Challenges of Digitalizing the Work of CRAs

Clinical research associates (CRAs) spend most of their time working in study centers. But the first lockdown during the corona pandemic in particular affected their way of working and raised a question: Should the profession of CRAs be digitalized and thus performed remotely?

 

What responsibilities do CRAs have?

Clinical research associates (CRAs) or Clinical Monitors play a crucial role in clinical trials. During a study, they ensure compliance with the trial protocol, Good Clinical Practice (GCP) and the legal requirements for handling drugs and medical devices. To do this, they check source documents such as patient records or protocols on site at the study centers. This so-called source data verification ensures patient safety and data integrity.

CRAs are also the link between trial centers and sponsors or contract research organizations (CROs). A large part of their work consists of reporting to the project managers as well as informing investigators about their responsibilities during the clinical trial. CRAs must therefore be thoroughly familiar with the study project, know the laws and regulations and have a basic medical understanding in order to explain all procedures in a comprehensible manner.

 

How has the pandemic affected clinical monitoring?

The COVID-19 pandemic affected the working situation of many CRAs. Countless study centers closed during the first lockdown, on-site visits were canceled and clinical trials were delayed or even stopped. This shift created uncertainty for many freelance CRAs. As a result, some decided to take up permanent employment, e.g. with pharmaceutical companies, during the pandemic.

The pandemic also posed challenges for the industry: How should clinical trials be conducted during the lockdown while maintaining patient safety and data integrity? In response, the Federal Institute for Drugs and Medical Devices (BfArM) and the Paul Ehrlich Institute (PEI) published supplementary recommendations to the "Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) Pandemic" published by the European Union¹.

They proposed the following measures for source data verification:

• Cancellation or postponement of already planned monitoring visits

• Extending the intervals between on-site visits

• Switching to study centers that are not or less affected by the pandemic

• Provision of copies of the source documents for the monitors by the study centers, personal information of the patients is made anonymous

• Direct and controlled remote access for monitors to source data management systems

• Passive access for monitors to source data through live image transmission with the trial center

 

What is remote monitoring and what advantages does it offer?

Remote monitoring refers to the process of monitoring and reviewing study data and other relevant study activities remotely. Electronic systems and technologies enable CRAs to perform source data verification (SDV) and source data reviews (SDR) remotely - SDV and SDR become rSDV and rSDR (r = remote).

This approach utilizes various digital tools and platforms to facilitate access to study data and enable efficient verification of source data, protocol compliance and other study activities. These include web-based study management systems, electronic health records and communication platforms for sharing information with study staff.

Remote monitoring enables real-time monitoring of study data, resulting in faster identification of potential problems or inconsistencies. By using remote monitoring, CRAs can also save travel costs and time by not having to regularly travel to study sites to review data.

 

Obstacles on the way to digitalizing clinical monitoring

The corona pandemic clearly showed the limits of existing structures and digitalization for clinical monitoring. Many saw this as a wake-up call and an opportunity for clinical research.

However, there have yet to be any major changes in clinical monitoring. Although the ever-increasing digitization of source data offers a prerequisite for rSDV, inconsistent or even absent legal requirements make the approval of an rSDV procedure and its establishment nearly impossible. This was also evident during the pandemic:

• Remote access to source documents only took place in justified exceptional cases and only to the extent absolutely necessary.

• Only the most crucial information was checked digitally. In addition, anonymized or pseudonymized documents cannot be considered source documents. Documents that were subject to a remote review often had to be reviewed again on site.

• In most cases, on-site visits remained in a safe working environment, as there was more confidence in dealing with the coronavirus after the first lockdown due to distancing and hygiene rules.

In addition, many study centers lack the technical infrastructure that would guarantee protection against unauthorized access by third parties. And even in those centers where it does exist, there is often a lack of experience in dealing with remote monitoring, so that training and errors in the first projects can initially lead to higher time and cost expenditure.

It takes several years of practical application and experience to clarify responsibilities, refine work processes and draw up laws and regulations. For remote monitoring at an international level, harmonized security and confidentiality standards would also need to be established between the data protection authorities of the various countries.

 

Should the work of CRAs be digitalized?

Many people question whether the work of clinical monitors should be digitized. What points speak against digital clinical monitoring?

• Training and coaching of the investigator team is easier for many on site and in person

• Study centers are often involved in several projects at the same time; on-site verification of proper implementation gives both sides more security

• Little experience with digital technologies makes additional on-site training necessary for the investigator team

On the other hand, if the study center already has experience and the necessary infrastructure, video calls for digital initiation visits or coaching of the investigator team from a distance would be a viable option.

Due to the individuality of each study, it is important to find a balance between remote and on-site monitoring in the various projects. The monitoring concept is determined according to the risk profile of a clinical trial. A digital approach to clinical monitoring should only be pursued if adequate data protection is guaranteed and the benefits justify any risks. In most cases, however, a risk-based monitoring that combines on-site and remote approaches can be more efficient than a purely on-site concept.

Whichever method the sponsor chooses, the most important thing remains: for efficient clinical monitoring, the strategy should be described in detail and comprehensibly in the trial and monitoring plan. The methods, technologies used and responsibilities of all parties involved should be understandable for the competent authorities and commissions as well as for the investigator team and CRAs.

 

¹https://www.bfarm.de/DE/Arzneimittel/Klinische-Pruefung/KPs_bei_COVID-19.html