Pharmacogenomics: from promises to public health benefits
Pharmacogenetics – the relationship between an individual’s response to particular drugs and their genetic ‘make-up’ – promises to improve health care in a number of ways. However, many questions remain to be answered before the promised benefits are realised in routine clinical practice.
The most basic of these include the scale and applicability of the technology and the timeframe for its adoption, and the need for robust evidence of cost-effectiveness and clinical utility.
We believe social science offers important insights into the development and, equally as significant, introduction of new technologies like pharmacogenetics (PGx).
The potential uses
Recent scientific advances coupled with development of new research tools has resulted in rapid growth in interest in pharmacogenetics (PGx). As many commentators have noted, the technology replaces the ‘one size fits all’ approach characteristic of current therapy with one that seeks to deliver ‘the right drug at the right dose to the right person’.
The possible uses of PGx may be summarised as follows:
reducing drug attrition by identifying metabolic pathways likely to give rise to adverse drug reactions (ADRs) early in clinical studies – the most common use for PGx by pharmaceutical companies in drug development;
new drug development for “niche” markets based on genotype or gene expression, such as targeted cancer drugs (which may be ‘blockbusters’ in terms of sales);
development of previously withdrawn products or ‘failed’ drug candidates for targeted groups (‘drug rescue’);
reducing ADRs of licensed drugs by targeting patients according to genotype;
improving efficacy of licensed drugs by targeting patients according to genotype.
Of these five possibilities, the drug industry is concentrating on the first two, with smaller genomics companies focusing on the third option, either independently or in collaboration with pharmaceutical companies. The last two options offer the opportunity to apply PGx to the potentially important area of already licensed drugs, a subject which we return to below.
Are drug label changes sufficient?
The approach adopted by regulatory agencies towards PGx is a crucial factor with regard to uptake. In the US, the Food and Drug Administration (FDA) is encouraging PGx via its policy of including PGx information on certain drug labels, as part of the agency’s wider Critical Path initiative that aims to encourage innovation and make new treatments available sooner. The ‘drug label’, which lists the indications, mechanism of action, dosage and possible side effects, is viewed by the agency as the primary source of information for physicians (although, interestingly, there is little data to show that doctors actually read them) and has therefore given high priority to this policy. However, this policy is not without its critics. To date, these label changes have said nothing about whether a test should be conducted prior to prescribing, nor even if a test is actually available to use. Neither is anything mentioned about the important issue of interpretation of test results – an important part of PGx-based prescribing since we are talking about probabilities of an association between particular gene variants and the likelihood of a serious adverse event, for example.
US health management organisations (HMOs), such as Kaiser Permanente, Blue Shield, and Aetna, are also exploring the potential benefits of PGx. They must decide whether to reimburse for tests and if adoption is likely to reduce their costs as well as bring benefits for patients.
Investing in already licensed drugs that would generate the greatest public health benefits?
As noted above, pharmaceutical companies are investing considerable sums in PGx. But it is important to note that this investment is focused on developing new products based on PGx principles, not applying these techniques to already licensed drugs as there is little commercial incentive to undertake the latter. The significance of this is that applying PGx to widely-used generic medicines, rather than expensive new products, may provide the greatest benefits in terms of public health.
We have referred to the lack of evidence with regard to the demonstrated benefits of PGx in ‘real-world’ clinical situations. The lack of commercial interest in licensed drugs raises the possibility of a form of market failure.
So, who is going to undertake the required clinical trials and generate the evidence base upon which to base decisions about adoption of PGx in the case of generic drugs? Responsibility for evidence of clinical utility – a key requirement for uptake – and test development will essentially reside with other sectors like diagnostics companies and health care providers. We believe there is a case for public intervention (or perhaps public-private initiatives) to undertake such studies so that decisions can be made about the benefits or otherwise in different therapeutic areas. The UK Department of Health’s funding of six studies in 2004, as part of a wider plan aimed at encouraging the uptake of genetics in the UK’s National Health Service (NHS), is an example where public support has been provided to develop the evidence base.
Based on the report “False positive”:
For more information about the social science research we are pursuing on PGx go to:
Return to the dossier on:
|Based on :||False Positive? The commercial & clinical development of pharmacogenetics|
|Authors :||Paul Martin, Ph.D., Graham Lewis, Ph.D., Andy Smart, Ph.D., Andrew Webster, Ph.D.|
|Adapted by :||Graham Lewis, Ph.D., Andrew Webster, Ph.D.|
Paul Martin, Graham Lewis, Andrew Smart & Andrew Webster (2006). False Positive? The commercial & clinical development of pharmacogenetics. The University of Nottingham.
Pirmohamed, M and Lewis G (2004) The Implications of Pharmacogenetics and Pharmacogenomics for Drug Development and Health Care In Regulating Pharmaceuticals in Europe: Striving For Efficiency, Equity and Quality, edited by Elias Mossialos, Monique Mrazek and Tom Walley, Open University Press.
Webster A, Martin P, Lewis, G and Smart, A, Integrating pharmacogenetics into society: in search of a model, Nature Reviews Genetics, 2004, 5(9) 663-669.
Webster. A, (2007) Health, Technology and Society: A Sociological Critique (London: Palgrave Macmillan).