Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

Concepts in Pharmacogenomics and Personalized Medicine
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educational efforts that will help improve knowledge, skills, and attitudes to
effectively translate pharmacogenomic evidence into clinical practice. 152,162
CHALLENGES OF PHARMACOGENOMICS
AND PERSONALIZED MEDICINE
Availability of Testing
A major challenge to the implementation of pharmacogenomics into clinical practice
is pharmacogenomic testing availability. 154,163,164 Conducting pharmacogenomic
testing requires specialized genotyping equipment and training of onsite personnel.
154,163,164 Consequently, there may be limited availability of genotyping equipment,
lack of suitable training of personnel, and costs associated with such testing.
Although centralized laboratories (Labcorp) to perform such testing are available,
feasibility information such as the turnaround time for test results or test sensitivity
and specificity vary. 165 Practice settings may not have access to testing kits and laboratories
in order to conduct testing. In one study, a questionnaire was sent to individuals
representing hospitals, laboratories, and universities throughout New Zealand
and Australia (n = 629) to determine utilization rates of pharmacogenomic testing for
drug-metabolizing enzymes. 77 The overall response rate was 81.1% (n = 510), with
2% of facilities currently performing clinical genotype testing. 77 Additional evidence
includes another study, whereby 20% of respondents from North American medical
practices have available warfarin pharmacogenomic testing. 163
Small Sample Size
Due to the low prevalence of a specific variant allele in a studied population, numerous
pharmacogenomic studies were conducted with small sample sizes. In studies
with omeprazole and other PPIs, there was an unequal distribution of homozygous
EMs, heterozygous EMs, and PMs, with a smaller number of PMs (Table 1.1).
A small sample size in a clinical study is problematic. It is a study design limitation
that increases the probability of an error and/or misinterpretation of study results
due to lack of statistical power. 166 Ideally, a pharmacogenomic study should have
sufficient statistical power of at least 80%, with an equal stratification of subjects
across groups. However, this may not be achievable as many variant alleles carry
a population frequency of 1–2% and/or the minimum detectable difference used to
determine sample size is an unknown value. 4,166,167 Attempts to improve statistical
design have been reported with CYP2C9 and VKORC1 testing with warfarin. The
authors reported that a sample size of 1238 patients is needed to achieve a minimum
difference of 5.49% with an 80% statistical power. 166
Knowledge and Education of Healthcare Professionals
Knowledge deficiencies in genetics and pharmacogenomics exist among healthcare
professionals in all disciplines 168 and preclude such individuals from implementing
pharmacogenomics and/or personalized medicine into clinical practice.
One study evaluated warfarin pharmacogenomic knowledge among pharmacists