What is INFORM?
The aim of the INFORM project (INdividualized Therapy FOr Relapsed Malignancies in Childhood) is to biologically characterize tumors of pediatric patients suffering from a relapsed or a refractory high risk disease without available therapy. State-of-the art next-generation sequencing techniques are applied to get a “fingerprint” of each individual tumor. An expert panel of experienced pediatric oncologists, bioinformaticians, biologists and pharmacologists classifies and weighs the aberrations/targets found for each patient according to clinical relevance and uploads this information in a centralized database. The local treating physician has access to these data. It is up to his/her decision whether and how this information will be used for the further therapy.
Who is involved in INFORM?
- Pediatric Oncology of DKFZ, University Hospital and NCT Heidelberg
- The National Pediatric Entity specific Trial Center, giving advice
- The Central Pathology Laboratory in Heidelberg, performing quality control, DNA/RNA isolation and target verification
- The DKFZ Bioinformatics department, performing data analysis and interpretation
- The DKFZ Core Facility, performing Next Generation Sequencing (NGS)
- The NCT Trial Center responsible for the data management and project management
Which tool is suitable for the project?
The Electronic Data Capture system MARVIN from XClinical is in use. MARVIN is a web-based software, enabling data entry and data management for studies conducted in several centers. It supports all functions needed for the data management of clinical trials according to the current guidelines. It is used by the GPOH (Gesellschaft für Pädiatrische Onkologie und Hämatogie) for the documentation of their clinical trials and registry studies for several pediatric entities.
How is the INFORM registry organized?
Patients included in the registry pass through several processes. MARVIN is used for all activities within the INFORM project:
- Registration of the patient: Each treating physician in the local hospital registers the patient in the MARVIN database and enters demographic and anamnestic data.
- Shipment of samples: The local hospital enters information about the tumor samples to be sent to the Central Pathology Laboratory in Heidelberg. To omit mistakes a print out of the shipment form, compiled in MARVIN, must be added to the samples to be transferred. The Central Pathology Laboratory uses MARVIN for detailed documentation of the sample –processing.
- Analysis and interpretation of the samples: pediatric oncologists and bioinformaticians classify and discuss the results of the molecular analysis. They have access to the patient’s data in MARVIN to get additional information about the medical history of the patient.
- Communication of the results: The results (druggable targets) gained by molecular sequencing are then uploaded in MARVIN following the discussion in the INFORM tumor board. After a cross check and electronically signature the data are accessible to the treating physician. The report is published in a preliminary version. The report is finalized after a verification process (confirming the alterations with a validated method) of the Central Pathology Laboratory and the signature of a pathologist.
- Collection of follow-up data: After publication of the results the treating physician is fully responsible for the further therapy. The information, if targeted therapy was administered, how the physician got access to the medication, and how it was funded is also documented in MARVIN. A reason is asked if no targeted therapy was prescribed, (e.g. poor performance status of the patient, targeted drug not available). All data of the patient are collected up to 24 months after the samples arrived in Heidelberg, until death or until the patient is lost to follow-up, whichever occurs first. Information about responses, toxicities and additional oncological treatments is also collected.
What was/is the role of the data management of the NCT Trial Center within the INFORM project?
The data management of the NCT Trial Center collects requirements of all involved parties. It coordinates the process and prepares the setup of the MARVIN system. The INFORM registry was launched in January 2015. The NCT trial center is now also responsible for the user Management of INFORM and serves as helpdesk for questions regarding the INFORM registry in MARVIN. All uploaded data are checked for completeness and plausibility. If follow up data are not entered on time, a reminder, is send.
Which experiences are gained?
The integration of all processes of the INFORM project into one database is highly beneficial. MARVIN was mainly developed for the realization of clinical trials, but not for special requirements e.g. the organization of shipment of tumor samples. A few restrictions had to be accepted, e.g. the lay-out of the shipment forms. The major advantage is that all data of a patient are available in a unique system, minimizing paperwork and redundancy of data and leading to a quick data flow. The privacy is also guaranteed since MARVIN works according to the GCP (Good Clinical Practice) guidelines: only pseudonymized data are stored. All parties involved work very effective wishing to handle this project as fast as possible. In the meantime 3-4 children/week are being enrolled into the INFORM project. MARVIN is well accepted by all contributors.
For more information about the INFORM project, see the INFORM website».