The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has developed a guidance document dedicated to the use of electronic source data in clinical investigations related to medicines and medical devices.
The current version of the document was published by the FDA in September 2013. It is important to mention that FDA guidance documents are intended to provide an overview of the applicable regulatory requirements, as well as certain recommendations to be taken into consideration by the medical device manufacturers and other parties involved. These guidance documents do not introduce new rules or requirements, and the recommendations contained therein are non-binding in their nature. The Agency additionally emphasizes that an interested party may suggest an alternative approach to be applied, provided such an approach complies with the current regulatory requirements and has been discussed with the FDA before being implemented.
The present document provides recommendations regarding the capture, review, and retention of electronic source data in the context of FDA-regulated clinical investigations. The regulating authority acknowledges the increasing importance of collecting and processing data related to clinical investigations in an electronic format in order to improve and facilitate the procedures associated thereto while ensuring the reliability, quality, integrity, and traceability of data from electronic source to electronic regulatory submission.
In particular, the scope of the guidance covers the regulatory matters related to source data used for an electronic case report form (eCRF). In this regard, the guidance highlights the following aspects:
- Identification and specification of authorized source data originators,
- Creation of data element identifiers to facilitate examination of the audit trail by sponsors, FDA, and other authorized parties,
- Ways to capture source data into the eCFR using either manual or electronic methods,
- Clinical investigator(s) responsibilities with respect to reviewing and retaining electronic data,
- Use and description of computerized systems in clinical investigations.
At the same time, the questions related to electronic structures and standards related to electronic submissions are actually falling outside the scope of the present FDA guidance.
The Agency acknowledges that due to the increasing use of electronic data collection systems, the scope of data captured in an electronic format increases significantly. This includes digital medical images from medical devices or electronic health records maintained by healthcare institutions. According to the applicable regulation, an electronic record is defined as any combination of text, graphics, data, audio, pictorial, or other information represented in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system. The eCRF mentioned above constitutes an example of an electronic record and contains the information communicated to the sponsors under the appropriate clinical investigation protocol.
According to the guidance, source data includes the records of clinical findings, observations, or other activities conducted in the course of a clinical investigation. This information is vitally important for both the sponsor of a clinical trial and the regulating authority in order to be able to assess the safety and performance of a medical device subject to review.
It is stated that source data should be attributable, legible, contemporaneous, original, and accurate (ALCOA). Additionally, it should comply with any and all regulatory requirements for record-keeping. The authority expects that capturing source data electronically and transmitting it to the eCRF should:
- Eliminate unnecessary duplication of data,
- Reduce the possibility for transcription errors,
- Encourage entering source data during a subject’s visit, where appropriate,
- Eliminate transaction of source data prior to entry into an eCRF,
- Facilitate remote monitoring of data,
- Promote real-time access for data review,
- Facilitate the collection of accurate and complete data.
Electronic Source Data: Basics
As mentioned, electronic source data is data that has been initially recorded in electronic format. Thus, the initial process associated with electronic source data is data capture. When describing the data capture process, the FDA refers to the concept of a data element, which is the smallest unit of observation captured for a subject in a clinical investigation. For instance, this could include various measurements performed. The data element is closely related to the appropriate data originator (i.e., a source data derives from).
Data originators could include:
- Clinical investigator(s) and delegated clinical study staff,
- Clinical investigation subjects or their legally authorized representatives,
- Consulting services (e.g., a radiologist reporting on a computed tomography (CT) scan),
- Medical devices (e.g., electrocardiograph machine and other medical instruments such as a blood pressure machine),
- Electronic health records (EHRs),
- Automated laboratory reporting systems (e.g. from central laboratories),
- Other technology.
The authority states that the sponsor of a clinical trial should be responsible for preparing a complete list of data originators. If log-in credentials are required to assess the details required for the identification of data originators, the responsible entity shall also ensure all necessary security measures are in place in order to prevent unauthorized access. If the source data is automatically recorded in the eCRF, a system should be designed ensuring the information recorded will also contain the details necessary to identify the particular data originator the data in question derives from. For instance, in the case of data directly received from a medical device, the appropriate data element identifier should be created to identify the particular medical device.
As mentioned above, data could be entered into the eCRF in two ways:
According to the document, most data elements can be entered into the eCRF after being collected without additional delay. This form of direct entry reduces the risks associated with inaccurate transcription, which often exists in the case of paper media used at the intermediary step. If the process still requires the use of paper media, such elements should be duly stored in accordance with the applicable record-keeping requirements. Hence, the direct entering date into the eCRF will also reduce the regulatory burden for a sponsor related to ensuring compliance with record-keeping regulations. At the same time, the regulating authority is entitled to request a responsible entity to provide all documentation related to all the steps of the data collection process to verify the effectiveness of the procedures applied.
It is also important to mention that in the case of medical images, the data entered into the eCRF should constitute the clinical interpretation of such images and not the images themselves. Thus, the assessment of a specialist operating with such images will be a data element to be recorded. At the same time, the data originator will be a clinical investigator requesting such an assessment and not a specialist (e.g., radiologist) who processes the images.
In summary, the present FDA guidance covers the most important aspects related to the collection and processing of electronic source data. The approach described in the document is intended to facilitate the use of novel data capture technologies while ensuring the accuracy and reliability of data related to clinical trials.
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