Case Report Forms (CRFs), which are now more commonly known as Electronic Case Report Forms (eCRFs) given the industry's shift to digital technologies and move away from paper over the past two decades, are the most frequently used tools to capture clinical data of subjects enrolled on clinical trials at investigational sites.
The eCRF is created in line with the clinical protocol to facilitate in the accurate collection of data in line with the ALCOA principles.
The creation of the eCRF can be a complex procedure depending on the complexity and volume of data required. To help overcome these challenges there are key components that must occur before embarking on the design of the eCRF.
The first of these is selecting the right technology platform for your company. Once you have chosen your technology platform you must ensure that you are working on a validated system that has been through computer software validation (CSV).
Once you have a validated environment you can then start to build your eCRF and the validation data checks to help ensure that the clinical data is being captured and cleaned accurately.
The aim of the eCRF is to collect the study clinical data in line with the principles outlined by ALCOA. The below steps will help with this process:
Data requiring collection will be in adherence to the demands of the clinical protocol and require certain fields such as subject and clinical site identifiers to be present, to help meet this requirement there will be standards that can be utilized to help create eCRFs for different therapeutics areas and indications.
Once the eCRF has been created you need to ensure the data you are capturing is accurate. This ensures the critical information linked to adverse events, concomitant medications and other key elements can be applied accordingly to the end point analysis. Clear quality control steps should be established such as data collection and validation guidelines. These will cover all aspects of how to collect and manage the data, to also how to manage potential missing data, which should be backed up by robust quality gates to ensure that the methods mentioned are working correctly and in line with the rigorous regulatory requirements.
The data that we need to collect in line with the clinical protocol is critical, and how we capture that data is equally important. We can use an example from a dermatology clinical trial, imagine the subject is taking a topical treatment for a skin condition, and we have created a data field to confirm if the subject did in fact have a rash or reaction. This may appear that you have captured the requirements, however there may also be the need to capture the severity or size rash/reaction. This is where you must ensure that you have understood the relevance of the data that you are collecting and cleaning in line with the study protocol.
Historically traditional paper CRFs would require manual validation in case site staff made any data entry errors. To ensure that data collected is accurate in the modern era, eCRFs have built in validation to help manage data in order to meet the primary goal of collecting data which can be included as part of the drug submission process. Therefore eCRFs will require a set of robust electronic checks to validate the data. These can vary from simplistic range checks for blood pressure or cross functional/interrelated checks across numerous domains. These checks are essential for ensuring the data entered at the clinical site is as error free as possible and all inconsistencies have been reviewed and verified resulting in clean data.
The design of eCRFs must now consider external sources as the number of external data sources within the clinical trial environment has increased significantly over the past 5-10 years. This is where data integrations are pivotal to the deign of your eCRF and study. The eCRF must be designed with the validation requirements of the integration in mind along with and standards associated with these integrations.
The use of Application Programming Interfaces (API’s) are essential to ensuring real time transfer of the external data. Without these data would had to be loaded it in manually which would be cumbersome and restrict access to real time data. Similar to the initial design of the eCRF, the validation of these API’s is critical to ensure your data is accurate.
To safeguard your study from a technology perspective it is essential that you stay on top of all regulations pertaining to the FDA/EMEA and other regulatory bodies. You may want to heavily consider the option of risk-based monitoring and making sure your system, documentation and processes are adaptable and flexible to move with shifting regulations. Engage with your quality assurance (QA) group to make sure you have a mechanism in place to identify any changes that affect you; this relationship if also key with your technology vendor if you are utilizing the software as a service model.
The vast majority of clinical trials will operate with an eCRF as its basis for data capture/collection. It is essential that you spend the upfront time to implement strong processes for the initial eCRF build but also have a roadmap in mind for how you will develop and enhance this technology. For example, how it may interact in a decentralized environment or a study with 30,000 subjects and the difficulties that may come with a study of that size.
Ensuring that you stay current with all the innovations that the industry is looking to adopt, while maintaining regulatory compliance is something that you must always strive for. Finally, remember that the main goal of a well designed eCRF is to provide analysis worthy data to support drug to market submissions, and a well maintained eCRF built on a strong core of procedures is essential in making this happen.
Quanticate’s Clinical Data Management team are dedicated to ensuring high quality clinical data and have a wealth of experience in data capture, processing and collection tools. Our team offer flexible and customized solutions across various EDC platforms and are experts in CRF design. If you would like more information on how we can assist your clinical trial submit an RFI.