Biomarkers are the bridge between basic and clinical research. It enables us to speed up the process of drug development (Winterer, G. The Handbook of Neuropsychiatric Biomarkers. Springer 2009). An NIH (National Institute of Health) study group committed to the following definition of biomarkers: A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention (Biomarkers Definitions Working Group. Clin Pharmacol Ther 2001). This biomarker definition is relatively broad encompassing both physiological indicators (functional biomarkers) such as blood pressure, heart rate and brain function measures as well as molecular measures (molecular biomarkers) like gene expression, proteins, immunological markers etc.
Biomarkers are particularly useful when translating pre-clinical to clinical findings (bench-to-bedsite). Biomarkers can be helpful:
- When difficulties arise in the decision-making process with regard to investigational new drug (IND) applications, i.e, when trying to extrapolate results from preclinical animal studies to the use in humans.
- For proof-of-principle and proof-of-concept studies. In the field of drug research, a company will often undertake research initially, to prove that the core ideas are workable (proof-of-principle) and feasible, before going further (first-in man studies, first-in-patients studies). The use of “biomarker-enhanced” proof-of-concept studies helps to establish viability, technical issues, and overall direction.
- For stratification of patients. During phase-I, early phase-II and in the subsequent process during late phase-II and phase-III (or even phase-IV studies), biomarkers can be helpful, i.e., to stratify proband and patient groups („personalized medicine“).
How does it work?
PI PharmaImage takes care of the required infrastructure for biomarker investigations wherever your patients or probands are located in Europe. This includes:
- Planning and set-up of the (biomarker) study.
- Training of staff for the collection (biological samples, imaging and electrophysiological data etc.).
- Storage and transport of imaging/electrophysiological data and biological samples.
- Documentation of sample/data acquisition
- Data and sample analyses are mostly conducted in Berlin
Normative Reference Databank
Any valid biomarker study requires normative reference data for comparison. Reference data vary based on several factors, including the sociodemographic background of the healthy population from which imaging data or biological samples were obtained and the specific methods and/or instruments used to collect the data/samples.
Why is reference data important?
- Providing validated reference data/material (population level data) would be too expensive for many academic (or private) institutions.
- Sample stratification: when selecting your normal control or patient group, e.g. for a drug trial, it is important to know beforehand what is “normal” and what is “on the edge”.
In this regard, PI PharmaImage is in a worldwide unique position. Cross-sectional and longitudinal population-based normative reference data (3Tesla neuroimaging, electrophysiology, cognitive performance) and biological samples (blood, plasma) from > 4000 adult subjects across all age ranges with an emphasis on elderly subjects are available. The reference databank is continuously expanded. All data sets included undergo regular QC. Sociodemographic data are available for all subjects and all subjects have undergone extensive cognitive testing (mostly using the Cantab® test battery). Biomarker data can be combined with demographic and cognitive endpoints. Sample stratification can be conducted on the basis of predefined cut-offs for any imaging, electrophysiological or molecular measure as well as combination of measurements. Alternatively, using the normative reference post hoc evaluations may facilitate a better understanding of the obtained study results – positive or negative
Imaging & Electrophysiology Biomarkers
PI PharmaImage offers a wide range of in-house neuroimaging and electrophysiology capabilities. Generally, imaging and electrophysiological experiments are conducted close to the patients/probands wherever they are (CROs, hospitals or at the patient´s home ). Imaging facilities are contracted on-site and/or electrophysiological equipment is provided by PI PharmaImage for the duration of the study. PI PharmaImage also takes care of on-site staff training if required which includes regular monitoring. Data are transferred via cloud service and analyzed by PI PharmaImage staff in Berlin (Germany). Our imaging protocols are closely adapted to the protocols of ADNI (Alzheimer´s Disease Neuroimaging Initiative). Based on our population-based reference databank of electrophysiological and multimodal imaging data (cross-sectional, and longitudinal data from > 3000 healthy adult subjects across all age ranges which includes test-retest data), pre-selection (stratification) of study subjects (healthy, patients) can be conducted before volunteers/patients enter the study (e.g. drug trial). Finally, study results including statistical analyses and reports are delivered to our customers.
While the core competence of PI PharmaImage is in the field of neuroimaging and electrophysiology, we also support investigations with molecular biomarkers, in particular, we provide a large population-based reference database and take care of the required infrastructure (e.g. storage and transportation).
- The reference database (and biobank) is from the same subjects like the imaging and neurophysiological data. It includes blood and plasma samples (and CSF from a subgroup) for genetic, gene expression (mRNA/miRNA), metabolic and immunological marker investigations, as well as for the investigation of neurodegenerative markers and markers to assess blood-brain function among others. The reference database and state-of-the art biobank is continuously expanded (currently N > 3000 healthy adult subjects across all age ranges.
- For biobanking and molecular investigations, PI PharmaImage closely works together with additional partners. Preferred partners are Atlas Biolabs and Immundiagnostik (http://www.immundiagnostik.com/en/home.html) among others. Atlas offers a wide range of Omics platforms, next generation sequencing (NGS) capabilities. Close cooperations also exist with a number of academic research labs across Europe which allows us to include sophisticated biomarkers in the study design.
International Fund Raising
PI PharmaImage provides support with fund raising to academic and private organizations being active in biomedical research. PI PharmaImage assists in finding an adequate strategy, building national and international consortia and delivering an administrative and management framework.
We offer over 20 years of expertise with successful fund raising and project management:
- European Union (EU)
- Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) Bundesministerium für Forschung und Technologie (BMBF)
- Pharmaceutical Industry (Phase-I-IV)
Major expertise with large national/international biomedical research consortia (EU, DFG)
Services offered by PI
Services are offered as modules. Whatever you need for your clinical study you can select from the following list:
- Formal Support with National and International Grant Applications, Study Proposals for Industry, Ethics Applications.
- Administration/Coordination of Projects (including contacting EU Officials)
- Study Set-up incl. Biomarker Panels, Sample Tracking and Logistic (Storage/Transport), Contracting Imaging Facilities for Data Collection
- Clinical Data Management incl. eCRF, Data Storage and Transfer via Cloud Service
- Monitoring, Registration of Drug Trials, Supporting Import/Export of Experimental Drug Substances for Research requiring Import and/or Export Authorizations
- Clinical Data (Statistical) Analyses, Biomarker/Imaging Data Analyses
- Reporting (Final Reports, SAE Reporting)
- Legal Activities, Negotiations, Consortium Agreements, Intellectual Property Protection, Contacting Legal Bodies (e.g. EMA)
- Dissemination Activities, Project Web Sites, Public Awareness of Projects, Organization of Meetings and Events, Training Activities also see “Other Services”.
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