Abstract
It has long been recognised that individuals respond to medicines in different ways and that response is related to an individual’s genetic make-up. The study of this relationship between genetic variation and drug response is known as pharmacogenetics or pharmacogenomics (PGx) – although there is some debate about their meanings, the two terms are often used interchangeably. In many cases the existence of genetic variation affects the likelihood of adverse drug reactions and whether or not a drug will be efficacious. Understanding this relationship offers the possibility of targeting treatment according to people’s genetic profiles – so-called ‘personalised medicine’ – and improving the development, testing and use of medicines by replacing the ‘one size fits all’ approach characteristic of current therapy with one that delivers ‘the right drug at the right dose to the right person’.
However, the potential therapeutic and economic benefits of PGx depend on whether, and if so, how, the technology is incorporated into both the drug development process and clinical practice. This study is concerned with the latter domain. It will provide an international analysis of the approach that regulators are adopting towards such products, the extent to which appropriate molecular diagnostics are being developed, and the basis upon which clinicians and other health professionals are likely to incorporate PGx into medical practice in the coming years.
Social science research specifically related to PGx has tended to concentrate on providing an overview of the ‘promise’ of PGx and the social and ethical questions this raises. Although there has been research on the reclassification of disease with reference to PGx and breast cancer and Alzheimer's disease, this focuses on clinical laboratory developments rather than incorporation of PGx into public health systems. Studies have also sought to identify the influences on consultants and general practitioners prescribing behaviour and health care professionals’ perceptions of pharmacogenomics but again this is not empirically based.
The research proposed here is significantly different in focus from the above in that it will contribute in a fundamental way by focusing on a hitherto unexplored element: factors influencing the uptake of PGx in clinical practice, and how the diagnostic element of this two-part technology will be incorporated into health delivery systems.
Project description
The wider context of the study is concerned with innovation and the introduction of new technologies into health care systems more generally, A considerable body of work in the sociology of science and technology emphasises the need to understand innovation in terms of linked, interacting elements, emphasising the characteristics of socio-technical development as a complex system. This work relates to the large body of research within science and technology studies that examines technological innovation in terms of socio-technical process, rather than it being viewed as essentially technically determined. What we call socio-technical systems have to be built and then orchestrated effectively in order for innovation to succeed. In other words, there usually has to be a ‘co-construction’ or co-evolution of new technologies in parallel with new social institutions for successful adoption.
Medical innovation expresses similar dynamics: there is no simple linear path from the laboratory to the clinic. The problems it addresses are shaped not merely by perceived clinical need, but by the intersection of different frameworks of understanding, and different institutional and cultural processes. Therefore, we should anticipate that the current development and location of PGx in the health care system will depend on the resolution of tensions of a technical, professional, commercial and ethical nature.
This theoretical approach connects with a broad range work on what have been called ‘epistemic communities’, which we define here as networks of professionals, often from different backgrounds and disciplinary affiliations, but with recognized expertise and competence in a particular domain and an authoritative claim to policy-relevant knowledge within a particular knowledge area. Such communities may maintain a common purpose and commitment despite ambiguous data, such as, in this case, the viability of incorporating PGx into clinical practice and the benefits of so doing. As such, the overlapping networks that have emerged around the introduction of PGx and the drive for genetics-based diagnostics will also be analysed in terms of this concept.
PGx technology and regulation
Medicines incorporating PGx data will comprise a therapeutic agent and diagnostic (Dx) test – i.e. the product will take the form of a kit. The patient will first undergo a test to determine their genotypic profile, and the clinician will use this information to determine if there is a suitable (PGx-based) drug for the condition presented. The latter stage may be automated to some degree, to minimise the knowledge required for appropriate prescribing behaviour. This is the general model for PGx whether treatment takes place in the doctor’s surgery or a specialist clinic.
Several PGx tests are already on the market. As well as pharmacogenetics-based diagnostics, genomics companies are vigorously developing disease-based diagnostics, such as in the area of oncology. Given the lack of definitive information on why doctors presently fail to incorporate existing tests into their practice, this is an area that will benefit from additional research. Development of appropriate diagnostics is also crucial to clinical use, and the PGx diagnostics industry will be the cornerstone of PGx development and subsequent clinical acceptance. With the imminent arrival of many more such interventions, policy makers need to understand how clinicians use/do not use such technology currently, and what influences their decisions, and what is likely to do so in the future.
The approach that regulatory authorities adopt towards PGx products, including diagnostic components, is another key question facing industry and clinicians as such products will require co-approval by regulatory authorities around the world. Will PGx-based data be considered just like other clinical data or will regulators impose new demands? More specifically, what stance will regulators adopt towards clinical acceptance issues? Agencies in the USA, EU, and global forums such as the International Conference on Harmonisation have only recently started to examine the implications of PGx. However, the FDA has intimated that clinician acceptance will be a crucial component in assessment, and indications are that regulators will want assurance that practitioners will use a PGx test/treatment if it is approved
Drawing on the theoretical tools outlined above, the project will track the factors influencing the uptake of new diagnostics-based therapies based on pharmacogenetics; determine the approach of regulators to the issue of clinical acceptance in terms of regulatory assessment in US, Europe and Japan, paying particular attention to areas of inter-regional agreement and dispute; and analyse trends and developments in the diagnostics industry relating to PGx development and incorporation into clinical practice. The project builds on earlier research on pharmacogenetics and will achieve these goals through the analysis of documentary evidence, and semi-structured interviews with purposively selected academic and industry scientists, regulators and other stakeholders in the UK, Europe and the USA. The project is advised by an expert Advisory Group, with membership chosen from a broad range of expertise and interests.
Relevance to users
The research will be relevant to the following groups:
1. Clinicians confronted with decisions on whether to incorporate pharmacogenetic-based products into treatment regimes, and their professional associations;
2. Individual patients and patient groups, through a better understanding of patient relations with clinicians in an increasingly ‘geneticised’ world;
3. Professional and scientific associations relating to diagnostics;
4. The diagnostics industry generally;
5. Pharmaceutical companies engaged in the clinical and commercial development of pharmacogentic products;
6. Regulators responsible for assessing medicinal products containing pharmacogentic data and generating policy on such products;
7. Government officials and others responsible for healthcare delivery systems.
Anticipated contribution to the programme
The project relates to three core themes of the ESRC Science in Society programme, namely the governance and incorporation of new technologies; the social impacts of regulatory regimes; and the incorporation of genomics technologies into society, especially with regard to the complex mechanisms by which judgments are made about new developments in genomics.
