Defining Genetic-Testing Delivery and Promotional Strategies for Personalized Medicine

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DEFINING GENETIC-TESTING DELIVERY AND PROMOTIONAL STRATEGIES FOR PERSONALIZED MEDICINE

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Christina Mitropoulou1, Despina Giannouri2, Kariofyllis Karamperis3, Sam Wadge3 and George P. Patrinos2,4,5 1

The Golden Helix Foundation, London, United Kingdom 2Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece 3Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom 4Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates 5Zayed Center of Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates

19.1 INTRODUCTION In recent years, significant advances have been made in our understanding of the genetic basis of inherited disorders and the correlations between mutant genotype and clinical phenotype, both for monogenic and multifactorial conditions.1,2 These advances, in conjunction with the advent of high-throughput genetic analysis and deep resequencing, have served to reshape the field of modern medical practice3 and are reflected in the rapid development of the genetic-testing industry.4,5 Nowadays, there are a wide variety of public entities and private companies that offer a broad range of antenatal and postnatal molecular genetic-testing services for monogenic and multigene disorders, classical and molecular cytogenetic analysis for chromosomal rearrangements, pharmacogenomic testing, and even predictive genomics for genetic disorders (see also Chapter 10). In addition, many laboratories also offer molecular genetic-testing services in microbiology and virology. At the same time, genetic-testing services are becoming more affordable so that we can already envisage genome resequencing for as little as $1000. However, the rapid expansion of the genetic-testing industry has not come without problems. In particular, some laboratories still offer genetic-analysis services using in-house (home-brew) kits rather than quality-controlled and certified assays. In addition, test results are not invariably interpreted by a qualified professional (e.g., a genetic counselor), whereas other laboratories are not yet accredited for the provision of genetic-testing services.6 Moreover, it transpires that in several cases, genetic analysis is routinely conducted without obtaining informed consent from those persons requesting the test. This raises serious ethical concerns in relation to the preservation of the

Applied Genomics and Public Health. DOI: https://doi.org/10.1016/B978-0-12-813695-9.00019-4 © 2020 Elsevier Inc. All rights reserved.

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anonymity of the individuals tested7 (see also Chapter 13), the fate of their genetic material, and, most importantly, the safeguarding of test results in order to avoid genetic stigmatization.8 There are different models for the provision of genetic-testing services, based on which all the existing genetic-testing laboratories currently operate. In this chapter, we provide an overview of the existing models for the delivery of genetic-testing services and we analyze the various means to promote these services to the end users, that is, patients and their families. We also allude to efforts undertaken in various countries to map the genetic-testing services’ environment.

19.2 GENETIC-SERVICE DELIVERY MODELS Delivery models for the provision of genetic-testing services can be classified into five distinct categories according to which a health-care professional plays the most prominent role in patient pathways to care: 1. 2. 3. 4. 5.

Genetic Genetic Genetic Genetic Genetic

services services services services services

provided by geneticists as part of primary care provided by the medical specialist integrated into large-scale population-screening programs provided using the direct-to-consumer (DTC) model

In all of these models, there are four key players that participate in different order, depending on the model: (1) the patient, who wishes to undertake the genetic testing, (2) the general practitioner (GP) or medical specialist who refers the patient to the genetic laboratory, (3) the genetic laboratory that performs the genetic test, and (4) the genetic counselor or clinical geneticist, who explains the results to the patient. A detailed description of these models is provided in the following subsections.

19.2.1 GENETIC SERVICES PROVIDED BY GENETICISTS In this model the professional team that requests the genetic services may include clinical and/or laboratory geneticists, genetic counselors, and other health-care professionals (e.g., genetic nurses). The professional team is responsible for risk assessment, counseling, and genetic testing of individuals or families affected or at risk of genetic disorders. Depending on the case, the genetic team collaborates with other medical specialists (e.g., oncologists, cardiologists, neurologists, and psychiatrists) who could also be part of the genetic service. Classical examples of this model are genetic services for rare diseases. According to this model, patients could access genetic services through two different paths: 1. Patient—GP/medical specialist—genetic counselor/clinical or laboratory geneticist . genetic laboratory 2. Patient—genetic counselor/clinical or laboratory geneticist—genetic laboratory The first path involves a patient seeking medical assistance from a GP or any medical specialist who then makes a referral to the genetic service, where a genetic counselor or a clinical or

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laboratory geneticist can perform a risk assessment. If a genetic test is relevant and available, they may suggest genetic testing to the patient; then, samples are collected, and tests are performed in the genetic laboratory. Based on the results of the test, genetic counselors or medical geneticists recommend surveillance and/or intervention. Clinical management of genetic conditions may involve various medical specialists, other than geneticists (e.g., oncologists, cardiologists, neurologists, and psychiatrists). The second path involves a patient who without a medical referral, inquires about a genetic service directly, where a genetic counselor or a medical geneticist can perform a risk assessment. Subsequently, the latter path is identical to the former path from this point onward. The majority of the genetic tests offered under this model include newborn screening.

19.2.2 GENETIC SERVICES AS A PART OF PRIMARY CARE In this model, primary-care units play a prominent role, in which GPs must have specific genetic skills and can undertake an initial risk assessment using standardized referral guidelines. In some cases, GPs refer patients, who are categorized as “high risk,” to genetic services, while in other cases, they can provide genetic counseling, request genetic testing, and interpret the results from the genetic tests. Again, in this model, there are three possible paths: 1. Patient—GP—genetic counselor—genetic laboratory 2. Patient—GP—genetic laboratory—genetic counselor 3. Patient—GP—genetic laboratory The first path involves a patient who contacts a GP, who first undertakes the initial risk assessment and subsequently makes referrals to a genetic service, where a genetic counselor or a clinical and/or laboratory geneticist performs counseling and suggests genetic testing to the patient. The second path is similar to the first one, but instead, genetic counseling is offered to patients after the delivery of the genetic results. Thus patients were seen by the genetic counselor only after the genetic test. The third path involves a patient who contacts a GP capable of performing the risk assessment, undertaking genetic counseling, and suggesting genetic testing.

19.2.3 GENETIC SERVICES PROVIDED BY THE MEDICAL SPECIALIST In this model, genetic tests can be requested directly by medical specialists (e.g., oncologists, cardiologists, neurologists, and psychiatrists) who are capable of managing patients suffering from genetic disorders without requiring consultation from medical geneticists. In this case, medical specialists can request genetic testing, communicate genetic test results to their patients and families, and set up treatment with or without consultation from a clinical or laboratory geneticist. Again, there are two main paths for this model: 1. Patient—medical specialist—genetic laboratory 2. Patient—medical specialist—genetic counselor—genetic laboratory The first path involves a patient who contacts (with or without a GP referral) a medical specialist who is capable of performing a risk assessment, undertaking genetic counseling, and suggesting

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genetic testing. A variation of this model includes the involvement of a genetic nurse instead of a medical specialist. The second path involves a patient who contacts a medical specialist, who will undertake the initial risk assessment, and then requests genetic counseling, collaborating with the medical geneticist or genetic counselor for the management of the patient.

19.2.4 GENETIC SERVICES INTEGRATED INTO LARGE-SCALE POPULATIONSCREENING PROGRAMS In this model, genetic services are provided as part of well-organized population-screening programs such as newborn screening, cancer screening, and Ashkenazi Jewish genetic screening. There are three possible paths for this model: 1. Patient—GP/medical specialist—genetic counselor/clinical geneticist—genetic laboratory 2. Patient—GP/medical specialist—genetic laboratory 3. Patient—genetic counselor/clinical geneticist—genetic laboratory The first path involves a patient who takes part in a large-scale population based screening program; a health-care professional, who is involved in the screening program, can perform an initial risk assessment and refer the patient for genetic counseling. The genetic counselor or clinical geneticist can then undertake genetic counseling, suggest genetic testing, and, based on the results of the test, can recommend the appropriate intervention. A variation of this theme is when genetic counseling is offered to patients after the genetic analysis. The second path involves a patient who takes part in a population-based screening program. In this case a duly-qualified physician involved in the screening program can perform risk assessment, undertake genetic counseling, and suggest genetic testing. Based on the results of the genetic test, the physician can recommend surveillance and/or the necessary intervention. Lastly, the third path involves a patient who first contacts a genetic counselor or a medical geneticist, who can undertake genetic counseling, suggest genetic testing, and, based on the results of the test, can suggest surveillance through available populationbased screening programs and/or the necessary intervention. This model is more common in countries with large-scale screening programs such as the United States and the United Kingdom.

19.2.5 GENETIC SERVICES PROVIDED USING THE DIRECT-TO-CONSUMER MODEL In this model, private genetic-testing laboratories or, worse, companies that outsource these genetic-testing services offer genetic-testing services typically through websites. Health-care professionals are not involved in the process and medical referrals are not required for genetic testing through DTC companies. In other words, patients are self-referred. Furthermore, the private companies usually do not offer risk assessment and genetic counseling. In this model, patients purchase the genetic test, usually online, take their own sample at home using a buccal swap kit that is delivered to their home or purchased from a pharmacy, send it to the genetic laboratory, and receive the results directly by electronic or regular mail. Some DTC companies

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offer genetic counseling but only post testing.9 This model is quite popular in the United Kingdom and the United States, among other countries9,10.

19.3 MARKETING IN PUBLIC HEALTH Public health has always been called upon to address major health problems at local, national, regional, and even global level, such as the control of transmittable diseases, the improvement of the physical environment, the quality of valuable goods such as water and food supplies, the provision of medical care, and the relief of disability and destitution. In order to achieve what is mentioned earlier, social marketing plays a decisive role, as an effective approach for developing programs to promote healthy behaviors.11 In recent years, social marketing is being applied to an even wider range of public-health activities and programs, from the safe drinking water campaign in Madagascar to the promotion of mosquito nets in Nigeria.12 Social marketing practice and successful social-marketing campaigns can be found all over the world. Countries active in applying social-marketing techniques to public health vary at the levels of economic and technological developments and differ in social, cultural, and regulatory environments.12

19.4 MARKETING IN GENETIC-TESTING SERVICES In the post-genomic era, a new public-health challenge is that of genetic testing. The completion of the Human Genome Project created a completely new field of genome research that was then included in clinical practice to promote the health of the population. In 2005, by unanimous decision, a group of 18 specialists created an organization to integrate genome-based knowledge and technologies into health services and public policy for the benefit of population health called the Public Health Genomics. As is obvious, the multiple possibilities offered by genetic tests have attracted many pharmaceutical companies and industries.13 Despite widespread discussions on the reliability and use of genetic tests (see also Chapter 10), they are rapidly growing, attracting more and more companies and consumers alike. It seems that genetic-testing practices are rapidly increasing in rare-disease diagnostics and for personalized medicines, which in turn, are fueling the growth of this market. According to recent statistics, the total number of genetic tests that are actively marketed by Clinical Laboratory Improvement Amendments certified laboratories in the United States was 74,448, representing approximately 10,000 unique test types for the year 2018. On the other hand, there are 135,000 inactive genetic tests either because the lab stopped offering them, or because the test changed and assigned a new one. It is estimated that 10 new genetic tests are added daily. Based on the above statistical data, 86% of genetic tests were single-gene tests, while the remaining tests are panel-based including 9311 multianalyte assays (via algorithmic analyses), 85 noninvasive prenatal tests, 122 whole exome sequencing tests, and 873 whole genome analysis tests, which included whole genome sequencing tests.14 Prenatal tests accounted for the highest percentage of spending on genetic tests and spending on hereditary cancer tests accounted for the second highest. Apart from single tests, the market for multipanel gene panels has continued to grow. The frequency of these testing products in the United States represents more

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than 8% of the total number (9488) on the market during the year 2018. The significant delay between the introduction of tests and insurance coverage is often a major problem for proper promotion and production of some products, significantly affecting its sales14. The clinical sequencing market is growing at a compound annual growth rate of 28% and is forecasted to be worth $7.7 billion worldwide by 2020. This growth is due to the growing demand for tests with better performance characteristics and clinical validity compared to other applications such as prenatal screening and monitoring cancer recurrence. In addition the dramatic reduction in the cost of sequencing, development of informatic tools and the ability to analyze complex data, and of new methods, such as circulating cell-free DNA techniques, and improving data in the interpretation of results are considered to be some of the reasons for their unexpected growth in worldwide markets.14 So far, it seems that whole exome sequencing is not only the predominant force in the market compared to other next-generation technologies but also to different types of genetic tests (Fig. 19.1). More precisely, clinicians seem to be interested in whole exome sequencing due to its more comprehensive diagnostic approach than single-gene, panel, or some microarray testing—yet providing more focused and medically actionable results than whole genome sequencing.15

19.5 DEFINING THE MARKETING STRATEGY FOR GENETIC-TESTING SERVICES Briefly, marketing is defined as the management process, which is responsible for identifying how to anticipate and satisfy the customer requirements. As a more in-depth opinion, Kotler defines marketing as “. . . a process by which individuals and groups acquire what they need and desire, through the creation exchange of products and values with others”16. According to Janice DenegriKnott, Mike Molesworth, and Richard Scullion (University of Bournemouth, Dorset, United Kingdom), “. . . in some ways, marketing is as old as the ancient civilization of Greece.” Ultimately, the marketing orientation of businesses began in the 1960s with the production and sales orientations. According to the new philosophy, businesses should first identify what the consumer wants and then try to produce it rather than produce what they can and then try to change needs of consumers. It is understood that marketing began within an introverted environment focusing on what a business produced. Today, modern marketing operates within an extrovert environment with multipurpose tools such as those in social media, which provide valuable insights into the business for the prevailing demand in markets and consumer preferences. The goal is therefore to achieve more effective customer satisfaction through an integrated marketing-strategy program.17

19.5.1 TARGET AUDIENCE The target audience of the genetic-testing services is considered to be health-care professionals, namely, physicians and pharmacists, public bodies, for example, hospitals, private clinics, and laboratories, and the state, for example, the Ministry of Health. The indirect target audience is considered to be the end users of genetic testing, since we believe that the DTC model (see earlier) does

19.5 DEFINING THE MARKETING STRATEGY FOR GENETIC-TESTING

FIGURE 19.1 A catalog of genetic testing services in the market.

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not meet the ethical requirement for a health-care service. Therefore genetic-testing services should be promoted to the health-care professional community in order to properly inform the interested parties.

19.5.2 THE MARKETING MIX The marketing mix is the combination of human and material resources needed to fulfill the programs and objectives of the business in one market.17 The strategy of the marketing mix manages the aforementioned resources to maximize the growth in sales. A well-designed set of strategies not only includes an attractive pricing and the development of new products, but additionally must be promoted in the best possible way to the public based on integrated communication programs. Proper communication is the key factor in creating and maintaining good customer relationships of trust. At this point, it should be noted that the value of the factors and the improvement of the company’s development strategy varies according to the product and creates particular parameters that can vary according to the final product being distributed on the market.17 The marketing mix, which is often referred to as “4Ps” (Fig. 19.2), deals with the following: •

Product: In this case, products are defined as the genetic-testing services. Once the product comes into the market, it goes through four stages, namely, import, growth, maturation, and decline, also known as a product life cycle. At the import stage, the product is promoted to make it public and available on the market. As this phase is unlikely to be profitable, the products/genetic-testing services should be monitored continuously until there is an increase in sales. Otherwise, the safest alternative would be to withdraw the product. As soon as the product sales begin to rise, it enters the growth phase, which is characterized by increased sales and profits. The stage of maturity is also the most popular for products already on the market where the genetic-testing laboratory scores the most profits and the competition becomes stronger. In this phase, genetic-testing laboratories are constantly developing new ideas and

FIGURE 19.2 Outline of the 4Ps concept of the marketing mix.

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•

•

•

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investing money in product research and development, in order to compete with other assets, stay on the market, and succeed. During the final stage of decline, as profits are no longer high for that product, it may be withdrawn from the market.18 Genetic tests, particularly those related to pharmacogenomics or genetic predisposition to an inherited disease, are considered to belong to the second stage of development as more and more people are sensitized, informed, and interested to look for a timely diagnosis, which will improve the quality of their lives. Price: It is the monetary value at which the consumer purchases the product or service—in this case, genetic-testing services. The price range of a genetic-testing service could start from as low as 50h or $ to up to thousands of h or $. In the case of whole genome, whole exome, or targeted resequencing, data interpretation is often provided as an additional service. Apart from the monetary value of the genetic testing service, the emotional and psychological cost and time constraints the target group bears to overcome barriers and successfully adopt the desired behavior are equally important issues. The amount that a customer has to pay for a genetic test plays a crucial role for the development of the product. Based on the fact that health is a key priority for most people, the price must be affordable to be distributed and used in multiple groups of interest. Furthermore, this has a big impact on the entire marketing strategy as well as a great effect on the sales and demand of the product. Nowadays, genetic and pharmacogenomic-testing services cost less than 300h in Europe and the United States, allowing them to grow rapidly and use more and more. Place: This refers to the way the product is distributed to the customer. In the case of the genetic testing service, this is provided through accredited (or not) genetic-testing laboratories, specifically where the target group will be exposed to the product, where it will interact and think about the subject, and perform the desired behavior. Globally, genetic disorders and the development of genetic diseases vary as environmental factors are known to play an important role in genetics. Genetic and pharmacogenomic tests must be provided based on the needs of each population and their afflicting condition. For that reason the development of each genetic test depends on that, while the way the product is distributed to the customer is also equally important. Promotion: Promotion is probably the most important stage in the development of each product and refers to the way it reaches the end user/customer and how the user is ultimately prompted to purchase it. In this case, special emphasis should be given to the promotional strategy and message for the target audience and the marketing medium. In the first case the promotional message should clearly state the importance of analyzing the results of a genetic test by a specialist while prompting physicians to suggest them to their patients when they consider the need for such an examination. As far as the marketing medium is concerned, genetic-testing services are unique and, as such, require particular attention for their advertising and promotion. Contrary to the majority of consumer products, the most appropriate and scientifically sound promotional means would be scientific journals and websites that appeal to health-care professionals as well as informational days for doctors to raise awareness about the usefulness and relevance of these tests for their patients. Direct marketing of genetic tests to the general public, using promotional media, such as ads in television and newspapers, cold calls or mass postal or e-mail, is considered to be inappropriate for such a specialized type of service. Prior to the promotion of a genetic test, it is considered necessary to inform and recruit appropriate medical staff as they should provide the customer with all the necessary information and guide.

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Proper education is highly recommended for health-care professionals and scientists, such as geneticists, physicians, genetic counselors, especially, given their lack of genomics knowledge (see also Chapter 12). The main approaches, such as branding, advertising, public relations, corporate identity, social media outreach, sales management, special offers, and exhibitions, are integral parts of the promotion strategy. Policy: In the case of public-health marketing, policy is the fifth broad level of marketing decision (hence a fifth P in the 4Ps marketing mix), which has been added to the basic framework according to the Center for Disease Control and Prevention. Policy refers to the creation or usually the modification of existing legislation and regulations trying to encourage or require the desired behavior change.

19.5.3 DIVERSITY Genetic-testing services differ greatly from a hematological or biochemical test. Genetic testing can be offered in a wide variety of types, such as preclinical, prenatal, or even preimplantation genetic diagnosis, single variant or panel-based multivariant genetic screening, targeted resequencing, whole exome and whole genome sequencing, and pharmacogenomic testing.

19.5.4 CONFIDENCE As previously mentioned, the target audience for genetic tests is physicians and patients. For both of these groups, different approaches must be sought. When it comes to physicians, it is necessary to adequately inform them about the benefits from using these tests for the early diagnosis of genetic diseases, rationalizing drug use, and hence, minimizing the risk of developing adverse drug reactions for their patients. This would assist them in more targeted drug prescriptions. This is particularly needed for the older generation of physicians whose genetics education level is low. Similarly, patients are also required to get informed about the benefits of personalized treatment based on their genetic profile and the benefits of undertaking a genetic test, which provides an enormous amount of information about the health outcomes. Also, being able to diagnose a genetic disease will lead the patient to early prevention and to avoid future treatment costs and, most importantly, to improve the quality of his/her life.

19.5.5 STRENGTHS, WEAKNESSES, OPPORTUNITIES, AND THREATS ANALYSIS SWOT analysis is very important for launching a new product and takes into consideration the strengths, weaknesses, opportunities, and threats from launching this product or service. Strengths and weaknesses are part of internal analysis, while opportunities and threats are elements of external analysis. In the case of the genetic-testing services the following elements are part of the SWOT analysis.

19.5.5.1 Strengths • •

Analysis of the human genome has led to the early prognosis and diagnosis of diseases Testing the general public at relatively very low prices compared to the benefits they get

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Improving the quality of life of the patients Reducing the health-care costs from the reciprocal reduction of adverse reactions and informed health decisions

19.5.5.2 Weaknesses • • •

Inability to interpret and understand the results of genetic tests by consumers without the assistance of a qualified health-care professional A time-consuming process of exporting the results Pitfalls in the technology used for genetic testing

19.5.5.3 Opportunities • • • • • •

Continuous technology and industry development and scientific progress Implementation of next-generation sequencing technology in molecular diagnostics Raising general public and end-user awareness Ability to treat diseases at a personal level and individualize treatment with fewer adverse reactions Lower costs for drug treatment modalities Development of new diagnostic applications, such as array-on-demand, for the diagnosis of the genetic basis of unknown genetic diseases.

19.5.5.4 Threats • • • • • • • • • • • • •

Use of genetic tests at home using, for example, the DTC model Performing genetic testing without the informed consent from the interested party Ensuring patients’ anonymity and personal data protection assurance Lack of sufficient funding Lack of the necessary legal framework governing the genetic testing service environment Improper promotion of genetic testing by doctors, mostly those with incomplete genetic knowledge Lack of genomics awareness of the general public Lack of a stable health-care environment Lack of a well-defined and consistent national strategy on genomic medicine Insufficient support of genetic-testing services by pharmaceutical companies and other stakeholders due to conflict of interests Lack of accreditation of genetic-testing laboratories Lack of reimbursement of genetic tests by payers and insurance companies Denial of insurance based on genetic profile and genetic stigmatization

19.5.6 POLITICAL, ECONOMIC, AND SOCIAL POLICIES, TECHNOLOGICAL DEVELOPMENTS, LEGISLATION, AND THE ENVIRONMENT ANALYSIS The PESTLE analysis focuses on the analysis of the external environment and presents the prevailing conditions, challenges, and changes that may be encountered by an enterprise, relating to the

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political (P), economic (E), and social (S) policies, technological developments (T), legislation (L), and the environment (E). As far as the implementation of the PESTLE analysis for genetic-testing services is concerned, political stability is necessary for the legislation of the necessary bills such as the establishment of the genetic specialties or the taxation environment for the genetic-testing services. In terms of economy the slow pace of the economy may result in the improper promotion of the genetic-testing services through the Internet, while the high unemployment rate and the low wages leave little room for choice for such a high specialized type of testing, such as genetic testing, as compared to the classic annual hematological and biochemical tests. In other words, in an uncertain economic environment with an even more uncertain future, priorities are set to ensure basic needs, such as food and housing, and unfortunately not something as specialized as the genetic tests. The most important parameter of the PESTLE analysis for the genetic testing services is the social circumstances. In particular, lack of genetic awareness from the general public (see also Chapter 12) can negatively impact on the understanding of the significance of the genetic tests. In fact a large percentage of the general public would be interested to carry out a genetic test, although not all of them are duly informed about, for example, the role of genetic material and the means for DNA isolation. Of equal importance are the ethical considerations in the PESTLE analysis. Genetic tests are not just consumer products, which can be directly promoted to the consumer and as such, it is of utmost importance to ensure that genetic-testing services are promoted to the general public in the most appropriate way to safeguard public health and at the same time the interests of the patients. Often, however, promotion of these genetic-testing services is not adequately performed, since the end user is either misled or misinformed about the usefulness of these tests. For example, certain genetic laboratories promote these tests via brochures sent to prospective consumers by mass e-mail campaigns or misinform the end user about the usefulness of a genetic test such as those tests that are aimed to predict athletic performance or dietary intake. Also, very often, the genetic test results are not received directly from the genetic laboratories, but they are mailed to the end users using either electronic or regular mail. This is totally unacceptable, since this approach not only bypasses the genetic counselor but also creates an issue with patient’s anonymity. Also, the availability of some genetic tests online may create more ethical issues such as in the case of the paternity test that can be ordered without the consent of both parties. The legal requirements are also important to be clearly set, especially those safeguarding the person being tested. The most well-known legislation is the GINA Act in the United States, while similar legislation measures are also in place in other countries (see also Chapter 14). Also, the DTC genetic-testing provision model is currently poorly covered by the existing legal framework, while there is huge heterogeneity in the respective legislation framework among different countries, mostly in Europe (Mai et al., 2011). Similar legislation measures are also in place for the required accreditation of the genetic-testing laboratories requiring international external quality audits and certain accreditations such as the ISO 15189:2007 in the EU or the College of American Pathologists certification in the United States. Lastly, the analysis of the various technological conditions refers to the genetic-testing technologies, which are constantly developing, not only positively impacting on the science itself but also having a direct impact on the genetic-testing costs.

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19.6 DEFINING THE LANDSCAPE OF GENETIC TESTING IN VARIOUS COUNTRIES The landscape of private genetic-testing services is still poorly developed in many parts of the world. Even though genetic-testing services are mostly well regulated in the United States and Western European countries, such as The Netherlands, the United Kingdom, and Switzerland, in other European countries, Asia, and the Middle East, genetic-testing services often face several issues, mostly resulting from the lack of proper regulatory framework, which consequently leads to a number of different ethical issues. EuroGentest (http://www.eurogentest.org) has attempted to rectify this deficiency by initiating a drive to harmonize genetic-testing services in Europe. In parallel, OrphaNet (http://www.orpha.net) has attempted to database the plethora of genetic-testing laboratories in Europe but these efforts have often been hampered by the willingness of some laboratories to communicate the requested details of their operations. It is therefore clear that in the emerging era of personalized genomics, the task of “fine-mapping” genetic-testing services in Europe is assuming ever greater urgency. The detailed description of the genetic-testing environment lies outside the scope of this chapter. Instead, we opted to summarize in the following subsections, the current landscape of genetictesting services in two health-care environments, that of Greece and Malaysia, in an effort to highlight the need of harmonizing and introducing proper legislative measures for better regulation of the genetic testing service environment to the benefit of the patients.

19.6.1 OVERVIEW OF GENETIC TESTING SERVICES IN MALAYSIA The Malaysian population is characterized by a multitude of genetic disorders due to its vast ethnic diversity. The landscape of genomic testing and genetic counseling services in Malaysia is quite diverse. There are 20 Malaysian, mostly private, genetic-testing laboratories, all located in Peninsular Malaysia, offering genomic services including genomic testing and counseling. Such services include paternity testing, family tree analysis, ancestry and prenatal testing, clinical tests, animal testing as well as lifestyle genomic tests (wellness and fitness). Interestingly enough, clinical and lifestyle (wellness and fitness) genomic tests are the most common genomic services pursued in Malaysia (40% of the genetic-testing laboratories), followed by prenatal testing services (35%).19 In contrast, various relationship/ancestry tests are only provided by very few genetic testing laboratories (15%), while an equal number of genetic laboratories offer pharmacogenomic testing services. Interestingly, two genetic-testing laboratories offer several DTC testing services (paternity, relationship, and infidelity tests), both of them offering “discreet delivering options.” Statements such as “discreet testing services” and “discreet samples” are also included in the online material of other genetic-testing laboratories. Also, genetic counseling services appear to be extremely limited, since most genetic-testing laboratories solely offer “DNA test reports” that provide the test results accompanied by ways to interpret them. Some paternity tests include conclusive results that “confirm” or “exclude” the alleged father. Only one private molecular diagnostics company offers complete genetic counseling support for physicians and patients. This may perhaps be explained by the fact that there is still no formal recognition of the role of genetic counselors in the country and there are no legal requirements for the

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provision of genetic-counseling services. In particular, there are few genetic counselors, who often lack the knowledge, expertise and skills to properly inform interested parties.

19.6.2 GENETIC-TESTING SERVICES IN GREECE In Greece the first genetic-testing services appeared in Athens in the early 1960s, the first being Cytogenetics Laboratories. Since the early 2000s the number of genetic-testing laboratories has increased significantly. However, the country still lacks formal genetics centers organized within a national genetic-testing network such as in the case of the United Kingdom. Also, the number of physicians trained in clinical and/or laboratory genetics is very extremely limited, especially since the clinical and laboratory genetics specialties were only established in Greece in 2018. Sagia et al.20 have previously surveyed genetic-testing laboratories in Greece. This study indicated that the majority of them are involved in the provision of molecular genetic analysis for inherited disorders, followed closely by classical and/or molecular cytogenetic testing and molecular genetic testing for microbiology and predictive genomics. Physicians appear to be the main target group for the genetic laboratories, followed by the general public and other interested parties such as other genetic laboratories, diagnostic centers, hospitals, and pharmaceutical companies. The main specialties that the diagnostic laboratories mainly address are obstetricians/gynecologists, followed by pathologists, cardiologists, psychiatrists, and other specialties, namely, oncologists, pediatricians, hematologists, and neurologists. This may not be unexpected since obstetricians and gynecologists usually order molecular genetic and, particularly, cytogenetic tests to screen for fetal malformations, particularly in cases with a family history. In addition, psychiatrists, cardiologists, and oncologists are the physicians who order pharmacogenomic tests more frequently, since these are the disciplines in which pharmacogenomic testing has been most widely adopted. In Greece, genetic-testing services are also provided using the DTC model, where 26 laboratories were previously identified offering DTC genetic tests.21 In particular, these private genetictesting laboratories offer genetic tests for predisposition to complex diseases, paternity testing, pharmacogenomics, nutrigenomics, antiaging, and genetics of athletic performance. From these, two genetic-testing laboratories are partnering with major pharmacy groups to promote their services using the over-the-counter business model.22 Interestingly, these companies do not operate as medical entities but rather as genetic-analysis laboratories, indicating that the interpretation of the results from the genetic tests is the sole responsibility of the person(s) who requested the genetic test. This is particularly the case for the vast majority of the genetic-testing laboratories that only “sell” genetic tests online and in some cases outsource the actual genotyping to other genetic laboratories abroad. It is therefore not surprising that such private genetic-testing laboratories often offer genetic-testing services for pharmacogenomics and/or paternity testing together with genetic services for inbred animals (e.g., race horses) and/or genetically modified organisms.

19.7 CONCLUSION AND PERSPECTIVES The provision of genetic services, along with research in the fields of genomics and genetics, has evolved in recent years to meet the increasing demand of consumers interested in the prediction of

REFERENCES

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genetic diseases and various inherited traits. In this chapter, we attempted to summarize and classify delivery models for the provision of genetic testing, presented the steps to be undertaken when defining the optimal promotional strategy for genetic testing services while we also presented the landscape of provision of genetic-testing services in two countries, Europe and Asia. New models of genetic-service delivery are currently under development worldwide for addressing the increasing demand for accessible and affordable genetic-testing services. These models require the seamless integration of genetics into all medical specialties, collaboration among different health-care professionals and stakeholders, and the redistribution of professional roles. We believe that there is no generic model for the provision of genetic-testing services. On the contrary, an appropriate model for genetic-service provision must be ideally defined according to the type of health-care system, the genetic test provided within a genetic program, and the cost-effectiveness of the intervention, once this is determined (see also Chapter 16), as only genetic applications with proven efficacy, solid scientific evidence, and cost-effectiveness should be implemented in healthcare systems and made available to all citizens.

ACKNOWLEDGMENT Part of this work was supported by the European Commission grant COST CHIPME (IS3101) and is part of the GoGreece initiative.

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FURTHER READING Dequeker E, Ramsden S, Grody WW, Stenzel TT, Barton DE. Quality control in molecular genetic testing. Nat Rev Genet. 2001;2(9):717 723. Kricka LJ, Fortina P, Mai Y, Patrinos GP. Direct-access genetic testing: the view from Europe. Nat Rev Genet. 2011;12(10):670.