RESUMO
Pragmatic clinical trials (PCTs) have an established presence in clinical research and yet have only recently garnered attention within the landscape of genomic medicine. Using the PRagmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2) as a framework, this paper illustrates the application of PCT principles to The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study, a trial of pharmacogenetic testing prior to statin initiation for cardiovascular disease prevention in primary care. The trial achieved high engagement with providers (85% enrolled of those approached) and enrolled a representative sample of participants for which statin therapy would be recommended. The I-PICC Study has a high level of pragmatism, which should enhance the generalizability of its findings. The PRECIS-2 may be useful in the design and evaluation of PCTs of genomic medicine interventions, contributing to the generation of evidence that can bridge the gap between genomics innovation and clinical adoption.
Assuntos
Testes Farmacogenômicos , Ensaios Clínicos Pragmáticos como Assunto , Atenção Primária à Saúde/métodos , Projetos de Pesquisa , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Estudos de Viabilidade , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Variantes FarmacogenômicosRESUMO
Demonstrated improvements in patient outcomes will facilitate the clinical implementation of pharmacogenetic testing. Using the association between solute carrier organic anion transporter family member 1B1 (SLCO1B1) and statin-associated muscle symptoms (SAMSs) as a model, we conducted a systematic review of patient outcomes after delivery of SLCO1B1 results. Using PubMed and Embase searches through December 19, 2017, we identified 37 eligible records reporting preliminary or final outcomes, including six studies delivering only SLCO1B1 results and five large healthcare system-based implementation projects of multipharmacogene panels. Two small trials have demonstrated at least short-term improvements in low-density lipoprotein cholesterol after SLCO1B1 testing among previously statin intolerant patients. Evidence from large implementation projects suggests that SLCO1B1 results may change prescribing patterns for some high-risk patients. No study has reported improvements in SAMSs or cardiovascular events or tracked the economic outcomes of SLCO1B1 testing. Ongoing studies should collect and report outcomes relevant to pharmacogenetics stakeholders.