Pharmacogenomics Implementation and Hurdles to Overcome; In the Context of a Developing Country

Document Type : Research article

Authors

1 Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

2 Medical Genomics Research Center, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.

3 Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

4 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

5 Department of Department of Industrial Management, Faculty of Management and Economics, Tarbiat Modares University, Tehran, Iran.

10.22037/ijpr.2021.114899.15091

Abstract

Having multiple dimensions, uncertainties and several stakeholders, the costly pharmacogenomics (PGx) is associated with dynamic implementation complexities. Identification of these challenges is critical to harness its full potential, especially in developing countries with fragile healthcare systems and scarce resources. This is the first study aimed to identify most salient challenges related to PGx implementation, with respect to the experiences of early-adopters and local experts’ prospects, in the context of a developing country in the Middle East. To perform a comprehensive reconnaissance on PGx adoption challenges a scoping literature review was conducted based on national drug policy components: efficacy/safety, access, affordability and rational use of medicine (RUM). Strategic option development and analysis workshop method with cognitive mapping as the technique was used to evaluate challenges in the context of Iran. The cognitive maps were face-validated and analyzed via Decision Explorer XML. The findings indicated a complex network of issues relative to PGx adoption, categorized in national drug policy indicators. In the rational use of medicine category, ethics, education, bench -to- bedside strategies, guidelines, compliance, and health system issues were found. Clinical trial issues, test's utility, and biomarker validation were identified in the efficacy group. Affordability included  pricing, reimbursement, and value assessment issues. Finally, access category included regulation, availability, and stakeholder management challenges. The current study identified the most significant challenges ahead of clinical implementation of PGx in a developing country. This could be the basis of a policy-note development in future work, which may consolidate vital communication among stakeholders and accelerate the efficient implementation in developing new-comer countries.

Graphical Abstract

Pharmacogenomics Implementation and Hurdles to Overcome; In the Context of a Developing Country

Keywords


References
(1) Johnson JA and Weitzel KW. Advancing
pharmacogenomics as a component of precision
medicine: how, where, and who? Clin. Pharmacol.
Ther. (2016) 99: 154-6.
(2) Charlab R and Zhang L. Pharmacogenomics:
historical perspective and current status. Methods
Mol. Biol. (2013) 1015: 3-22.
(3) Kasztura M, Richard A, Bempong NE, Loncar
D and Flahault A. Cost-effectiveness of precision
medicine: a scoping review. J. Public Health (Oxf).
(2019) 64: 1261-71.
(4) Plöthner M, Ribbentrop D, Hartman J-P and
Frank M. Cost-effectiveness of pharmacogenomic
and pharmacogenetic test-guided personalized
therapies: a systematic review of the approved
active substances for personalized medicine in
Germany. Adv. Ther. (2016) 33: 1461-80.
(5) Tekola-Ayele F and Rotimi CN. Translational
genomics in low- and middle-income countries:
opportunities and challenges. Public Health
Genomics. (2015) 18: 242-7.
(6) Ghaddar F, Saba K and K Zgheib N. Teaching
pharmacogenetics in low and middle income
countries (LMICS): an empirical study of the
lessons learned. Curr. Pharmacogenomics Pers.
Med. (2012) 10: 217-25.
(7) Pang T. Pharmacogenomics and personalized
medicine for the developing world - too soon or
just-in-time? a personal view from the world health
organization. Curr. Pharmacogenomics Pers. Med.
(2009) 7: 149-57.
(8) Patrinos GP, Pasparakis E, Koiliari E, Pereira
AC, Hünemeier T, Pereira LV and Mitropoulou
C. Roadmap for establishing large-scale genomic
medicine initiatives in low- and middle-income
countries. Am. J. Hum. Genet. (2020) 107: 589-95.
(9) Mitropoulos K, Al Jaibeji H, Forero DA, Laissue
P, Wonkam A, Lopez-Correa C, Mohamed Z,
Chantratita W, Lee MTM, Llerena A, Brand A, Ali
BR and Patrinos GP. Success stories in genomic
medicine from resource-limited countries. Hum.
Genomics. (2015) 9: 11.
(10) Khorrami Z, Rezapour M, Etemad K, Yarahmadi
S, Khodakarim S, Mahdavi Hezaveh A, Kameli M
and Khanjani N. The patterns of non-communicable
disease multimorbidity in Iran: A multilevel
analysis. Sci. Rep. (2020) 10: 3034.
(11) Mehrjoo Z, Fattahi Z, Beheshtian M, Mohseni
M, Poustchi H, Ardalani F, Jalalvand K, Arzhangi
S, Mohammadi Z, Khoshbakht S, Najafi F, Nikuei
P, Haddadi M, Zohrehvand E, Oladnabi M,
Mohammadzadeh A, Jafari MH, Akhtarkhavari
T, Gooshki ES, Haghdoost A, Najafipour R,
Niestroj LM, Helwing B, Goaamann Y, Toliat MR,
Malekzadeh R, Nürnberg P, Kahrizi K, Najmabadi
H and Nothnagel M. Distinct genetic variation
and heterogeneity of the Iranian population. PLoS
Genet. (2019) 15: e1008385.
(12) Chong HY, Allotey PA and Chaiyakunapruk
N. Current landscape of personalized medicine
adoption and implementation in Southeast Asia.
BMC Genom. (2018) 11: 1-15.
(13) Warnich L, I Drogemoller B, S Pepper M,
Dandara C and EB Wright G. Pharmacogenomic
research in South Africa: lessons learned and
future opportunities in the rainbow nation. Curr.
Pharmacogenomics Person. Med. (2011) 9: 191-
207.
(14) Bashir NS and Ungar WJ. The 3-I framework:
a framework for developing public policies
regarding pharmacogenomics (PGx) testing in
Canada. Genome. (2015) 58: 527-40.
(15) Nikfar S, Kebriaeezadeh A, Majdzadeh R and
Abdollahi M. Monitoring of national drug policy
(NDP) and its standardized indicators; conformity
to decisions of the national drug selecting
committee in Iran. BMC Int. Health Hum. Rights.
(2005) 5: 5.
(16) Munn Z, Peters MD, Stern C, Tufanaru C,
McArthur A and Aromataris EJBmrm. Systematic
review or scoping review? Guidance for authors
when choosing between a systematic or scoping
review approach. BMC Med. Res. Methodol.
(2018) 18: 143.
(17) Peters MDJ, Godfrey CM, Khalil H, McInerney P,
Parker D and Soares CB. Guidance for conducting
systematic scoping reviews. Int. J. Evid. Based
Healthc. (2015) 13: 141-6.
(18) Arksey H and O’Malley LJIjosrm. Scoping
studies: towards a methodological framework. Int.
J. Soc. Res. Methodol. (2005) 8: 19-32.
(19) Levac D, Colquhoun H and O’Brien KKJIs.
Scoping studies: advancing the methodology.
Implement. Sci. (2010) 5: 69.
(20) Moher D, Liberati A, Tetzlaff J and Altman DG.
Preferred reporting items for systematic reviews
and meta-analyses: The PRISMA statement. Int. J.
Surg. (2010) 8: 336-41.
(21) Eden C and Ackermann F. Cognitive mapping
expert views for policy analysis in the public
sector. Eur. J. Oper. Res. (2004) 152: 615-30.
103
Ayati N et al. / IJPR (2021), 20 (4): 92-106
(22) Neimeyer RA and Levitt H. Constructivism/
Constructionism: Methodology. In: Smelser NJ and
Baltes PB (eds.) International encyclopedia of the
social & behavioral sciences. Oxford: Pergamon;
(2001) 2651-4.
(23) Callier SL, Abudu R, Mehlman MJ, Singer
ME, Neuhauser D, Caga-Anan C and Wiesner
GL. Ethical, legal, and social implications of
personalized genomic medicine research: current
literature and suggestions for the future. Bioethics.
(2016) 30: 698-705.
(24) Lee S. Pharmacogenomics and the challenge of
health disparities. Public Health Genom. (2009)
12: 170-9.
(25) Lee SS-J. Racializing Drug design: implications
of pharmacogenomics for health disparities. Am. J.
Public Health. (2005) 95: 2133-8.
(26) Marx-Stolting L. Ethical implications of
pharmacogenetics: shaping the future of the field.
Curr. Pharmacogenomics. (2006) 4: 261-9.
(27) Wertz DC. Ethical, social and legal issues in
pharmacogenomics. Pharmacogenomics J. (2003)
3: 194-6.
(28) Fleck LM. Pharmacogenomics and personalized
medicine: wicked problems, ragged edges and
ethical precipices. N. Biotechnol. (2012) 29: 757-
68.
(29) Gupta S, Smith TR and Broekman ML. Ethical
considerations of neuro-oncology trial design in
the era of precision medicine. Neuro-Oncol. (2017)
134: 1-7.
(30) Shields AE. Ethical concerns related to
developing pharmacogenomic treatment strategies
for addiction. Addict. Sci. Clin. Pract. (2011) 6: 32-
43.
(31) McKinnon RA, Ward MB and Sorich MJ. A critical
analysis of barriers to the clinical implementation
of pharmacogenomics. Ther. Clin. Risk Manag.
(2007) 3: 751-9.
(32) Johansen Taber K and Dickinson B.
Pharmacogenomic knowledge gaps and
educational resource needs among physicians in
selected specialties. Pharmgenomics Pers. Med.
(2014) 7: 145.
(33) Marcinak R, Paris M and Kinney SRM.
Pharmacogenomics education improves pharmacy
student perceptions of their abilities and roles in its
use. Am. J. Pharm. Educ. (2018) 82: 6424.
(34) Frueh FW and Gurwitz D. From pharmacogenetics
to personalized medicine: a vital need for
educating health professionals and the community.
Pharmacogenomics. (2004) 5: 571-9.
(35) Owusu-Obeng A, Weitzel KW, Hatton RC, Staley
BJ, Ashton J, Cooper-Dehoff RM and Johnson
JA. Emerging roles for pharmacists in clinical
implementation of pharmacogenomics. Pharmacol.
(2014) 34: 1102-12.
(36) Weitzel KW, Aquilante CL, Johnson S, Kisor DF
and Empey PE. Educational strategies to enable
expansion of pharmacogenomics-based care. Am.
J. Health-Syst Pharm. (2016) 73: 1986-98.
(37) Yau A, Abd Aziz AB and Haque M. Knowledge,
attitude and practice concerning pharmacogenomics
among pharmacists: A systematic review. J. Young
Pharm. (2015) 7: 145-54.
(38) Bombard Y, Rozmovits L, Trudeau M, Leighl
NB, Deal K and Marshall DA. The value of
personalizing medicine: medical oncologists’
views on gene expression profiling in breast cancer
treatment. Oncol. J. (2015) 20: 351-6.
(39) Brall C and Schröder-Bäck P. Personalised
medicine and scarce resources: a discussion
of ethical chances and challenges from the
perspective of the capability approach. Public
Health Genomics. (2016) 19: 178-86.
(40) Faulkner E, Annemans L, Garrison L, Helfand M,
Holtorf A-P, Hornberger J, Hughes D, Li T, Malone
D, Payne K, Siebert U, Towse A, Veenstra D,
Watkins J and Personalized medicine development
and Reimbursement working group. Challenges
in the development and Reimbursement of
personalized medicine—Payer and manufacturer
perspectives and implications for health economics
and outcomes research: A report of the ISPOR
personalized medicine special interest group. Value
Health. (2012) 15: 1162-71.
(41) Karas Kuželički N, Prodan Žitnik I, Gurwitz
D, Llerena A, Cascorbi I, Siest S, Simmaco M,
Ansari M, Pazzagli M, Resta CD, Brandslund
I, Schwab M, Vermeersch P, E Lunshof J,
Dedoussis G, S Flordellis C, Fuhr U, C Stingl J,
van Schaik RHN, G Manolopoulos V, Marc J
and the pharmacogenomics education working
group (PGxEWG). Pharmacogenomics education
in medical and pharmacy schools: conclusions of
a global survey. Pharmacogenomics. (2019) 20:
643-57.
(42) Etchegary H and Wilson B. Bringing personalized
medicine to the community through public
engagement. J. Pers. Med. (2013) 10: 647-59.
(43) Frueh FW, Goodsaid F, Rudman A, Huang
SM and Lesko LJ. The need for education in
pharmacogenomics: a regulatory perspective.
Pharmacogenomics J. (2005) 5: 218-20.
(44) Çelik E, Şencan MN and Clark MP. Factors
affecting rational drug use (RDU), compliance and
wastage. Turkish J. Pharm. Sci. (2013) 10.
(45) Gast A, Mathes T. Medication adherence 
104
Pharmacogenomics Implementation Hurdles
influencing factors—an (updated) overview of
systematic reviews. Syst. Rev. (2019) 8: 112.
(46) Haga SB and LaPointe NMA. The potential
impact of pharmacogenetic testing on medication
adherence. Pharmacogenomics J. (2013) 13: 481-
3.
(47) Charland SL, Agatep BC, Herrera V, Schrader
B, Frueh FW, Ryvkin M, Shabbeer J, Devlin JJ,
Superko HR and Stanek EJ. Providing patients with
pharmacogenetic test results affects adherence to
statin therapy: results of the Additional KIF6 Risk
Offers Better Adherence to Statins (AKROBATS)
trial. Pharmacogenomics J. (2013) 14: 272-80.
(48) Grant RW, Hivert M, Pandiscio JC, Florez JC,
Nathan DM and Meigs JB. The clinical application
of genetic testing in type 2 diabetes: a patient and
physician survey. Diabetologia (2009) 52: 2299-
305.
(49) Borden BA, Lee SM, Danahey K, Galecki P,
Patrick-Miller L, Siegler M, Sorrentino MJ, Sacro
Y, Davis AM, Rubin DT, Lipstreuer K, Polonsky
TS, Nanda R, Harper WR, Koyner JL, Burnet DL,
Stadler WM, Kavitt RT, Meltzer DO, Ratain MJ and
O’Donnell PH. Patient-provider communications
about pharmacogenomic results increase patient
recall of medication changes. Pharmacogenomics
J. (2019) 19: 528-37.
(50) Heale BSE, Khalifa A, Stone BL, Nelson S
and Del Fiol G. Physicians’ pharmacogenomics
information needs and seeking behavior: a study
with case vignettes. BMC Med. Inform. Decis.
Mak. (2017) 17: 113.
(51) Tarczy-Hornoch P, Amendola L, Aronson SJ,
Garraway L, Gray S, Grundmeier RW, Hindroff
LA, Jarvik G, Karavite D, Lebo M, Plon SE, Allen
EV, Weck KE, White PS and Yang Y. A survey
of informatics approaches to whole-exome and
whole-genome clinical reporting in the electronic
health record. Genet. Med. (2013) 15: 824-32.
(52) Devine EB, Lee C-J, Overby CL, Abernethy N,
McCune J, Smith JW and Tarczy-Hornoch P.
Usability evaluation of pharmacogenomics clinical
decision support aids and clinical knowledge
resources in a computerized provider order entry
system: A mixed methods approach. Int. J. Med.
Inform. (2014) 83: 473-83.
(53) Manolio TA, Chisholm RL, Ozenberger B, Roden
DM, Williams MS, Wilson R, Bick D, Bottinger EP,
brilliant MH, Eng C, Frazer KA, Korf B, Ledbetter
DH, Lupski JR, Marsh C, Mrazek D, Murray MF,
O’Donnell PH, Rader DJ, Relling MV, Shuldiner
AR, Valle D, Weinshilboum R, Green ED and
Ginsburg GS. Implementing genomic medicine in
the clinic: the future is here. Genet Med. (2013) 15:
258-67.
(54) Overby CL and Tarczy-Hornoch P. Personalized
medicine: challenges and opportunities for
translational bioinformatics. J. Pers. Med. (2013)
10: 453-62.
(55) Relling MV and Klein TE. CPIC: Clinical
Pharmacogenetics implementation consortium of
the pharmacogenomics research network. Clin.
Pharmacol. Ther. (2011) 89: 464-7.
(56) Swen JJ, Nijenhuis M, van Rhenen M, de BoerVeger NJ, Buunk A-M, Houwink EJF, Mulder H,
Rongen GA, van Schaik RHN, van der Weide J,
Wilffert B, Deneer VHM, Guchelaar HJ and on
behalf of the Dutch Pharmacogenetics Working
Group (DPWG) of the Royal Dutch Pharmacists
Association (KNMP). Pharmacogenetic
information in clinical guidelines: The European
perspective. Clin. Pharmacol. Ther. (2018) 103:
795-801.
(57) Wilke RA, Xu H, Denny JC, Roden DM, Krauss
RM, McCarty CA, Davis RL, Skaar T, Lamba J and
Savova G. The emerging role of electronic medical
records in pharmacogenomics. Clin. Pharmacol.
Ther. (2011) 89: 379-86.
(58) Hicks JK, Dunnenberger HM, Gumpper KF,
Haidar CE and Hoffman JM. Integrating
pharmacogenomics into electronic health records
with clinical decision support. Am. J. Health-Syst.
Pharm. (2016) 73: 1967-76.
(59) Bell GC, Crews KR, Wilkinson MR, Haidar
CE, Hicks JK, Baker DK, Kornegay NM, Yang
W, Cross SJ, Howard SC, Freimuth RR, Evans
WE, Broeckel U, Relling MV and Hoffman JM.
Development and use of active clinical decision
support for preemptive pharmacogenomics. J. Am.
Med. Inform. Assoc. (2014) 21: e93-9.
(60) Osheroff JA, Teich JM, Middleton B, Steen EB,
Wright A and Detmer DE. A roadmap for national
action on clinical decision support. J. Am. Med.
Inform. Assoc. (2007) 14: 141-5.
(61) Peterson JF, Bowton E, Field JR, Beller M, Mitchell
J, Schildcrout J, Gregg W, Johnson K, Jirjis JN,
Roden DM, Pulley JM and Denny JC. Electronic
health record design and implementation for
pharmacogenomics: a local perspective. Genet.
Med. (2013) 15: 833-41.
(62) Welch BM and Kawamoto K. Clinical decision
support for genetically guided personalized
medicine: a systematic review. J. Am. Med. Inform.
Assoc. (2013) 20: 388-400.
(63) Hippman C and Nislow C. Pharmacogenomic
testing: clinical evidence and implementation
challenges. J. Pers. Med. (2019) 9: 40.
(64) Rosenman MB, Decker B, Levy KD, Holmes AM, 
105
Ayati N et al. / IJPR (2021), 20 (4): 92-106
Pratt VM and Eadon MT. Lessons learned when
introducing pharmacogenomic panel testing into
clinical practice. Value Health. (2017) 20: 54-9.
(65) Abou Diwan E, Zeitoun RI, Abou Haidar L,
Cascorbi I and Khoueiry Zgheib N. Implementation
and obstacles of pharmacogenetics in clinical
practice: An international survey. Br. J. Clin.
Pharmacol. (2019) 85: 2076-88.
(66) Dong OM and Wiltshire T. Advancing precision
medicine in healthcare: addressing implementation
challenges to increase pharmacogenetic testing in
the clinical setting. Physiol. Genomics. (2017) 49:
346-54.
(67) Dias MM, Sorich MJ, Rowland A, Wiese MD
and McKinnon RA. The routine clinical use of
pharmacogenetic tests: what it will require? Pharm.
Res. (2017) 34: 1544-50.
(68) Mohamed AH. Pharmacogenomics translation;
From bench to bedside. Drug Metab.
Pharmacokinet. (2013) 28: A33-4.
(69) Caudle KE, Keeling NJ, Klein TE, WhirlCarrillo M, Pratt VM and Hoffman JM.
Standardization can accelerate the adoption of
pharmacogenomics: current status and the path
forward. Pharmacogenomics. (2018) 19: 847-60.
(70) Aguilar H, Sanchez E, Braña I, Vivancos A
and Rodon J. Molecular screening programmes
for precision medicine: lessons learned from
personalized medicine trials. Expert Rev. Precis.
Med. Drug Dev. (2016) 1: 419-30.
(71) Rodon J, Soria JC, Berger R, Batist G, Tsimberidou
A, Bresson C, Lee JJ, Rubin E, Onn A, Schilsky
RL, Miller WH, Eggermont AM, Mendelsohn J,
Lazar V and Kurzrock R. Challenges in initiating
and conducting personalized cancer therapy trials:
perspectives from WINTHER, a Worldwide
Innovative Network (WIN) Consortium trial. Ann.
Oncol. (2015) 26: 1791-8.
(72) Saad ED, Paoletti X, Burzykowski T and Buyse
M. Precision medicine needs randomized clinical
trials. Nat. Rev. Clin. Oncol. (2017) 14: 317-23.
(73) Vivot A, Li J, Zeitoun J-D, Mourah S, Crequit
P, Ravaud P and Porcher R. Pharmacogenomic
biomarkers as inclusion criteria in clinical
trials of oncology-targeted drugs: a mapping of
ClinicalTrials.gov. Genet. Med. (2015) 18: 796-
805.
(74) Trepicchio WL and Mulligan G. Translation of
biomarkers into clinical utility. Pharmgenomics
Pers Med: Springer (2008) 239-51.
(75) Barsanti‐Innes B, Hey SP and Kimmelman J. The
challenges of validating in precision medicine: the
case of excision repair cross‐complement group 1
diagnostic testing. Oncol. J. (2017) 22: 89.
(76) McDermott JE, Wang J, Mitchell H, WebbRobertson B-J, Hafen R, Ramey J and Rodland KD.
Challenges in biomarker discovery: combining
expert insights with statistical analysis of complex
omics data. Expert Rev. Med. Devices (2013) 7: 37-
51.
(77) Rägo L, Sillo H, ‘t Hoen E and Zweygarth M.
Regulatory framework for access to safe, effective
quality medicines. Antivir. Ther. (2014) 19: 69-77.
(78) Melzer D, Raven A, Ling T, Detmer D and
Zimmern R. Pharmacogenetics: policy needs for
personal prescribing. J. Health Serv. Res. Policy.
(2005) 10: 40-4.
(79) Tan-Koi W, Lim ES and Teo Y. Health regulatory
communications of well-established safetyrelated pharmacogenomics associations in six
developed countries: an evaluation of alignment.
Pharmacogenomics J. (2017) 17: 121-7.
(80) Prasad K and Breckenridge A. Pharmacogenomics:
a new clinical or regulatory paradigm? European
experiences of pharmacogenomics in drug
regulation and regulatory initiatives. Drug Discov.
Today (2011) 16: 867-72.
(81) Hopkins M. Regulatory and Quality Assurance
Frameworks for PGX: A Comparative Study of the
US, EU and Four EU Member States. (2006) [cited
2019 April, 17]. Available from: URL: https://www.
york.ac.uk/res/pgx/publications/eur22214wp3.pdf.
(82) Nimmesgern E, Norstedt I and Draghia-Akli R.
Enabling personalized medicine in Europe by the
European Commission’s funding activities. J. Pers.
Med. (2017) 14: 355-65.
(83) Bombard Y, Abelson J, Simeonov D and Gauvin
F-P. Citizens’ perspectives on personalized
medicine: a qualitative public deliberation study.
Eur. J. Hum. Genet. (2013) 21: 1197-201.
(84) Browman GP, Vollmann J, Virani A and Schildmann
J. Improving the quality of ‘personalized medicine’
research and practice: through an ethical lens. J.
Pers. Med. (2014) 11: 413-23.
(85) Budin-Ljøsne I and Harris JR. Patient and interest
organizations’ views on personalized medicine:
a qualitative study. BMC Med. Ethics (2016) 17:
1-10.
(86) Weda M, Kienhuis A, van der Heyden L, Matic
M, Rodenburg W, van Drongelen A and Janssen
S. Personalised medicine products: evaluation
of the regulatory framework. (2014) Available
from: URL: https://www.rivm.nl/bibliotheek/
rapporten/360211001.pdf.
(87) Carrera PM and Olver I. The financial hazard
of personalized medicine and supportive care.
Support. Care Cancer. (2015) 23: 3399-401.
(88) Carroll JC, Makuwaza T, Manca DP, Sopcak N, 
106
Pharmacogenomics Implementation Hurdles
Permaul JA, O’Brien MA, Heisey R, Eisenhauer
EA, Easley J, Kryzanowska MK, Miedema B,
Pruthi S, Sawka C, Schneider N, Sussman J,
Urquhart R, Versaevel C and Grunfeil E. Primary
care providers’ experiences with and perceptions
of personalized genomic medicine. Can. Fam.
Physician. (2016) 62: E626-35.
(89) Shimazawa R and Ikeda M. Approval gap of
pharmacogenomic biomarkers and in-vitro
companion diagnostics between the United States
and Japan. J. Clin. Pharm. Ther. (2014) 39: 210-4.
(90) Wurcel V, Perche O, Lesteven D, Williams D-A,
Schäfer B, Hopley C, Jungwirth R, Postulka A,
Pasmans R, Hermansson LL, Ott M and Glorioso V.
The value of companion diagnostics: overcoming
access barriers to transform personalised health
care into an affordable reality in Europe. Public
Health Genom. (2016) 19: 137-43.
(91) Buzyn A, Blay J-Y, Hoog-Labouret N, Jimenez
M, Nowak F, Deley M-CL, Pérol D, Cailliot C,
Raynaud J and Vassal G. Equal access to innovative
therapies and precision cancer care. Nat. Rev. Clin.
Oncol. (2016) 13: 385-93.
(92) Schilsky RL. Implementing personalized cancer
care. Nat. Rev. Clin. Oncol. (2014) 11: 432-8.
(93) Administration IFD. National Formulary
Information: Iran Food and Drug Administration.
(2020) [cited 2020 March , 30]. Available from:
URL: WWW.FDA.GOV.IR.
(94) Cohen J, Wilson A and Manzolillo K. Clinical and
economic challenges facing pharmacogenomics.
Pharmacogenomics J. (2012) 13: 378-88.
(95) Mansfield EA. FDA perspective on companion
diagnostics: an evolving paradigm. Clin. Cancer
Res. (2014) 20: 1453-7.
(96) Pacanowski MA, Leptak C and Zineh I. Nextgeneration medicines: past regulatory experience
and considerations for the future. Clin. Pharmacol.
Ther. (2014) 95: 247-9.
(97) Hudson TJ. Personalized medicine: A
transformative approach is needed. Can. Med.
Assoc. J. (2009) 180: 911-3.
(98) Nielsen LF and Moldrup C. Lay perspective on
pharmacogenomics: a literature review. J. Pers.
Med. (2006) 3: 311-6.
(99) Abelson J, Giacomini M, Lehoux P and Gauvin
F-P. Bringing ‘the public’into health technology
assessment and coverage policy decisions: from
principles to practice. Health Pol. (2007) 82: 37-50.
(100) Wedlund PJ and de Leon J. Pharmacogenomic
testing: the cost factor. Pharmacogenomics J.
(2001) 1: 171-4.
(101)Garrison L and Towse A. Value-based pricing
and reimbursement in personalised healthcare:
introduction to the basic health economics. J. Pers.
Med. (2017) 7: 10.
(102) Gibson S, Raziee HR and Lemmens T. Why the
shift? taking a closer look at the growing interest
in niche markets and personalized medicine. World
Med. Health Policy. (2015) 7: 3-27.
(103) Keeling P. Personalized medicine: the absence
of ‘model-changing’ financial incentives. J. Pers.
Med. (2007) 4: 73-81.
(104) Akhmetov I and Bubnov RV. Innovative payer
engagement strategies: will the convergence lead
to better value creation in personalized medicine?
EPMA J. (2017) 8: 5-15.
(105) Antoñanzas F, Rodríguez-Ibeas R and JuárezCastelló CA. Personalized medicine and
pay for performance: should pharmaceutical
firms be fully penalized when treatment fails?
PharmacoEconomics. (2018) 36: 733-43.
(106) Hresko A and Haga S. Insurance coverage policies
for personalized medicine. J. Pers. Med. (2012) 2:
201-16.
(107) La Caze A. Does pharmacogenomics provide
an ethical challenge to the utilisation of costeffectiveness analysis by public health systems?
PharmacoEconomics. (2005) 23: 445-7.
(108) Rawlins MD and Culyer AJ. National institute
for clinical excellence and its value judgments. Br.
Med. J. (2004) 329: 224-7.
(109)Gavan SP, Thompson AJ and Payne K. The
economic case for precision medicine. Expert Rev.
Precis. Med. Drug Dev. (2018) 3: 1-9.
(110)Shabaruddin F, Payne K and Fleeman N.
Economic evaluations of personalized medicine:
existing challenges and current developments.
Pharmgenomics Pers. Med. (2015) 8: 115.
(111)Buchanan J, Wordsworth S and Schuh A. Issues
surrounding the health economic evaluation of
genomic technologies. Pharmacogenomics (2013)
14: 1833-47.
(112)Rafi I, Crinson I, Dawes M, Rafi D, Pirmohamed
M and Walter F. The implementation of
pharmacogenomics into UK general practice: a
qualitative study exploring barriers, challenges
and opportunities. J. Community Genet. (2020) 11:
269–77.