ethical issues in personalized medicine

DDSTR-388; No of Pages 4

THERAPEUTICSTRATEGIES

DRUG DISCOVERY

TODAY

Ethical issues in personalized medicineRuth ChadwickCesagen, Cardiff University, 6 Museum Place, CARDIFF, CF10 3BG Wales, UK

Drug Discovery Today: Therapeutic Strategies Vol. xxx, No. xx 2013

Editors-in-Chief

Raymond Baker – formerly University of Southampton, UK and Merck Sharp & Dohme, UK

Eliot Ohlstein – AltheRx Pharmaceuticals, USA

Personalized medicine

The search for personalized medicine is not a new

phenomenon, but it is only with developments in

genetic knowledge – and pharmacogenomics in parti-

cular – that the ‘personalization project’ stands a rea-

listic chance of improving health on a wide scale.

Despite recent advances, the risk of hype is still pre-

sent, as can be seen by expectations and claims sur-

rounding direct-to-consumer genetic testing. The

move towards personalized medicine may disadvan-

tage some patients in some social contexts, by shifting

the allocation of resources in the health care system.

Risks also surround the increasing accumulation of

health data that goes hand in hand with personalized

medicine: a study has been able to identify individual

research participants from stored genetic data.

Introduction

Thinking about the ethical issues associated with the objec-

tives and practice of personalized medicine requires us to

think clearly about what is meant by ‘personalization’. Close

inspection of this term reveals multiple possible meanings,

although there is arguably a core meaning which appears to

have arisen alongside the development of pharmacoge-

nomics. The very concept of ‘personalization’ seems to be

already imbued with ethical associations, appearing to rein-

force an individualist paradigm in ethics, although it may

emerge that the choice of terminology between ‘personaliza-

tion’ and ‘individualisation’ is significant. It will also become

clear, however, that ‘personalization’ is related in interesting

and different ways to concepts of responsibility. On the one

hand personalization may be perceived as a ‘project’ which

Please cite this article in press as: Chadwick, R. Ethical issues in personalized m

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Section editor:Steve Holgate – Faculty of Medicine Clinical andExperimental Sciences, Southampton General Hospital,Southampton, UK; Barbara Prainsack – Department of SocialScience, Health and Medicine, King’s College London,London, UK.

increases responsibility for the individual [1] and persona-

lized medicine fits into that. By contrast, personalization, in

so far as it requires ‘big data’, puts responsibilities on those

who curate the data.

In addition there is a host of other ethical issues raised by

personalized medicine, relating to: problems of hype; alloca-

tion of health care resources, both intra- and internationally;

issues related with perceptions of different social groups;

issues of implementation; issues related to control of data.

What is personalization?

Although the concept of personalization in medicine has to a

considerable extent become associated with genomics, it may

be helpful to remember that there is a longer history in which

debates over personalization in a wider sense have taken

place. For example, the debates over treating the patient as

a person with beliefs and wishes, and respecting patient

autonomy; the difference between treating ‘symptoms’ and

treating the patient as a whole person; the perception of

medical practice as the application of professional judgment

to the individual case – all these could be interpreted as

aspects of personalization [2].

Personalization really came into its own in a technical

sense, however, as interest increased in pharmacogenomics.

Although the latter had been implemented to some extent

since the mid-twentieth century, it became high profile as

an issue from the late 1990s onwards. The central idea

of pharmacogenomics, of prescription being informed by

edicine, Drug Discov Today: Ther Strategies (2013), http://dx.doi.org/10.1016/

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Drug Discovery Today: Therapeutic Strategies | Personalized medicine Vol. xxx, No. xx 2013


information about the variation in genetic make-up between

individuals, introduced a specific sense to personalization: in

effect, personalization became ‘geneticized’. The purported

ethical imperative driving this was underpinned by an argu-

ment about the need to reduce the incidence of mortality and

morbidity resulting from adverse drug responses (ADRs). It

should be noted that although personalization may suggest

avoiding harm to and increasing benefit for the individual,

there is a clear public health argument here. Personalized

prescribing could be genetically informed not only in relation

to the choice of drug, but also as regards dosage. As has been

pointed out in the literature, however, it might be more

accurate to call such a strategy ‘stratification’ rather than

‘personalization’ [3] – dividing the population into different

groups such as good and poor responders.

While such patient stratification may be important and

desirable from an ethical point of view, in so far as it is likely

to produce less harm and more benefit as a result of medical

intervention, it seems a somewhat awkward account of what

it means to ‘personalize’.

With the advent of whole genome sequencing (WGS) the

possibility of ‘tailoring’ medical advice and treatment to the

individual throughout a lifetime becomes at least an in

principle possibility, although the term ‘tailoring’ was used

by the UK Department of Health in 2003, before WGS was on

the horizon [4]. Under this vision all the multiple variations

between individuals could be taken into account. The use of

the tailoring metaphor is interesting. In the clothing indus-

try there is of course a distinction between clothes tailored

for the individual, and those ready to wear for the mass

market, and it might be tempting to think that this mirrors

the distinction between personalized and blockbuster

approaches to pharmaceuticals. However, within tailored

clothing there is also a distinction between ‘bespoke’ and

‘made to measure’. Whereas ‘bespoke’ clothes are created

without the use of a pre-existing pattern, ‘made to measure’

alters a standard-sixed pattern to fit the customer. The move

from genetic testing to WGS arguably suggests a move from

‘made to measure’ to ‘bespoke’. There is a caveat here, how-

ever, and that is that the word ‘bespoke’ comes from

‘bespeak’ which suggests that the individual is in control

of the process. This may be where the analogy between

personalized medicine and tailoring breaks down, as we shall

see when we come to discuss implementation.

It is important not to overlook the fact that although the

ethical argument for personalized medicine was initially to

prevent ADRs, and thus the argument for it deemed non-

controversial from that point of view, once a richer version of

tailoring comes on stream attention also inevitably turns to

benefits. The issues then include not only ‘how can we

prevent harm to this person,’ but ‘how can we maximise

the benefit?’ And that becomes increasingly complex when

allocation decisions have to be made [5�].


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More recently a new form of personalization has emerged,

relating not so much to the variation in the genetic informa-

tion of the patient per se affecting drug response, but regarding

the disease-type of the patient. Accessing the particular genetic

factors at work within tumours, for example, shows us that

‘cancer’, of the breast or otherwise, is not just one disease: there

are many subtypes. So analysing the genetic make-up of the

tumour of a patient also divides the patient population into

different types, but according to their condition rather than by

factors affecting predisposition or response.

The difference between personalization according to

genetic factors affecting response to particular drugs and

factors informing the specific disease type may not always

be clear, as can be seen from research in the variation in

response to asthma medication [6]. One in seven asthma

sufferers has a genetic variant – the arginine-16 genotype

of the beta-2 receptor. In a study carried out by researchers in

Brighton and Dundee in children, all of whom had this

variant; half were given salmeterol and the other half mon-

telukast. Those on the latter responded better. Although the

report stated that more research was needed before a genetic

test for Arg16 should be implemented, this is suggestive of a

personalized medicine approach for children with asthma.

The Department of Health commented, however, that

asthma itself is increasingly being thought of as a group of

conditions rather than a single disease:

By looking at specific genes in people and finding out their

specific genotype, patients may, in the future, be able to use

medicines that are precisely targeted to their own type of asthma

[7].

Problems of hype

The history of developments in genetics offers precedents in

which new developments appeared to promise much, only to

disappoint, at least in the early stages. The troubles faced by

gene therapy provide a good example. Similarly, there is a

worry that it may not be possible to fulfil the promises for

personalization, at least not for a long time. The possible

pathways to personalization appear to have more twists and

turns than was originally anticipated.

It has become increasingly clear that there are multiple

gaps in our understanding of the factors affecting gene

expression. Research in epigenetics and metabolomics is

producing information about how an individual’s genome

interacts with diet, lifestyle and other environmental triggers

[8]. Speaking of reconstruction model of the human meta-

bolome, co-author Pedro Mendes commented:

‘The results provide a framework that will lead to a better

understanding of how an individual’s lifestyle, such as diet, or a

particular drug they may require is likely to affect them

according to their specific genetic characteristics. The model

takes us an important step closer to what is termed ‘persona-

lized medicine’, where treatments are tailored according to the




Vol. xxx, No. xx 2013 Drug Discovery Today: Therapeutic Strategies | Personalized medicine


patient’s genetic information’ (BBSRC; URL: http://

www.bbsrc.ac.uk/news/health/2013/130305-n-study-maps-

human-metabolism.aspx).

Allocation of health care resources

Turning to resource issues, there are challenges of distribu-

tion both intra- and internationally. Singer and Daar’s classic

piece on pharmacogenomics and genetic ancestry [9] argued

eloquently against a situation in which the benefits of perso-

nalized medicine not only reinforced an individualistic ‘bou-

tique-style’ model of health care but also operated to the

disadvantage of less developed countries. They argued a case

for the possible benefits of ‘drug resuscitation’ in relation to

products that had been taken off the market in the west but

which could be beneficial in settings where the population

had relevantly different genetic factors.

Distribution of resources within a society continues to be a

very difficult issue, and one which may possibly be exacer-

bated by personalized medicine. Fleck et al. discuss the pro-

blem of information emerging that, in relation to the

prescription of a very expensive drug for cancer, some people

may benefit to the sum of a couple of weeks while others may

benefit with two years’ extra life [10]. It is not clear what

criteria would be appropriate in such a situation.

From one point of view, it might be argued that despite the

variation in benefit, each person is entitled to receive the drug.

From another, it might be argued that prescribing should be

done to maximise benefit. McClellan et al. have argued that

given the inherent limitations of the tools, reliance on an

individual’s genetic information as part of medical decision-

making could serve to perpetuate existing disparities [5].

This development challenges the presentation of persona-

lized medicine in wholly positive terms, as reducing harm

through adverse effects, and thus being of benefit – a ‘no-

brainer’. Once we go beyond prevention of harm to produ-

cing positive benefit – then issues of equity arise.

Perceptions

When a new technology is introduced, there are always

questions, not only whether there are any new ethical issues,

but also whether there are any public perception issues that

might be challenging. This might be the case, for example,

where personalization or stratification coincides with other

ways of dividing up the population, that might, historically,

coincide with discrimination, such as racial or ethnic cate-

gories. This has certainly been discussed in relation to Bidil,

for example, a drug which was not safe and effective for the

American population in general but was found to be useful for

the African-American section of the population. And further-

more even a proposal such as that of Daar and Singer,

depending on how it is presented, could be perceived as

offloading, in less developed countries, products not wanted

by the more affluent west.


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Implementation

Some of the worries about personalized medicine arise in

connection with its implementation. The rise of companies

offering direct to consumer tests, for example, has led to

criticisms over how the results might be interpreted, con-

veyed and misused. There are also concerns about what tests

are offered, and about the time at which tests may be offered –

while it may be considered acceptable for an autonomous

adult to decide to undertake genetic testing, what of whole

genome sequencing at birth, or even prenatally, for the

purposes of personalized predictive medicine? [11] There is

a view that genetic testing prenatally will become the stan-

dard of care [12]. Over the past fifteen years or so, however,

the argument for a right not to know genetic information

about oneself has been advanced, on the grounds that such

knowledge may change one’s whole perception of one’s

future life for the worse. If widespread sequencing becomes

the norm, to remain in ignorance may cease to be an option,

and yet we should not necessarily think that knowledge here

brings greater autonomy [13]. The person ‘bespeaking’ the

test is not identical with the one tested. There are also issues

about the extent to which a genetic counselling model can be

transferred to the new possibilities, or whether a consumer

model is more appropriate [14].

For those who do want genetic testing and are prepared to

pay for it, the price is falling, which may alleviate some of the

concerns about access, but there are nevertheless concerns

about control of the resulting data.

The data

The possibilities of personalization are inextricably linked

with ‘big data’. This proliferation of collections of stored data

about individuals can be seen also in relation to the data

being collected by social media organisations such as Face-

book, big corporations; and the prospects of personalizing

information and advertising for users. These examples also

show that big data brings with it big responsibilities [15].

Attention is increasingly turning to the question whether the

way forward is through external regulation, as in the pro-

posed new European regulation on data protection, or

through developing products to put individuals more in

control of their information.

Conclusion

The promise of personalized medicine is prevalent as a rheto-

rical device: implementation is more complicated, partly

because of the complexity of the mass of information emer-

ging, partly because of concerns about implementation. As to

whether the promise will prove to offer more hope than hype it

is too early to say [16]. There have already been concerns about

the possibility of maintaining data security of patients [17]. It is

also foreseen that the sources of data will increase, not only

with developments in sequencing, but also with the greater


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Drug Discovery Today: Therapeutic Strategies | Personalized medicine Vol. xxx, No. xx 2013


statistical power resulting from the linking of biobanks, and

with the use of technologies such as smart phones to monitor

individuals. Personalized medicine is still in its infancy.

Conflict of interest

The author has no conflict of interest to declare.

Acknowledgements

I am grateful to Alan O’Connor for research assistance for this

article.

The support of the Economic and Social Research Council

(ESRC) is gratefully acknowledged. This work is part of the

Research Programme of the ESRC Genomics Network at

Cesagen (ESRC Centre for Economic and Social Aspects of

Genomics).

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ethical issues in personalized medicine

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