Expected Impact

Short-term and long-term scientific, technological, and/or socioeconomic impacts

Scientific impact - Short-term, CliniMARK will develop BBP guidelines that will speed-up development of research-grade biomarker detection tests, and increase the reproducibility of clinical feasibility studies. During the COST Action runtime, the network will apply these guidelines to 2 technologies and 1 disease area (COPD), and determine its clinical feasibility before the project end. On the long-term, the developed BBP guidelines can serve as a template in biomarker development for a multitude of medical indications (cardiovascular, cancer, etc.). As a results, development of research-grade tests, and clinical feasibility studies of biomarkers will be achieved faster and with less resources. Ultimately, this will lead to an increase in the number of thoroughly and reproducibly studied biomarkers as targets for new diagnostic assays.
Technological impact - To develop the BBP guidelines, relevant existing methods for biomarker detection, validation and assay development will be evaluated. This allows the identification of critical hurdles in sensitivity and reproducibility of mass spectrometry, sample preparation methods, immuno-assays, clinical information storage in databases, data storage and analysis protocols, and user-friendliness of protocols and training of personnel for platform techniques in clinical chemistry laboratories. By identifying these critical hurdles, new Europe-wide studies can be established to significantly improve existing technologies and assist in novel technology development for biomarker validation and clinical implementation. The CliniMARK network will design those studies, establish new consortia from its network, and apply for European funding programmes (e.g. Horizon 2020) for the required financial resources. Societal/economic impact - Life science companies: The increased quality of clinical biomarker feasibility studies will provide life science companies in Europe with more accurately validated biomarkers.
This will lead to an increased confidence in published biomarkers and adoption for successful commercial development of diagnostic tests. Since the return on investment for European life sciences companies will increase, they will be more competitive in the worldwide biomarker diagnostic market. Physicians: The increased number of biomarkers with established reproducible feasibility and new diagnostic tests for these biomarkers will aid physicians to diagnose patients in more detail, allowing personalized treatments and better chances of survival and/or quality of life. This will first be achieved for the demonstrator project of COPD, but later also for other disease indications. Patients: The availability of better biomarkers will improve diagnosis, prognosis, and predict response to treatment of patients at a personal level. As a result, patients will receive personalized treatments, greatly improving their survival and quality of life. European healthcare system: Through improved diagnosis, prognosis, and prediction of response to treatment, patients will receive more effective treatments. This will decrease health cost expenditures. Ultimately, the correct use of reliable biomarkers will both improve healthy outcome throughout Europe and decrease health care expenses.

Measures to Maximise Impact

Plan for involving the most relevant stakeholders

CliniMARK will impact on several stakeholders (Figure 3 below). During the first half year of CliniMARK, representatives for all these stakeholders will be actively approached through the personal network of the network of proposers, LinkedIn, Facebook, Twitter, Google adds, adds in Biomarker journals
(e.g. Clinical Chemistry, Bioanalysis, J. Chromatography B, Molecular Cellular Proteomics), flyers at conferences (e.g. ASMS, AACR, MSACL), and a specific search and personal invitation of individuals. Representatives of regulatory authorities, and European Union (EU) will be invited to join meetings as independent guests and will be approached for consultation meetings.
Members that apply to the CliniMARK Action will be assigned to the Working Group of their choice. Members that occupy a senior position at their respective institute will be encouraged to actively take the lead in Working Group discussions to design the guidelines, while junior members will be encouraged to participate in Working Group discussions, and participate in short-term-scientific exchanges, work-shops, and training schools.

Figure 3

Stakeholders of CliniMARK

Dissemination and/or Exploitation Plan

For dissemination of the CliniMARK results, specific target groups have been identified: (1) Scientific community/journals/publishers, (2) Young scientists, (3) Patients, (4) Clinicians, (5) Leading experts from industry,
(6) Regulatory authorities/patent attorneys, (7) EU, (8) SMEs, (9) Big diagnostic and pharmaceutical companies, and (10) General public. CliniMARK will actively approach professional networks, patient organizations, and key opinion leaders for dissemination through classic dissemination channels.
This is coordinated by the Core Group, which contains the grant holder and the Working Group Chairs. In addition, Working Group 4 will investigate new channels for dissemination (e.g. through an online platform).

Potential for Innovation versus Risk Level

Potential for scientific, technological and/or socioeconomic innovation Breakthroughs

At the scientific level, CliniMARK will support the significant existing efforts in biomarker research. The standardized BBP approaches of CliniMARK will lead to more time-efficient biomarker detection studies and clinical feasibility studies. The proposals to improve existing methodologies, standardize data deposition, and make accessible repositories will further increase the effectiveness and comparability of current research efforts. In summary, CliniMARK will enable existing biomarker efforts to be more successful.
At the technological level, CliniMARK will analyse the shortcomings of existing technologies in a multi-disciplinary manner. In addition, a research plan will be designed to improve existing mass spectrometry, immuno-assay, and multiplex approaches. Through the pan-European, multidisciplinary CliniMARK network approach, a focused development plan will be designed, including research proposals and timelines for technological innovations throughout the process from biomarker discovery to clinical validation. This integrative approach forms a focused and efficient framework for Europe to become the technological centre of excellence in biomarker research.
At the level of the society, CliniMARK will have several important contributions. - Through improved diagnosis, prognosis, and prediction of response to treatment, patients will receive more effective treatments. This will decrease health cost expenditures. Ultimately, the correct use of reliable biomarkers will both improve the health status throughout Europe and decrease health care expenses. - Increased public awareness on the exciting field of biomarkers and its potential clinical applications.
The risk level: BBP will only have effect if adherence to the guidelines is high. Currently, with journals not adhering to guidelines themselves, no incentive exists for scientists to adhere to guidelines. To improve adherence, CliniMARK follows an approach with 3 foci: (1) Including major initiative in biomarker and biobanking research (BBMRI, EATRIS, ELIXIR), (2) Development of a new online tool for capacity building with hard-coded BBP, and (3) Collaboration with scientific journals to develop a policy that encourages publications using the BBP. Another risk is the heterogeneity of the network of experts from different disciplines, all with their own preferred techniques and methods, who will have to reach consensus on a BBP guideline. By including experts on standardization and regulation, the Action can draw from experience on successful implementation of guidelines in other areas of bioanalysis. For example, the diagnostics and the pharmaceutical industries adhere to such guidelines as do the clinical chemistry laboratories. CliniMARK thus does not have to ''reinvent the wheel'' but can learn from good practices elsewhere.
The innovation potential versus Risk level of CliniMARK: When taking into account EU investments in biomarker research, which adds up to over €200 million over the years 2014-2017, the potential of the CliniMARK COST Action to benefit all these efforts, and the relatively modest investment that is needed to set up this Action, the return on investment for this project is expected to be very good.