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\begin{document}

\title{Knowledge, Attitude, Future Expectations, and Perceived Barriers of
Medical Students and Physicians Regarding Pharmacogenomics in Jordan}



\author[1]{Abdallah Alzoubi}%
\author[1]{Hashem Kana'an}%
\author[1]{Dua'a Alhazaimeh}%
\author[1]{Salam Gharaibeh}%
\author[1]{Tareq Mukattash}%
\author[1]{Khalid Kheirallah}%
\affil[1]{Jordan University of Science and Technology}%


\vspace{-1em}



  
  \date{June 14, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: Pharmacogenomics (PG) is a modern tool of personalizing
treatment protocols to improve the efficacy and safety of drug
prescriptions. These benefits are offset by a slow uptake in clinical
application due to a host of physician factors, patient factors, and/or
health system factors. Our study, thus, aimed to determine the
knowledge, attitude, future expectations, and perceived barriers of
medical students and physicians in Jordan regarding PG testing. Methods:
A descriptive, cross-sectional study was conducted between
February-August 2019. Physicians and senior medical students from
academic and non-academic institutions in North Jordan (n=424) were
surveyed. A structured, self-administered questionnaire was designed and
piloted for the purpose of the study. A scoring system for each
dimension assessed was calculated and presented using means. Mean scores
were compared by sociodemographic and professional variables. Results:
The response rate was 70.7\%. The mean total PG knowledge score (\selectlanguage{ngerman}±SD)
was 5.42 (±1.51) out of 10, with a significantly higher mean among
respondents aged \selectlanguage{english}[?]30 years (5.21 +- 1.62) compared to those \textless{}30
years-old (5.54 +- 1.43; p= 0.03). The mean total PG attitude score was
21.18 (+-2.58) out of 24, with significant differences by seniority
levels evident (p= 0.03). The future expectations of PG among our sample
were high, with a mean score of 10.44 (+-1.64) out of 12. The top three
perceived barriers in applying PG were the high cost, lack of clinical
guidelines, and limited knowledge and awareness. Conclusion: Physicians
and medical students in Jordan have low overall knowledge, albeit
strongly positive attitude and future expectations toward PG, despite
the perceived high cost and lack of clinical guidelines. Thus, we
strongly recommend adopting a comprehensive educational strategy that
aims to integrate PG concepts into medical curricula, and promote the
culture of continuous medical education about PG among practitioners.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Keywords: Pharmacogenomics, PG, KAP, Jordan, Personalized
Medicine, Survey}

\textbf{What is already known about this topic?}

Pharmacogenomics (PG) is a tool of personalizing treatment protocols to
improve the efficacy and safety of drug prescriptions. These benefits
are offset by a slow uptake in clinical application due to limited
resources and poor understanding of PG among healthcare providers,
particularly in developing countries like Jordan.

\textbf{What does this article add?}

Physicians and medical students in Jordan have low overall knowledge,
albeit positive attitude and future expectations toward PG, despite the
perceived high cost and lack of clinical guidelines. Our results call
for an urgent national educational/training strategy about PG.

\textbf{Introduction}

Inter-individual variability in pharmacological responses to medications
poses a significant burden on the capacity of healthcare systems
worldwide\textsuperscript{1}. The modern concept of ``personalized
medicine'' aims at its core to facilitate selecting the right drug for
the right patient at the right dose with the minimum of adverse drug
reactions (ADR)\textsuperscript{2}. ADRs are a serious cause of
hospitalizations and deaths in the United States\textsuperscript{3}.The
percentage of patients who respond positively to their medications
ranges from 25-60\%\textsuperscript{4}. Almost 40\% of patients suffer
from a treatment failure, in the form of negative therapeutic effects
and negligible desired benefits, necessitating switching from one
medication to another\textsuperscript{5}.

Non-genetic factors, such as age, weight, gender, co-morbid disease
states, and drug-drug interactions, are well-documented to contribute to
such variability in clinical responses to drugs\textsuperscript{6}.
However, genetic variation among individuals remains a principal cause
of the heterogeneity of drug responses in practice\textsuperscript{7}.
Hence, pharmacogenomics (PG), the integrated analysis of the role of
genomics on responses to drugs\textsuperscript{8}, is a promising new
approach that targets tailoring therapeutic regimens based on a person's
genetic makeup\textsuperscript{9}, thus improving the efficacy and
safety of drug prescriptions\textsuperscript{10}, avoiding
ADRs\textsuperscript{11}, and enhancing patient health
outcomes\textsuperscript{12}. Most importantly, PG has an immense
potential for improving cost-effectiveness of
pharmacotherapy\textsuperscript{13} .

To date, more than 100 medicines have been included in the Food and Drug
Administration (FDA) repository of drugs labeled for PG analysis prior
to administration\textsuperscript{14}, particularly those with a narrow
therapeutic index and a fatal toxic potential\textsuperscript{15}, such
as antineoplastic\textsuperscript{16},
anticonvulsant\textsuperscript{17}, and anticoagulant
drugs\textsuperscript{18}. However, there remains a slow uptake of PG
applications in mainstream clinical care\textsuperscript{19}, and many
of the FDA-recommended PG tests are unfortunately not in routine
use\textsuperscript{20}. Although criteria for proper clinical
actionability of a novel test fundamentally apply to the available PG
tests\textsuperscript{21}, including analytic
validity\textsuperscript{22}, clinical validity\textsuperscript{23}, and
clinical utility\textsuperscript{24}, the alarming limited knowledge and
awareness of PG concepts among healthcare providers seem to critically
hinder its application\textsuperscript{25}.

The responsibility of healthcare providers in improving the overall
quality of clinical care has incentivized recent efforts to integrate PG
testing in clinical practice\textsuperscript{26}. Pharmacists and
physicians alike are nowadays aware of the need to adjust their clinical
roles to become more patient-oriented towards enhancing implementation
of personalized pharmacotherapy services\textsuperscript{27}. However,
limited resources and poor understanding of PG persist to be a problem
in developing countries like Jordan\textsuperscript{28}. Furthermore,
there are currently no comprehensive studies exploring correlates of PG
practice among the whole stratum of medical students, interns,
residents, and specialists, from all fields of medical practice in
Jordan. Thus, this study aimed to assess the knowledge, attitude, future
expectations, and practice of medical students and clinicians in
hospitals in Northern Jordan regarding PG testing, in addition to
determining their perceived barriers to its application.

\textbf{Methods}

Study design, population, and settings:

A descriptive, cross-sectional study was conducted in the period
February to August 2019. The study population included senior medical
students in their 4\textsuperscript{th} year of study and above at
Jordan University of Science and Technology (JUST) and Yarmouk
University (YU), in addition to interns, residents, general
practitioners (GP), and specialist doctors. Study settings included
academic institutions like King Abdullah University Hospital (KAUH),
hospitals of the Ministry of Health (MOH) and the Royal Medical Services
(RMS), private clinics and hospitals, and Non-Governmental Organizations
(NGOs) in Northern Jordan. A questionnaire was specifically developed
and piloted for the purpose of this study. Face-to-face interviews were
carried out with eligible participants to explain the aim of the study,
collect the informed consents, and to distribute the questionnaire.

Sampling technique:

All senior medical students, interns, residents, GPs, and specialists
studying or working in the above stated hospitals were eligible to
participate in the study. Multi-stage sampling technique was used to
recruit eligible participants. Students from the two participating
medical schools were approached before their lectures and asked to
participate. Those who agreed to take part in the study where scheduled
for an interview. One teaching hospital (KAUH), three MOH hospitals, and
two RMS hospitals, representing all major hospitals in North Jordan,
were utilized to recruit interns, residents, GPs, and specialists. Two
days of the week were randomly selected to recruit participants from the
major departments/division within each hospital. During which, the
researcher randomly approached eligible participants before attending
their clinics and asked them to participate. Those who agreed to take
part in the study were scheduled for an interview. Physicians in private
clinics and NGOs in the geographical area were also recruited by the
same procedure.

Study questionnaire:

A structured questionnaire was used to collect the study data. The
questionnaire was adapted from several instruments used elsewhere
considering the aim of the current study\textsuperscript{29-34}. Face
and content validity of the questionnaire was achieved through an expert
panel of physicians, pharmacists, and biostatisticians. The
questionnaire was then piloted in a sample of 20 doctors and 20 students
and necessary edits were made. Those were not included in the final
results.

The questionnaire consisted of five main sections with a total of 35
questions; sociodemographic characteristics, PG knowledge, attitudes,
future expectations, and barriers to practice. Sociodempgraphics
included questions regarding age, gender, level of seniority, and
primary work setting of the respondents. PG knowledge was assessed using
ten questions covering general information about PG, such as definition,
availability in Jordan, and inter-individual gene variation. Attitudes
towards PG were assessed using eight questions regarding the proposed
clinical and therapeutic advantages of PG testing. Future expectations
and practice questions (n=4) identified drugs with current and/or
potential PG application. Nine barriers to practicing PG were utilized
to identify the top perceived barriers to practice PG.

Scoring technique:

Responses to knowledge questions were presented on a 2-point scale
format, and scored as either 0 (when incorrect) or 1 (when correct).
Total knowledge score ranged from 0 to 10 and was calculated by summing
responses to the ten knowledge questions. For the attitudes, responses
were scored on a 3-point Likert scale ranging from ''agree'' (coded as
3), to disagree (coded as 1). Total attitude score, ranging from 0-24,
was calculated as indicated above. For the future expectations and
practice section, responses were scored on a 3-point Likert scale as
follows: ''agree'' (coded as 3), ''neutral'' (coded as 2), and
''disagree'' (coded as 1). The total future expectations and practice
score ranged from 0-12, representing the sum of total scores of the four
statements in this section. For the barriers section, responses were
coded as no or yes.

After scoring of items, and in order to elucidate the effect of
seniority and exposure to up-to-date medical advancements on the
perceived knowledge, attitude, and future expectations of PG, we
stratified respondents based on age, using a cutoff point of 30 years.

Statistical analysis:

Data analysis was performed using the Statistical Package for Social
Sciences (SPSS) program version 23 (IBM Inc., New York, USA).
Descriptive statistics were employed for analysis. Categorical variables
were presented as proportions and frequencies. T-test and One-Way
Analysis of Variance (ANOVA) were performed to compare mean scores by
demographic and professional variables. P-value of less than 0.05 was
considered statistically significant.

\textbf{Results}

Characteristics of study respondents:

Of the 600 questionnaires distributed, only 424 were completed, with a
response rate of 70.7\%. As shown in Table 1, the sample included 127
medical students (30\%), 44 interns (10.4\%), 34 GPs (8\%), 110
residents (25.9\%), and 109 specialists (25.7\%), representing academic
institutions (50.2\%), the MOH (18.2\%), the RMS (18.6\%), private
clinics and hospitals (9\%), and NGOs (4\%). The majority of respondents
were less than 30 years of age (63.2\%).

Knowledge of PG:

The mean total knowledge score (\selectlanguage{ngerman}±SD) for respondents was 5.42 (±1.51)
out of 10. Of interest, about three quarters of participants were aware
of the commercial availability of PG tests in Jordan (n = 317, 74.8\%).
No significant differences in the mean total knowledge scores were
detected by gender (p=0.84), seniority level (p= 0.45), and by primary
work settings (p= 0.19), as shown in Table 2. Significant differences
were detected in the mean knowledge score by age, as respondents \selectlanguage{english}[?]30
years old had significantly higher mean score (5.21 +- 1.62) compared to
their counterparts in the \textless{}30 years group (5.54 +- 1.43; p=
0.03), as detailed in Table 2.

Attitude toward PG:

The mean (+-SD) total attitude score was 21.18 (+-2.58) out of 24. The
vast majority of respondents had a positive attitude on all surveyed
attitude items. For instance, approximately 77\% of respondents agreed
that PG testing will help to improve drug efficacy, 72\% believed that
it will help to decrease the time it takes to find the optimal dose of a
drug, and almost 77\% agreed that it will enable them to effectively
control drug therapy expenditures. Encouragingly, 64.2\% of our sample
expressed interest in attending training sessions or workshops on PG in
the future.

Moreover, there were no significant differences in mean total attitude
score based on gender (p=0.13), age groups (p= 0.19), or primary work
settings (p= 0.35). However, stratifying respondents according to
seniority levels showed a significant difference in mean total attitude
score, as the specialist physicians were found to have a higher mean
attitude score (21.69 +- 2.54) compared to residents (20.57 +-
2.65;\emph{p=0.03} ), as detailed in Table 2.

Future expectations and practice of PG:

Overall, the mean total future expectations and practice score of PG
among respondents was 10.44 (+-1.64) out of 12. There were no significant
differences in the mean total future expectations and practice score
between males and females (p=0.83), or for respondents aged \selectlanguage{english}[?]30 versus
those aged \textless{}30 (p= 0.05), as shown in Table 2. However,
classifying respondents based on the various primary work settings
revealed a significant difference in mean total future expectations and
practice score (p= 0.01), as outlined in Table 2.

Perceived Barriers to Applied PG Testing in Jordan:

Our study had the advent of gauging the perceived barriers to practice
of PG testing in Jordan by clinicians and medical students (Table 3).
The majority of respondents (90.1\%) voted that the prohibitive high
cost of PG testing is the most important barrier to practice PG in
Jordan, followed by lack of clinical guidelines (88.4\%), limited
provider of knowledge and awareness (86.8\%), and lack of insurance
coverage (83.7\%). Other less frequent perceived barriers by our sample
included: lack of time and resources to educate patients (76.9\%),
result takes too long for treatment decisions (74.3\%), patients'
anxiety regarding test results (55.9\%), and that test results will not
likely affect the treatment decision-making process (31.4\%).
Intriguingly, a minority of clinicians and medical students (39.6\%)
believed that their cultural and/or religious beliefs would affect the
clinical practice of PG in North Jordan.

\textbf{Discussion}

The use of PG testing in clinical practice essentially aims to optimize
treatment protocols, minimize the frequency of ADRs, and generally
improve therapeutic outcomes\textsuperscript{35}. Since physicians are
the most valuable source in passing medical information to
patients\textsuperscript{36}, they should have a basic understanding of
PG and conceptualize its validity. Ideally, physicians should also be
aware of the most recent advancements in PG research. Our study,
therefore, took impetus from this fact, and gauged the knowledge,
attitude, and practice of PG among medical students and clinicians in
different academic and non-academic health sectors, in addition to
identifying the perceived barriers to its future application. The major
highlight of this study is that physicians and medical students in North
Jordan have, overall, low knowledge, however strongly positive attitude
and future expectations toward PG, in spite of the perceived high cost
and lack of clinical guidelines.

Despite our finding of poor overall knowledge about PG among medical
students and physicians, a deeper look into knowledge items suggests a
promising future for PG in Jordan. Indeed, the majority of respondents
were aware of PG and its importance in clinical practice, and the
foreseen benefits on pharmaco-economy. Almost two thirds of the
respondents were aware that PG tests are available in Jordan and could
identify which medications require a genetic testing. Therefore, our
results should be discussed in the wider context of novelty and recent
emergence of PG as a concept. Poor overall knowledge of PG was actually
evident in several similar studies around the world. For instance,
Elewa\emph{et al.} showed in 2015 a low mean awareness score among
Qatari doctors and pharmacists about PG\textsuperscript{29}.
Furthermore, Abdela \emph{et al.} reported in 2017 a generally low
knowledge about PG among Ethiopian healthcare
providers\textsuperscript{33}. Similar results were additionally
obtained from India\textsuperscript{37} and Kuwait\textsuperscript{34}.

Interestingly, stratifying our respondents based on age using a cutoff
point of 30 years revealed a significant difference in the mean total PG
knowledge score between the younger and older generation. Those below 30
years of age were significantly more knowledgeable about PG than those
above 30 years of age. This interesting finding could in part be
attributed to the wide access and reliance of the younger generation on
the modern and advanced means of education and learning, such as the
social media applications and the various reputable open educational
resources. Furthermore, one cannot overlook the fact that those
students, interns, and residents have grown in an era of the expansive
global interest in genetics post conclusion of the big human genome
project in 2003\textsuperscript{38}. Despite this seemingly higher
knowledge level of the younger generation, we must emphasize here that
academic institutions in Jordan still do not cover topics related to PG
applications in their curricula. This indeed could largely explain the
low overall knowledge scores among Jordanian students and physicians
alike.

A previous study from Jordan by Jarrar in 2019 assessed the perception
and knowledge of internist physicians about PG from various private and
public Jordanian hospitals\textsuperscript{39}. The study reported a
generally good knowledge regarding the basic principles of PG, albeit
still not widely practiced. It must be noted, however, that the author
only included internist physicians in the study, and did not explore the
perceptions of other medical and surgical disciplines, as well as
medical students, interns, and residents, contrary to our study.
Moreover, the report by Jarrar did not discuss issues related to future
expectations and perceived barriers to PG application.

Several studies worldwide highlighted the overall positive attitude of
healthcare professionals toward PG and its importance in improving the
quality of health services they provided. These include studies from the
USA\textsuperscript{40}, Canada\textsuperscript{41},
Kuwait\textsuperscript{34}, Qatar\textsuperscript{29} ,
India\textsuperscript{37}, and Jordan\textsuperscript{39}. Our results
here reinforce such observations. Counterintuitive to our aforementioned
findings on knowledge, specialists had a slightly stronger positive
attitude towards PG application than residents (p=0.03), possibly
because the latter fear that such tool might add an extra load on their
job duties. Nonetheless, this finding encouragingly sheds light on the
importance of PG in clinical practice from the point of view of the most
senior professionals. Our results, as well as of others, of a low
overall knowledge coupled with a strongly positive attitude about PG
among physicians represent an urgent call for a quick goal-oriented
educational strategy. Such strategy should comprehensively aim to
integrate PG concepts into medical curricula, promote the culture of
continuous medical education for practitioners, and introduce PG
application into clinical practice.

On the other hand, the overall future expectations and practice score in
our sample was remarkably high. The majority of respondents were
interested in applying PG in their future practice, representing a
promising outcome of our study. In spite of the statistically
significant differences in future expectations of respondents depending
on age and primary work settings, perhaps due to variability in sample
sizes of these groups, the overall context remains bright.

The current study had the advent of gauging the perceived barriers to
practice of PG testing in Jordan by clinicians and medical students.
According to our survey, the major concern of clinicians was the
expensive cost of PG tests coupled with a lack of insurance coverage, in
agreement with several other studies published
elsewhere\textsuperscript{29,40}. Additionally, lack of approved
clinical guidelines and the limited provider knowledge and awareness
about PG were high among our respondents. Importantly, this finding
emphasizes our belief that our clinicians still struggle to interpret PG
test results and would find it difficult counseling the patients about
their consequences. Intriguingly, only a minority of our clinicians and
medical students (39.6\%) believed that their cultural and/or religious
beliefs would affect the clinical practice of PG in a conservative
community like North Jordan.

Our study manifests a few limitations. First, the response rate was
fairly low. However, we assume that a higher response rate might have a
more detrimental impact on the overall knowledge and attitude of
participants. Second, generalizability of our results is of concern, as
the sample was recruited solely from North Jordan, although national
differences in knowledge, attitude, and practice of PG by geographic
location have not been previously reported. Furthermore, we believe that
this study presents a pilot assessment that has a potential on national
aspects. Third, the scales utilized in the current study were collapsed
into the minimum categories. Such approach is justified by the evidence
showing that Arabs, similar to other non-European-American groups, are
less likely to use middle response categories when presented a greater
number of options\textsuperscript{42,43}.

In conclusion, physicians and medical students in Jordan have low
overall knowledge, however strongly positive attitude and future
expectations toward PG. High cost, lack of clinical guidelines and
insurance coverage, and poor awareness are among the major barriers
towards PG applications in Jordan. Our study supports the findings of
several other studies worldwide to adopt PG and calls for urgent
training and educational programs to enhance its practical practice.

\textbf{Disclosures}

The authors report no conflicts of interest.

\textbf{Ethical Approval}

Informed consent was obtained from all individual participants included
in the study. The study design and procedure were approved by the
Institutional Review Board at Jordan University of Science and
Technology.

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\textbf{Tables}

\emph{Table 1}\textbf{: Major characteristics of study participants (N =
424).}

\emph{Table 2}\textbf{: Distribution of total knowledge, attitude, and
future expectations and practice scores according to certain
sociodemographic and professional variables.}

\emph{Table 3}\textbf{: Frequency distribution of perceived barriers to
practice of PG testing in Jordan.}

\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/337111/articles/462762-knowledge-attitude-future-expectations-and-perceived-barriers-of-medical-students-and-physicians-regarding-pharmacogenomics-in-jordan}

\textbf{Hosted file}

\verb`Table 2.docx`  available at \url{https://authorea.com/users/337111/articles/462762-knowledge-attitude-future-expectations-and-perceived-barriers-of-medical-students-and-physicians-regarding-pharmacogenomics-in-jordan}

\textbf{Hosted file}

\verb`Table 3.docx`  available at \url{https://authorea.com/users/337111/articles/462762-knowledge-attitude-future-expectations-and-perceived-barriers-of-medical-students-and-physicians-regarding-pharmacogenomics-in-jordan}

\selectlanguage{english}
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