Ethical, Legal, and Social Issues

in Pharmacogenomics

by

Reynaldo Cortes, Jr., RPh

John Robert Omandac, RPh

Submitted to

Dr. Adorico M. Aya-ay

on

February 2017

Contents
Introduction 3
Scientific Background 4
Human Genome Project 5
Ethical Issues 5
Genetic Discrimination 5
Stigmatization 7
Privacy and Confidentiality 7
Balancing Harms and Benefits 8
Legal Issues 9
Informed Consent 9
Ownership of Data and/or Samples 10
Intellectual Property 12
Disclosure Obligations and
Reporting Requirements 13
Social Issues 15
Race and Ethnicity 15
Testing in Vulnerable Populations 16
Availability of Testing 17
Knowledge and Education of
Health Care Professionals 18
Conclusions 19
Bibliography 20

Introduction

On completion of the Human Genome Project in 2003, the

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field of pharmacogenetics and pharmacogenomics has rapidly
developed with the intent of individualizing therapy to maximize
efficacy and minimize toxicity. There are many challenges and
barriers that impact the implementation of pharmacogenomics
into clinical practice. These include ethical, legal, and social
issues that highlight risk, benefit, and public and professional
acceptance.

Attempts to establish a framework to accelerate integration

of appropriate pharmacogenomic and human genome discoveries
into clinical practice have been reported. Haddow and Palomaki
first reported the ACCE model for evaluating data on genetic
tests. ACCE that takes its name from the four main criteria for
evaluating a genetic testanalytic validity, clinical validity,
clinical utility, and associated ethical, legal, and social
implicationsis a model process that includes collecting,
evaluating, interpreting, and reporting data about DNA (and
related) testing for disorders with a genetic component in a
format that allows policy makers to have access to up-to-date and
reliable information for decision making.

One of the major components for evaluation includes the

associated ethical, legal, and social implications. The authors
identified challenges and barriers to genetic testing including
genetic discrimination, stigmatization, privacy/confidentiality, and
personal/family social issues. Additional challenges highlighted
legal issues regarding consent, ownership of data and/or samples,
patents, licensing, disclosure obligations, and reporting
requirements. Although the ethical, legal, and social issues
revolve around establishing safeguards in the context of genetic
testing, these components are applicable to pharmacogenomic
testing. Several examples in this chapter will highlight these
issues in relation to genetic testing to aid in the understanding of
specific concepts and application. The purpose of this chapter is
to provide a framework of the ethical, legal, and social issues
surrounding the rapidly evolving field of pharmacogenomics.

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Scientific Background

Before a drug can exert its desired pharmacological action,

it generally undergoes a series of steps including absorption,
transport through blood and epithelial tissues, metabolism
primarily in the liver, and interaction with its intended cellular
targets. This process requires the action of many specialized
proteins that function in structural, catalytic, transport and
signaling roles. Given the complexity of this process, it is not
surprising that several factors can affect patients response to
drugs. These include the age of the patient, nutrition, intestinal
flora, co-morbidity, gender, etc.

Moreover, evidence over the past 50 years has increasingly

shown that individual variation in the genes that code for the
proteins involved in drug disposition, metabolism and drug effect
can contribute to individual differences in drug response. Since
many drugs have a low therapeutic index, genetic variations may
result in under-dosing or over-dosing, often with serious and even
fatal side effects. Genetic variations may also affect disease
susceptibility. Although this is not necessarily linked to
pharmacogenomics, the two are often discussed together.

In 1959, Vogel initially coined the term "pharmacogenetics"

to describe the relationship between genetic variation in genes
coding for drug metabolizing enzymes and drug response. Since
then, technological advances in tandem with large scale
sequencing projects, such as the Human Genome Project allowed
researchers to scan the genomes of many individuals
simultaneously to look for variation in gene sequence or
expression. The large data sets that these genetic studies are
generating for biomarkers that will be useful in predicting disease
susceptibility, screening for drug response, and/or predisposition
to adverse drug reactions. The field of pharmacogenomics draws
on this knowledge to optimize current drug treatment and design
novel therapeutic agents. Henceforth, we will use the term
pharmacogenomics to cover both pharmacogenetics and
pharmacogenomics.

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 Integration of pharmacogenomics into clinical practice is
most promising in fields where few therapies exist, where existing
therapies have a narrow therapeutic index or where the risk-
benefit ratio of these therapies is high. For example, genotyping
for mutations in the gene coding for thiopurine methyltransferase
(TPMT), an enzyme that detoxifies drugs used in the treatment of
leukemia, can prevent adverse reactions associated with their
use. Pharmacogenomics can also be used to make crucial
decisions in drug development when proceeding from one phase
of a clinical trial to the next, more expensive, phase.

Human Genome Project

Beginning in 1990 the Human Genome Project, involving

collaborators from China, France, Germany, Japan, the United
Kingdom and the United States of America, sought to determine
the sequence of the chemical base pairs that make up human
DNA and to identify all genes in human DNA. The other goals of
the project were to store this information, improve tools for its
analysis, transfer technologies to the private sector and address
the ethical, legal and social issues (ELSI) that might arise. In April
2003 the completion of the project was announced in and a
completed sequence of the human genome was released, which
is now available for analysis

Ethical Issues

Genetic Discrimination

Individuals who obtain pharmacogenomic and/or genetic

testing may be exposed to genetic discrimination. Genetic
discrimination refers to when an individual, with a known genetic

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disorder or genetic polymorphism, is treated differently by his or
her employer or insurance company. Knowledge of genetic and/or
pharmacogenomic information may be used to deny, limit, or
cancel health insurance. There is suggestion that health insurers
should have limited access to such information. Insurers would be
able to use pharmacogenomic information for drug formulary
management, but should be prohibited from using the same
information in determining copayments or premiums, or
negotiating contracts.

Additional concerns regarding genetic discrimination include

employers using such information to only employ or retain
individuals who do not have the genetic disorder or genetic
polymorphism, limiting access to social services, and in the
delivery of health care. Consequently, genetic discrimination
potentially generates social, health, and economic burdens for
society due to decreasing opportunities of genetically predisposed
individuals in a range of scenarios.

Several reports of genetic discrimination have been

documented. In 2001, the Equal Employment Opportunity
Commission (EEOC) filed suit against the Burlington Northern
State Santa Fe (BNSF) Railroad. Without the knowledge and
consent of its employees, BNSF tested 36 employees for a genetic
condition associated with carpal tunnel syndrome as part of a
comprehensive diagnostic exam. BNSF employees were examined
by company-paid physicians and were not informed that genetic
testing was being performed. Those employees who refused
testing were also threatened with possible job termination. BNSF
defended such testing as a means of determining if repetitive
stress injuries were work-related. Under the Americans with
Disabilities Act, the EEOC argued that such testing as a basis for
employment was unlawful and a cause for illegal discrimination.
The suit was eventually settled, with BNSF admitting that testing
employees for a genetic condition was performed and that such
testing was no longer being conducted. In a case history study (n
= 41), genetic discrimination involved insurance companies (n =
32) in areas of applications or coverage changes for health, life,

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disability, mortgage, and auto insurance. Seven cases involved
employment in areas relating to hiring, termination, promotion,
and transfer. Due to the fear of discrimination, the authors also
noted that respondents either withheld mentioning such
information to health care providers, insurers, and employers or
provided incomplete or dishonest information on insurance
application forms.

Stigmatization

Stigmatization is defined as a social process that begins

with distinguishing and labelling some feature of a person such as
occupation, disease, or skin color. An individual may experience
stigmatization from family, friends, and coworkers on knowledge
that a specific disease will not respond to therapy or if one is
identified as a poor metabolizer of a specific medication. This
may lead the individual to feeling lonely, isolated, hopeless, and
depressed.

A classic example was during the 1980s, with human

immunodeficiency virus/acquired immunodeficiency syndrome
(HIV/AIDS) described as a sexually transmitted infection
diagnosed in patients identified as homosexuals or intravenous
drug users. Patients, as well as parents, children, and caregivers
for HIV-positive patients, were susceptible to stigmatization.
Negative connotations by the public included misperceptions that
people associated with such behaviors were immoral, predatory,
and dangerous. Consequently, pharmacogenomic testing may
also reveal similar negative connotations and public perceptions,
as evidenced with traditional genetic testing.

Privacy and Confidentiality

Patients, health care professionals, and policy makers are

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concerned about security and loss of privacy. The capacity for
such information to be adequately stored and rapidly
disseminated and the relative ease of accessibility all pose a risk
for a loss of privacy. Examples of methods to ensure privacy
include use of de-identified subject data, use of password-
protected and/or encrypted files, and limiting access. Additionally,
in the United States, federal legislation such as the Health
Insurance Portability and Accountability Act (HIPAA) and private
sector self-regulation exists.

The HIPAA Privacy Rule provides federal protections for

personal health information held by covered entities (e.g., health
care providers, hospitals, pharmacies, insurance companies) and
provides patients the rights regarding personal health
information. However, uncertainty remains in the capacity and
ability of current systems to ensure privacy, security, and
confidentiality. For example, health care practitioners who use
telemedicine technologies to disseminate pharmacogenomic
information may be faced with contrasting federal and state law
privacy standards. In one scenario, if a provider orders a genetic
test from one state and the results of the test are made available
electronically to another out-of-state provider, clarification is
warranted as to which state privacy laws are followed.
Additionally, HIPAA only applies to employer-based and
commercially based issued health insurance and does not apply
to individuals who seek private health insurance in the individual
market.

Balancing Harms and Benefits

Foreseeable harms should not outweigh anticipated benefits

for participants in pharmacogenomic research. Minimizing harm
implies a duty to ensure that research subjects are not subjected
to unnecessary risks of harm and that their participation in
research is essential to achieving the scientific outcomes
necessary for future treatment for the subjects themselves, other

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individuals, or society as a whole. Pharmacogenomic research
includes the potential for physical risk and negative psychological
impact. The physical risks are related to using a drug in which the
drug itself has the potential to cause harms such as intolerable
side effects. The psychological impact may include being
excluded from enrolling in a clinical study if the individual does
not have the genetic polymorphism or genotype, which may lead
to despair if other treatments have failed or are not available.

The implementation of a pharmacogenomic test to

determine if an individual may respond appropriately to a given
drug before beginning treatment may also result in a dilemma for
health care providers and patients. For example, what is
appropriate therapy for an individual who is not a candidate to
receive a specific therapy based on a pharmacogenomic test
result and for whom there are no other known treatments? Is it
morally permissible to offer the treatment anyway with the
knowledge of there being little chance for response or possibly
even inducing harm? This is very unlikely to occur as most health
care providers would find this option to be in conflict with their
inherent duty to do no harm. However, this could theoretically
create fear among consumers, which may result in patients
unwilling to take the associated test for fear of being abandoned
in their treatment.

Legal Issues

Informed Consent

With genetic testing, the DNA collected will not just include
the known genetic polymorphisms obtained from participating in
a research study but may also include information about the
individual's entire genome. As a result, these DNA samples could
provide invaluable information about not only the participant but

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also possibly his or her extended family, which could be entirely
unrelated to the original study. Typically, such additional
information would not be revealed to the original participants but
rather be used in an anonymous fashion. However, this possibility
should be discussed up front as part of obtaining informed
consent. Although future use of such data may not be known at
the time of consent, specific language should be described in the
informed consent form. Consideration of using narrow or broad
terminology may be appropriate to help participants understand
how their information may be used.

In pharmacogenomic research one of the fundamental

requirements to enter a study is to test individuals for a particular
genotype of interest. Study participation in such research will
reveal personal health information, which would not be known in
other clinical studies. This particular knowledge does not
necessarily compromise privacy and confidentiality but does
require it be addressed in the consent process as well as
dissemination of results that may or may not be revealed to the
participants.

Several issues related to the informed consent process for

pharmacogenomic testing warrant discussion. First, there appears
to be no standard at the national or international level concerning
how to consent individuals for research that involves genetic
testing. Although some have attempted to address these issues,
there currently exist two informed consent standards. The
professional standard evaluates what a reasonably prudent
physician with the same background, training, and experience,
practicing in the same community, would have disclosed to a
patient in the same or similar situation. 1 In contrast, the patient
standard attempts to address what a reasonable patient in the
same or similar situation would need or want to know to make an
informed decision regarding a medical intervention or treatment.
Second, there is an inconsistency as to the placement of a
consent form for genetic testing that was completed by the
patient as part of a clinical study. Some advocate placement of
the consent form in the patient's medical record, while others

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suggest that such information be kept separate from the patient's
medical record. Our own experience has been that some
institutional review boards (IRBs) do not recommend consent
forms (for studies where genetic testing is to be done) to be
placed in the medical record. Rather, such information should be
kept in a file by both the investigator and the IRB. This attempts
to ensure privacy by avoiding inadvertent disclosure of such
information to anyone reviewing the patient's medical chart.

Ownership of Data and/or Samples

Pharmacogenomic testing requires collection of DNA. A

biological specimen (e.g., blood, saliva, or tissue) is obtained from
the patient. Due to genomic scale-up (e.g., genomic sequencing
of patients), such specimens are stored in repositories known as
biobanks. At times, biological specimens are aliquoted whereby
material is used for pharmacogenomic testing and any remaining
specimen is archived. The archiving of biological specimens in a
biobank facilitates use of the same sample for future exploratory
research with no defined time limit for use. These biological
samples and their respective data are invaluable, not only to
academic or medical geneticists but also to pharmaceutical
companies and the biotechnology industry.

Claims of ownership of the biological specimen involve the

subject-donor, the institution whereby research was conducted,
and the individual investigator. Due to a lack of clearly defined
regulations and multiple stakeholder involvement, the issue of
ownership of biological specimens, such as those reserved for
pharmacogenomic testing, remains contentious. From a subject-
donor perspective, his or her biological specimen is considered a
property right and denying such a right over biological material is
unfair. The contrasting perspective defends an absolute non-
patrimonial view, denying the possibility of the existence of a
property right.

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 In the Moore v Regents of the University of California case,
the plaintiff sued the defendant claiming deprivation of property
interest, lack of adequate informed consent, and breach of
fiduciary duty. Mr Moore's biological specimens were collected by
the defendant's physician for a research project. Unknown to the
patient, the results of the research led to a patent application by
the defendant. The state court ruled that Mr Moore did not retain
the right of ownership of his biological specimen that was used to
develop a new therapy/product. In addition, the court also noted
that disclosure to the patient of additional research or economic
interests was necessary.

Research is underway to examine the issues related to the

ownership of data and/or samples. Legal writers have suggested
theories related to trusteeship, benefit sharing, commodity, and
waste models. Current research is focused on understanding
the different perspectives from the multiple stakeholders and to
develop policies. Input should be acquired from all interested
stakeholders including the general public, researchers, as well as
the private sector. It also seems reasonable given the global
nature of research and development that these regulations be
formulated at an international level.

Intellectual Property

Approximately 20% of all human genes are under US

patents. In 2005, this equated to 4,382 of the 23,688 genes
described in the National Center for Biotechnology Information
database. US patent laws are intended to stimulate innovation
and to protect the discoveries of inventors. For a period of 20
years, a patent provides the inventor the exclusive right to
manufacture, use, and sell the discovery. To qualify for a patent,
the invention needs to be useful, novel, and not obvious. In the
context of genomic medicine and pharmacogenomics, gene
patents remain a contentious issue. The most common argument
against gene patents is that since genes are naturally occurring

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biological processes, they exist to be discovered and not
invented. In contrast, such an argument is considered
unpersuasive since isolating DNA does not occur naturally and
that the patent system has long recognized useful applications of
discoveries as inventions. In Diamond v Chakrabarty, the US
Supreme Court ruled that genetically engineered bacteria were
subject to patent protection as they did not occur in nature.
Although the genes themselves are not patentable, patent
protection is allowable under the auspices of DNA that is
modified, purified, or isolated resulting in a form that is
nonexistent in nature.

In 2009, a lawsuit was filed by the American Civil Liberties

Union (ACLU) and others against Myriad Genetics for their US
patent on the human genes BRCA1 and BRCA2. BRCA1 and BRCA2
mutations are associated with an increased risk of breast and
ovarian cancers. Myriad Genetics currently owns at least seven
patents directed at BRCA1 and BRCA2. The plaintiffs argued that
the BRCA genes were products of nature and were thus outside
the realm of patent protection. Myriad Genetics cited the
Diamond v Chakrabarty ruling and asked for dismissal. In a
surprising ruling to many in the patent field, US District Court
Judge Robert W. Sweet ruled in favor of the plaintiffs and
invalidated seven BRCA patents by Myriad Genetics. In June 2010,
Myriad Genetics filed a notice of appeal in the US Court of Appeals
for the Federal Circuit. In July 2011, the Federal Circuit ruled in
favor of Myriad Genetics and declared that BRCA1 and BRCA2
genes were patent-eligible under Section 101 of the US Patent
Act.

Although it is not clear if the plaintiffs will appeal the

Federal Circuit ruling, efforts are underway to consider regulatory
and patent reform. In 2011, the America Invents Act was signed
into law and highlighted US patent reform. However, whether
such law is applied to US patent cases involving
pharmacogenomic and/or genetic testing remains to be seen.
Others have suggested more stringent application of patent
criteria for DNA sequences. Expanding access to DNA sequences

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in publically available databases such as GenBank and the
International HapMap Project will also provide researchers access
and the ability to analyze genes associated with disease.

Disclosure Obligations and Reporting Requirements

Ancillary information is defined as additional information

pertaining to the predisposition to diseases or conditions,
prognostic information, or information relevant to other classes of
drugs for which the individual is not currently seeking treatment
or manifesting symptoms. Pharmacogenomic testing potentially
generates ancillary or incidental information unrelated to the
original purpose for which the test was ordered. For research
related to such testing, common practice has been to provide
informed consent to individuals noting that genetic test results
will not be disclosed, incidental or otherwise. However, some
have expressed concerns that such a practice needs to be
readdressed due to the advent of increasing technologies allowing
for whole-genome sequencing, increasing accessibility of
information, and increasing demand for the disclosure of such
information.

A recent study assessed the public perspectives regarding

pharmacogenetics testing and managing ancillary information. In
a focused group session (n = 45), most participants agreed that
physicians were obligated to disclose ancillary information.
Participants argued that the benefit of learning of ancillary risk
information was an opportunity for preventive measures and a
lack of knowledge of an individual's family history as reasons to
warrant disclosure. However, participants also expressed
concerns about insurance implications, the potential need for
additional follow-up testing, and of the psychological harms,
anxiety, and stress associated with the disclosure of ancillary
information. In another focus group study, perspectives regarding
pharmacogenetics testing and managing ancillary information of
primary care professionals and geneticists (n = 21) were also

14
examined. Among physicians, agreement was noted regarding the
obligation to disclose ancillary information. Interestingly,
geneticists believed that disclosure was not always necessary due
to the complexities of genetic risk results.

There is currently no consensus or system in place for

communicating information to research participants that could
have either a direct or indirect influence on care, especially when
these findings are discovered years after the original study.
Should ancillary findings be returned to parents when children
have been the subject in research? Do parents have an ethical
duty to disclose the results to their child? Do researchers have an
ethical duty to communicate research results? Communicating
pharmacogenomic or genomic test results to children raises some
questions such as who should receive the results (e.g., the child,
his or her legal representative, his or her doctor) and in what
capacity. These questions are particularly important because the
information could have an impact on a child's clinical care and the
parents may not be equipped to understand the impact on the
overall health of their child. Because of the potential
psychological effect on the participants siblings and other family
members, it is essential that the information and its implications
be properly explained to the research participants and their
parents. This raises similar issues in the consent process: how can
complex information be simplified without distorting their
meaning, or how can it be presented without sounding too
optimistic.

Social Issues

Race and Ethnicity

Numerous examples exist regarding the prevalence of

genetic polymorphisms varying between ethnic groups. CYP2C19

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is responsible for the metabolism of numerous drugs, including
proton pump inhibitors (PPIs), tricyclic antidepressants,
diazepam, and antiplatelet therapies (e.g., clopidogrel). At least
27 CYP2C19 variant alleles have been identified, with a higher
prevalence of the CYP2C19*2 and CYP2C19*3 variants observed
in Asians versus Caucasians and African Americans. These variant
alleles result in a functional loss of CYP2C19enzyme activity. This
may be of clinical significance regarding PPI efficacy as
pharmacokinetic variability and Helicobactor pylori eradication
rates are attributed, in part, to CYP2C19 genetic polymorphisms.
In several studies, H. pylori eradication rates were reported to be
higher in Asians.

Carbamazepine is an anticonvulsant and has been linked

to life-threatening hypersensitivity reactions such as Stevens
Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The
risk of a carbamazepine-induced SJS/TEN has been associated
with individuals who possess the human leukocyte antigen(HLA)-
B*1502allele. Interestingly, Caucasians who test positive for the
HLA-B*1502 allele may not be at risk for carbamazepine-induced
hypersensitivity. This is in contrast to Asian populations (e.g., Han
Chinese, Indonesia, Malaysia, Taiwan, Thailand, the Philippines,
and Vietnam), whereby the prevalence of the HLA-B*1502 allele is
approximately 1015%. In Han Chinese patients, there was 100%
association with the HLA-B*1502 allele and carbamazepine-
induced SJS/TEN. In a follow-up study, 59 of 60 patients who
reported a carbamazepine-induced SJS/TEN were positive for HLA-
B*1502. In individuals of Thai ancestry, the odds ratio for
developing carbamazepine-induced SJS/TEN was 54.76 (95% CI:
14.62205.13, P = 2.89 1012) for those who were positive for
HLA-B*1502. Based on the strength of these data and others, the
US Food and Drug Administration and prescribing information
recommend that individuals of Asian ancestry be tested for the
HLA-B*1502 allele prior to initiating carbamazepine.

The association of pharmacogenomic testing with race and

ethnicity is a contentious issue. Pharmacogenomic testing and/or
research may stratify patients according to racial or ethnic groups

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resulting in genetic discrimination and stigmatization. With known
health disparities regarding access to medical care among ethnic
groups, there is concern that there will also be limited
accessibility to pharmacogenomic testing. Regarding drug
development and research, the population prevalence for certain
genetic polymorphisms may result in the use of race as a primary
criterion for participation in pharmacogenomic research. Although
the passage of the National Revitalization Act of 1993 mandated
inclusion of racially identified groups into research, theoretically,
drug development may compromise the availability and access to
pharmacogenomic testing and/or research in ethnic groups
among industrialized and nonindustrialized countries. However,
new guidelines, procedures, and practices are in development for
engaging with the scientific community that offer opportunities to
bridge the gap between genomic science and indigenous and/or
developing communities.

Testing in Vulnerable Populations

Pharmacogenomic research that is being performed needs

to adhere to the principle that all individuals involved in any type
of medical research are presumed to have the capacity and right
to make free and informed decisions. Certain populations, such as
children, may not have the capacity to make free and informed
decisions. The majority of drugs used by children are done so
without actually being tested specifically for their use. Assuming a
drug that is safe and effective in adults will also be safe and
effective in children is problematic due to known differences in
developmental factors between children and adults. The Better
Pharmaceuticals for Children Act of 1997 (renewed in 2002 as the
Best Pharmaceuticals for Children Act [BPCA]) and the Pediatric
Research Equity Act (PREA) have supported more direct research
on existing and new drugs for use in children and have led to
significant improvements in safety and efficacy.

One method to protect children against the possible

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negative effects of participation in research is to use both consent
and assent. Research protocols recognize that children should
participate and want to participate in important decisions about
their lives when developmentally appropriate, and that if they are
too young to consent, their assent should be obtained. In a
pediatric research setting, the decision-making process regarding
subject participation is more complex than when working with an
adult population. It is generally accepted that children do not
have the maturity or experience necessary to make an informed
decision regarding their participation and therefore should include
the input of a parent or adult guardian, the child (when
appropriate), and the researcher. The input of the researcher may
be particularly useful when determining the medical benefits and
risks of the child's research participation. This is helpful because
parents may find it difficult to weigh the possible advantages and
disadvantages of their child's participation in pharmacogenomics
research.

Vulnerable persons also include those with diminished

competence and/or decision-making capacity due to medical
conditions. This may include individuals diagnosed with
schizophrenia, bipolar disorders, depressive disorders, and some
dementias. At times, these medical conditions result in the
affected individual having variable patterns of coherence for
which decision making is known to follow a general pattern of
decline. Most individuals with limited capacity are in some way
still able to object or assent to research. However, individuals who
have permanently lost the ability to self-reflect may be
decisionally incapable. These individuals will need to involve
assistance from family members and caregivers in order to
participate in research. The participation of persons from such
groups will be vital to ensure that drug development is specific to
the predisposing genetic factors for a disease.

Availability of Testing

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 A major barrier to implementing pharmacogenomics into
clinical practice is the availability of pharmacogenomic testing. In
one study, questionnaires were sent to 629 individuals
representing hospitals, laboratories, and universities throughout
New Zealand and Australia. The objective of the study was to
determine utilization rates of pharmacogenomic testing for drug
metabolizing enzymes. The results reported that 2% of
respondents had genotyping tests available. In another study,
poor availability of 20% was reported in North America medical
practices for warfarin pharmacogenomic testing.

Numerous factors that influence the availability of

pharmacogenomic testing include assay equipment, training of
staff, and cost. Conducting pharmacogenomic testing requires
specialized genotyping equipment and training of personnel on
site. Practice settings may not have access to testing kits and
laboratories in order to conduct testing. Although centralized
laboratories (e.g., LabCorp) where testing can be performed are
available, feasibility information such as the turnaround time for
test results or test sensitivity and specificity varies or is lacking
from laboratory sources. For example, anywhere from 5 to 10
days may be needed from obtaining the blood sample to
determining and disseminating CYP2C9 and CYP2D6 genotyping
test results.

Knowledge and Education of Health Care Professionals

Knowledge deficiencies in genetics and pharmacogenomics

exist among health care professionals in all disciplines. In a
survey on warfarin pharmacogenomic testing, five knowledge-
based questions were developed and surveyed among health care
professionals who provide anticoagulation services. The survey
response rate was low (22%), with participants including mostly
pharmacists (64%) and nurses/nurse practitioners (23%).
Knowledge was poor in areas of CYP2C9 and VKORC1allele
frequencies, the length of time required to perform a test, and

19
interpreting test results. Approximately one third of respondents
correctly answered the knowledge-based questions. In an
Internet-based survey of genetics education in psychiatry
residency programs, more than 50% of respondents felt that their
training in pharmacogenomics was minimal. A recent systematic
review also concluded similar findings that health care
professionals generally felt limited in their knowledge of
pharmacogenomics. The lack of knowledge in pharmacogenomics
is also consistent among pharmacy, medical, and nursing
students.

Various initiatives are underway in order to train and

educate health care professionals on pharmacogenomics. The
National Coalition for Health Professional Education in Genetics
(NCHPEG) is a working group of specialists with experience in
genetics and health professions. NCHPEG identified 18 core
competencies, with the purpose of encouraging health care
professionals to integrate genetics knowledge, skills, and
attitudes into routine health care. Examples in knowledge
competencies include understanding basic genetics terminology,
identifying genetic variations that facilitates prevention,
diagnosis, and treatment options, and identifying available
resources to assist those seeking genetic information or services.
Such competencies have been adapted in part by professional
organizations. In 2002, the American Association of Colleges of
Pharmacy (AACP) Academic Affairs Committee reported
pharmacist-specific competencies in pharmacogenetics and
pharmacogenomics, which were derived from 2001 NCHPEG
competencies. Examples include a pharmacist being able to
identify patients in whom pharmacogenetic testing is indicated,
identify an appropriate pharmacogenomic test for a patient, and
provide recommendations based on pharmacogenomic testing
results. Other professional organizations have also developed
recommendations or position statements for pharmacogenomics
education.

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Conclusions

While the science of pharmacogenomics has moved along

rapidly, particularly since the completion of the Human Genome
Project, a thorough plan to address the ethical, legal, and social
issues remains to be developed and implemented. Currently there
is no international standard for genetic testing. Input is required
from the multiple stakeholders such as the subject-donor, the
institution whereby research was conducted, regulatory agencies,
professional organizations, health care professionals, and those
involved in pharmacogenomic research. Guidelines need to be
considered and harmonized internationally to protect individuals
and reduce the chance of discrimination based on genetic testing,
and be synchronized with the advancing field of
pharmacogenomics.

21
Bibliography

(2007). The Ethical, Legal and Social Implications of

Pharmacogenomics in Developing Countries. World Health
Organization, Human Genetics, Chronic Diseases and Health
Promotion.

Bertino, J., Kashuba, A., Ma, J., Fuhr, U., & DeVane, C. (2012).
Pharmacogenomics An Introduction and Clinical Perspective
(1st ed.). McGraw-Hill Education / Medical.

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