Medical Management Series
The medical monitor’s role in the development of the CRF and other plans
The Case Report Form (CRF)
Collaborative efforts between the medical monitor and data management colleagues are essential during the development of the CRF to institute a user friendly and dynamic CRF system that can achieve maximal accuracy for complete data capture and transfer, thereby facilitating effective study review and analysis. Due diligence towards the development of the CRF by this pooling of medical and data management expertise, along with clear and concise associated CRF completion guidelines, will lead to saving valuable resources throughout the course of study and also elevates the quality of data delivered.
The primary objective of designing the CRF is to facilitate gathering complete and accurate data in one place by making it as easy as possible to transcribe data from source documents without duplication of information. The CRF should be designed with the primary and secondary endpoints as the main goal of data collection.
The electronic case report form (eCRF), usually supplied by selected vendors, is customized to the study objectives and indication so that essential data for regular review and for final analysis is captured completely. The pre-coded answer options are incorporated to all applicable forms, keeping free text data fields to a minimum.
Standard coded forms of data collection are employed whenever possible to ensure consistency in data reporting and facilitate easier data extraction and interpretation during statistical analysis. The timely availability of accurate and complete data also facilitates medical decision making, especially when safety issues arise for any of the study subjects.
Medical input and review are instrumental for a wide range of plans, documents, and procedures that are not related to medical management, but to the other key documents that require careful review by the medical monitor.
The CRF Completion Guidelines
The objective of the CRF completion guidelines is to lay out the study-specific data entry guidelines within the CRF, by defining each datapoint and the associated instructions to be followed by the investigational site personnel while performing data entry during the study.
The Statistical Analysis Plan (SAP)
The SAP is authored by the study statistician and requires input and review from the medical monitor before approval. Contents of the SAP includes various patient populations, endpoint definitions and variables, safety and efficacy analyses criteria, and templates for Tables, Listings, and Figures (TLFs). The TLF templates are focused on during the review to assess the proscribed methods of presenting and evaluating the data-driven parameters that reflect the objectives of the study.
The Data Management Plan (DMP)
The data management plan is usually authored by the data manager and needs to be reviewed by the medical monitor to confirm the data collection practices, review plans, and data exchange procedures.
The DMP outlines the various procedures used to manage the study data and sets the specifications for collecting, organizing, validating, storing, backing up, and disseminating clinical data throughout the lifecycle of the study.
Forms, Templates, and Trackers
The forms and templates used for reporting significant study information, such as each SAE, pregnancy, overdose, and major protocol deviation (and their corresponding trackers) should be reviewed by the medical monitor prior to implementation in the study to ensure that all relevant information is completely and appropriately captured.
Laboratory Conversion Factors
Whenever local site laboratories are used for study-related laboratory assessments, it is advisable to establish a standardized conversion factor list to harmonize the lab results collected from various sites. This would facilitate medical review and interpretation of the lab data. This list can be prepared by the study statistician, followed by review and approval by the medical monitor.
Wherever feasible, the automatization of this conversion within the eCRF is recommended as this minimizes errors via manual handling of data, in addition to saving valuable time for the medical monitor, the data manager, and the biostatistician, during both the regular reviews and at the time of database lock.
DSMB and DMC Charters
The medical monitor should also review the applicable charters for the external Data and Safety Monitoring Board (DSMB) or Data Monitoring Committee (DMC). This review should ensure that all relevant information with regard to the required data and procedure for decision-making by those committees are reflected in the corresponding charter.
Further Reading
Mohamed El Malt, MD, PhD and Vijayanand Rajendran, MD. (2016) Medical management in clinical trials: A roadmap to operational excellence (Part 2-Study Setup). Journal for Clinical Studies 8(3): 20-23
Krishnankutty B (2014) Basics of case report form designing in clinical research, Perspect Clin Res 5(4): 159–166.
Lu Z, Su J (2010) Clinical data management: current status, challenges, and future directions from industry perspectives. Access J Clin Trials 2:93-105.
Medical Management in Clinical Trials:
A Roadmap to Operational Excellence
Europital is a full service CRO operating worldwide and has provided Medical Management for over 10 years. If you would like to receive a free copy of our book, Medical Management in Clinical Trials: A Roadmap to Operational Excellence, or you have a question regarding Medical Management in Clinical Trials please contact us. Your question will be answered by our Chief Medical Officer.
Dr. Mohamed El Malt, MD, PhD
Chief Medical Officer
T: +32 9331 6030
E: [email protected]
W: https://europital.com