Pharmacogenomics and public health: implementing ‘populationalized’ medicine

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ISSN 1462-241610.2217/PGS.12.52 © 2012 Future Medicine Ltd Pharmacogenomics (2012) 13(7), 803–813

Pharmacogenomics and public health: implementing ‘populationalized’ medicine

Pharmacogenomics, an evolving discipline in translational research aiming to exploit one’s genomic information to predict drug efficacy and/or toxicity, is increasing in both popularity and research, often compared to an explosion of information [1,101]. While most commonly applied in personalized medicine and pharmaceutical research, populationbased analysis and implementation is also possible. The use of pharmaco genomics in personalized medicine has the potential to maximize therapeutic benefit and avoid adverse drug reactions (ADRs), whereas in research it enables drug companies to create safer and more efficient drugs. On a population level, particularly in resourcepoor settings, it can achieve these same goals while using the funds of the government more efficiently [102].

Multiple drugs are known to be affected by nucleotide changes in the human genome, whereas others are known to be metabolized through highly variable pathways, resulting in either reduced drug efficacy, development of an ADR or possibly both [2–6]. Recent research around tamoxifen has revealed a high level of variability in the CYP2D6 pathway. For example, approximately 10% of Caucasians are unable to metabolize this drug, whereas 29% of Ethiopians metabolize it much too quickly. Both groups are left with suboptimal treatment and potentially dangerous side effects [7,8]. As such,

implementation of pharmacogenomics, which could increase effective treatment, is worthy of consideration.

Although the public tends to be more interested in predictive genetic testing for disease, the potential benefit of predictive pharmacogenomic testing may prove more worthwhile [9]. Given the recent global financial crisis, governments of all financial capacities are aiming to optimize spending. European countries with emerging economies, such as Greece and Poland, are working towards pharmacogenomic implementation in their national health formularies [10]. At the same time, countries with stable economies, such as Germany, are investigating the costsaving benefits of pharmacogenomics [10]. In resourcepoor settings, where multiple drug choices may not exist, or the burden of infectious diseases is high, a larger potential is expected. For example, Tanzania recently participated in a genotyping campaign from the Pharmacogenomics for Every Nation Initiative (PGENI) [103], which discovered that the antimalarial drug provided by the Ministry of Health was less effective and created a higher risk of adverse drug events in the Tanzanian population [11]. When asked about participating in the PGENI project, Director General of the Commission for Science and Technology Hassan Mshinda was quoted as saying, “If you are poor, actually you need more

Pharmacogenomics are frequently considered in personalized medicine to maximize therapeutic benefits and minimize adverse drug reactions. However, there is a movement towards applying this technology to populations, which may produce the same benefits, while saving already scarce health resources. We conducted a narrative literature review to examine how pharmacogenomics and public health can constructively intersect, particularly in resource-poor settings. We identified 27 articles addressing the research question. Real and theoretical connections between public health and pharmacogenomics were presented in the areas of disease, drugs and public policy. Suggested points for consideration, such as educational efforts and cultural acceptability, were also provided. Including pharmacogenomics in public health can result in both health-related and economic benefits. Including pharmacogenomics in public health holds promise but deserves extensive consideration. To fully realize the benefits of this technology, support is needed from private, public and governmental sectors in order to ensure the appropriateness within a society.

KEYWORDS: drug use n pharmacogenomics n population n public health Lindsey Mette1, Konstantinos Mitropoulos2, Athanassios Vozikis3 & George P Patrinos*1Charité – Universitätsmedizin, Berlin School of Public Health, Berlin, Germany 2Golden Helix Institute of Biomedical Research, Athens, Greece 3University of Piraeus, Economics Department, Piraeus, Greece *Author for correspondence: University of Patras, School of Health Sciences, Department of Pharmacy, University Campus, Rion, GR-26504, Patras, Greece Tel.: +30 2610 969 834 Fax: +30 2610 969 834 [email protected]

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Review Mette, Mitropoulos, Vozikis & Patrinos

evidence before you invest, rather than if you are rich” [12].

Genetic information is a valuable tool in medical decisionmaking, both individually and at a population level [5,13]. However, the use of genetic information is not innocuous. While the authors recognize genetic discrimination as a potential threat to both individuals and populations, the topic was excluded from this review. Highly individualized genetic medicine remains far in the future, and in order for pharmaco genomics to realize its full potential, careful consideration of its implementation is essential. Without a proper regulatory framework, the complete implementation of pharmacogenomics is improbable [13].

In this study, we conducted a narrative literature review surrounding the research question of how pharmacogenomics can be used beneficially in public health. In particular, we reviewed what has been published in the field of both pharmacogenomics and public health, regarding how the two sciences can constructively intersect, particularly in resourcepoor settings with the ultimate goal of determining the role pharmacogenomics plays in public health.

MethodsWe conducted a narrative literature review, in which available information was reviewed and analyzed in order to gain knowledge and understanding about the potential connections between pharmacogenomics and public health. Special attention was given to the relationship between pharmacogenomics and infectious diseases that pose a major burden in developing countries. Furthermore, recommendations for applying pharmacogenomics to a national health plan were analyzed and synthesized, in order to develop a comprehensive list of considerations which may be applicable to future analyses.

A systematic literature search was carried out multiple times in the PubMed database with Medical Subject Heading (MeSH) search terms. The initial search looked at publications related to the study topic in general, while subsequent searches focused on subpoints. A variety of search terms were used in order to deliver the most relevant results. These terms included ‘pharmacogenetic’, ‘pharmacogenomic’, ‘public health’, ‘policy’, ‘malaria’, and ‘tuberculosis’. Additional terms were used to narrow the results. The search parameters and the number of hits per parameter are listed in Supplementary table 1 (see www.futuremedicine.com/doi/suppl/10.2217/pgs.12.52).

These searches resulted in a total of 1446 studies. Only studies published since 2000 were

considered for review, as the first working draft of the Human Genome Project was completed in 2000. We also employed the limitation of ‘English language’ on account of our language abilities. The previously mentioned limitations narrowed the search results to 1186 publications, of which the Charité – Universitätsmedizin library has access to 945. Thirty one of the retrieved results were duplications. The remaining 914 studies were then evaluated in terms of relevance to the study topic. The exclusion criteria are listed in Supplementary box 1.

Ultimately, a total of 914 publications were obtained including those from the PubMed search. Of those, 887 publications were irrelevant based upon the abovementioned exclusion criteria. Finally, 27 publications were included in the literature review. The overall search strategy is demonstrated in Figure 1.

n LimitationsThe English language restriction potentially eliminated important and relevant publications, particularly on account of the native languages in developing countries that were a research focus. Also, the literature search was limited to publications indexed within the USA National Library of Medicine PubMed database. While extensive, it certainly does not include all publications. Furthermore, the research was limited to articles which were available through the Charité – Universitätsmedizin library. The limitations imposed by the database and the library may have excluded articles relevant to the study topic. Finally, while the researchers acknowledge the impact of chronic disease on the health of the population globally, the results were restricted to infectious diseases burdening low and middleincome countries in order to specifically focus on these settings. To this point, specific countries and/or healthcare systems were not analyzed outside of their representation in the retrieved articles.

Of the 27 publications analyzed, two journals accounted for twelve of the publications (Nature Reviews Genetics: 6; Pharmacogenomics: 6). In addition, four authors appeared in five or more publications (Séguin: 5; Hardy: 5; Singer: 11; Daar: 11). The views of these authors, in combination with the aims of the aforementioned journals, therefore shaped a significant portion of the retrieved results.

ResultsThe literature obtained from the PubMed searches was critically read to identify emergent

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Pharmacogenomics & public health Review

themes reflective of the study objective, including the intersection of pharmacogenomics and public health, and public policy recommendations. table 1 details the analysis parameters. On account of the narrow search parameters, many of the retrieved studies contained overlapping themes such as keys for implementing pharmaco genomics into public policy. All 27 articles analyzed are summarized in Supplementary table 2.

Existing and theoretical connections between pharmacogenomics and public health are well documented [11,14–38], as is the potential for pharmacogenomics to improve public health [14–19,21,23–25,27,31,33–36,38]. We have therefore decided to summarize our analysis in the themes and subthemes outlined in box 1:

� Interactions between pharmacogenomics and public health;

� Pharmacogenomics and drugs;

� Pharmacogenomics and diseases;

� Benefits of including pharmacogenomics in public health policy;

� Key factors for implementing pharmacogenomics into public health policy;

� Related points for consideration in policy formation.

Interactions between pharmacogenetics/pharmacogenomics & public healthIncluding pharmacogenomics into national healthcare plans has the potential to make healthcare more cost effective by ensuring better treatment, proper medication prescription and identification of subpopulations at risk of disease and ADRs [14,17,18,20,21,23,26–29,31,33–39]. Furthermore, it can be a mechanism to save lives through better medicine development and provision [11,15–18,20,21,23,26–28,31,33–39]. Indirect benefits of pharmacogenomics include increased research, which not only holds the evident benefit of health translation, but economic benefits as well by creating a knowledgebased economy, developing research capacity and reversing ‘brain drain’ [14,17,18,20,21,23,27,31,34–36,38]. The discussion of the appropriateness of this technology in these settings has been divided into two concepts: luxuries versus necessities and healthcare inequalities.

n Luxuries versus necessitiesPharmacogenomics has been viewed as a luxury of advanced medical treatment. However, the

idea of luxury versus necessity (e.g. healthcare) varies within and between populations. In the western world, healthcare is a necessity; in lowincome countries (LIC) it is a luxury [27]. Similarly, LIC can least afford to waste their already limited resources in healthcare [34]. The use of pharmacogenomics in resourcepoor settings would introduce costeffective treatment strategies, better diagnosis and treatment, identify atrisk individuals, guide national health policy decisionmaking, and perhaps improve the nation’s health, thereby improving their economic capabilities [18,23,27,31,34]. Arguably, pharmacogenomics “should be seen as a public good to benefit all of humanity, especially those most in need” [27].

n Healthcare inequalitiesOne of the hopes of pharmacogenomics is to provide the best treatment, through improved

Potentially relevant articlesidentified and screened

by titlen = 1446


by titlen = 1186


by titlen = 945


by titlen = 914

Articles analyzed for the literature review

n = 27

Articles not available in EnglishArticles published prior to 2000

n = 260

Articles not accessible throughCharité – Universitätsmedizin

n = 241

Duplicate articlesn = 31

Articles not related to study topicn = 887

Figure 1. Screening strategy for the literature review.



diagnosis and prescription [18,20,26,31,32,37,39]. Yet achieving that goal while access to healthcare or medications is still laced with inequality is challenging. Even in settings with universal healthcare, inequalities exist [17,19,23,35,39]. As recently stated, “in order to get the benefit of health, of genomics, universal health insurance is probably a prerequisite” [35]. This is seen in Thailand, which has universal healthcare but access to medications is problematic [35]. Additionally, pharmacogenetic testing is not covered by national health plans. This current pharmacogenetic trickledown effect in Thailand has limited access to the wealthy [35]; the same is true in India [23].

The other type of inequality is felt globally. Termed the ‘genomics divide’ it addresses the separation between developed and developing countries in terms of genomic medicine [14,15,19,27,28,38]. Healthcare innovation, technology and research rarely focus on or benefits populations in LIC [14,21,27,38]. Moving forward, the research, development and implementation of pharmacogenomics needs to focus on disadvantaged populations and ensuring equitable access to and distribution of healthcare resources [17–19,27,28]. Simply put by one scientist, “What can first world science do, not for the west, but for the rest” [28].

Pharmacogenomics & drugsMultiple possibilities exist for improving public health by incorporating pharmacogenomics into medicine. One of the hopes for pharmaco genomics is to elucidate the differences in drug response between patients [15,18,21,23,24,26,29–31,33–35,37,39], which would allow for better drug development [20,21,27,30,37,39] and opportunities to predict patient drug response

prior to dosing [18,23,27,30,36,37,39]. However, due to the varying therapeutic indices across populations, many countries are questioning the effectiveness within their own populations in comparison to the initial study population [20,26,27,31,35,39].

The cost of ADRs – both social and economic – is a reality pharmacogenomics hopes to reduce, if not eradicate. By identifying patient responder groups and incorporating pharmacogenomic technologies in pharmaceutical development, ADRs can largely be prevented [16,18,23,26,27,30,33–35,37,39], thereby improving health and translating to a costeffective means of healthcare provision [15,16,18,21,27,29,31,33,37]. Especially important in the context of LIC is the access to medicine, both physical and financial. Researchers are moving towards guiding policymakers in the creation of national drug formularies, in order to take population data, variation and cost–effectiveness into account [18,26,31].

Pharmacogenomics & diseasesThe three infectious diseases which pose the largest burden globally – malaria, tuberculosis and HIV/AIDS – were the most frequently addressed diseases in the discussion of public health and pharmacogenomics [11,14,16,18,22–24,27,31,32,35–38]. These diseases affect millions of individuals worldwide, primarily in developing countries. While treatments to combat these diseases exist, they are often insufficient, expensive and difficult. Isoniazid, a common drug in tuberculosis treatment, has variable metabolism dependent on the status of multiple genes and is considered one of the first examples of pharmacogenetics [32]. Accordingly, many have identified tuberculosis as another target for pharmacogenomics and genomic technology, with hopes

Table 1. Checklist of relevant topics.

Topic Pharmacogenomics Pharmacogenomic research in global burden diseases

Public policy

Relevance in regards to pharmacogenomics

Clarification of pharmacogenomics and pharmacogenetics

Is pharmacogenomic research being conducted on these diseases? If yes, does it account for variables other than genetic?

Do suggestions exist for incorporating pharmacogenomic technologies into national healthcare public policy?

Relevance in regards to public health

What are the arguments in favor and against pharmacogenomics from the field of public health, including sociological and epidemiological branches?

Are epidemiological studies on these diseases taking genetic factors into account? How does pharmacogenomic research propose to use its results?

Do frameworks exist to guide professionals and policy-makers on whether to use pharmacogenomic data?

Relevance in regards to gender and/or diversity

How are specific minority groups defined? Is pharmacogenomic research gender and ethnically sensitive?

Is the research focused towards a gender or cultural group? Does research have negative implications for a particular group?

What has been published on the protection of individuals or groups participating in genetic research?



of increasing treatment efficacy while decreasing costs [11,14,15,18,21,38]. India has placed a research priority on drug development, while South Africa is utilizing genomic technology to determine tuberculosis susceptibility and drug metabolism in its population [14,27].

Similarly, the antimalarial drug amodiaquine is not currently recommended for firstline treatment, on account of a high frequency of ADRs. However, the drug is metabolized differently across populations, affecting Caucasians much more frequently than Africans, where malaria is much more common and problematic. This varying response to amodiaquine has recently been identif ied by polymorphisms in the CYP2C8 gene [11,22,31]. Appropriately, Zanzibar, Ghana, Malaysia and Bolivia have undertaken efforts in genotyping to determine the prevalence and significance, of CYP2C8 variants in their populations [11,26,31].

Pharmacogenomics has found success in HIV/AIDS, where the antiretroviral treatment, abacavir, has been associated with a hyper sensitivity reaction to patients who harbor a HLA-B*3701 allele. This reaction varies between populations; however it has been noted to occur in 20% of Thai patients [30,35,37]. An alternative therapy exists, although it is twice as expensive [35]. India and South Africa, two countries with a high HIV prevalence, believe pharmacogenomics has the potential to greatly impact their nation’s health, and have thus named it a research priority [14,38]. It is hoped that by using pharmacogenomics, nations will improve patient treatment and efficacy, which will not only save scarce financial resources, but lives as well [18,27,35,36].

Benefits of including pharmacogenomics in public health policyThe impact of pharmacogenomics on developing countries has remained minimal. Small populations – whether in terms of nationality, genetic profile or disease – have historically been uninteresting to researchers and pharmaceutical companies [15,18,35]. Thus, many describe the necessity of sparsely populated or LIC to invest in pharmacogenomics within their own borders, to focus on local health needs ignored on the international level [14,18,19,24,25,31,33–38]. By doing so, local disease and drug metabolism patterns will be uncovered, resulting in better and more equitable healthcare and delivery [14,15,18,24,27,33–36,38].

In addition, rationale for the use of pharmacogenomics in LIC frequently revolves around the

argument for best allocation of resources. In terms of national resources, it is in the poorest settings where pharmacogenomics can have the largest impact [31]. Using this technology allows for costeffective medication prescription [36,37], thereby increasing prevention, diagnosis and treatment [23,26,33,39], all of which decrease national healthcare costs and allow for a redistribution of scarce resources [14,18,33]. It was suggested that resourcepoor settings should replicate existing, successful models in order to implement this strategy to maximize both human and financial resources [38]. Ghana recently implemented pharmacogenomic medicine using populationbased data as opposed to individual data, which is too expensive for standard use [26].

Furthermore, including pharmacogenomics in public health policy is an investment in both health and research. The lack of communication and collaboration between science and government was frequently noted [14,15,19,23,31,33,34], as well as that between academic research and the private sector [14,15,17,19,35,38]. The possibility of ‘north–south’ collaborations between developed

Box 1. Themes and subthemes identified in the literature review.

Interactions between pharmacogenomics & public health � Luxuries versus necessities

� Healthcare inequalities

Pharmacogenomics & drugs � Reducing adverse drug reactions

� Developing better drugs

Pharmacogenomics & diseases � Malaria

� Tuberculosis

� HIV/AIDS

� Miscellaneous diseases

Benefits of including pharmacogenomics in public health policy � Local health benefits

� Resource allocation

� Cultivating collaboration

� Using science as a marketable good

Key factors for implementing pharmacogenomics into public health policy � The affordability, accessibility and acceptability (AAA) principle

� Education

� Surveillance

� Political will

� Policy formation

Related points for consideration in policy formation � Genomic sovereignty

� Commercialization

� Ethical, legal and social issues

� Race and ethnicity



and developing countries was similarly presented as an opportunity to build the local science capacity of LIC [15,19,24,28,31,33–36,38]. These international collaborations increase the likelihood of LIC receiving beneficial healthrelated technologies [34]. However, national regulatory frameworks may prevent international collaboration, which could be disadvantageous [23,34,35]. Examples of successful existing international collaborations, such as the PanAsian HUGO [34,35,104], PAHO [19,33,105] and PGENI [31,34], were presented as possible models for replication.

Finally, genomic knowledge is a public good for public benefit, not only in countries with large budgets and highly developed science sectors [24,27]. It carries the potential to shape national policy, social understanding and education [14,18,23]. Through governmentsupported investment in genomic technologies, countries are afforded an opportunity to enter the global knowledgebased economy [23,24,27,33–35] and leverage their research results to spur local innovation [14,24,33,34]. Furthermore, a commitment to this research attracts foreign companies to conduct research in these locations, which further builds scientific capacity and generates capital [23,24,33–35].

Key factors for implementing pharmacogenomics into public healthThe decision to implement pharmacogenomics into public health is multifaceted and requires the combined efforts of multiple sectors of society.

n Affordability, acceptability & appropriateness The affordability, acceptability and appropriateness of pharmacogenomics are key elements to its successful implementation. With a particular respect to LIC, the genomic technology and resulting drugs must be affordable, both to individuals in need and the national governments trying to procure them [15,18,19,21,27,34,35]. Governments subsidizing genomic research also must appropriate sufficient funding to promote research without cutting funding in other important areas [14,15]. Public acceptance of this technology is crucial, and various methods have been suggested to increase social acceptability, including public education efforts [14,17,25,27], protection against genetic discrimination [23], and spending an appropriate amount of public funding in this field [35]. Finally, the implementation of this technology must be suitable in terms of society,

health and disease, technology and governance. The diseases targeted and the use of this technology must complement the country’s health profile [17,19,24,27,34] while utilizing socially and scientifically acceptable methods [18]. National governments who elect to use this technology must provide researchers appropriate incentives while continuing to monitor the research and implementation of pharmacogenomics into public health [14,17,19,24,25,27,34].

n Education & political willTo effectively implement pharmacogenomics into society, politicians must be aware of the capabilities, limitations and implications of pharmacogenomics on a society to ensure appropriate and effective policy formation [17,24,31,38]. Healthcare professionals must receive increased education in pharmacogenomics in order to comply with the policies and best serve the population [14,17–20,23,24,26,31,35,38]. Finally, educational efforts to the greater public are essential [14,15,17–21,24,25,29,33–35,38]. Thailand and Mexico have governmentsponsored educational events and publications distributed in their societies that explain pharmacogenomics [24,33,35]. However, in LIC where education is a privilege and not a guarantee, delivering this information is challenging [15,17,23,24,33].

In addition, implementation of a national public health policy is dependent on the commitment of the government. Government funding is essential to not only implement a policy but also to promote research in this area [14,17,23,24,33–35]. Frequent changes in political power threaten existing programs, which creates a continuous need for mobilizing political support [14,15,19,28,36,38]. Successful campaigns have demonstrated how investing in pharmaco genomics can strengthen a nation’s health and economy [14,15,19,23,24,28,32–35,38]. India, Thailand and Mexico have all succeeded in creating national policies to implement pharmaco genomics [14,23,33–35]. These countries, in addition to South Africa, have all undertaken nationwide research programs in order to maximize the government subsidy and the nation’s benefit.

n Policy formationThe formation of a public policy on pharmacogenomics is countryspecific; however there are a series of suggestions for consideration. Communication between the science sector, stakeholders and the government is of extreme importance to ensure the proper interpretation and beneficial application of research results.



Policies must account for healthcare delivery issues [14,17,18,20,21,23,26,38], be feasible [15,36], consist of clear goals [14,24] and incorporate proper regulatory frameworks and evaluation methods [17,23,34,35,37]. Policies must also promote further scientific research and translation [23,26], encourage public–private partnerships [14,17,23,34,38] and define methods to maximize and create investment capital [21,23,24,38]. Socially, the policy must adequately reflect societal needs and values, enhance public education and clearly describe ethical guidelines [14,17,23,31,38,39].

Related points for consideration in policy formationThe benefits and challenges of implementing pharmacogenomics into public health are clearly identified. However, there are additional issues that may arise and require careful consideration, ideally prior to implementing such a policy. One such issue is genomic sovereignty. The human genome is recognized as a global public good, not owned by a single entity or institution and not designed to benefit a select few, but the entire population [33–35]. This is especially true in terms of biocolonialism and genetic piracy, where research is conducted in populations who are unwilling or unable to research themselves [34,35]. India’s massive population and resulting diversity is viewed as a genomic sovereign resource; the same is true of Mexico [23,33,34]. Mexican authorities assume responsibility for discovering their own information, in part owing to a concern that Mexico will become dependent on the countries holding this information and subsequent technologies it produces [33]. The level of legislation surrounding genomic research varies greatly between countries. Thailand and India lack national legislation, but have guidelines in place regarding the export of genomic information [23,33,34]. Mexico, conversely, has national laws designed to protect its genomic sovereignty and prohibit the research or transportation of genomic information without government permission [33,34]. However, there are concerns that legislation limiting the export of genomic information will impede research collaboration between nations, which can be very valuable to LIC [23,34,35].

Another issue is commercialization. One way to incentivize genomic research within a country is to promote commercialization [14,21,23,33–35,38]. Many articles addressed the need for national support of commercializing research in order to ensure development [14,23,24,33–35,38]. Mexico’s Instituto Nacional de Medicina

Genomica de Mexico (INMEGEN) [106] and Thailand’s Center of Excellence for Life Sciences (TCELS) [107] are two such examples of national support [34,35]. The importance of public–private partnerships in research was emphasized, owing to the limited resources LIC have to dedicate to such research [14,15,17,23,34,35,37,38]. The development of a commercial research sector is a strategy to generate economic and health benefits to developing countries [14,28,34]. Interestingly, only African countries viewed this as an opportunity to foster international collaboration [24,38]. The promotion of commercialized research also raises some concerns. Researchers in Thailand and South Africa felt it was unethical to commercialize research results, while researchers in Thailand and India valued peerreviewed publications more highly than commercial incentives [23,34,35]. When a country promotes research commercialization it is vital to balance these commercialization efforts with the principles of public health and human rights [14,37,39].

Ethical issues surrounding the commercialization of research [28,35], biobanking [23], distribution of goods, cost–effectiveness analyses [21,30], informed consent, standard of care [18,27,28,38] and legal issues surrounding intellectual property must be addressed by leaders in countries implementing pharmacogenomics. Also addressed is the concern of creating a genetic underclass [27,28]. The protection of identity in any form of genomic research is vital to eliminating further opportunity to discriminate against a racial, ethnic or social group within a society [18,21,28,35,39]. There is uncertainty as to whether employing pharmacogenomic research will increase stigmatization [15,25,27,28,38,39] or reduce it [23,27]. What are readily agreed upon are the inequalities and the potential to increase access to healthcare for those currently disadvantaged [15,19,24,28,39]. In order to protect communities and ensure ethical research, capacity building in Ethical, Legal, and Social Issues (ELSI) is essential [14,15,19,24,33,36,38]. To accomplish this, policymakers must be wellinformed regarding genomics and associated issues affecting populations [24,33,38]. Equally important is the engagement of the public in supporting genomic research [24,35] and informing the public about genomics and ELSI [17,19,23,24,34]. Finally, the social cost of such technology must be addressed, weighing individual choice against the public good [25,27].

DiscussionAlthough incorporating pharmacogenomics into LIC initially seems illogical, it is gaining



acceptance, since in a resourcepoor setting, the financial consequences of ADRs to the national healthcare system, as well as the general population, will be more severe as compared to developed nations. What was previously considered a tool for personalized medicine is now paving the path towards ‘populationized’ medicine (see Figure 2). However, to realize the benefits of including pharmacogenomics on a national level, both social and political considerations must be taken in order to ensure the desired outcome.

From a policy perspective, laws prohibiting discrimination, particularly genetic discrimination, will be essential to protect the population. One way to contribute towards a healthier political/medical/social climate is to provide genetics education to the general population, such as TCELS has, through public meetings, media appearances and educational material distribution [35]. Prior to creating educational campaigns, program officials must determine the current social climate and understanding of pharmacogenomics, in order for the campaigns to have the maximum impact. While only a few studies have examined public attitudes regarding genetics – and even fewer regarding pharmacogenomics – the results have thus far shown a favorable attitude towards genetics and genetic testing services [40].

Increasing social awareness allows the public to be a more informed stakeholder in the discussion surrounding public health policies. The same is true of educating doctors and scientists. Recent surveys in Greece show physicians are more willing to undergo genetic testing than to prescribe it, suggesting a lack of education in how to interpret and apply the results in patient care [40]. Further supporting this suggestion is the gap between patient expectation and physician understanding in clinical genetics [5]. Thus, the scientific community has called for increased

genetic content in medical education programs. European PGENI regional coordinating center, the Golden Helix Institute of Biomedical Research [41,108], regularly organizes and hosts the ‘Golden Helix Pharmacogenomics Days’ to facilitate knowledge transfer from timely research to clinical practice [42]. Increasing the genetics education will better allow these professionals to effectively implement created policies.

Pharmacogenomics can increase access to medicine by increasing the amount and functionality of available medicines, provided that implementing pharmacogenomics results in improved resource allocation and better drug provision; it can also restrict access if the developed drugs are too expensive for regular use. To this end, public health strategies regarding the use of generics and interchangeable drug products can be a solution that has already yielded some positive results in many countries; when combined with pharmacogenomics, not only will the quality of life of the patients be improved but the healthcare cost savings can also be further reduced.

Access to essential medicine is a human right, yet barriers to these medicines remain a major problem. Also important is the appropriateness of this technology in a society. In the event that implementing pharmacogenomics improves treatments, improves the health of society, increases education and employment opportunities and discourages discrimination, the appropriateness may still be in question. Medical modernization that does not strive to incorporate traditional healing methods threatens to marginalize traditional healers and their associated practices. Therefore, incorporating this technology has the potential to lead to the abandonment of current traditional and natural medicine treatments, thereby resulting in a loss of culture. Survival International, a human rights organization, warns against the dangers of strictly adhering to western medicine and disregarding traditional treatments and healers, claiming that doing so brings more harm than good [109]. The technology also may be delivered in a culturally unacceptable manner. For instance, in a populationbased analysis, the populations chosen for representation must accurately reflect the structure of society without creating or reinforcing social divisions. Historically, research in pharmacogenomics across populations has used racial criteria, as opposed to ethnic. While welldocumented, the clinical relevancy of racial grouping remains in question. The Frequency of Inherited Disorders Pharmacogenomics database (FINDbase) aims

Nat

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enet

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atab

aseGenome data

Genome data

EnvironmentPublic health

guidelines

Personalized medicine

‘Populationalized’ medicine

Figure 2. Pharmacogenomics in personalized and ‘populationalized’ medicine.



to bring ethnicspecific differences to attention. The database exclusively documents pharmacogenomic markers in various populations and ethnic groups globally, currently hosting data on over 150 populations [43,110]. Finally, patients must continue to be treated as individuals, not as representatives of a particular subpopulation. Populationbased pharmacogenomics should be used as a guide towards national health policy decisionmaking, and does not serve to undermine the inherent uniqueness of each individual or the opportunity of individual personalized medicine.

Owing to potential complications arising from genetic information, the task of policymakers in public health policy formation is difficult. In countries where these policies have already been effectively introduced, the will of the government was essential. One successful approach towards gaining favor of the government is being able to prove the economic benefits associated with this type of a policy. Increasing health and gross domestic product, decreasing waste (i.e., through ineffective treatments), and opportunities for better resource allocation are attractive outcomes, especially to governments with

extremely limited resources. Furthermore, promises of developing scientific infrastructure and increasing partnerships with global organizations have potential to increase a national economy. By enacting legislation, nations can guard resources, encourage local innovation and foster the ability to participate globally in genomic research. An alternative to selfdetermined and funded pharmacogenomic research within a country is a partnership model, such as PGENI. This permits Health Ministries to obtain information and expert consultation for decisionmaking without the financial commitment. However, the government is still responsible for protecting its residents, its genomic sovereignty, and the decisions that are made as a result of this gathered information. Policymakers should also consider sustainability, to ensure continuing drug affordability and continued research translation towards better health.

ConclusionIn areas with limited resources, populationbased pharmacogenomics may be a worthy investment, whether selffunded or accomplished through collaboration. However, in order to achieve a

Executive summary

Background � Pharmacogenomics serves personalized medicine to increase treatment benefits and minimize adverse drug reactions. Using pharmacogenomics on a population level can accomplish the same benefits, in addition to using health resources more efficiently.

Methods � Here, we conducted a narrative literature review of what has been researched and published in the field of both pharmacogenomics and public health. The literature review focused on how the two sciences can constructively intersect, particularly in resource-poor settings.

Benefits of including pharmacogenomics in public health policy � The benefits of including pharmacogenomics in public health policy can be realized on multiple levels of society, including local health benefits, resource allocation, increased scientific collaboration and the marketability of scientific knowledge.

Interactions between pharmacogenomics & public health � The implementation of pharmacogenomics into national healthcare plans has the potential to make healthcare more cost effective by ensuring the best treatment of individuals, the proper prescription of medication and identification of subpopulations at risk of disease and adverse drug reactions.

Keys for implementing pharmacogenomics in public health � The recent shift towards incorporating pharmacogenomics into low–medium income countries is gaining acceptance in the science community. However, in order to realize the benefits of including pharmacogenomics in public health policy, both social and political considerations are essential to ensure the desired outcome.

Points for consideration � Stakeholder engagement is necessary to properly assess this issue from areas outside of economic benefit. The feasibility of this technology needs to be assessed in terms of cost–benefit analyses, sustainability, education and scientific infrastructure.

Conclusion � In areas with limited resources, population-based pharmacogenomics may be a worthy investment, whether self-funded or accomplished through collaboration.

Future perspective � Further studies should aim to assess the public’s view on incorporating this technology into national healthcare plans.



public health policy capable of incorporating pharmacogenomics, public and political investment is necessary. Regardless of the country setting, the protection of citizens and populations within the country is of the highest importance. One of the acclaims of genomics is the integrative approach it takes towards health and disease. A public health genomic policy should aim to be equally as integrative.

Future perspectiveThe use of populationbased pharmacogenomics is in its infancy, but early successes provide a promising outlook. While this literature review focused mainly on infectious diseases and lowincome countries, future studies should investigate the impact of pharmacogenomics on chronic disease treatment or how to implement such a strategy in nonuniversal healthcare systems. Furthermore, additional economic models are needed. To date the majority of cost–effectiveness analyses are

calculated on an individual patient basis, not populationbased. In terms of LIC, studies analyzing the increase of a nation’s GDP, the reduction of disabilityadjusted lifeyears in relation to pharmacogenomic healthcare expenditure would be beneficial.

AcknowledgementsThe authors apologize to all of our colleagues whose important work could not be directly cited.

Financial & competing interests disclosureThis work has partly fulfilled the requirements of the Master’s Thesis of L Mette. Part of this work has been finan-cially supported in part by the Golden Helix Institute of Biomedical Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Pharmacogenomics and public health: implementing ‘populationalized’ medicine