6 research outputs found
Les enjeux de la translation des technologies : le cas des tests de pharmacogénétique au Québec
ProblĂ©matique : LâarrivĂ©e des tests de pharmacogĂ©nĂ©tique a Ă©tĂ© annoncĂ©e dans les
médias et la littérature scientifique telle une révolution, un tournant vers la médecine
personnalisĂ©e. En rĂ©alitĂ©, cette rĂ©volution se fait toujours attendre. Plusieurs barriĂšres lĂ©gislatives, scientifiques, professionnelles et Ă©thiques sont dĂ©crites dans la littĂ©rature comme Ă©tant la cause du dĂ©lai de la translation des tests de pharmacogĂ©nĂ©tique, du laboratoire vers la clinique. Cet optimisme quant Ă lâarrivĂ©e de la pharmacogĂ©nĂ©tique et ces barriĂšres existent-elles au QuĂ©bec? Quel est le contexte de translation des tests
de pharmacogĂ©nĂ©tique au QuĂ©bec? Actuellement, il nâexiste aucune donnĂ©e sur ces questions. Il est pourtant essentiel de les Ă©valuer. Alors que les attentes et les
pressions pour lâintĂ©gration rapide de technologies gĂ©nĂ©tiques sont de plus en plus
Ă©levĂ©es sur le systĂšme de santĂ© quĂ©bĂ©cois, lâabsence de planification et de
mécanisme de translation de ces technologies font craindre une translation et une
utilisation inadéquates.
Objectifs : Un premier objectif est dâĂ©clairer et dâenrichir sur les conditions dâutilisation et de translation ainsi que sur les enjeux associĂ©s aux tests de pharmacogĂ©nĂ©tique dans le contexte quĂ©bĂ©cois. Un deuxiĂšme objectif est de cerner ce qui est vĂ©hiculĂ© sur la PGt dans diffĂ©rentes sources, dont les mĂ©dias. Il ne sâagit pas dâĂ©valuer si la
pharmacogĂ©nĂ©tique devrait ĂȘtre intĂ©grĂ©e dans la clinique, mais de mettre en
perspective les espoirs vĂ©hiculĂ©s et la rĂ©alitĂ© du terrain. Ceci afin dâorienter la rĂ©flexion quant au dĂ©veloppement de mĂ©canismes de translation efficients et de politiques associĂ©es.
MĂ©thodologie : Lâanalyse des discours de plusieurs sources documentaires (n=167)
du QuĂ©bec et du Canada (1990-2005) et dâentretiens avec des experts quĂ©bĂ©cois
(n=19) a été effectuée. Quatre thÚmes ont été analysés : 1) le positionnement et les
perceptions envers la pharmacogénétique; 2) les avantages et les risques reliés à son
utilisation; 3) les rĂŽles et les tensions entre professionnels; 4) les barriĂšres et les
solutions de translation.
RĂ©sultats : Lâanalyse des reprĂ©sentations vĂ©hiculĂ©es sur la pharmacogĂ©nĂ©tique dans
les sources documentaires se cristallise autour de deux pÎles. Les représentations
optimistes qui révÚlent une fascination envers la médecine personnalisée, créant des
attentes (« GĂ©nohype ») en regard de lâarrivĂ©e de la pharmacogĂ©nĂ©tique dans la
clinique. Les représentations pessimistes qui révÚlent un scepticisme (« Génomythe »)
envers lâarrivĂ©e de la pharmacogĂ©nĂ©tique et qui semblent imprĂ©gnĂ©s par lâhistorique
des reprĂ©sentations mĂ©diatiques nĂ©gatives de la gĂ©nĂ©tique. Quant Ă lâanalyse des
entretiens, celle-ci a permis de mettre en lumiĂšre le contexte actuel du terrain
dâaccueil. En effet, selon les experts interviewĂ©s, ce contexte comporte des dĂ©ficiences lĂ©gislatives et un dysfonctionnement organisationnel qui font en sorte que lâutilisation
des tests de pharmacogĂ©nĂ©tique est limitĂ©e, fragmentĂ©e et non standardisĂ©e. Sâajoute
à ceci, le manque de données probantes et de dialogue entre des acteurs mal ou peu
informés, la résistance et la crainte de certains professionnels.
Discussion : Plusieurs changements dans la réglementation des systÚmes
dâinnovation ainsi que dans le contexte dâaccueil seront nĂ©cessaires pour rendre
accessibles les tests de pharmacogénétique dans la pratique clinique courante. Des
mécanismes facilitateurs de la translation des technologies et des facteurs clés de
réussite sont proposés. Enfin, quelques initiatives phares sont suggérées.
Conclusion : Des efforts au niveau international, national, provincial et local sont indispensables afin de rĂ©soudre les nombreux obstacles de la translation des tests de pharmacogĂ©nĂ©tique au QuĂ©bec et ainsi planifier lâavenir le plus efficacement et sĂ»rement possible.Problematic: The advent of pharmacogenetic testing was heralded in the media and in scientific literature as a revolution and the dawn of a new era of personalized medicine. This revolution has yet to arrive. The literature describes several legislative, scientific,
professional and ethical barriers that are causing a delay in the translation of
pharmacogenetic testing into clinical practice. In Quebec, is there optimism about
pharmacogenetics and do these barriers exist? And in what context is the integration of pharmacogenetic testing taking place? At present, these questions remain unanswered. Yet they are of critical importance. While there are growing expectations and pressure on the Quebec health system to rapidly incorporate genetic technology, the lack of planning and of mechanisms for the translation of this technology may jeopardize its adequate transfer and use.
Objectives: The first objective was to gain clearer and fuller insight and understanding
into the conditions of use and translation of pharmacogenetic testing in Quebec and its
related issues. The second was to identify the message being conveyed about
pharmacogenetics in various sources, including the media. The issue at hand was not whether pharmacogenetics should or should not be integrated into clinical practice, but rather to put into perspective the hopes being set forth regarding pharmacogenetics and the realistic nature of the enterprise. The purpose of the exercise was to provide a framework for thinking about the development of efficient translation mechanisms and
the policies associated with it.
Methodology: Discourse analyses of several documentary sources (n=167) in Quebec
and Canada (1990-2005) and interviews with Quebec experts (n=19) were conducted.
Four themes were explored: 1) the positioning and perception of pharmacogenetics; 2)the advantages and risks associated with its use; 3) the roles of various professionals and the tensions that exist among them; 4) the barriers and solutions to translation.
Results: Analysis of the representations of pharmacogenetics in the documentary
sources revealed a divide between two distinct poles. On the one hand, the optimistic representations showed a fascination with personalized medicine, creating expectations (âGenohypeâ) regarding the introduction of pharmacogenetics to the
clinical setting. On the other hand, the highly sceptical pessimistic representations
(âGenomythâ) of pharmacogenetics seemed to be permeated by the history of negative
media representations of genetics. Furthermore, analyses of the interviews shed light on the current social, political and clinical context. In fact, according to the experts interviewed, this context is characterized by legislative shortcomings and a dysfunctional organizational structure, which have led to a limited, fragmented and non-standardized use of pharmacogenetic testing. Added to this is a lack of clinical data, an absence of communication among various ill-informed or uninformed players and both resistance and fear among certain professionals.
Discussion: Many regulatory changes to the innovation system and current context
are needed to ensure access to pharmacogenetic testing in the present clinical setting. Mechanisms to facilitate the translation of technology and the key factors needed for success are also described. Finally, several flagship initiatives are suggested.
Conclusion: International, national, provincial and local efforts are required to
overcome the various barriers to the translation of pharmacogenetic testing into clinical practice in Quebec and thus plan the future in the safest, most efficient manner possible
3D Cohort Study : The Integrated Research Network in Perinatology of Quebec and Eastern Ontario
Background: The 3D Cohort Study (Design, Develop, Discover) was established to help bridge knowledge gaps
about the links between various adverse exposures during pregnancy with birth outcomes and later health
outcomes in children.
Methods: Pregnant women and their partners were recruited during the first trimester from nine sites in Quebec
and followed along with their children through to 2 years of age. Questionnaires were administered during
pregnancy and post-delivery to collect information on demographics, mental health and life style, medical history,
psychosocial measures, diet, infant growth, and neurodevelopment. Information on the delivery and newborn
outcomes were abstracted from medical charts. Biological specimens were collected from mothers during each
trimester, fathers (once during the pregnancy), and infants (at delivery and 2 years of age) for storage in a
biological specimen bank.
Results: Of the 9864 women screened, 6348 met the eligibility criteria and 2366 women participated in the study
(37% of eligible women). Among women in the 3D cohort, 1721 of their partners (1704 biological fathers) agreed to
participate (73%). Two thousand two hundred and nineteen participants had a live singleton birth (94%). Prenatal
blood and urine samples as well as vaginal secretions were collected for â„98% of participants, cord blood for 81%
of livebirths, and placental tissue for 89% of livebirths.
Conclusions: The 3D Cohort Study combines a rich bank of multiple biological specimens with extensive clinical,
life style, and psychosocial data. This data set is a valuable resource for studying the developmental etiology of
birth and early childhood neurodevelopmental outcomes
Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT
© 2021 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.Background: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine.
Methods: There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients.
Results: None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41Ă10-9) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70Ă10-8), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant.
Conclusions: We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.info:eu-repo/semantics/publishedVersio
A discrete event simulation model to assess the economic value of a hypothetical pharmacogenomics test for statin-induced myopathy in patients initiating a statin in secondary cardiovascular prevention
Background
Statin (HMG-CoA reductase inhibitor) therapy is the mainstay dyslipidemia treatment and reduces the risk of a cardiovascular (CV) event (CVE) by up to 35%. However, adherence to statin therapy is poor. One reason patients discontinue statin therapy is musculoskeletal pain and the associated risk of rhabdomyolysis. Research is ongoing to develop a pharmacogenomics (PGx) test for statin-induced myopathy as an alternative to the current diagnosis method, which relies on creatine kinase levels. The potential economic value of a PGx test for statin-induced myopathy is unknown.
Methods
We developed a lifetime discrete event simulation (DES) model for patients 65 years of age initiating a statin after a first CVE consisting of either an acute myocardial infarction (AMI) or a stroke. The model evaluates the potential economic value of a hypothetical PGx test for diagnosing statin-induced myopathy. We have assessed the model over the spectrum of test sensitivity and specificity parameters.
Results
Our model showed that a strategy with a perfect PGx test had an incremental cost-utility ratio of 4273 Canadian dollars (Can12,000, the PGx strategy is favored in 90% of the model simulations.
Conclusion
We found that a strategy favoring patients staying on statin therapy is cost effective even if patients maintained on statin are at risk of rhabdomyolysis. Our results are explained by the fact that statins are highly effective in reducing the CV risk in patients at high CV risk, and this benefit largely outweighs the risk of rhabdomyolysis