The future of laboratory medicine - A 2014 perspective.

Predicting the future is a difficult task. Not surprisingly, there are many examples and assumptions that have proved to be wrong. This review surveys the many predictions, beginning in 1887, about the future of laboratory medicine and its sub-specialties such as clinical chemistry and molecular pathology. It provides a commentary on the accuracy of the predictions and offers opinions on emerging technologies, economic factors and social developments that may play a role in shaping the future of laboratory medicine

The Master Observational Trial: A New Class of Master Protocol to Advance Precision Medicine.

This commentary introduces a new clinical trial construct, the Master Observational Trial (MOT), which hybridizes the power of molecularly based master interventional protocols with the breadth of real-world data. The MOT provides a clinical venue to allow molecular medicine to rapidly advance, answers questions that traditional interventional trials generally do not address, and seamlessly integrates with interventional trials in both diagnostic and therapeutic arenas. The result is a more comprehensive data collection ecosystem in precision medicine

Privacy and Accountability in Black-Box Medicine

Black-box medicine—the use of big data and sophisticated machine learning techniques for health-care applications—could be the future of personalized medicine. Black-box medicine promises to make it easier to diagnose rare diseases and conditions, identify the most promising treatments, and allocate scarce resources among different patients. But to succeed, it must overcome two separate, but related, problems: patient privacy and algorithmic accountability. Privacy is a problem because researchers need access to huge amounts of patient health information to generate useful medical predictions. And accountability is a problem because black-box algorithms must be verified by outsiders to ensure they are accurate and unbiased, but this means giving outsiders access to this health information. This article examines the tension between the twin goals of privacy and accountability and develops a framework for balancing that tension. It proposes three pillars for an effective system of privacy-preserving accountability: substantive limitations on the collection, use, and disclosure of patient information; independent gatekeepers regulating information sharing between those developing and verifying black-box algorithms; and information-security requirements to prevent unintentional disclosures of patient information. The article examines and draws on a similar debate in the field of clinical trials, where disclosing information from past trials can lead to new treatments but also threatens patient privacy

Minimal residual disease in Myeloma: Application for clinical care and new drug registration

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes

Minimal residual disease in Myeloma: Application for clinical care and new drug registration

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology

How to read a next-generation sequencing report-what oncologists need to know.

Next-generation sequencing (NGS) of tumor cell-derived DNA/RNA to screen for targetable genomic alterations is now widely available and has become part of routine practice in oncology. NGS testing strategies depend on cancer type, disease stage and the impact of results on treatment selection. The European Society for Medical Oncology (ESMO) has recently published recommendations for the use of NGS in patients with advanced cancer. We complement the ESMO recommendations with a practical review of how oncologists should read and interpret NGS reports. A concise and straightforward NGS report contains details of the tumor sample, the technology used and highlights not only the most important and potentially actionable results, but also other pathogenic alterations detected. Variants of unknown significance should also be listed. Interpretation of NGS reports should be a joint effort between molecular pathologists, tumor biologists and clinicians. Rather than relying and acting on the information provided by the NGS report, oncologists need to obtain a basic level of understanding to read and interpret NGS results. Comprehensive annotated databases are available for clinicians to review the information detailed in the NGS report. Molecular tumor boards do not only stimulate debate and exchange, but may also help to interpret challenging reports and to ensure continuing medical education

Pharmacogenomic Precision Medicine: Best Practice Toolkit for Improving Patient Screening for Adult Metastatic Cancer Patients

Precision medicine utilizes pharmacogenomic testing as a therapeutic approach. Genomic testing can assess the impact of an individual\u27s genome on their reaction to specific medications. The main objective is to find variants that may affect an individual\u27s response to a given medication. The implementation of pharmacogenomics in oncology facilitates informed decision-making by clinicians in drug selection and dosage determination

Deoxy technologies: a medical technology startup project: business plan for UK market

L26, O32DEOXY Technologies is a seed-stage medical technology project whose future core business will be based on an innovative Gene Expression profiling (GEP) nanotechnology, developed and patented at Harvard University. The project is located at Ludwig-Maximilian University (Germany) and its goal is to develop diagnostic tests for clinical market where price, speed and automation are competitive advantages. DEOXY Technologies intends to become a global and "lean" company focused on development and manufacturing of molecular tests (in vitro medical devices). This is a strategic analysis and a feasibility study for the breast cancer market. Breast cancer is the most frequent female cancer affecting 12% of women, worldwide and is seen as a paradigm of precision medicine success. The promoter identifies a clinical application for the GEP technology and proposes an alliance with an USA biomarker-focused company whose assets are complementary to the technology. The strategic analysis was based on a macroenvironmental analysis for the entrance market: United Kingdom, where regulatory and reimbursement contexts were systematized, and for Germany the country of development and manufacturing, where the impact of governmental support and the integration in a biotechnology cluster are critical favorable factors. In the microenvironmental analysis the high barriers to entrance and the importance of planning an exit strategy were underlined. The economic and financial viability analysis revealed that governmental funding is a critical success factor, as demonstrated by the positivity of the APV and emphasized the importance of a market expansion plan before starting operations. The scenario analysis explored how reimbursement and healthcare policies may impact the economic and financial viability of the project.A DEOXY Technologies é um projeto, baseado numa nanotecnologia inovadora de análise perfis de expressão genética (APEG), descoberta e patenteada na Universidade de Harvard. O projeto está integrado na Universidade de Ludwig-Maximilians, (Alemanha) e é candidato a fundos de investimento governamentais. A DEOXY Technologies acredita que por possuir uma tecnologia inovadora pode desenvolver máquinas de APEG e testes moleculares para o mercado clínico, onde o preço, automatização e rapidez serão vantagens competitivas. A DEOXY Technologies planeia tornar-se uma empresa global e "lean", focada no desenvolvimento e produção de testes moleculares "in vitro". Este plano de negócios contém a análise estratégica e económico-financeira para o mercado do cancro da mama, em Inglaterra (Reino Unido). O cancro da mama é o cancro mais frequente na mulher, afetando 12% desta população, e é paradigmático do sucesso da medicina de precisão. O promotor identifica uma necessidade clínica e para sua concretização propõe uma aliança com uma empresa biotecnológica detentora de ativos intelectuais complementares aos da DEOXY Technologies. A estratégia proposta baseia-se na análise PEST para o Reino Unido, contendo a regulamentação e etapas-chave para obter reembolso, e análise PEST para Alemanha, destacando-se a relevância do apoio governamental e da inserção num cluster biotecnológico como fatores críticos de sucesso. Da análise micro-ambiental salientam-se as barreiras à entrada e a importância da estratégia de saída nesta indústria. O estudo de viabilidade económico-financeira revelou que os fundos governamentais são um fator critico para a exequibilidade e viabilidade económico-financeira do projeto, sendo o valor atualizado ajustado o único indicador positivo. A análise de cenários demonstra como as políticas de cuidados de saúde influenciam a estratégia e a viabilidade económico-financeira do projeto