RESUMEN
Advances in the technologies to enable patient-centric sampling (PCS) have the potential to improve blood sample collection by enabling clinical trial participants to collect samples via self-collection or with the help of a caregiver in their home. Typically, blood samples to assess pharmacokinetics and pharmacodynamics of a drug during clinical development are collected at a clinical site via venous blood draw. In this position paper by the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the potential value PCS can bring to patients, to the clinical datasets generated, and to clinical trial sponsors is discussed, along with considerations for program decision making, bioanalytical feasibility, operations, and regulatory implications. With an understanding of the value of PCS and considerations when implementing during clinical drug development, we can bring the promise of PCS closer to reality and enable decentralized clinical trials.
Asunto(s)
Desarrollo de Medicamentos , Atención Dirigida al Paciente , HumanosAsunto(s)
COVID-19 , Ensayos Clínicos como Asunto/normas , Técnicas y Procedimientos Diagnósticos/tendencias , Atención Dirigida al Paciente/métodos , Manejo de Especímenes , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/patología , Ensayos Clínicos como Asunto/métodos , Técnicas y Procedimientos Diagnósticos/normas , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Técnicas de Diagnóstico Molecular/tendencias , Pandemias , Atención Dirigida al Paciente/normas , Atención Dirigida al Paciente/tendencias , Estándares de Referencia , Proyectos de Investigación , SARS-CoV-2 , Manejo de Especímenes/métodos , Manejo de Especímenes/normas , Manejo de Especímenes/tendencias , Telemedicina/métodos , Telemedicina/normas , Telemedicina/tendencias , Estados Unidos/epidemiologíaRESUMEN
To eliminate the diastereomer interference on Telcagepant (MK-0974) determination during clinical study support, on-line high turbulent-flow liquid chromatography (HTLC) methods, HTLC-A and HTLC-B that covered dynamic range of 0.5-500 nM and 5-5000 nM, respectively, were developed. To meet the requirement of rapid assay transfer among multiple laboratories and analysts, a solid-phase extraction (SPE) assay was derived from the existing HTLC-B assay under the same dynamic range. The on-line HTLC assays were achieved through direct injection of plasma samples, extraction of analyte with a Cohesive C18 column (50 mm x 0.5 mm, 50 microm), followed by HPLC separation on a FluoPhase RP column (100 mm x 2.1 mm, 5 microm) and MS/MS detection. The off-line SPE assay used Waters Oasis HLB microElution plate to extract the analytes from plasma matrix before injecting on a FluoPhase RP column (150 mm x 2.1 mm, 5 microm) for LC-MS/MS analysis. Under both on-line and off-line assay conditions, the diastereomer 1c was chromatographically separated from MK-0974. Cross-validation with the pooled samples demonstrated that both on-line and off-line assays provided comparable data with a difference of < 2.6%. The assays were proved to be specific, accurate and reliable, and have been used to support multiple clinical studies. The pros and cons of on-line and off-line assays with regard to man power involved in sample preparation, total analysis time, carryover, cost efficiency, and the requirement for assay transfer are discussed.