Clinical exams in practice - monitors chat out of the sewing box

At medXteam, clinical data is our core focus. As a CRO, we not only conduct clinical trials (studies) with medical devices in accordance with the MDR and ISO 14155, but also offer support in the area of ​​monitoring required by GCP. This article explains what is important both on-site and during remote monitoring, and what potential pitfalls to avoid.

Abbreviations

GCP (Good Clinical Practice)

MDR Medical Device Regulation; EU Regulation 2017/745

Underlying regulations

EU Regulation 2017/745 (MDR)
General Data Protection Regulation (GDPR)
Medical Devices Implementation Act (MPDG)
ISO 14155

1 Introduction

Clinical trials are an essential part of medical research and development. They allow new therapies and medications to be tested for efficacy and safety before being made available to the general public. A crucial factor for the success of such studies is monitoring. Monitors play a central role in ensuring the integrity, safety, and reliability of the trials. In this blog post, we take a look behind the scenes and highlight the pitfalls that can arise when monitoring clinical trials. We will discuss the key points that monitors should consider to ensure the successful conduct of the studies.

2. What should be considered during on-site monitoring?

2.1 Communication

Effective communication is paramount for the success of any clinical trial. Monitors must ensure seamless communication between the sponsor, the study team, and other stakeholders, such as Contract Research Organizations (CROs). Regular meetings and progress reviews are essential to keep all parties informed and to identify and address potential issues early on.

Ensuring good communication:

• Regular meetings: These should take place both in person and virtually to ensure that all participants are informed and involved. In-person meetings allow for detailed discussions of complex topics and help avoid misunderstandings. Virtual meetings offer flexibility and enable more frequent communication, which is particularly beneficial in international studies.
• Progress reports: These reports should be detailed and prepared regularly to document the current status of the study and ensure transparency. They should include information on the study's progress, any problems encountered and their solutions, as well as planned next steps. Clear and concise reporting helps keep all stakeholders informed and maximizes the study's efficiency.

2.2 Preparation

Thorough preparation is key to the success of any monitoring activity. Monitors should ensure that all necessary steps are taken in advance to guarantee a smooth process. This begins with sending a confirmation letter in a timely manner and ensuring that all relevant people and data are available.

2.3 Sending a Confirmation Letter in a timely manner:

• Scheduling: It is important that all relevant members of the study team are present. The duration of the visit should be estimated and communicated in advance. This allows for efficient planning and ensures that all necessary information and resources are available.
• Access to patient and study data: Monitors must ensure they have access to all necessary data to perform their duties effectively. This includes both physical and electronic data. Seamless data access is crucial to avoid delays and ensure the accuracy of reviews.

2.4 Current status of the study:

• Relevant study documents: Monitors should ensure that all relevant documents, such as the study protocol and patient information, are up-to-date and meet the latest requirements. This also includes verifying that all documents are complete and filled out correctly. Thorough preparation helps to identify and resolve potential problems early on.

2.5 Ensuring Compliance

Compliance with regulations and legal requirements is of paramount importance for the integrity of a clinical trial. Monitors must ensure that the study is conducted in accordance with ICH-GCP guidelines and other relevant regulations. This includes verifying approvals, training, and the storage of study materials.

Compliance review:

• Approvals: Monitors should verify that the study has been approved by the relevant authorities and ethics committees. This is a crucial step to ensure that the study complies with legal requirements and is ethically sound.
• Training of the study team: It is important that the study team is properly trained and has access to all relevant documents. Thorough training ensures that the team understands and correctly implements the study requirements and protocols.
• Storage of study materials: All study documents should be stored securely, e.g., in locked cabinets. Test materials requiring refrigeration should be stored accordingly. Proper storage is crucial to ensure the integrity of the study materials and to minimize potential risks.

2.6 Patient safety

Patient safety is paramount in clinical trials. Monitors must ensure that all patient information is accurate and complete and that all safety precautions are followed. This includes reviewing patient information and documenting serious adverse events (SAEs).

Ensuring patient safety:

• Patient information: Monitors should verify that all patient information is correct and fully signed. A comparison with the screening and patient ID lists is essential. This helps confirm patient identity and ensures that all necessary consents are in place.
• Documentation of (S)AEs: All serious adverse events (SAEs) must be correctly documented and reported. Monitors should ensure that this documentation is complete. Thorough documentation is crucial to ensure patient safety and to identify and address potential risks early on.

2.7 Data accuracy and completeness

The accuracy and completeness of the data are crucial for the validity of the study results. Monitors must regularly check the entries in the clinical databases and ensure that the study data match the source data. This includes both remote monitoring and on-site source data verification.

Data accuracy verification:

• Remote monitoring: It is often possible to check entries in clinical databases remotely. This offers flexibility and allows for more frequent data review.
• Source Data Verification: During on-site monitoring, the study data should be compared with the source data. It is important to ensure that all deviations from the protocol are documented. A thorough review of the source data helps to guarantee the accuracy and completeness of the study data and to identify and correct potential errors early on.

3. Remote Monitoring in Practice:

Remote monitoring enables location-independent data control and regular verification of the quality of entries. The focus is on the completeness, traceability, and plausibility of the entered information. In practice, however, it is frequently observed that data is entered incompletely or late. This can compromise data integrity and delay analysis.

A functioning communication flow between the monitor and the study team is therefore essential – especially when questions arise or data gaps are identified. Unfortunately, it is frequently evident, particularly in remotely conducted activities, that information loss or delays occur. Clear responsibilities, timely responses to queries, and a structured data flow help to avoid these pitfalls.

• Remote monitoring can be a huge relief – but only if it is well integrated into the overall study process.

3.1 Monitoring in times of increasing digitalization

With advancing digitalization, the requirements for monitoring are also changing. Electronic documentation, e-consent procedures, and decentralized study formats present monitors with new challenges – but also offer opportunities. Stronger IT skills, a good understanding of digital workflows, and the ability to communicate effectively remotely are increasingly becoming core competencies.

3.2 Study Documentation

Complete and up-to-date documentation is essential for the success of a clinical trial. Monitors must ensure that all essential documents in the Investigator's File are complete and current. This includes regularly reviewing and updating the documents.

Review of study documentation:

• Essential documents: Monitors should regularly check that all necessary documents are present and up-to-date in the Investigators File. Thorough documentation is crucial to ensure the integrity of the study and to identify and resolve potential problems early on.

4. Pitfalls in monitoring

Despite careful planning and execution, various pitfalls can arise during the monitoring of clinical trials. These can jeopardize the integrity and success of the study if they are not identified and rectified in a timely manner.

This includes, for example, the following points:

Source Data:

Incomplete documentation: Very often, the documentation for monitoring visits is incomplete. Sometimes it is only obtained during the visit itself, which is very time-consuming. There have even been cases where patient files were outsourced without notification. This leads to significant delays and makes data verification more difficult.

Relevance of data: Protocols often use the term "relevant" in relation to prior medication, pre-existing conditions, etc. This definition of "relevant" is, of course, very broad and frequently leads to discussions with the principal investigators (PIs). A clear definition and communication of the relevant data is crucial to avoid misunderstandings.

Minor organizational issues: Problems often arise from seemingly minor details, such as initials and the evaluation of study examinations (lab work, ECG, etc.). This appears to be an organizational issue at some centers. The study nurse often has to chase after the doctors to get this actually quite simple task completed. Better organization and clear responsibilities could remedy this.

Organization at the study center / Study implementation:

Staff overload: Unfortunately, it is almost always the case that study coordinators and study nurses are overburdened. It seems that the principal investigators (PIs) do not fully grasp the complexity of a study. The same often applies to sub-investigators, who are "plumbed" on a study in addition to their other responsibilities. This leads to poor compliance and incomplete source data.

Lack of seriousness: Sometimes, as a monitor, you get the feeling that studies are "not taken seriously." This is something that can happen almost as an afterthought. Of course, this isn't true and leads to poor study execution and incomplete source data. Clear communication of the study's significance and requirements could help here.

Cumbersome and poor data systems:

Poorly designed e-CRF: One example is a study conducted with a very poorly designed e-CRF. The e-CRF is cumbersome and confusing for study nurses and CRAs. This often leads to unnecessary queries, frustrating both center staff and CRAs. Improved design and user-friendliness of the data systems could remedy this.

Query Resolution:

Lengthy duration: Solving queries typically takes too long. This is often due to the problems mentioned above. Faster and more efficient query solutions are crucial to avoid hindering the progress of the study.

5. Conclusion

Monitoring clinical trials is a demanding and responsible task. Monitors must consider a multitude of aspects to ensure the integrity, safety, and reliability of the studies. Effective communication, thorough preparation, adherence to regulations, ensuring patient safety, verifying data accuracy, and complete documentation are crucial. By paying attention to these points, monitors can contribute to the successful execution of clinical trials and the delivery of valid results.

6. How we can help you

We would be happy to support you in the development, implementation, and use of a database-driven system. As your CRO, we will also handle the complete data management and monitoring via the EDC system.

We support you throughout your entire project with your medical device, starting with a free initial consultation, help with the introduction of a QM system, study planning and execution, right up to technical documentation - always with primary reference to the clinical data on the product: from the beginning to the end.

Do you already have some initial questions?

You can get a free initial consultation here : free initial consultation