Toward a clinical practice guide in pharmacogenomics testing for functional polymorphisms of drug-metabolizing enzymes. Gene/drug pairs and barriers perceived in Spain

Abstract

The development of clinical practice recommendations or guidelines for the clinical use of biomarkers is an issue of great importance with regard to adverse drug reactions. The potential of pharmacogenomic biomarkers has been extensively investigated in recent years. However, several barriers to implementing the use of pharmacogenomics testing exist. We conducted a survey among members of the Spanish Societies of Pharmacology and Clinical Pharmacology to obtain information about the perception of such barriers and to compare the perceptions of participants about the relative importance of major gene/drug pairs. Of 11 potential barriers, the highest importance was attributed to lack of institutional support for pharmacogenomics testing, and to the issues related to the lack of guidelines. Of the proposed gene/drug pairs the highest importance was assigned to HLA-B/abacavir, UGT1A1/irinotecan, and CYP2D6/tamoxifen. In this perspective article, we compare the relative importance of 29 gene/drug pairs in the Spanish study with that of the same pairs in the American Society for Clinical Pharmacology and Therapeutics study, and we provide suggestions and areas of focus to develop a guide for clinical practice in pharmacogenomics testing.

Clinical Implementation of Pharmacogenetic Testing in a Hospital of the Spanish National Health System: Strategy and Experience Over 3 Years

“…The difficulties of integrating pharmacogenetics into clinical practice are well recognized in the literature. A survey conducted in 2012 among members of the Spanish Societies of Pharmacology and Clinical Pharmacology classified the perceived barriers in Spain into three major groups related to low institutional promotion, the lack of clinical guidelines and protocols, and economic and institutional issues as well as ethical, legal, and social implications . These reported hurdles are similar to those found in other countries .…”

Functional Polymorphisms in Xenobiotic Metabolizing Enzymes and Their Impact on the Therapy of Breast Cancer

“…These above conclusions regarding the constraints for clinical applicability of pharmacogenomic data in breast cancer management meet the consensus view on the use of qualifying biomarkers in drug safety (Agúndez et al, 2012). It appears, thus, that the limitations of pharmacogenomic studies are not a particularity of Oncology, and that the use of genetic information as biomarkers requires medical and scientific consensus and the development of adequate guidelines for clinical practice.…”

Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica

“…Por lo tanto, el desafío actual para la terapia personalizada es definir perfiles genéticos individuales y poblacionales para predecir la respuesta a los fármacos y la progresión de las enfermedades 21,25,[67][68][69] . La información para hacer frente a este reto sólo puede obtenerse a partir de estudios casos/control y/o estudios prospectivos con base farmacogenómica.…”

“…Algunas de estas limitaciones han sido analizadas previamente 25 e incluyen la falta de análisis costo-efectividad, necesidad de identificación de nuevos biomarcadores de toxicidad de medicamentos y su respuesta, limitaciones técnicas y variaciones étnicas. Adicionalmente, sabemos que existe variabilidad por factores no genéticos, dando lugar a la idea de que la farmacogenómica es sólo uno de los varios factores a considerar en el ajuste de la dosis.…”

“…Si bien la farmacogenética ha encontrado un extenso campo de aplicación en la oncología, también se ha evaluado su aplicación en otras áreas terapéuticas, como la analgesia, psiquiatría, cardiología y neurología, entre otras 6,16,[24][25][26] .…”