incentivises innovation. It is a mind set as much as a regulatory approach.