The Future of Precision Medicine : Potential Impacts for Health Technology Assessment

Objective Precision medicine allows health care interventions to be tailored to groups of patients based on their disease susceptibility, diagnostic or prognostic information or treatment response. We analyse what developments are expected in precision medicine over the next decade and consider the implications for health technology assessment (HTA) agencies. Methods We perform a pragmatic review of the literature on the health economic challenges of precision medicine, and conduct interviews with representatives from HTA agencies, research councils and researchers from a variety of fields, including digital health, health informatics, health economics and primary care research. Results Three types of precision medicine are highlighted as likely to emerge in clinical practice and impact upon HTA agencies: complex algorithms, digital health applications and ‘omics’-based tests. Defining the scope of an evaluation, identifying and synthesizing the evidence and developing decision analytic models will more difficult when assessing more complex and uncertain treatment pathways. Stratification of patients will result in smaller subgroups, higher standard errors and greater decision uncertainty. Equity concerns may present in instances where biomarkers correlate with characteristics such as ethnicity, whilst fast-paced innovation may reduce the shelf-life of guidance and necessitate more frequent reviewing. Discussion Innovation in precision medicine promises substantial benefits to patients, but will also change the way in which some health services are delivered and evaluated. As biomarker discovery accelerates and AI-based technologies emerge, the technical expertise and processes of HTA agencies will need to adapt if the objective of value for money is to be maintained

Sensitive Assay for Mycoplasma Detection in Mammalian Cell Culture

Mycoplasma contamination in mammalian cell cultures is often overlooked yet is a serious issue which can induce a myriad of cellular changes leading to false interpretation of experimental results. Here, we present a simple and sensitive assay to monitor mycoplasma contamination (mycosensor) based on degradation of the <i>Gaussia</i> luciferase reporter in the conditioned medium of cells. This assay proved to be more sensitive as compared to a commercially available bioluminescent assay in detecting mycoplasma contamination in seven different cell lines. The <i>Gaussia</i> luciferase mycosensor assay provides an easy tool to monitor mammalian cell contaminants in a high-throughput fashion

Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging

Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging

Multiplex blood reporters for simultaneous monitoring of cellular processes

Contains fulltext : 125685.pdf (publisher's version ) (Open Access)Reporters secreted into the conditioned medium of cells in culture or into blood in vivo have shown to be useful tools for simple and noninvasive monitoring of biological processes in real-time. Here, we characterize the naturally secreted Vargula luciferase as a secreted blood reporter and show that this reporter can be multiplexed with the secreted Gaussia luciferase and alkaline phosphatase for simultaneous monitoring of three different cellular processes in the same biological system. We applied this system to monitor the response of three different subsets of glioma cells to a clinically relevant chemotherapeutic agent in the same well in culture or animal in vivo. This system could be extended to any field to detect multiple processes in the same biological system and is amenable for high-throughput screening to find drugs that affect multiple cellular populations/phenomena simultaneously

Directed Molecular Evolution Reveals Gaussia Luciferase Variants with Enhanced Light Output Stability

Gaussia Luciferase (Gluc) has proven to be a powerful mammalian cell reporter for monitoring numerous biological processes in immunology, virology, oncology, and neuroscience. Current limitations of Gluc as a reporter include its emission of blue light, which is absorbed by mammalian tissues, limiting its use in vivo, and a flash-type bioluminescence reaction, making it unsuited for high-throughput applications. To overcome these limitations, a library of Gluc variants was generated using directed molecular evolution and screened for relative light output, a shift in emission spectrum, and glow-type light emission kinetics. Several variants with a 10–15 nm shift in their light emission peak were found. Further, a Gluc variant that catalyzes a glow-type bioluminescence reaction, suited for high-throughput applications, was also identified. These results indicate that molecular evolution could be used to modulate Gluc bioluminescence reaction characteristics

Sensitive Assay for Mycoplasma Detection in Mammalian Cell Culture

Mycoplasma contamination in mammalian cell cultures is often overlooked yet is a serious issue which can induce a myriad of cellular changes leading to false interpretation of experimental results. Here we present a simple and sensitive assay to monitor mycoplasma contamination (mycosensor) based on degradation of the Gaussia luciferase reporter in the conditioned medium of cells. This assay proved to be more sensitive as compared to a commercially-available bioluminescent assay in detecting mycoplasma contamination in seven different cell lines. The Gaussia luciferase mycosensor assay provides an easy tool to monitor mammalian cells contaminants in a high-throughput fashion

Multiplex Blood Reporters for Simultaneous Monitoring of Cellular Processes

Reporters secreted into the conditioned medium of cells in culture or into blood in vivo have shown to be useful tools for simple and noninvasive monitoring of biological processes in real-time. Here, we characterize the naturally secreted <i>Vargula</i> luciferase as a secreted blood reporter and show that this reporter can be multiplexed with the secreted <i>Gaussia</i> luciferase and alkaline phosphatase for simultaneous monitoring of three different cellular processes in the same biological system. We applied this system to monitor the response of three different subsets of glioma cells to a clinically relevant chemotherapeutic agent in the same well in culture or animal in vivo. This system could be extended to any field to detect multiple processes in the same biological system and is amenable for high-throughput screening to find drugs that affect multiple cellular populations/phenomena simultaneously