Obstacles, risks and problems in regulated clinical studies‍

Clinical investigations, clinical studies, performance studies or other scientific projects involving medical devices are complex endeavours that, like other things, such as building a bridge, belong in the hands of experienced specialists.

In addition to careful conceptualisation and planning, the implementation of complex projects requires constant risk management, whereby risks and problems are identified, controlled and monitored at an early stage.

Risk management of clinical studies - challenges for specialists

Before such a project can even begin, all individual elements and also the whole as the sum of all parts are evaluated carefully, iteratively and on the basis of the current data situation with regard to possible risks and problems. The safety, dignity and integrity of all participants in such a project can only be guaranteed if all laws and regulations, international guidelines, additional regulatory, technical and scientific aspects are strictly adhered to and such a project can only be successfully completed in the sense of the scientific question.

At the beginning of a project, a balance must be struck between the best possible preparation and the start of the project. All elements of risk management are relevant for this balancing act. MEDIACC has developed a standardised procedure for assigning clinical investigations, clinical studies, performance studies or other scientific projects to a specific risk class using a multidimensional process with multifactorial analysis.

We take a brief look at the cards and provide insights into the identification and possible management of these challenges based on our many years of experience in minimising risks and problems.

Possible problems and risks in clinical studies are:

(Important: understandably, this is not a comprehensive list, but rather an overview and example and does not present individual problems).

1. regulatory challenges

• Complexity of regulations: The identification, assignment of a clinical-scientific project and its subsequent compliance with MDR, IVDR, MPDG and ISO 14155:2021-05 as well as with digitally conducted clinical studies (DDCT-MED®) of the EMA/INS/GCP/856758/2018 and other binding international guidelines requires many years of practical experience and a deep understanding of the regulatory requirements. Errors in interpretation or implementation can lead to (serious) injuries or illnesses among study participants or study personnel, delays or even the - necessary - cancellation of a study.
• Changes in regulations: Regulatory requirements may change during the course of a study, requiring adjustments and additional resources. This also means that new, unforeseeable problems and situations can arise during the course of a project that make adjustments necessary. In the last few years, extensive legislative changes and new regulations have come into force, for the implementation of which good personnel are often not yet trained or educated. In addition, there are often no harmonised, let alone readable, interpretations in this area.

2. project management and coordination

• Multidisciplinary cooperation: Clinical studies (trials, performance studies or other scientific studies) require the cooperation of various specialist disciplines, clinics or other companies. A lack of clear coordination from the outset leads to communication problems and inefficient workflows. Different processes and standard operating procedures (SOPs), if they exist at all, must be harmonised and, if necessary, standardised. A common culture makes sense for the duration of the project and is often desired. However, this is often not taken into account and the lack of resources can lead to further problems or higher costs later on.
• Long-term planning: Studies that last one or more years after initial conception require long-term planning and flexible adaptation strategies in order to be able to react to unforeseen events. These challenges usually come from all areas of daily life and inevitably accumulate with longer duration or higher complexity due to factors that are included in the other points.

3. financial risks

• Budget overruns: Clinical studies are costly. A lack of knowledge and experience on the part of sponsors in the medical device sector makes it difficult to allocate an adequate budget despite consultation. Often, unrealistic expectations are placed on such a project or it is not planned carefully, and further possible savings requests then lead to high follow-up costs. In addition, unforeseen expenses arising from any other problem can quickly cause the budget to be exceeded. Careful financial planning, maintaining a sufficient buffer and regular reviews are essential.
• Funding bottlenecks: All studies can be affected by funding bottlenecks for various reasons, especially if economic conditions change, additional funds are required or a study runs faster than planned. Often, unpredictable waiting and processing times at authorities and ethics committees with resulting disruptions to processes also lead to problems. These often put a strain on good commercial planning, procedures and experience.

4 Data management and quality assurance

• Data integrity, availability, confidentiality and authenticity: The collection, processing and storage of study data must meet the highest quality standards in order to ensure the integrity, availability, confidentiality and authenticity of the data. Errors in data management can jeopardise the validity of the study results. For this reason, an information security management system is essential, see also here.
• Incomplete, incorrect or unusable data sets: Regular monitoring, quality assurance and audits are necessary to ensure that the study complies with regulatory requirements and that data quality is guaranteed. This effort alone ensures that a clinical study can ultimately be meaningful at all.

5 Participant recruitment and retention

• Recruitment difficulties: Recruiting a sufficient number of study participants can be a challenge, especially in the case of rare diseases or complex inclusion criteria. A fundamental distinction must be made between recruitment in centres with the help of clinical staff or, for example, via various channels on the Internet and then in specialised call centres (e.g. DTC-MED®). Comprehensive, trustworthy, easy-to-understand and transparent information in studies designed to be appealing to study participants determines whether people are willing to take part in a clinical study.
• Participant retention: The long-term retention of participants with prompt adherence to all visits, the correct and complete completion of questionnaires, adherence to all study requirements and endurance of all procedures that may be stressful and invasive for them is a central aspect. In addition to the use of motivational elements that do not interfere with the study, it is essential to provide good and personalised support. Of course, this also applies to clinical studies conducted entirely digitally. High dropout rates impair the validity of the entire study.

6 Ethics and consent

• Informed consent process: The process for obtaining informed consent must be transparent and comprehensive to ensure that participants are fully informed about the study and participate voluntarily.
• Ethics committees: Ethics committee approval is required and their requirements may vary, creating additional challenges for study authorisation. An integral part of a trial protocol submitted to the ethics committee for consultation is a risk analysis with risk-benefit-risk determination, whereby risks must be minimised to an acceptable level by all possible measures in order for the project to be approved at all.

7 Medical devices and indications

• Risk classes of medical devices: Products in higher risk classes are subject to stricter regulatory requirements and require more extensive clinical data and overall more extensive monitoring, documentation and risk minimisation measures. This increases the type and scope of the necessary work.
• Indications and special features of particular disease entities: clinical investigations or studies for products developed for very specific indications may have difficulties in recruiting sufficient numbers of participants. Disease entities that are frequently affected by serious adverse events, spontaneously changing disease courses or frequently changing concomitant therapies are more complex to design and more difficult to conduct. Occasionally, clinical trials are so stressful that they are very challenging.

8 Special features of digital clinical studies (DDCT-MED®)

• Digital and legal environment: not sufficiently regulated by modern laws and guidelines. The technical possibilities enable ethically sound, efficient, greater participation and significantly safer processes and working methods. However, laws and guidelines are not keeping pace with these developments to a sufficient extent. This leads to a lack of guidance for players in this field and also a lack of acceptance and consecutive rejection by authorities and commissions.
• Information security management system: Comprehensive measures and strict adherence to innovative processes are necessary to protect the security, integrity, availability, confidentiality and authenticity of the highly sensitive data collected and to ensure usability. The great opportunities that arise from the use of digital technologies, such as more efficient processes, scalability and improved data security, come at a high cost in an agile environment and require well-trained digital-savvy personnel to carry out these studies.

For a more comprehensive list, see here‍

8. scientific accuracy

• Study design, research question: Only answering the correct question with the appropriate study design in the right environment leads to credible, meaningful and reliable results that are later accepted by experts in authorities or guidelines. Thorough and careful knowledge combined with many years of experience are the key to success through relevance, feasibility, internal and external validity and credibility.
• Compliance with the requirements of the clinical investigation plan: Even if this central document contains all the essential information for implementation with the utmost care and in sufficient detail, all work steps must be consistently derived from it, trained and practised. Scientific credibility, methodological quality and regulatory requirements can only be met if all parties involved adhere to this throughout the entire process.

9 Black swans in the reality of clinical research

• The occurrence of situations or problems that have not yet arisen can be reduced, but not completely prevented, by using specialists with many years of experience.

Conclusion - consistent risk management as the basis for clinical studies

Conducting clinical studies is a complex endeavour that involves numerous challenges and risks. Careful planning, effective project and consistent risk management and compliance with regulatory requirements are crucial for success. Early identification and management of potential problems can ensure the integrity and validity of a trial and ultimately contribute to the improvement of medical care. These elements form the basis of an effective risk management system that helps all parties involved in a clinical study or trial to proactively identify, assess and manage risks in order to achieve the objectives with a successful trial.

‍

The basic rule for clinical investigations - as for any complex project - is that everything that can go wrong will go wrong and it is at the interface between project preparation and reality that it will be decided whether the project will (still) be a success.

For more information or an initial non-binding discussion , please contact us.