Need help?

800-5315-2751 Hours: 8am-5pm PST M-Th;  8am-4pm PST Fri
Medicine Lakex

Rhetoric and hype: wheres the ethics in pharmacogenomics?

Am J Pharmacogenomics 2003; 3 (6): 375-383  Adis Data Information BV 2003. All rights reserved.
Rhetoric and Hype
Where's the ‘Ethics' in Pharmacogenomics?

Bryn Williams-Jones1,2 and Oonagh P. Corrigan1,3 1 Centre for Family Research, Faculty of Social and Political Sciences, University of Cambridge, Cambridge, UK2 Homerton College, University of Cambridge, Cambridge, UK3 Cambridge Genetics Knowledge Park, University of Cambridge, Cambridge, UK 3. Question 1: Is Pharmacogenomics an Imminently Achievable Vision? . . . . . . . . . . . . . . . . . . . . . . . . . . 379 There is increasing discussion in public and academic forums about the anticipated benefits of pharmacoge- nomics, as well as the attendant social and ethical implications of this research. Yet there is often an implicitassumption that the benefits of pharmacogenomics are ‘just around the corner' and will significantly outweighthe costs. Furthermore, it is argued that the associated ethical issues are not as profound as those that emerge inother areas of genetics, and that experience gained wrestling with these other issues provides ample ethical andregulatory tools to deal with any problems arising with pharmacogenomics.
We contend that this vision of ethical and social issues associated with pharmacogenomics is not so clear-cut.
The scientific evidence is more complex and contested than the public, academics, and policy makers, have beenled to believe, and while there may be real clinical benefits from this research, they are not likely to arrive in thenear future. Pharmacogenomics research is also occurring in a terrain occupied by a multitude of different andpowerful actors, with diverse and often competing interests. It is therefore essential to investigate the broadersocial and political context, unravel the various interests pressuring for early implementation, and deconstructthe hype in order to appreciate a fuller range of ethical and social consequences associated with the currentdevelopments of pharmacogenomics.
Williams-Jones & Corrigan 1. A Vision for the Future
expected to result from pharmacogenomics research. However, aswith other developments in the areas of genetics – such as stem There are many utopian visions for the future of pharmacoge- cell research, gene therapy, or cloning – increasing attention is also nomics. One such vision is illustrated by the following extract, being paid to the potential social and ethical implications. Most of from the News & Events: Medicine by Design page of the National the ethical literature has focused on concerns about potential Institute of General Medical Sciences (National Institutes of problems associated with genetic testing, issues of equity, and Health [NIH]) website – interestingly, while other pages on this informed consent. Like genetic testing, pharmacogenetic tests website are recent, this particular page has not been updated since have raised concerns about access to healthcare services, and privacy and confidentiality insofar as disclosure of genetic infor- "September 29, 2015. You wake up feeling terrible. You've mation may result in discrimination and stigmatization or loss of been sick for days, and you know it's time to see a doctor. In the health or life insurance.[8] Issues of equity in access to pharmaceu- office, the physician looks you over, listens to your symptoms, and ticals have arisen, with the fear that pharmacogenomics will lead prescribes a drug. So far, there is nothing futuristic about this to ‘orphan genotypes' – the possibility that some people might not scene. But the drugs you'll take in the next century are likely to receive needed drugs because their genotypes or drug response differ in appearance and action from the medicines you take today.
profiles are too rare to warrant expenditure in drug development.[9] … Drug molecules will be rationally designed – with the aid of In the case of pharmacogenetic add-on studies to clinical drug computers – to fit with the precision of keys into lock-like cell trials, the ethical issues center on the implementation of informed surface proteins, called receptors. … Prescribing and regulating consent processes and the potential coercion of research subjects, drug dosage will become less of an art and more of a science. The as well as the control of genetic materials and information in DNA current, rather crude methods of deciding dosage based on your banking.[10-12] Some commentators have noted that these issues are weight and age will be replaced by more sophisticated ways to not particularly novel or unique to pharmacogenomics, suggesting tailor a drug regimen to your genetically determined ability to that we already have the ethical and regulatory resources needed to process medicines. In the future, a blood test in the doctor's office deal with most problems raised by pharmacogenomics.[13,14] Fur- could reveal if you have the enzymes you need to process a given thermore, the ethical literature tends to take the promises of drug. If, for example, you do not manufacture as much of a pharmacogenomics as given.
particular enzyme as other people, the doctor will recommend Recent work from the field of sociology has investigated the lower – yet still effective – doses of drugs that interact with that role of hype and ‘visions' in shaping developments in pharma- enzyme. In short, the medicines you take in the next century cogenomics,[15] arguing for a more social science-based ethical should attack disease organisms and diseased cells more forceful- analysis that focuses on the preliminary and contested nature of the ly, while sparing healthy cells. Moreover, better vaccines, pre-symptomatic screening for disease, and a better understanding of science behind pharmacogenomics and the key actors involved in how chronic diseases arise will all mean that you may not get sick shaping its development. In this paper we employ such a perspec- in the first place. These predictions about the future can be made tive in order to identify what we consider to be salient, but often with confidence, thanks to the incredible strides now being made overlooked, ethical and social issues concerning current develop- in pharmacology and other areas of basic biology."[1] ments in pharmacogenomics. Pharmacogenomics is being driven This vision, imagined not only by the NIH and other govern- by a variety of powerful actors in the biotechnology and pharma- ment agencies but also by major sectors of the pharmaceutical ceutical industries, various government departments, and patient industry,[2,3] is premised largely on current developments in groups. Thus, alongside an examination of the ‘standard' ethical pharmacogenomics.1 According to much of the scientific litera-
issues (detailed discussion of the ‘standard' ethical issues can be ture, in the not too distant future a plethora of benefits such as found elsewhere[8,13,14,16,17]), it will also be critical to take account more cost-effective drug development[4,5] and personalized medi- of the broader context, which will be the focus of our investiga- cine that better responds to individuals' differing needs,[6,7] are tion. To this end, we examine: ‘Pharmacogenomics' is the name given to a broad-based pharmaceutical industry-led initiative, based on developments brought about by the Human Genome Project, coupled with functional genomics and high-throughput screening methods, which aims to capitalize on these insights to discover newtherapeutic targets and interventions and to elucidate the constellation of genes that determine the efficacy and toxicity of specific medications.
‘Pharmacogenetics' is the term used to define the narrower spectrum of inherited differences in drug metabolism and disposition linked to individualgenetic variations. Although the two terms are often used interchangeably in the literature we aim to keep the terms distinct while recognizing that this issomewhat arbitrary.
 Adis Data Information BV 2003. All rights reserved.
Am J Pharmacogenomics 2003; 3 (6) Rhetoric and Hype • the extent to which large pharmaceutical companies are en- groupings we have made of the various actors. Instead, our intent thused with pharmacogenomics is to give a rough sketch of the different attitudes that some of themain actors have with regards to pharmacogenomics R&D.
• the implications of the complex interaction between large phar- maceutical and small biotechnology companies in drug devel-opment 2.1 The Enthusiasts • the extent to which interests of various governmental depart- ments such as industry, health, finance and drug licensing agencies coincide or conflict with national political and eco- Among the main enthusiasts (at least overtly) are some of the nomic agendas,2 and
major companies of the pharmaceutical industry. Drug develop- • the role played by healthcare providers such as pharmacists and ment is an extremely time consuming and costly operation, taking physicians in the deployment of pharmacogenomics.
10–15 years and 300–600 million US dollars ($US),[18] with a More generally, we identify sources of hype and rapid imple- success rate of about one in ten, only a fraction of which will be mentation. Rather than focus on the future implications of ‘blockbusters'. A blockbuster drug such as the anti-ulcer drug pharmacogenomics in clinical practice, we argue that such consid- ranitidine hydrochloride (Zantac3) can transform the fortunes of
erations may be somewhat premature and detract attention from a company. Thanks largely to the success of this top-selling drug, issues pertaining to current research and development (R&D). In UK-based GlaxoSmithKline is now one of the largest and most examining these broader socioethical concerns, we address two successful pharmaceutical companies in the world. In 1987, fundamental questions that underpin our concern about hype: are Zantac earned around US$500 million on world-wide sales of the hoped-for optimistic visions of pharmacogenomics achievable US$1500 million.[19] But the difficult task of bringing novel mole- in the near future; and what are the costs and risks of such a cules to market and maintaining a 15% financial growth rate venture? While a certain amount of hype may be necessary for expected by shareholders is putting increasing pressure on ‘big developing interest in and enrolling political and financial support pharma' to find other more efficient and profitable approaches to for research, too much hype can lead to unrealistic expectations drug development.[20] Development of new blockbuster drugs is that mobilize corollary services before the science is substantiated, becoming increasingly difficult,[21] so when put in the context of resulting in a discrediting of the science and undermining of public an extremely competitive market, it should not be surprising that trust. In order to address these questions, it is important to first the promise of pharmacogenomics is very alluring.
identify the key actors involved in the development of "Industry analysts predict that, by improving medical outcomes pharmacogenomics, outline their relative positions, and see how by the use of pharmacogenomics enhanced drugs and diagnostics, they are involved in creating a positive vision for pharmacoge- pharmaceutical companies could benefit to the order of US$200 million to US$500 million in extra revenue for each drug. Patients,physicians, and managed care organizations will also benefit from 2. The Key Actors
more effective treatments and lower overall healthcare costs. Forthese reasons, pharmaceutical companies have begun to integratepharmacogenomics into drug development programs." (Norton,[4] The key actors involved in the development, production, and application of pharmacogenomics can be roughly divided into three camps: those who are active, enthusiastic promoters of Sectors of the industry, and indeed non-industry scientists, are pharmacogenomics; those who are less sure (but hopeful) about hailing pharmacogenomics as ‘revolutionary' insofar as it promis- the endeavor; and the skeptics or undecided who are dubious about es to advance drug development from its status as an ‘art' to one of the potential benefits and timelines of this research. This categori- a fully fledged ‘science'.[2] But the so-called ‘rule of thirds' in drug zation is not intended as a systematic analytic framework – there development – that one-third of drugs will be effective, one-third will clearly be overlap and blurring of boundaries between the ineffective, and one-third damaging – means that for some compa- categories, as well as complexity within the somewhat arbitrary nies the major draw of pharmacogenomics may also be the ability By ‘government departments', we mean those bodies or agencies within national governments that are responsible for particular areas of government functioning. Our intent is to generalize for types of government department and not to refer to specific national agencies, although there are obviously
important national distinctions in the constitution and function of such bodies. Similarly, we believe that the international scope of medical and
pharmaceutical research and the transnational nature of many of the major pharmaceutical companies make broad generalizations about attitudes
towards pharmacogenomics appropriate for our discussion of rhetoric and hype.
The use of tradenames is for product identification purposes only and does not imply endorsement.
 Adis Data Information BV 2003. All rights reserved.
Am J Pharmacogenomics 2003; 3 (6) Williams-Jones & Corrigan to avoid litigation (given rising costs), despite the rhetoric of to pharmaceutical companies interested in building ‘partnerships' personalized medicine. For example, Karen Cassidy of Penn- to support comprehensive product promotion.[34] sylvania brought legal action against GlaxoSmithKline claimingthat 30% of the population, who have a genotype known as HLA- 2.2 The Followers DR4+, are predisposed to a treatment-resistant form of Lymedisease. GlaxoSmithKline was accused of failing to screen patients adequately for the condition, despite facing questions on the issue While many of the major pharmaceutical companies are en- from the US FDA.[22] couraging pharmacogenomics research, some within the industry Pharmacogenetic tests, such as those for the cytochrome P450 are responding, if not with fear, then at least with some trepida- (CYP) 2D6 family of enzymes,[6] are currently being used in tion.[27] Even within an individual company, views on the future of clinical research, and small biotech companies such as Genelex[23] pharmacogenomics can vary greatly. Official corporate statements are currently advertising these tests (CYP2D6, CYP2C9, and do not always coincide with personal views of researchers, and CYP2C19) direct-to-consumer[24] and making them available for there are often differences between departments. Scientists in the purchase over the Internet.[25,26] If a small company can develop a genetics unit, for example, may be enthusiastic about the com- variety of inexpensive and accurate diagnostic tests, they are that pany's future plans for developing pharmacogenomics, while re- much more likely to secure continued venture capital support searchers outside the genetics team or staff in the marketing while garnering interest from the large pharmaceutical companies.
department may be much less enthusiastic. As the UK director of Private healthcare organizations also have a keen interest in such the clinical genetics unit of one such company explained in 2002: developments, because of the potential competitive advantage in ". in our company we've never done anything like this before.
attracting and retaining members of private health plans for those And that's certainly viewed with suspicion. The pharmaceutical companies who are first to offer tailored healthcare to their mem- industry is not the most responsive to change. Our working prac- tices are standardized and highly regulated, and if I think aboutwhy are they so resistant to all this…I've come to the conclusion that it is actually all to do with business, it's a risky business, drug Finance and health departments in developed nations are wor- development…it's all about reducing risk, managing risk …" ried by the rapidly mounting costs of healthcare delivery and the (Corrigan OP, personal communication).
significant rising proportion of this being spent on pharmaceuti- It appears that some pharmaceutical companies are uneasy cals.[28,29] Thus, a hope is that potential cost savings will be about pursuing what they see as a high-risk enterprise. At the UK realized from increased efficiency of a more refined (less trial and head office of a major pharmaceutical company and proponent of error) prescribing method, that reduces the costs of morbidity and pharmacogenomics, the company's pharmacogenomics research mortality from adverse drug reactions (ADRs).[27] Further, by unit was housed in a temporary prefabricated building with no supporting pharmacogenomics R&D, governments are also hop- foundations of that was not even listed on the main corporate ing to encourage the creation of marketable knowledge that will facilities map. This is a striking metaphor, suggesting unstable lead to start-up biotechnology companies, high-technology em- underpinnings and an uncertain future.
ployment, and ultimately lay the groundwork for the ‘knowledge- based economy'.[30-32] Drug licensing agencies have a close working relationship with the pharmaceutical industry, often leading to ‘regulatory cap- ture',[35] so there may be significant pressure to respond favorably There is also a great deal of interest from some patient groups to pharmacogenomics.[36] In contrast with finance or some health and support organizations. Their hope, which is in line with the departments, government agencies more concerned with the provi- visions put forward by proponents of pharmacogenomics, is that sion of healthcare at the population level may view pharmacoge- pharmacogenetic tests will permit better selection of appropriate nomics as another ‘high-tech quick fix' to larger systemic issues medications to avoid ADRs, while pharmacogenomics research requiring a change in philosophy instead of new technologies.
will lead to better drugs for both common and rare conditions.
Patient groups are increasingly involved in charitable fundraising 2.2.3 Medical Professionals
for medical research and advocacy to push for coverage of new Early implementation of pharmacogenetic testing, in particular diagnostics, drugs, or medical treatments,[33] and their growing tests made available ‘direct-to-consumer' and ‘over the Internet' influence on policy makers means that these groups are attractive by small biotechnology companies, in concert with increased  Adis Data Information BV 2003. All rights reserved.
Am J Pharmacogenomics 2003; 3 (6) Rhetoric and Hype awareness of ADRs and litigation of physicians and pharmacists 3. Question 1: Is Pharmacogenomics an Imminently
for mis-prescribing medications, may influence medical profes- sionals to demand the implementation of pharmacogenetic testing The hopes of pharmacogenomics are based on two research to mitigate liability. Nevertheless, some professionals, for exam- strategies. First, pharmacogenetic tests of individuals are being ple the UK Royal Pharmaceutical Society, see pharmacogenomics developed to more accurately predict drug response in order to as a way of revolutionizing their role and interaction with pa- reduce the numbers of ADRs (as mentioned in section 3.1.1 with CYP2D6), optimize drug selection and improve drug efficacy – ‘the right drug for the right patient at the right time'.[6,36] Secondly, To many, pharmacogenomics promises to be the first functional pharmacogenomics research analyzing single nucleotide polymor- technology to come from the significant public and private invest- phisms (SNPs) to identify individual correlation of genes with ment in the Human Genome Project, and this is important given disease and comparisons of genomic variation across populations the failure of gene therapy to deliver on its promises.[38,39] Thus, is being pursued in the hope of developing new areas of pharma- for a number of actors, though recognizing the need for further ceutical research while enhancing the development of safer drugsfor specific populations.[3] research to develop the science from genotype to phenotype,pharmacogenomics is a very attractive option and one to be positively supported. In the words of one proponent: "We expect that there will be a move from diagnosis by While the Human Genome Project may be largely com- symptoms to diagnosis by symptoms and mechanisms. Diseases plete,[47,48] conservative estimates are that we are at least decades will be seen to be heterogeneous and not uniform. Care standards away from actually having a functional understanding of the will be tailored to the individual patient rather than standard genome and the proteome.[49] Despite significant progress in build- approaches used for everyone. And perhaps there will be an end to ing a SNP map of tens of thousands of markers for the coding the one-size-fits-all ‘blockbuster' medicine – a medicine used to region of the human genome,[50] the connection between genotype treat everyone – and emergence of the ‘minibusters': medicines and phenotype in drug metabolism and disease manifestation for subsets of patients based upon their pharmacogenetics" (see remains complex and elusive. Investigations of how individuals McCarthy,[40] page 143).
and groups react to particular medications will rarely result in onlyone gene locus being responsible for metabolism of a drug, but rather most of the inherited response to drugs will be polygenic.
Even within the same family of drug metabolizing enzymes (or Many working in the field of public health, however, are drug transporters), there exist multiple pathways that partially skeptical. They argue that genetic technologies, in general, are obscure the clinical effects of the genetic polymorphism,[51,52] likely to have very specific benefits for relatively small numbers of dramatically increasing the possible permutations and the diffi- people in the developed world, and will not be an effective means cultly of linking cause and effect.
of improving population health.[41,42] By contrast, promoting pub-lic health or non-health services that addressed the broader deter- 3.2 Other Variables and Clinical Trials minants of health (e.g. income disparity, affordable housing, ordiet) would be far more effective.[43-45] Within the medical and Genetics is not the only relevant factor in drug efficacy. There scientific communities pursuing pharmacogenomics research, is far more variation in drug response due to how individuals there are also some dissenting voices calling for caution and actually take their medications (e.g. consistency of timing and patience. Some of the benefits of pharmacogenomics may be dosage) than with respect to genetic variation. Age is an extremely realized, they argue, but this science may not provide the hoped- important variable in drug response, especially for groups such as for cost savings, and research will take much longer than anticipat- children and the elderly who are more likely to experience toxic ed to produce clinical applications.[46] Similarly, some of the big effects from prescribed medications.[53,54] ‘Environmental' com- pharmaceutical companies that are publicly in favor of ponents such as diet, lifestyle, other medications, or alcohol con- pharmacogenomics may privately be very pessimistic (especially sumption may significantly affect drug functioning or produce the administrators and accountants) about the short- to medium- ADRs.[55] Yet in pharmaceutical clinical trials designed to test term benefits, and thus actively seek to undermine or at least slow safety and efficacy of new drugs, the study samples are small the research area.[15] This leads us to our first major question, are (rarely more than a few thousand participants, until at least phase the hoped-for positive visions of pharmacogenomics realizable? IV) and relatively homogeneous, with groups such as women and  Adis Data Information BV 2003. All rights reserved.
Am J Pharmacogenomics 2003; 3 (6) Williams-Jones & Corrigan the elderly frequently under-represented.[56] Clinical trials do not and potentially conflicting agendas, such as offering (and building take into account how a drug will actually be used in real life demand for) pharmacogenetic tests not coordinated with particular situations and, thus, will only detect a few major ADRs and rarely drugs. This is not to say that the situation is untenable for large those that occur due to long-term exposure, or that result from a pharmaceutical companies, who could buy up small biotechnology combination of social and environmental factors.[57] companies or negotiate attractive licensing or partnership arrange- The implications for pharmacogenomics are obvious. Deter- ments. However, the large companies may be wholly uninterested mining which genetic markers accurately correlate with positive or in taking this direction, and instead wish to focus on the more adverse drug response will be extremely difficult, given the com- efficient and effective drug development for particular population plex interaction of multiple genetic components with environment, genotypes. The new reality is that the terrain is complex, harder to diet, cultural background, and variable patient compliance. Far predict and shape, and brings with it substantial financial uncer-tainty and risk for industry.[62] from simplifying the clinical trial process, as had been hoped bymany proponents,[3,40] large clinical trial populations may actually This uncertainty also has implications for the governments who be required in order to isolate the impact of a drug. It will also be subsidize and support research and purchase pharmaceutical prod- challenging to establish trials of sufficient size given the small size ucts. An over-attention to pharmacogenomics may be misplaced if of the target populations, while a large trial with a diverse popula- research does not ‘pay off' in the short to medium term. This could tion will compound the difficulty of accounting for all the relevant lead to missed opportunities with already functional technologies, variables. And even the exemplars of the first generation of diverting attention from more systemic issues such as the need for pharmacogenetics, such as trastuzumab (Herceptin) and aba- better hospital staff training to reduce high rates of drug adminis- cavir, remain contentious – for Herceptin, there is debate about tration errors.[63] Moreover, if a multitude of pharmacogenetic whether or not it is an instance of pharmacogenetics,[58,59] while in tests and ‘designer drugs' are to enter the market, significant the case of abacavir its purported ‘hyped' utility[60] is question- government resources will have to be dedicated to drug oversight ed.[61] As with research into gene therapy, the enormous complexi- and regulation in conjunction with cost-effectiveness analyses to ty of genetics and genomics research means that much work determine which drugs should be covered by health insurance, and remains and clinical applications are unlikely to be ‘just around the for which populations.[14,64] 4.2 Public Acceptability 4. Question 2: What are the Costs and Risks of
this Venture?

A significant concern for proponents of pharmacogenetics and pharmacogenomics is public anxiety, insofar as any developmentwith the term ‘genetics' attached may create alarm and negatively 4.1 Financial Risk affect product marketability. Pharmacogenetics may be linked in In developing an understanding of the complexity and diversity the ‘public mind' with other more contentious issues, such as of individual response to medications, pharmacogenomics re- genetic testing and concerns about privacy and health insurance, search is narrowing the definition of disease by elucidating geneti- cloning, or genetically modified foods. Even if this link is not a cally distinct subtypes, and reducing the size of the target popula- reality, scientists who advocate for pharmacogenomics – such as tion that will respond safely and effectively to a particular med- Allen Roses[2,3,60] and Alun McCarthy[40] of GlaxoSmithKline – ication. Pharmacogenomics is thereby undermining the possibility are sufficiently concerned that they are at pains to differentiate for developing and marketing blockbuster drugs. Thus, instead of pharmacogenetics from other more ethically problematic forms of competing with a few other companies to launch the ‘gold genetic intervention. "This is not gene therapy or genetically standard' blockbuster drug treatment, a multiplicity of drugs will modified foods or genetic engineering. We must consider need to be developed for particular disease subtypes and patient pharmacogenetic applications separately and acknowledge a dis-tinct set of ethical, legal, social and regulatory variables."[2] response profiles. This makes it less likely that one company willhave the major market share, and the market becomes segmented.
Pharmaceutical industry representatives are clearly trying to From the viewpoint of some large pharmaceutical companies, avoid the mistakes made by Monsanto in their marketing and there may be over-diversification in the sector. There will be deployment of genetically modified organisms.[65] In demonstrat- increased competition with other large companies,[21] and a need to ing their awareness of the social and ethical issues raised in the work with small biotechnology companies to obtain new drug academic science and ethics literatures (e.g. genetic privacy, in- targets.[20] Yet those biotechnology companies may have different formed consent, DNA banking), they are also showing how the  Adis Data Information BV 2003. All rights reserved.
Am J Pharmacogenomics 2003; 3 (6) Rhetoric and Hype industry is responding proactively to these concerns.[66] Alongside governments and professional organizations, large pharmaceutical There has been a great deal of hype and rhetoric in recent years companies engaged in pharmacogenomics research are imple- about the benefits of pharmacogenetics and pharmacogenomics – menting policies (outlined in public information leaflets and we are told that such research will produce personalized medicine videos) designed to prevent discrimination based on genetic infor- within a decade, revolutionize the way pharmaceuticals are devel- mation, to strengthen patients' and consumers' autonomy and oped, and fundamentally change the nature of healthcare delivery.
ability to make informed decisions, protect individual privacy, and This picture in some respects resembles that painted for gene to ensure access to appropriate drugs (e.g. the ‘orphan drug' or therapy in the 1990s. Gene therapy was surrounded by a great deal ‘orphan genotype' problem). However, in these ethical analyses, of excited anticipation, with researchers, investors, and industry the purported benefits of pharmacogenomics are taken at face enthusiastically embracing this technology, a move that later value and simply assessed in contrast to the potential risks. For proved premature given the complexity of both understanding example, while the recent UK Nuffield Council on Bioethics gene function and developing safe and effective delivery mechan- consultation on pharmacogenetics[16] raised numerous points isms. The pharmaceutical industry is a powerful force with major about the economic and regulatory implications and a variety of interests (at least in the long term) in seeing pharmacogenomics other ethical issues, it does not fundamentally challenge nor as- flourish, an endeavor requiring substantial and sustained venture- sessed the ethical impetus for pharmacogenetics – that this tech- capital investment. We should, thus, be equally skeptical about nology will necessarily eliminate ADRs.4 In claiming this ethical
claims associated with pharmacogenomics. It is not a panacea for impetus, proponents of pharmacogenomics draw attention to the all that ails individuals, corporations, and governments. If pharma- serious detrimental impact of ADRs on public health and the cogenomics is going to deliver on its promises, the field will need ability of this technology to alleviate the problem. Not surprising- comprehensive research that incorporates the diversity of factors ly, there are also voices in the pharmaceutical industry concerned involved in drug metabolism and the genetic bases for dis-ease.[17,70] about pushing this approach too forcefully, fearing that pharma-cogenomics may increase instead of alleviate public anxiety by From discussions in the ethics literature of the associated social drawing attention to how many of the currently available drugs and ethical implications arising from predictions about the appli-cation of pharmacogenomics, it is clear that in many respects, the have serious adverse effects.
issues and their remedies will be similar to those encountered in A focus on concerns about the extent to which pharmacoge- other areas of genetics. However, there are further issues that need nomics can address (or further inflame fears about) ADRs tends to to be addressed. Unfortunately, the conventional approach to minimize discussion of the other causes of ADRs. While the ethical analysis of issues associated with emerging health technol- Nuffield Report briefly mentions "errors in prescribing, poor ogies too readily accepts scientific claims of clinical benefit. Our compliance by the patient, and interactions between a particular examination suggests the need for more critical reflection on the medicine and other substances, including othe medications",[16] it hype and rhetoric deployed by scientists and other key actors in the does not discuss other important variables such as age, sex. Atten- development of new technologies. This is of crucial importance tion to issues of ADRs may be both a scientific and ethical when such enormous financial incentives are at stake. Work that ‘smokescreen' – the likely success and benefits of pharmacoge- ‘maps' the key actors, reveals how these actors interact with each nomics are accepted without in-depth questioning of the limita- other, and clarifies the various agendas involved in building a tions of the science or other social or ethical implications. In vision that drives pharmacogenomics R&D[15] must play a key role particular, by not paying sufficient attention to the complexity of in understanding the ethical and social aspects of this developing genetics and environmental interactions, and the difficulty of field. This understanding will set the groundwork for broader distinguishing these different variables, there is a real danger of analysis of the diversity of costs and risks associated with further legitimating a logic of ‘geneticization' or ‘genetic deter- pharmacogenomics, a more conservative estimate of the timeline minism', which many commentators in the science, social science, for realization of clinical benefits, and an evaluation of the appro- and ethics communities have been challenging for decades with priate level of R&D support. Deflating the hype and ‘unpacking' regards to genetic testing, cloning, or eugenics.[67-69] the rhetoric is essential for a social and ethical critique of the The Nuffield Report concedes that only some ADRs are caused by genetic differences and acknowledges that the benefits, in terms of the promise of individually tailored medicine, have been exaggerated and that developments in pharmacogenetics are likely to lead to ‘probabilistic' rather than‘personalised' medicine.
 Adis Data Information BV 2003. All rights reserved.
Am J Pharmacogenomics 2003; 3 (6) Williams-Jones & Corrigan 19. Collier J. The health conspiracy. London: Century Hutchinson, 1989 overly optimistic vision of pharmacogenomics. In so doing, it 20. O'Reilly B, Schlosser J. There's still gold in them thar pills. Fortune 2001 Jul; 23: becomes possible to present an alternate vision that is more realistic about the potential benefits of pharmacogenomics, there- 21. Horrobin DF. Innovation in the pharmaceutical industry. J R Soc Med 2000; 93 (7): by enhancing instead of undermining public trust in this field of 22. Clark A. Tick puts drugs maker in the rough. Guardian 2002 Mar 7 [online].
Available from URL:,3604,663032,00.html [Accessed 2003 Apr 29] 23. Genelex. Health and DNA [online]. Available from URL: http:// [Accessed 2003 Sep 17] 24. Gollust SE, Hull SC, Wilfond BS. Limitations of direct-to-consumer advertising The authors would like to thank Paul Martin and Adam Hedgecoe for for clinical genetic testing. JAMA 2002; 288: 1762-7 sharing their ideas about pharmacogenetics, and Martin Richards and Chris 25. Williams-Jones B. Where there's a web, there's a way: commercial genetic testing MacDonald for their extremely helpful comments on drafts of this paper. Bryn and the Internet. Community Genet 2003; 6 (1): 46-57 Williams-Jones was supported by fellowships from the Social Sciences and 26. Gollust SE, Hull SC, Wilfond BS. Direct-to-consumer sale of genetic services on the Internet. Genet Med 2003; 5 (4): 333-7 Humanities Research Council of Canada, and Homerton College. Oonagh 27. Snedden R. The challenge of pharmacogenetics and pharmacogenomics. New Corrigan was supported by a research grant from the UK Wellcome Trust Genet Soc 2000; 19 (2): 145-64 Biomedical Ethics program.
28. Guillen AM, Cabiedes L. Reforming pharmaceutical policies in the European The authors have no conflicts of interest with regards to the content of this Union: a ‘penguin effect'? Int J Health Serv 2003; 33 (1): 1-28 29. Shah ND, Hoffman JM, Vermeulen LC, et al. Projecting future drug expenditures: 2003. Am J Health Syst Pharm 2003; 60 (2): 137-49 30. Ernst & Young Economics Consulting and Quantitative Analysis. The economic contributions of the biotechnology industry to the US economy. Prepared for 1. National Institute of General Medical Sciences. National Institutes of Health. News the Biotechnology Industry Organization. Ernst & Young Economics Consult- and events: medicine by design [online]. Available from URL: http:// ing and Quantitative Analysis, 2000 May [online]. Available from URL: http:// [Accessed 2003 Apr [Accessed 2003 Apr 29] 31. Ernst & Young. Convergence: the biotechnology industry report. Executive sum- 2. Roses AD. Pharmacogenetics and future drug development and delivery. Lancet mary. New York: Ernst & Young, 2000 [online]. Available from URL: http:// 2000; 355 (9212): 1358-61 3. Roses AD. Genome-based pharmacogenetics and the pharmaceutical industry. Nat vergence summary.pdf [Accessed 2003 Apr 29] Rev Drug Discov 2002; 1 (7): 541-9 32. Etzkowitz H, Webster A, Gebhardt C, et al. The future of the university and the 4. Norton RM. Clinical pharmacogenomics: applications in pharmaceutical R&D.
university of the future: evolution of ivory tower to entrepreneurial paradigm.
Drug Discov Today 2001; 6 (4): 180-5 Res Policy 2000; 29: 313-30 5. Bogdanovic S, Langlands B. Pharmacogenomics players. London: Financial Times 33. Mills F. Patient groups and the global pharmaceutical industry: the growing BioFrontiers Management Reports, 1999 importance of working directly with the consumer. London: URCH Publishing 6. Weinshilboum R. Inheritance and drug response. N Engl J Med 2003; 348 (6): 529- Ltd, 2000 Jan. Available from URL: groups.htm [Accessed 2003 Jun 9] 7. Evans WE. Pharmacogenomics: marshalling the human genome to individualise 34. Hayes L. The ties that bind: industry sponsorship of patient groups [online].
drug therapy. Gut 2003; 52 (90002): 10ii-18 Available from URL: 8. Moldrup C. Ethical, social and legal implications of pharmacogenomics: a critical try.html [Accessed 2003 Dec 4] review. Community Genet 2001; 4 (4): 204-14 35. Abraham J, Lewis G. Harmonising and competing for medicines regulation: how 9. Greely HT. Pharmacogenomics: promise, prospects, and potential problems. Lahey healthy are the European Union's systems of drug approval? Soc Sci Med 1999; Clinic Medical Ethics Newsletter 2002; 9 (1): 1-2, 8 10. Martin P, Kaye J. The use of large biological sample collections in genetics 36. Jazwinska EC. Exploiting human genetic variation in drug discovery and develop- research: issues for public policy. New Genet Soc 2000; 19 (2): 165-91 ment. Drug Discov Today 2001; 6 (4): 198-205 11. Spallone P, Wilkie T. The research agenda in pharmacogenetics and biological 37. Moffat A, Dawson W, Science Committee of the Royal Pharmaceutical Society of sample collections: a view from the Wellcome Trust. New Genet Soc 2000; 19 Great Britain. Pharmacogenomics: a new opportunity for pharmacists. In: Pharmacists: the scientists in the high street. Science Fact Sheet. London: Royal 12. Marks AD, Steinberg KK. The ethics of access to online genetic databases: private Pharmaceutical Society of Great Britain, 2001 Feb. Available from URL: http:// or public? Am J Pharmacogenomics 2002; 2 (3): 207-12 [Accessed 2003 Apr 29] 13. Buchanan A, Califano A, Kahn J, et al. Pharmacogenetics: ethical issues and 38. Danzon P, Towse A. The economics of gene therapy and of pharmacogenetics.
policy options. Kennedy Inst Ethics J 2002; 12 (1): 1-15 Value Health 2002; 5 (1): 5-13 14. Robertson JA, Brody B, Buchanan A, et al. Pharmacogenetic challenges for the 39. Gene therapy: work in progresss [editorial]. Nat Med 2002; 8 (7): 641 health care system: genetically based drug prescribing could decrease overall 40. McCarthy A. Pharmacogenetics: implications for drug development, patients and health costs and fuel new drug development. Health Aff (Millwood) 2002; 21 society. New Genet Soc 2000; 19 (2): 135-64 41. Baird PA. Genes, health and science policy: genetic technologies and achieving 15. Hedgecoe A, Martin P. The drugs don't work: expectations and the shaping of health for populations. Int J Health Serv 2000; 30 (2): 407-24 pharmacogenetics. Soc Stud Sci 2003; 33 (3): 327-64 42. Vineis P, Schulte P, McMichael AJ. Misconception about the use of genetic tests in 16. Nuffield Council on Bioethics. Pharmacogenetics: ethical issues. London: Nuffield populations. Lancet 2001; 357: 709-12 Council on Bioethics, 2003 Sep 23 [online]. Available from URL: http:// 43. Evans RG. Introduction. In: Evans RG, Barer ML, Marmor TR, editors. Why are [Accessed 2003 Oct some people healthy and others not?: the determinants of health of populations.
New York: Aldine de Gruyter, 1994: 3-26 17. Freund CL, Wilfond BS. Emerging ethical issues in pharmacogenomics: from 44. Mechanic D. Issues in promoting health. Soc Sci Med 1999; 48: 711-8 research to clinical practice. Am J Pharmacogenomics 2002; 2 (4): 273-81 45. Kaplan GA, Pamuk ER, Lynch JW, et al. Inequality in income and mortality in the 18. Bodenheimer T. Uneasy alliance: clinical investigators and the pharmaceutical United States: analysis of mortality and potential pathways. BMJ 1996; 312: industry. N Engl J Med 2000; 342 (20): 1539-43  Adis Data Information BV 2003. All rights reserved.
Am J Pharmacogenomics 2003; 3 (6) Rhetoric and Hype 46. Coats AJS. Pharmacogenomics: hope or hype [editorial]? Int J Cardiol 2000; 76 61. Lindpaintner K. The importance of being modest: reflections on the pharmaco- genetics of abacavir. Pharmacogenomics 2002; 3 (6): 835-8 47. Coghlan A. Final human genome sequence released [online]. Available from URL: 62. Sherrid P. Is there a market for personal medicine? US News World Rep 2003 Jan = ns99993621 [Accessed 2003 63. Taxis K, Barber N. Ethnographic study of incidence and severity of intravenous 48. National Human Genome Research Institute. International consortium completes drug errors. BMJ 2003; 326 (7391): 684-7 human genome project [online]. Available from URL: [Accessed 64. Lagay F. Pharmacogenomics: revolution in a bottle? American Medical Associa- tion [online]. Available from URL: 49. The human genome, in proportion [editorial]. Lancet 2001; 357 (9255): 489 gory/7459.html [Accessed 2003 Apr 29] 50. Holden AL. The SNP consortium: summary of a private consortium effort to 65. Millstone E. Analysing biotechnology's traumas. New Genet Soc 2000; 19 (2): develop an applied map of the human genome. Biotechniques 2002 Jun; Suppl.: 66. Dhanda RK. Guiding Icarus: merging bioethics with corporate interests. New 51. Vesell ES. Therapeutic lessons from pharmacogenetics. Ann Intern Med 1997; 126 York: Wiley-Liss, 2002 52. Evans WE, McLeod HL. Pharmacogenomics: drug disposition, drug targets, and 67. Lewontin R. The triple helix: gene, organism and environment. Cambridge (MA): side effects. N Engl J Med 2003; 348 (6): 538-49 Harvard University Press, 2000 53. Avorn J. Including elderly people in clinical trials. BMJ 1997; 315 (7115): 1033-4 68. Kegley JAK. Genetic information and genetic essentialism: will we betray science, 54. Choonara I. Clinical trials of medicines in children. BMJ 2000; 321 (7269): 1093-4 the individual, and the community? In: Kegley JAK, editor. Genetic know- 55. Corrigan OP. A risky business: the detection of adverse drug reactions in clinical ledge: human values and responsibility. Lexington (KT): International Confer- trials and post-marketing exercises. Soc Sci Med 2002; 55 (3): 497-507 ence on the Unity of the Sciences (ICUS), 1998: 41-66 56. Corrigan OP. ‘First in man': the politics and ethics of women in clinical drug trials.
69. Lippman A. Prenatal genetic testing and screening: constructing needs and rein- Fem Rev 2002; 72 (1): 40-52 forcing inequities. Am J Law Med 1991; 17 (1-2): 17-50 57. Fletcher AP. The safety of medicines. In: Griffin JP, O'Grady J, Wells FO, editors.
70. Moldrup C. When pharmacogenomics goes public. New Genet Soc 2002; 21 (1): The textbook of pharmaceutical medicine. Belfast: Queen's University of 58. Haseltine WA. Not quite pharmacogenetics [letter]. Nat Biotechnol 1998; 16 (13): Correspondence and offprints: Dr Bryn Williams-Jones, Free School Lane, 59. Lindpaintner K, Foot E, Caulfield M, et al. Pharmacogenetics: focus on pharmaco- dynamics. Int J Pharmaceut Med 2001; 15: 74-82 Centre for Family Research, Faculty of Social and Political Sciences, Univer-sity of Cambridge, Cambridge, CB2 3RF, UK.
60. Roses AD. 2025: the practice of neurology: back from the future. Arch Neurol 2001; 58 (11): 1766-7  Adis Data Information BV 2003. All rights reserved.
Am J Pharmacogenomics 2003; 3 (6)



Documento descargado de http:// el 11/01/2013. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. Rev Esp Cardiol. 2013;66(1):53.e1-e46 Artículo especial Este artículo completo solo se encuentra disponible en versión electrónica: Guía de práctica clínica de la ESC para el manejo del infarto agudo de miocardio en pacientes con elevación del segmento ST

Treatment of hypertension in patients 80 years of age or older

The new england journal of medicine established in 1812 Treatment of Hypertension in Patients 80 Years Nigel S. Beckett, M.B., Ch.B., Ruth Peters, Ph.D., Astrid E. Fletcher, Ph.D., Jan A. Staessen, M.D., Ph.D., Lisheng Liu, M.D., Dan Dumitrascu, M.D., Vassil Stoyanovsky, M.D., Riitta L. Antikainen, M.D., Ph.D., Yuri Nikitin, M.D., Craig Anderson, M.D., Ph.D., Alli Belhani, M.D., Françoise Forette, M.D.,