Our Services

• Selection /discussion of best-possible study designs for specific questions and clinical research problems
• Systematic reviews
• Writing of / support with study protocols in keeping with ICH GCP standards
• Support with / complete compilation, submission and defense of applications (competent regulatory authorities, ethics committees)
• Support with / complete compilation, submission and defense of grant applications (DFG, Federal Ministry of Education and Research, etc.)
• Study registration at clincaltrials.gov or drks.de 
• Writing of final reports and publications

• Clinical investigator(s) / Coordinating Investigator
• Coordination of study sites and clinical investigators 
• Preparation of TMF, ISF
• Data management
• Preparation of CRFs (Case Record Form)
• Development of FDA- und GCP-compliant, web-based study data base
• Support with / writing of data management plan 
• Complete study monitoring / query management
• Pharmacovigilance
• Preparation of safety reports for competent regulatory authorities, ethics committees, and Data Safety Monitoring Boards 
• Participation in Data Safety Monitoring Boards

• Statistical analyses as part of clinical studies 
• Preparation of biometric interim and final reports
• Participation in publications

In order to optimize and assure the quality of clinical studies, competent organization in all aspects is crucial. KKS / ZKS can take over the complete management of clinical trials.

Study planning and preparation:

• Consultation
• Evidence-based study planning (e.g. comprehensive literature search)
• Biometric planning (design, case number, endpoint definition)
• Support with acquisition of third-party funds (public funding, industry) if applicable
• Contracting
• Cost Calculation
• Feasibility analysis
• Organization of the application for approval by the competent ethics committees 
• Obtaining the approval from the competent higher federal authority
• Report to the relevant (local) authorities
• Further correspondence with the ethics committees and authorities even after completion of the studies
• Support with the conclusion of the subject insurance
• Negotiations with sub-service providers: (pharmacies, radiology, contract offices, third-party funds department, pathology, laboratory)

Creation, ongoing update and coordination of study documents:

• Case Report Forms (CRFs)
• Study protocol
• Information and Consent Forms (Patient Informed Consent Form)
• Trial Master File (TMF) and Investigator Site File (ISF)
• Drug Accountability, Signature Logs etc.
• as well as further study-specific documents (e.g. subject insurance)

Management of all contracts in coordination with the involved bodies

Other services:

• Continuous monitoring of study duration, milestones and budget
• Invoicing with third parties
• Monitoring of all processes in accordance with study protocol and SOP specifications
• Implementation of requirements of quality management (audits)
• Logistics of study material, study medication or medical devices
• Coordination of multi-center studies
• Organization of investigator meetings
• Preparation and distribution of logs and status reports
• Conception of newsletters informing participating centers and physicians about the current study status
   

The KKS / ZKS can undertake the biometric study planning and evaluation of prospective clinical studies in all indications.
The involvement of qualified biometrics at the earliest possible stage in study planning is decisive for high-quality studies and valid study results. The performance of statistical analysis in interim and final analyzes by qualified biometrics is also essential for valid study results. The evaluations are performed according to statistical analysis plans, which are already designed at the time of study planning.
Biometric study planning and evaluation includes the following aspects:

Study planning

• Design of statistical study design
• Preparation of a statistical analysis plan
• Advice on the choice of primary and secondary endpoints
• Case number estimation
• Calculation of the required number of patients
• Selection of the evaluation methodology
• Planning of interim analyzes
• Creation of biometric parts of study protocols
• Advice on design of electronic data collection (eCRF)
• Generation of randomization code

Study analysis

• Programming and validation of planned statistical analyzes
• Creation of tables, graphics, listings to present the results
• Proper interpretation of the results
• Creation of biometric reports
• Participation in the preparation of integrated clinical statistical study reports
• Participation in the presentation of the results at scientific congresses
• Participation in the publication in scientific journals

Data management is located at the interface between investigators, clinical monitoring and biometrics and works closely with other areas of the KKS / ZKS, such as project management, IT and quality assurance. The remit of data management extends from study planning to preparation of the data for statistical analysis. When carrying out data management, ICH GCP Guideline (ICH E6 (R2)) must be followed as well as other national laws and international guidelines. To ensure the validity of data from studies or other clinical research projects, quality management and quality control measures have been implemented in data management.
 

Study planning

• Review of the study protocol
• Design and creation of electronic questionnaires (electronic case report forms (eCRF))
• Creation of a data management manual, data validation plan and user manual for data entry
• Programming of data validation rules for query generation
• Quality assurance of the study database, study tools and programs through validation
• eCRF training

Study conduct and study closure

• Central patient registration and randomization
• Quality assurance of collected (completeness, consistency, plausibility and compliance with GCP and study protocol)
• Central data monitoring and query management in collaboration with clinical monitoring
• Upload of externally collected data (e.g. data from central laboratory)
• Creation of status overviews and reports (e.g. patient recruitment, documentation, queries, etc.)
• Coding of adverse events and drugs 
• Archiving and closure of database, transfer of study data to biometrics and client

The continuous monitoring of clinical trials is performed by the clinical monitor. The monitor acts also on-site - at study centers - and as the link between the sponsor and the investigator. His main tasks are the supervision of investigators, the verification of collected study data and the assurance of compliance with current guidelines and laws of all staff involved in the study at site level. As part of their work, the monitors contribute significantly to the implementation of the ICH GCP guidelines in conducting clinical trials.
The scope of the monitoring includes among others:

• Support by the selection of suitable study centers
• Monitoring visits to initiate study centers
• Training at study centers
• Provision of study documents 
• On-site monitor visits (interim and final visits)
• "Hotline" for inquiries from study centers
• Preparation of status reports
• Assurance of timely forwarding of essential documents

In order to optimize and ensure the quality of the conduct of clinical studies, study nurses from KKS / ZKS support the work of the responsible investigators at some locations. The investigator team and the study nurses are qualified through certified courses and work in accordance with national and international clinical trial regulations, i.a. Good Clinical Practice (ICH-GCP) and other legal requirements.

KKS / ZKS offer support for vigilance tasks in clinical trials in accordance with the applicable legal requirements.
Exemplary services can be offered in the field of pharmacovigilance in clinical trials with medicinal products:

• Advice on the planning and implementation of pharmacovigilance
• Creation of pharmacovigilance-specific documents 
• Electronic registration of SAEs in a specific database 
• SAE management (including tracking, query management) 
• Evaluation and reporting of suspected unexpected serious adverse reactions (SUSARs) to the authorities (electronic SUSAR reporting via a pharmacovigilance database), ethics committees, Data Safety Monitoring Boards (DSMB) and investigators involved 
• Matching of clinical database and pharmacovigilance database (SAE Reconciliation)  Preparation of annual Development Safety Update Reports (DSURs) and other periodic reports/listings 
• Support of the Data Safety Monitoring Boards (DSMB)

In general the IT infrastructures that can be used to prepare, execute and evaluate all types of clinical trials is provided by the IT Development and IT Support.
These infrastructures may include the following solutions to assist in clinical trial work:

• Operation of electronic data management systems for electronic data collection and processing
• Assurance of IT security
• Validation of GCP-relevant system landscape
• Operation of systems for statistical analysis
• Operation of systems for medical coding and pharmacovigilance
• Creation and maintenance of study websites
• Implementation and operation of tools to support processes in clinical trials (administration, cost calculation, time recording, controlling)

Furthermore, the IT teams form the interface with the respective university computer center.

A quality management and assurance system is essential for the adherence to and implementation of the mentioned range of services.
In accordance with the requirements of the ICH Guideline E6 "Good Clinical Practice", the KKS / ZKS have established a standardized, risk-based quality management system, which is continuously being improved and further developed. The employees of the quality management monitor planning, execution and evaluation of the clinical trials in accordance with the respective QM system.
Most quality assurance systems are based on standard operating procedures. SOPs are important quality management tools in clinical trials. One of the first tasks of the KKS-Network was to develop harmonised SOP templates on which the current SOPs of the individual centres are still based today.
As a clinical research service institution, KKS / ZKS are subject to regular monitoring by the competent authorities within the framework of inspections. 
In addition, monitoring by cooperation partners and clients takes place within the framework of vendor audits.

The conduct of clinical studies is becoming increasingly complex. Ensuring quality in clinical trials requires expertise and compliance with international standards. The courses offered by KKS / ZKS provide knowledge of the principles and methodology of clinical studies and introduce current guidelines and organizational aspects of the implementation. The topics range from planning the study, legal issues, adhering to Good Clinical Practice (ICH-GCP), creating study documents, to quality control and data management. The courses are curriculum based and certified.