Pharmaimage is a novel and timely type of Clinical Research Organization.
PI supports clinical researchers from academia and private institutions with the necessary expertise and guidance to conduct unicentric or multicentric clinical studies (Phase-I-IV). In an increasingly complex clinical research environment, PI offers support with: international fund raising/contract acquisition, editing of grant applications/study protocols, study design and study set-up, ethics application, regulatory issues, data collection, monitoring and data-analyses. One of our core competences is the implementation of biomarker solutions (imaging, physiological, molecular) including data analysis in the context of clinical studies. Since its inception, PharmaImage has been working closely together with academic institutions (University Hospital Düsseldorf, Charité – University Medicine Berlin) and traditional clinical research organizations (CROs) in Germany and abroad: including Hammersmith Medicines in London, the Charité Research Organization in Berlin, NUVISAN Pharma Services in Ulm, FOCUS Drug Development in Neuss, and JSW Life Sciences in Austria. PharmaImage has now contributed its expertise, logistics and infrastructure to more than 10 clinical phase-I/IIa studies. So far, contract research and consulting has been conducted for international pharmaceutical companies (R&D) like Janssen Pharmaceutica (Johnson & Johnson), Lundbeck, Pfizer, UCB, Boehringer-Ingelheim, Recordati and Ratiopharm. Pharmaimage GmbH is currently involved in two national and international research consortia: Nicotine – Molecular and Physiological Mechanisms in CNS (funded by the DFG: www.nicotine-research.com) and the EU-funded BioCog consortium: Biomarker Development for Postoperative Cognitive Impairment in the Elderly (www.biocog.eu). This includes a strategic alliance of Pharmaimage with the Charité University Medicine Berlin as well as other renowned academic institutions like the Max-Delbrück Center for Molecular Medinine (MDC) of the Helmholtz Association, the Cambridge University, University of Utrecht and Luxembourg Centre for Systems Biomedicine (Bioinformatics) among others as well as private partners like Atlas, Immundiagnostik, Cellulogic and Alta.
Serious adverse events (SAEs) during clinical phase-I studies (first dosing, dose escalation) are rare but can be devastating as exemplified by the recent incident at the clinical research organization (CRO) Biotrial in France or another incident during a trial that was conducted by the CRO Parexel (UK) in 2006.
In order to prevent at least some SAEs affecting brain function, Pharmaimage GmbH (Berlin, Germany) recently implemented a novel monitoring system. The system was tested in 2015 together with the CRO Hammersmith Medicines Research (HMR) in London (UK). To improve safety during clinical phase-I studies, the monitoring system was designed such that a highly sensitive assessment of SAEs affecting brain function such as epileptic seizures, diffuse encephalopathic (toxic) changes or strokes, which may lead to coma and death, is possible. When this kind of SAEs are detected early enough, further diagnostic and treatment intervention measures may prevent the worst case scenario. Accordingly, the Pharmaimage monitoring system is particularly valuable when any drug, which affects brain function, is tested in clinical phase-I studies (first in human study) – most notably when dose escalation is conducted.
Pharmaimage GmbH has established a real-time neurophysiological/video monitoring system using a secure web-based remote monitoring system for electroencephalographic (EEG) and video data. A trained neurophysiologist in Berlin is able to analyse signals in real-time while data acquisition elsewhere (e.g. in London) is ongoing. The system does not require particular expertise on-site at the CRU whereever it is located. Pharmaimage GmbH is providing and setting up the equipment for the duration of the study, Pharmaimage also provides on-site training of staff and standard-operating procedures (SOPs). Using the neurophysiological safety monitoring data, additional sophisticated pharmacodynamic analyses ("surrogate endpoint analyses") can also be conducted with the very same data set.
The newly established remote real-time monitoring system can be used as part of clinical drug trials (phase-I/II) conducted at CROs or research hospitals all over Europe and beyond.
Service Industry 4.0: Our novel real-time remote monitoring system is based on the concept of the "Internet of Things".
Specific services offered by PI
Services are offered as modules which can be customized:
Electrophysiology (EEG/ERP) hardware/software is provided to conduct EEG/ERP experiments at the clinical study site (any CRO/hospital in Europe or beyond). On-site technical training of local staff (e.g. study nurses) is provided if needed by Pharmaimage to conduct the electrophysiological (EEG/ERP) experiments. Quantitative (pharmacodynamic) EEG/ERP data analyses (e.g. power spectra, time-frequency analyses, source analyses) are conducted in Berlin. Pharmaimage recently also developed a novel EEG monitoring system for safety assessment during/after dosing/dose escalation e.g. for early detection of seizure activity (e.g. with glutamatergic compounds) or toxic encephalopathy. While the Pharmaimage EEG monitoring equipment can be located at any CRO/hospital (worldwide), the clinical EEG assessments are conducted in real-time (remotely) in Berlin by a certified clinical neurophysiologist (pharmaco-EEG expert). Safety monitoring data can be simultaneously used for pharmacodynamic measurements (e.g. surrogate outcome measures).
Neuroimaging experiments (fMRI, structural MRI) are conducted using MRI-scanners near the clinical study site. Scanner time is rented by Pharmaimage on-site (in the proximity of the CRO or hospital where the clinical study is conducted), Pharmaimage provides MR-sequences and staff (technical assistants/physicians) are trained on-site if required. Imaging data analyses (e.g. event-related/task-related, resting state fMRI, volumes of hippocampus or cholinergic nuclei) are conducted remotely in Berlin.
Drug challenge imaging paradigms (ketamine/nicotine) are also established. These paradigms allow testing of novel compounds whether they counteract or mimick the brain function resulting from the challenge drug.
Simultaneous fMRI/EEG experiments combining the sensitivity of EEG with spatial accuracy of MRI are possible, too.
Additional physiological measurements (ECG, skin conductance), tailored stimulation paradigms (e.g. cognitive, photic stimulation) can also be provided.
All electrophysiological or neuroimaging data are transferred securely from the study site to Pharmaimage in Berlin where data analyses are conducted.
The Pharmaimage hardware below can be delivered to the clinical study site (e.g. CRO)
- 4 complete EEG-recording BrainAmp DC 32-channel systems with 4 recording dongles, 4 laptops and 4 EasyCaps 32-channels
- 2 LED Photic-Light Stimulators with trigger box compatible to BrainAmp EEG recorders
Simultaneous fMRI/EEG investigations:
- 1 complete MR-compatible EEG-recording BrainAmp MR Plus system (32 channels) with 2 recording dongles, 2 laptops, 4 BrainCaps MR, 2 syncboxes
For stimulus delivery (auditory, visual), Presentation® software is used.
Endpoints/software standard packages:
- EEG (resting state/event-related): power spectra, coherence, time-frequency (e.g. gamma, theta oscillations, signal-to-noise ratio) incl. source analysis
- ERPs: P50, N100, P300, MMN incl. source analysis
- Additionally requested parameters are possible
Software: BrainVision Analyzer 2, BESA, sLORETA
Imaging endpoints (fMRI):
- Resting state, block design, event-related
- ROI, whole-brain voxelwise
- Functional connectivity analyses (seed-based, independent component analysis incl. default mode network analyses)
- Additionally requested parameters or MR sequences (e.g. perfusion) are possible
Software: Statistical Parametric Mapping (SPM12)
Imaging endpoints (structural MRI):
Sequences: MPRAGE, T2-SPACE, T2 (High-Res)
Whole-brain voxel-based morphometry, volume-based incl. subfield analyses (e.g. hippocampus, Ncl. Basalis Meynert), surface based analyses
Software: Freesurfer, DARTEL Toolbox
- Formal support with biomarker studies incl. clinical trial protocols, study proposals for industry, ethics applications
- Administration/coordination of projects
- Study set-up incl. on-site installation and maintenance of hardware/software for physiological/imaging measurements incl. on-site training of staff, logistics (storage/transport), contracting imaging facilities for data collection
- Clinical data management incl. standard operating procedures (SOPs), electronic case report forms (eCRFs), 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, electrophysiology/imaging data analyses
- Reporting (final reports, SAE reporting)
- Legal activities, negotiations, consortium agreements, intellectual property (IP) protection, contacting legal bodies (e.g. EMA)
- Dissemination activities, project web sites, public awareness of projects, organization of meetings and events, training activities