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Global pharmacogenomics: Where is the research taking us? a

a

Catherine Olivier & Bryn Williams-Jones a

Bioethics Program, School of Public Health, Université de Montréal, Montréal, QC, Canada Published online: 28 Feb 2014.

To cite this article: Catherine Olivier & Bryn Williams-Jones (2014) Global pharmacogenomics: Where is the research taking us?, Global Public Health: An International Journal for Research, Policy and Practice, 9:3, 312-324, DOI: 10.1080/17441692.2014.887137 To link to this article: http://dx.doi.org/10.1080/17441692.2014.887137

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Global Public Health, 2014 Vol. 9, No. 3, 312–324, http://dx.doi.org/10.1080/17441692.2014.887137

Global pharmacogenomics: Where is the research taking us? Catherine Olivier* and Bryn Williams-Jones Bioethics Program, School of Public Health, Université de Montréal, Montréal, QC, Canada

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(Received 8 August 2013; accepted 9 December 2013) Pharmacogenomics knowledge and technologies, which couple genomics information with pharmaceutical drug response, have been promised to revolutionise both drug development and prescription. One notable promise of pharmacogenomics is the potential to contribute to some of the Millennium Development Goals (MDGs), namely to increase justice in global health by incentivising public research laboratories and pharmaceutical companies to develop drugs for populations (e.g., in low- and middle-income countries) that have been neglected by the traditional drug development model. To evaluate the credibility of this promise, we examined – both quantitatively and qualitatively – those scientific papers indexed in PubMed and published between 1997 and 2010, with a view to describing the major orientations and tendencies characterising the development of pharmacogenomics research. Our results demonstrate that pharmacogenomics research has focused on three major noncommunicable categories of disease: cancer, depression and other psychological disorders and cardiovascular and coronary heart disease. Few publications – and thus, by extension, little scientific interest – concerned orphan diseases, infectious diseases or maternal health, indicating that pharmacogenomics research over the last decade has replicated the well-known 90/10 ratio in drug development. As such, we argue that research in the field of pharmacogenomics has failed in its promise to contribute to the MDGs by reducing global health inequalities. Keywords: pharmacogenomics; public health; ethics; global health; research

Introduction Pharmacogenomics, the science that studies the interaction between genomic information and drug response, has been described as holding the promise to allow personalised medicine to blossom to its full potential (Evans, 2007; McLeod & Evans, 2001).1 For example, pharmacogenomics tests are increasingly included in US Food and Drug Administration (FDA) recommendations for drug prescribing (Frueh et al., 2008; Lesko & Zineh, 2010), suggesting that the research associated with this technology has been somewhat successful. Specific promises associated with pharmacogenomics research and technologies are increased safety and security for individuals through better drug prescription and prognostics, that is, the right drug, for the right condition, for the right person or sub-group (Guttmacher & Collins, 2005). Other promises include increased efficiency in drug development through the ability to identify those patient sub-groups most likely to benefit from a drug and so to include in clinical trials, and those who might be at risk and so should be excluded from potentially dangerous trials. The

*Corresponding author. Email: [email protected] © 2014 Taylor & Francis

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resulting cost-savings of safer and more efficient clinical trials could then create an incentive for pharmaceutical companies to develop drugs for a wider range of diseases, including those that are rare or have been neglected (Olivier, Williams-Jones, Godard, Mikalson, & Ozdemir, 2008; Olivier & Williams-Jones, 2011; Pang, 2003). Yet, the success of pharmacogenomics drugs or other interventions have thus far been mitigated (Ma & Lu, 2011). For such promises to translate to the bedside, the upstream scientific research – whether conducted in university or industry laboratories – must first demonstrate interest and investment in these diseases (Pinxten, Denier, Dooms, Cassiman, & Dierickx, 2012). Rare and neglected diseases have often received limited interest from the pharmaceutical industry, leading to significant issues of justice in global health (Schroeder & Singer, 2011). It is generally acknowledged that the distribution of research and technology in global health (e.g., access to essential medicines) follows a 90/10 ratio: 90% of the funding for health research, including drug development, is invested in treating the wealthy 10% of the world’s population (Hale, Woo, & Lipton, 2005; Reich, 2000). This health gap between rich and poor populations led the United Nations to include drug development for the least advantaged under Objective 8 of the Millennium Development Goals (MDGs; United Nations (UN), 2013). To date, other national initiatives and policies such as the US Orphan Drug Act (1983) or the EU regulatory framework to stimulate research on rare diseases (2000) have failed to reduce local or global inequalities in access to drugs for rare or neglected diseases (Davies, Neidle, & Taylor, 2012; Pinxten et al., 2012). Barriers to the development of drugs that respond to the needs of low- and middleincome countries’ (LMIC) populations have been linked to two major challenges: (1) the difficulty in conducting clinical trials in the context of LMIC and (2) a low interest in upstream research for LMIC diseases (Bollyky, Cockburn, & Berndt, 2010; Lexchin, 2010). Pharmacogenomics technologies have been promised to address both of these challenges by creating incentives to stimulate drug R&D geared towards meeting the health needs of LMIC populations. Pharmacogenomics technologies provide the tools that allow molecular biology to participate more directly in pharmaceutical development through upstream research, making this science more appealing for a greater number of research teams. These technologies can also increase the long-term return on investment of novel drugs by providing better-suited treatments to individuals in need (Olivier et al., 2008). This latter promise of greater long-term return on investment makes newly developed pharmacogenomic drugs favourable candidates for further capital investment, as these drugs would arguably be at less risk of failure during the drug development process. Yet, past investment in pharmacogenomic drugs have shown limited success in delivering on the promises of better and more affordable care (Ma & Lu, 2011), raising questions about the potential of pharmacogenomics to deliver in the context of both highincome countries (HICs) and LMIC populations. In this paper, we present the results of an exploratory study that aimed to qualify the nature of the upstream research being conducted in the field of pharmacogenomics. Our objective was to identify the major orientations that pharmacogenomics research has followed since 1997 (when the term was first introduced) in order to determine if interests in LMIC prevalent diseases have increased with these technologies. Unfortunately, our results suggest that research based on pharmacogenomics knowledge and technologies replicates the 90/10-health gap ratio present in mainstream drug development. As such, pharmacogenomics does not appear to provide the hoped for incentive for drug R&D, falling as it does far short of the promises of its proponents that it would help increase justice in global health and so support the Millennium Development Goals (Howitt et al., 2012).

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Figure 1. Number of PubMed publications in pharmacogenomics between 1997 and 2012. Note: Data were collected using the search word ‘pharmacogenomics’ and corresponding year (e.g., ‘pharmacogenomics 1998’). The number of publications found for each year was corrected for noninclusive year data.

Method We conducted an exploratory quantitative and qualitative evaluation of the field of pharmacogenomics research since 1997. A PubMed search using the term ‘pharmacogenomics’, followed by the corresponding year (e.g., ‘pharmacogenomics 1997’), was conducted for each year between 1997 and 2012 in order to quantify the number of scientific publications in the field (n = 13,534 scientific articles since 1997; Figure 1). To gain some understanding into the nature or type of pharmacogenomics research being published, and whether tendencies changed over time, we analysed article abstracts published between 1997 and 2003, as well as in 2010 (n = 3829). Our inclusion criteria were as follows: the study had to be either a clinical study or a population study (i.e., using healthy human or patient participants), inquire about a specific polymorphism, be linked to either a disease or a drug response, and constitute original material. Review articles, case studies (i.e., with less than 10 participants) and meta-analyses were excluded. Based on these criteria, 626 articles were included in our data-set. Each of these articles was examined to determine the disease being investigated, the geographical location of the research team that conducted the study, and any association with a pharmaceutical company (e.g., sponsor, affiliation of authors). This information enabled us to map historical and current tendencies for the development of pharmacogenomics research (e.g., what diseases, drugs or population groups are being studied) and evaluate the efforts deployed by pharmacogenomics researchers to contribute to reducing inequalities in global health and address the population health needs of LMIC.

Results The number of journals from which the articles included in our study were selected increased between the 1997–2003 period (n = 79) and the 2010 period (n = 94). Between 1997 and 2003, most of the articles in our study were published in the journal Pharmacogenetics (n = 274/410), while in 2010, the highest number of articles published

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Number of articles included in our study, by year.

in one journal was 41 (n = 216) in the journal Pharmacogenomics. Further, the number of articles that met our inclusion criteria doubled between 2003 and 2010 (Figure 2). These results show that interest in pharmacogenomics technologies and knowledge increased consistently since 1997. Even though we were able to include a greater number of articles in our database for 2010, the proportion of articles published that did not constitute an original study (e.g., review, comment or debate articles) increased from 15% in 1997 to 54% in 2010 (Table 1). These results suggest that the proportion of original pharmacogenomics studies published in PubMed has actually declined. Our analysis also suggests that the interest of pharmaceutical industry-funded researchers to publish studies related to pharmacogenomics knowledge and technologies increased regularly between 1997 and 2002, but then dropped significantly in the following years (Table 2). With regards to topics of interest for pharmacogenomics researchers, our findings show that the primary area is oncology; with all cancers confounded, oncology accounts Table 1. Distribution of articles included, excluded and review articlesa by year of publication. Included articles Year of publication b

1997 1998 1999 2000 2001 2002 2003 2010 Total a

Excluded articles

Review articles

Total Nb

Nb

(%)

Nb

(%)

Nb

(%)

174 142 206 356 487 636 744 1084 3829

44 29 44 50 57 80 106 216 626

(25.3) (20.4) (21.4) (14.0) (11.7) (12.6) (14.2) (19.9) (16.3)

56 47 66 59 93 117 127 193 758

(32.2) (33.1) (32.0) (16.6) (19.1) (18.4) (17.1) (17.8) (19.8)

26 27 58 174 209 307 374 580 1755

(14.9) (19.0) (28.2) (48.9) (42.9) (48.3) (50.3) (53.5) (45.8)

Review articles include commentaries, debates, conference abstracts and promotional papers. The articles included in the year 1997 correspond to publications from 1996 and 1997 that came out in our research in PubMed using the term ‘pharmacogenomics 1997’. b

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Table 2. Proportion of articles published in Pharmacogenomics directly associated with pharmaceutical companies, by year. Year of publication

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1997 1998 1999 2000 2001 2002 2003 2010 Total

Amount (Nb)

Proportion (%)

14 9 16 46 61 95 73 32 346

8.0 6.3 7.8 12.9 12.5 14.9 9.8 3.0 9.0

for 22.8% of the articles included in our database (Figure 3). Other categories of disease that stimulated noticeable interest in pharmacogenomics research were depression and psychological disorders (14.7%) and coronary heart disease (13.6%). Interest for neglected or infectious tropical diseases and maternal health amount to only 3.8% of articles, although interest for these diseases more than doubled between 2003 and 2010 (Appendix 1). The other categories of disease that garnered some interest, as represented by articles published, include: neurological and degenerative disorders (4.2%), diabetes (3.4%), renal disorders and organ transplant (3.4%), auto-immune and genetic disorders (3%), arthritis mellitus and pain (2.9%), asthma and allergies (2.6%), and gastric ulcers and gastrointestinal diseases (1.6%; Figure 3). Population studies that aim to characterise the distribution of a specific polymorphism or of a drug response within or across populations constituted 15.8% of the studies published between 1997 and 2003, and in 2010; of note, 34% of pharmacogenomics studies published by research teams from the BRICS countries (i.e., Brazil, Russia, India,

Figure 3. Distribution of disease interests among the articles in Pharmacogenomics. Note: This distribution is given in percent of studies that related to a given disease category within the articles selected with our inclusion criteria.

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Figure 4. Geographical distribution research team number of publications for the top seven countries (the USA, Germany, Japan, the UK, China, Canada and France) and the top two LMIC (Brazil and India).

China and South Africa) were population studies (Table 3). The BRICS countries show a growing interest towards research in pharmacogenomics (Figure 4), accounting for 46% of 2010 publications included in our study (Figure 5). Somewhat surprising, however, was our finding of an apparent low interest on the part of BRICS research teams in neglected or infectious tropical diseases and maternal health, with only 2 out of 65 articles focusing on this category of disease (Table 3). Discussion Our study findings have made it possible to map how interest in the development of pharmacogenomics knowledge and technologies has unfolded in upstream research at the Table 3. Distribution of disease interest in pharmacogenomics articles published by teams in BRICS countries. Disease

Russia

1 4 0 0 0

0 0 0 0 0

1 0 1 5a 0

3 11 3 1 2

0 1 0 0 0

0 0 0 0 0 0 0 2 7

0 0 0 0 0 0 0 1 1

1 0 0 0 0 0 0 3 11

4 0 0 1 2 0 1 14 42

0 0 0 0 0 0 1 2 4

Cancers Depression and psychological disorders Coronary heart diseases Neurological and degenerative disorders Neglected or infectious tropical diseases and maternal health Diabetes Organ transplant and renal disorders Auto-immune and genetic disorders Arthritis and pain Asthma and allergies Gastric ulcers and gastrointestinal diseases Others Population study Total a

Interestingly, all the studies included here focused on epilepsy.

India China

South Africa

Brazil

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Figure 5.

Number of publications in pharmacogenomics by research teams in BRICS countries.

global level. Specifically, our findings show that research in pharmacogenomics focuses primarily on three categories of non-communicable disease that present an important disease burden/incidence in HICs but may be of lower incidence in LMIC (Di Cesare et al., 2013): (1) cancer, (2) depression and psychological disorders (mental health) and (3) cardiovascular and coronary heart disease.

The global burden of cancer Cancer is a leading cause of mortality worldwide, responsible for 13% of all deaths each year (WHO, 2013a). The prevalence and incidence of various forms of cancer are increasing rapidly among populations of LMIC, with these populations accounting for 60% of newly diagnosed cancers (Lopez-Gomez, Malmierca, de Gorgolas, & Casado, 2013). These statistics may support to some extent the argument for massive investment towards research in this area over other types of disease (Maher & Sridhar, 2012). Some cancers result from infectious diseases (e.g., liver cancer and hepatitis B virus, cervical cancer and human papillomavirus, stomach cancer and Helicobacter pylori) and have historically been more associated with LMIC populations; other cancers, believed to be associated with lifestyle and diet (e.g., lung, breast and colorectal cancers), have been more predominant in HICs. The growing incidence of these latter types of cancer in LMIC populations is changing to some extent the nature of the global burden of cancer; but it is already the case that around 70% of cancer deaths globally occur in LMIC populations. A major problem in LMIC populations is access to cancer treatments because of high drug prices, limited availability of traditional treatments and poor rates of screening or detection in the population (André, Banavali, Snihur, & Pasquier, 2013). So while the development of pharmacogenomic drugs or therapies that provide better cancer treatment (e.g., because of improved detection, increased efficacy with reduced adverse effects) may be positive for the populations of HICs, the high costs of these treatments will likely mean that there will be little uptake and thus a limited impact on LMIC populations. For example, even though campaigns have been developed to make Herceptin (one of the first pharmacogenomics drugs developed to treat breast cancer) more affordable and thus accessible for

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a wider population, the costs are still prohibitive for most LMIC populations: for example, in India, the treatment cost is estimated at Rs. 72,000 (approximately US$1340) per month (Silverman, 2013), in a context where the average per capita monthly income is Rs. 5130 (approximately US$88) (Financial Express, 2013). Further, Herceptin is far from being a grand panacea; while it has important benefits for those women in its target population, it does not cure but merely extends survival, usually by only a matter of months. Given its cost, it can be considered at best a limited success. In light of the longstanding problem of LMIC populations obtaining access to affordable essential medicines (Lexchin, 2010), implementation of novel chemotherapy treatments (e.g., metronomics) (André et al., 2013) or of less invasive and affordable public health measures have been suggested as more efficient and cost-effective approaches to address the needs of LMIC populations unable to afford high-cost pharmacogenomic oncology drugs (Di Cesare et al., 2013). Barring radical changes in pharmaceutical industry drug pricing and/or technological changes that significantly reduce the cost of pharmacogenomic therapies (e.g., low cost full genome sequencing), the above considerations lead one to conclude that the important efforts currently being deployed towards cancer research in pharmacogenomics are aimed at meeting the health needs of HICs, and so will have little effect in reducing inequalities in global health. Mental health as a marketable class of disease Diseases associated under the umbrella term ‘mental health’ have various origins and expressions, and while less directly associated with population mortality rates, mental illnesses can still have a significant impact on global health (WHO, 2013b). For example, depression is one of the most important single causes of disability worldwide and affects predominantly vulnerable groups, such as women and people living with HIV/AIDS (WHO, 2013b). Furthermore, the prevalence of mental illness has a significant impact on the economic situation of populations, both at the national and household levels (WHO, 2010; World Economic Forum, the Harvard School of Public Health, 2011). Individuals suffering from a mental illness are thus rightly considered as vulnerable and deserving of special measures to help them cope with their disease (Hurst, 2008). The determinants of mental illness include individual characteristics, such as genetic factors or the presence of other medical conditions, but also social, political, economic and environmental causes (WHO, 2013b). Consequently, drug treatments to help ease the suffering of affected individuals are only one piece of the puzzle in the management of the global burden of mental illness. Yet, both the general population and health professionals often perceive drugs as a first-line treatment for individuals with psychological disorders (Barker & Buchanan-Barker, 2012). Significant criticism has been levied at the pharmaceutical industry for engaging in disease mongering (Wolinsky, 2005) and other marketing practices that have made drugs for mental illnesses some of the most prescribed and marketed medications in the world. BCC Research (2012), which forecasts the market evolution for different pharmaceutical fields, has estimated that the global mental health pharmaceutical industry will be valued at US$88.3 billion in 2015. However, these drugs are among the ones inducing the most significant levels of adverse reactions in the population (Reynolds, 2012). It is no surprise, then, that there is substantial interest in pharmacogenomics research related to the treatment of depression and other psychological disorders (14.7% of the articles in our study). Since the validity of antipsychotic drug prescription is being challenged, we find problematic the fact that the promise of good financial returns from research in the field

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of mental health diverts much of this pharmacogenomics research energy towards this category of disease. We argue that this energy could better contribute to reducing inequalities in global health if directed towards neglected and infectious tropical diseases or maternal health. Furthermore, the most recent Model List of Essential Medicines from the WHO includes far more indications for drugs for infectious diseases (120 drug indications) than for drugs addressing mental health (15 drug indications; WHO, 2011b). This observation suggests that the current trend in pharmacogenomics research does not follow the WHO Model List of Essential Medicines and thus has limited potential to contribute to global health needs as currently defined.

Cardiovascular and coronary heart disease Cardiovascular and other heart diseases are the only category of disease identified in our study that are included in the top ten causes of death for populations of low-income, middle-income and high-income countries (WHO, 2011a). As a result, they constitute the dominant cause of death worldwide (Lenfant, 2013). They also constitute a category of disease for which pharmacogenomics research has provided important knowledge that can help guide clinical decision-making, notably concerning the use and dosing of warfarin (an anticoagulant) and clodiprogel (an antiplatelet agent) (Johnson et al., 2011). Our finding that this category of disease is among the top three areas in pharmacogenomics research is thus not surprising. Furthermore, the FDA has recommended that pharmacogenomics indications be included for nine drugs aimed at treating cardiovascular or other heart diseases currently on the market, among which figure warfarin and clodiprogel (US FDA, 2013). This number contrasts with the 37 drugs to treat cancers and 26 drugs under the psychiatry therapeutic area for which the FDA has approved specific pharmacogenomics indications. With warfarin and clodiprogel, pharmacogenomics research in the field of cardiovascular and other heart diseases has proven to be promising for reducing the overall death tolls associated with these diseases (Gladding et al., 2009; The International Warfarin Pharmacogenetics Consortium, 2009). However, the potential to reduce global health inequalities depends on the ways in which the findings from such research (e.g., improved detection and therapies) will be distributed (Howitt et al., 2012). For example, although generic forms of warfarin are being distributed at low cost, pharmacogenomics testing for this drug has been deemed non-cost efficient (there are also problems with clinical efficacy), thereby limiting the benefits that pharmacogenomics technologies can provide (Meckley, Gudgeon, Anderson, Williams, & Veenstra, 2010). Lost opportunities for such knowledge transfer to the bedside might explain the drop in the number of pharmaceutical industry-funded researcher publications observed in our results, suggesting a decrease of interest from the pharmaceutical industry in pharmacogenomics knowledge and technologies. Another problem we foresee with pharmacogenomics research for cardiovascular and coronary heart disease is that these are non-communicable diseases that can in part be prevented by modifying lifestyle or dietary habits (So & Ruis-Esparza, 2012). It may thus be more efficient for governments and non-governmental organisations implicated in global health to focus their efforts towards much needed prevention and control of these diseases (Maher & Sridhar, 2012), rather than investing large sums of money in the development of pharmacogenomic technologies that will prove to be inaccessible and provide limited benefits for LMIC populations (Dauda & Diereckx, 2012).

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Conclusion Neglected or infectious diseases and maternal health related conditions are still predominant causes of mortality, accounting for 45.5% of deaths in low-income countries (LIC) and 14.9% of deaths in middle-income countries (MIC) in 2008 (WHO, 2011a). In particular, in Africa and South Asia, these diseases surpass all non-communicable diseases as causes of death (Di Cesare et al., 2013). Not surprisingly, then, drug indications concerning infectious diseases are still predominant in the WHO Model List of Essential Medicines that aims to improve accessibility in LMIC. Research and health innovations aimed towards neglected or infectious diseases and maternal health are thus more likely to help reduce health inequalities at the global level. Yet, our results show that scientific interest in pharmacogenomics research for these areas is very limited, with a mere 3.8% of the publications included in our study focused on these illnesses. Equally problematic, in our view, is the apparently limited interest from LMIC pharmacogenomics research teams in studying neglected or infectious diseases and maternal health. Those countries with the most to gain from such pharmacogenomics research are not contributing to the upstream research that would reduce important global health inequalities (So & Ruis-Esparza, 2012). Our study demonstrates that internationally, US researchers are the most productive (in terms of numbers of articles) in publishing pharmacogenomics research; by extension, areas of interest for these research teams will likely have an impact on the recommendations to include pharmacogenomics indications for specific drugs coming from the FDA, and so will have a wider impact on pharmacogenomics drug distribution worldwide. Interestingly, seven drugs aimed at treating infectious diseases presently have FDA pharmacogenomics indications on their label (US FDA, 2013), a number similar to drugs aimed at treating cardiovascular diseases. This suggests that pharmacogenomics research on neglected and infectious diseases can provide valuable information for the treatment of populations in need, just as indications for cardiovascular disease has modified practices in heart disease treatment. The fact that these indications have been included in FDA recommendations, even though efforts deployed towards neglected and infectious diseases have been low, also suggest that pharmacogenomics knowledge and technologies can contribute to achieve some of the objectives included in the MDGs (Howitt et al., 2012), although proof of their efficiency is still needed (Frueh et al., 2008). Alongside increased downstream clinical research in LMIC to address local health needs, the missing piece of the puzzle to ensure greater justice in global health through the promises of pharmacogenomics knowledge and technologies lies in greater upstream research on neglected or infectious diseases and maternal health. The challenge, however, will be to imagine and deploy incentive systems (such as the innovative Health Innovation Fund proposed by Hollis and Pogge (2008)), so that both university and pharmaceutical industry researchers – whether working in low-, middle- or high-income countries – are encouraged to conduct upstream pharmacogenomics research in disease areas that will actually meet the needs of LMIC populations. Acknowledgements We would like to thank the Editors and Anonymous reviewers for their constructive comments and suggestions.

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Note 1. While often used interchangeably, ‘pharmacogenomics’ can be distinguished from ‘pharmacogenetics’ because the former is focused on the development and use of genomic information, that is, the description of characteristics of population groups with regards to drug response, whereas the latter is focused on individual genetic information, that is, individual characteristics or differences in drug response (McLeod & Evans, 2001). In practice, pharmacogenomics research has largely replaced research in pharmacogenetics, because the latter has turned out to be a far less fruitful avenue of research (e.g., few direct genotype-phenotype associations; discovery of numerous low frequency markers for drug response that nonetheless map onto identifiably population sub-groups) (Ma & Lu, 2011).

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Appendix 1

Table A1. Number of articles published within each category of disease of interest by year of publication. Category of disease Cancers Depression and psychological disorders Coronary heart diseases Neurologic and degenerative disorders Neglected tropical diseases and maternal health Diabetes Renal disorders and organ transplant Auto-immune and genetic disorders Arthritis and pain (analgesia) Asthma and allergies Gastric ulcers and gastrointestinal diseases Others Population study

1997 1998

1999 2000 2001

2002 2003

2010

8 6 2 0 2

15 2 1 1 0

11 5 4 1 3

16 6 3 3 3

16 10 7 5 1

14 9 10 4 1

18 14 15 4 4

45 40 43 8 10

3 0 1 1 0 1

1 1 2 0 0 0

2 0 1 1 0 1

1 0 1 2 2 0

0 2 0 3 2 1

4 2 7 4 3 2

1 5 2 4 2 3

9 11 5 3 7 2

6 14

3 3

9 6

3 10

3 7

3 17

12 22

13 20

Global pharmacogenomics: where is the research taking us?

Pharmacogenomics knowledge and technologies, which couple genomics information with pharmaceutical drug response, have been promised to revolutionise ...
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