Clinical monitoring provides a key method for ensuring that reliable clinical data, or clinical evidence, is collected during clinical trials for medical devices in order to support claims of safety and effectiveness.

What is clinical monitoring?

The clinical trial sponsor, who bears primary responsibility for the study, must ensure that all study-related activities are conducted in accordance with relevant regulations as well as clinical trial protocols. This is achieved through clinical monitoring.

During clinical monitoring the sponsor’s representative, the Clinical Research Associate (CRA), visits the investigational site, which can be a hospital or a private practice. During this visit the CRA ensures that the clinical study is conducted according to the Clinical Investigation Plan, and that data provided to the sponsor is comprehensive and accurate. In addition, the CRA reports observations made during these visits to the sponsor, who has to intervene correctively, if needed.

What does clinical monitoring mean for the investigation sites?

The investigational site is the place where any clinical monitoring requested by legislators and the sponsor must be carried out. However, a CRA visit may pose a significant extra burden for the investigational site.

Investigational site managers must take steps to prepare for CRA visits, including ensuring availability of necessary personnel during these visits; setting up CRA access to relevant records and study documentation; and ensuring that all study documentation is up to date.

The site’s day-to-day business such as patient care and emergency management, however, must not be allowed to suffer due to the CRA visit. In addition, many investigational sites conduct more than one study, leading to increased time pressure on site personnel.

Challenges for the Clinical Research Associate (CRA) role

To perform successful clinical monitoring at the investigational site, the CRA has to overcome several challenges.

• Quite often it is difficult to schedule an appointment with the investigational site because investigator and site personnel schedules are usually full;
• Once on site, a CRA may find that required documentation is unavailable, incomplete or stored at different locations;
• It is not uncommon that the CRA has to work in very confined spaces, which can make assessment of all the documentation needed quite difficult;
• The source data provided and the amount of clinical data collected, which needs to be verified within individual clinical studies, has an high impact on the CRA’s workload at the investigational site, with limited time to perform all needed monitoring activities;
•  Finally investigators as well as site personnel have limited availability to answer open questions.

Even at well-prepared sites, frequently the CRA faces limited functionality of tools and equipment used in a clinical trial. Other  challenges specific to individual clinical trials may also need to be addressed by the CRA.

Basis for successful monitoring

Open and respectful communication is fundamental to achieve a good relationship between the investigational site and the CRA, and ultimately to facilitate adequate clinical monitoring.

For example, the sponsor might request additional activities to support proper trial conduct and documentation, but which are often not done at the investigational site in question. Some of these trial activities might even be seen as superfluous or off-point by investigators and site personnel. Especially for these cases it is essential that the CRA discusses these concerns with the investigational site and explains the purpose of the planned activities. If the site’s concerns are well-founded or cannot be clarified, the CRA has to communicate the site’s concerns to trial management, which then has to determine the next course of action.

Furthermore, the CRA should always encourage the site to request additional information on processes not fully understood.

The better that all parties involved in the clinical trial process understand the activities and challenges involved, the more effective their collaboration will be.

Dietmar Falke is Head of Clinical Research at Emergo by UL.

Related medical device clinical research information:

• Medical device clinical trial management and monitoring
• Post-market clinical follow-up study support
• Webinar: Clinical data and post-market compliance under the EU MDR