Masterstudiengang "Drug Regulatory Affairs"


Precision Medicine and the N-of-1 Clinical Trial Concept ***

Dr. Gunther Kauselmann (Abschlußjahr: 2017)

Language: English
During the decade 2000-2010, the average cost to successfully place an innovative medicinal product on the market increased to US$ 2558 million, mainly due to late stage failures in demonstrating sufficient efficacy in pivotal clinical trials. Concurrently, the application of high-throughput OMICs technologies in human biomedical research substantially increased the scientific knowledge on mechanistic models of metabolism on cellular- tissue- and organ level. The identification of biomarkers and their changes during disease and disease progression are providing the basis for innovative strategies for targeted therapeutic interventions. The "Precision Medicine" (PM) -Initiatives in the EU and USA are pioneering an innovative approach to healthcare related medical science by investigating the organizational, technical, scientific, ethical and regulatory requirements to shape the new research- and healthcare-model. The PM-approach has already resulted in the creation of novel "Randomized Clinical Trials" (RCTs) concepts, including "Basket"- and "Umbrella" designs, using individual molecular signatures to assign patients to defined treatment groups. The "N-of-1 Clinical Trial" design is discussed as the ultimate strategy for developing individualized therapies for a distinct patient, who is the single unit of observation in a study. The adoption of precision medicine in clinical research requires fundamental changes in existing public health care systems. A “Precision Medicine Ecosystem” requires a network infrastructure linking hospitals, diagnostic laboratories, biobanks and research- and clinical databases. Furthermore, the international harmonization of standards for tissue acquisition and storage, management of biobanks and data transfer appears to be mandatory to fully utilize the globally expanding scientific knowledge and resources. The co-development of novel therapeutics and their companion diagnostic tests are expected to establish convincing biomarker-phenotype-correlations that are required for comparative effectiveness research (CER) and patient-centered outcome research (PCOR) relying on surrogate endpoints.
Nevertheless, an existing precision medicine infrastructure will have far reaching implications for society, as digital information and biopsies stored in databases and tissue repositories will provide the basis for future investigations using new software tools, algorithms and technologies with unknown potential. Consequently the traditional ethical principles as defined in the "Declaration of Helsinki" need to be expanded, balancing the interests of society to further develop public healthcare and the individual’s right to protect their own data sets from scientific, social and economic interest groups. Furthermore, new regulatory strategies need to adapt an early and continuous dialogue with competent authorities and "Health Technology Assessment" (HTA) bodies in order to facilitate the timely approval of clinical trial- and marketing authorization-applications as well as favorable reimbursement decisions by the statutory health insurance. The "N-of-1 Clinical Trial" design has the potential to qualify as one of the favorable clinical research concepts for generating valid and predictable data sets to accelerate drug development and to ensure the safety and efficacy of novel treatment options for patients in need.
Pages: 70, Annexes: pages : 5

Download Master-Thesis (PDF, 2 MB)