At medXteam, the focus is on clinical data. In this context, as CRO we not only carry out clinical trials with medical devices in accordance with MDR and ISO 14155, but also offer all other options and forms of data collection. No matter which form of data collection you choose: The foundation is solid planning but also dealing with the various options and the respective requirements. A good example of the fact that with the MDR requirements are not only becoming more stringent and increasing is what is presented in this blog post: namely the changed qualification requirements for study staff and the consequences that result from this, which in certain cases even lead to one lead to relief.

Abbreviations

MDR Medical Device Regulation; EU Regulation 2017/745

MPDG Medical Devices Implementation Act

MPAnpG Medical Devices Adaptation Act

MPG Medical Devices Act

LKP Head of Clinical Trials

Underlying regulations

EU Regulation 2017/745 (MDR)
Medical Devices Implementation Act (MPDG)

1 Introduction

The rapid development in the medical technology industry entails constant adaptation and further development of the legal framework. In particular, the introduction of EU Regulation 2017/745, better known as the Medical Device Regulation (MDR), and the national legislation derived from it in Germany through the Medical Device Adaptation Act (MPAnpG) and the Medical Device Implementation Act (MPDG) have profound effects on planning and Conducting clinical trials.

The consideration of whether to opt for a monocentric or a multicentric design for clinical trials in accordance with Articles 62, 74 or 82 of the MDR plays a central role. Although the MDR and the MPDG entail stricter regulation in many areas, there are also significant simplifications in certain aspects. Such facilitation particularly affects the design of clinical trials. For example, the approval hurdles are significantly lower for monocentric studies. But what exactly are the advantages they offer, and what challenges and requirements do they pose, particularly in terms of the qualifications of the required study staff?

This blog post sheds light on the critical differences and associated regulatory and organizational considerations in the context of clinical trial design. Particular attention will also be paid to the role and requirements of study staff, which are clearly defined and brought into focus by the new legislation.

2. Single-center study vs. multicenter study

The design of a clinical trial depends on various factors, including the type of medical device, the objective of the study and the available resources. Depending on which design is chosen, there are different requirements for the study staff and the organization of the study.

The choice of clinical trial design, whether monocenter or multicenter, has profound implications for implementation, budget, scheduling, and data quality. 

2.1 Monocentric study

A single-center study is a clinical trial conducted at a single center or location. The study team usually consists of an investigator. However, for larger studies at one location or when different departments are involved, the team can also consist of several investigators. In this case, one of the investigators will be appointed as the principal investigator, who will be responsible for the overall coordination of the study. In addition, other participants such as study nurses, who are responsible for patient care and data collection, may be part of the study team.

Advantages of single-center studies:

• Simplicity: Since only one location is involved, the processes are typically less complex.
• Cost: Because fewer staff and resources are required, costs are typically lower.
• Control: The investigator or principal investigator has direct oversight and control over all aspects of the study.
• Faster communication: With a smaller team and only one location, agreements and decision-making processes are usually faster and more direct.

However, this simplicity and cost savings may be offset by the limited patient pool and geographic limitation. There is a risk that the results will not be universal or that it will be difficult to recruit enough patients for the study. If many patients are required according to statistical sample size planning, this form of design cannot be chosen as it cannot then be implemented in a reasonable time frame.

2.2 Multicenter study

Multicenter studies are clinical trials that are conducted at multiple locations or centers. In such studies, the study team in each center typically consists of an investigator, a study nurse and, if necessary, other professionals involved. Despite the multiple center structure, the process in each center remains similar to that of monocentric studies. The difference is that such a study design requires a principal investigator site. This main investigation center provides the head of the clinical trial (LKP), who coordinates the entire study across all centers.

Advantages of multicenter studies:

• Patient pool: The participation of several centers enables access to a larger and heterogeneous patient population.
• Data base: The design allows for broader and more representative data collection as it comes from different populations and locations. The scientific validity also increases due to the involvement of several examiners and the external validity increases.
• Comparability: Direct comparisons and consistency checks can be carried out through different locations.

However, these advantages may be offset by increased costs, greater organizational effort and coordination requirements between centers.

• Core factors: costs, effort and study staff:
• Cost: Multicenter studies can be more expensive than single-center studies due to their size and complexity.
• Effort: The organizational effort for multicenter studies is significantly higher, especially with regard to the coordination of patient recruitment, data management and communication between the centers.

Study staff: This is one of the most critical aspects. The challenge is to ensure consistent protocols and practices across all centers. This particular sticking point and the associated considerations and strategies are discussed in detail below.

3. Development of qualification requirements for examiners: From MPG to MPAnpG

As the regulatory landscape for medical devices in Germany has evolved, the qualification requirements for people involved in conducting clinical trials have also changed.

3.1 Under the Medical Devices Act (MPG)

According to Section 20 of the Medical Devices Act (MPG), clinical trials had to meet certain requirements. A crucial aspect was that they had to be carried out in an appropriate facility and led by an "appropriately qualified examiner". The MPG gave clear requirements for the qualifications of this examiner: In addition to medical or dental training, he had to be able to demonstrate at least two years of experience in the clinical testing of medical devices.

This requirement applied to all auditors, regardless of whether they were auditors, main auditors or LKP.

3.2 Transition to the Medical Devices Adaptation Act (MPAnpG or MDPG)

With the introduction of the Medical Devices Adaptation Act, the requirements for the qualifications of study staff were specified and expanded.

Since there was no role definition in the MPG and this had to be taken from ISO 14155 before the MPDG came into force, the MPDG now defines at least the roles of main auditor and LKP in § 3 (5,6):

"According to Section 30 of the MDPG, there are clear distinctions between the investigator, the main investigator and the head of a clinical trial. While the principal investigator and investigator continue to play important roles in the clinical trial, the specific qualification of at least two years of experience in the clinical trial of medical devices is now explicitly assigned to the head of a clinical trial or other clinical trial. "

This means that, compared to the previous MPG, the qualification requirements have become more specific and are more specifically tailored to the different roles in the clinical trial process. This shows an increased awareness of the need for clearly defined and strict qualification criteria to ensure the quality and integrity of clinical trials. It also reflects the growing complexity and importance of clinical trials in the process of medical device development and approval.

3.3 Consequences and effects

The ongoing adaptation and refinement of the legal framework has a significant impact on how clinical trials of medical devices are carried out. In particular, the Medical Devices Implementation Act (MPDG) has brought about some fundamental changes that influence the organization and approval of clinical trials.

One such significant change made in the MPDG thus concerns the roles and qualifications of those involved in clinical trials. According to Section 30 of the MDPG, a distinction is now made between the investigator, the main investigator and the head of a clinical trial. It is crucial to recognize that the minimum two years of experience in the clinical testing of medical devices for any investigator, previously required in the MPG, is now only explicitly assigned to the head of a clinical trial or other clinical trial, even in a single-center study. This requirement therefore only applies to multicenter studies.

While auditors and principal auditors continue to play important roles in the process, the specific qualification requirement now applies only to the audit manager.

For single-center studies, this means that the approval process for a clinical trial is significantly simplified. By focusing the two-year experience requirement on the head of a clinical trial and not on each investigator involved, the hurdle for conducting such studies is significantly reduced, as the ethics committee no longer expects this requirement for the investigator and therefore no longer examines it.

4. Conclusion

The conclusion from these observations is evident: the choice between monocenter and multicenter design has a significant impact on the approval, costs, organizational effort and requirements for study staff of a clinical trial. Correct planning and consideration of all relevant aspects are therefore essential for the success of the project. It is crucial to think intensively about the requirements and select the appropriate personnel for the respective type of study.  

The choice between monocenter and multicenter design has significant implications for the approval, cost, effort, and study staff requirements of a clinical trial. Correct planning and consideration of all relevant aspects are therefore essential for the success of the project. It is crucial to think intensively about the requirements and select the appropriate personnel for the respective type of study.

This aspect in particular has a significant influence on the conduct of clinical trials. The Medical Devices Implementation Act (MPDG) has introduced significant changes, particularly with regard to the roles and qualifications of those involved in a clinical trial.

Section 30 of the MDPG and the associated clear distinction between the investigator, the main investigator and the head of a clinical trial have significantly simplified the approval process for monocentric studies. The specification that at least two years of experience in the clinical testing of medical devices is now explicitly attributed to the head of a clinical trial opens up new possibilities in the design of clinical trials and lowers the hurdles to their implementation.

A deeper understanding of the legal requirements and careful selection of the appropriate personnel for the specific type of study are essential key aspects. It is of central importance to deal intensively with these requirements and to plan accordingly.

However, this only applies to clinical trials carried out within the framework of the MDR (Articles 62, 74 and 82). All other clinical trials (e.g. PMCF studies within the intended purpose of the medical device and without stressful examinations remain unaffected. This means that there are no requirements of this type for the LKP in multicenter studies.

5. What we can do for you

If a clinical trial is to be carried out, basic safety and performance requirements must first be met and essential technical documentation must therefore be created.

In addition, all medical device manufacturers require a QMS, including when developing Class I products.

The clinical trial leads to the clinical evaluation, which in turn forms the basis for PMCF activities (including a PMCF study).

We therefore support you throughout your entire project with your medical device with primary reference to the clinical data on the product: from start to finish.

6. How we can help you

At medXteam we clarify whether and if so which clinical trial needs to be carried out under what conditions and according to what requirements during the pre-study phase: In 3 steps we determine the correct and cost-effective strategy in relation to the clinical trial required in your case Data collection.

We also provide support in the areas of development strategy, technical documentation and quality management.

Do you already have some initial questions?

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

At medXteam, the focus is on clinical data. We collect this through systematic literature searches or directly with the medical device as part of clinical trials. We already explained in an article last year how the literature search represents an interface and how the data can be collected digitally. We also act as quality management representatives for our customers and build quality management systems in this context. These can also be digitized, which means that our offering takes us one step further when it comes to digitization and automation.

Abbreviations

MDR Medical Device Regulation; EU Regulation 2017/745

eCRF electronic case report form

EDC Electronic Data Capture

Underlying regulations

EU Regulation 2017/745 (MDR)
Medical Devices Implementation Act (MPDG)

1 Introduction

The medical technology industry has undergone significant digital transformation in recent years. Technologies such as artificial intelligence and the Internet of Things have become driving forces that are revolutionizing the way we develop and use medical devices. This digital revolution also has an impact on the area of ​​quality management, especially in the context of medical devices.

Every manufacturer of medical devices is legally obliged to implement, live and continuously maintain a compliant quality management system (QMS) in accordance with the requirements of EU Regulation 2017/745 (Medical Device Regulation, MDR) and ISO 13485. This QMS forms a crucial pillar to ensure both the safety and effectiveness of the products as well as compliance and adequate implementation of regulatory requirements and legal requirements.

In this digital era, designing a digital technology environment from our quality management system provides the opportunity to drive innovation, efficiency and sustainable improvements to workflows, including optimized efficiency, increased product quality and robust documentation and tracking capabilities.

2. Digitization of literature searches and clinical trials

We successfully implemented the integration of digital technologies over two years ago in the area of ​​literature searches for clinical assessment but also for clinical trials in accordance with Articles 62, 74 or 82 of the MDR.

Digital literature search enables thorough and efficient collection of relevant clinical data necessary to assess the safety and performance of a medical device.

Fig. 1 Literature search in the center

The literature search can sometimes be very time-consuming and tedious. As part of the digitization of the technical documentation, the clinical assessment and therefore in particular the literature search were digitized and the process was automated.

Since medXteam focuses on clinical data, the focus is on literature searches. We implemented this process through our partner avasis as a certified Smart Expert Partner of Siemens Digital Industries Software in the areas of Teamcenter and Polarion.

Digitalization of clinical trials improves data collection, analysis and reporting, ultimately leading to more reliable results and more efficient processes. Through our EDC system from MaganaMed, we offer exactly that by implementing electronic CRFs (eCRF).

With the close integration of the clinical trial (whether for approval, as part of the clinical evaluation, for the collection of product data after it has been placed on the market or as part of a DiGA study) with the process of literature search and thus with the clinical evaluation, digitalization is also essential Clinical trial documents such as: b.

• Clinical trial plan (Appendix XV, Chapter II, Section 3 of the MDR)
• Clinical Investigator's Manual (Appendix XV, Chapter II, Section 2 of the MDR)
• preclinical assessment

possible.

These digital approaches have proven to be extremely valuable and set new standards for transparency, efficiency and accuracy. However, the influence of digitalization goes far beyond these areas. In a regulated environment such as that of medical technology, digitalization offers the opportunity to improve many aspects of quality management.

3. Digitalization in quality management

3.1 Advantages and necessity of digitizing quality management

Digital literature searches and clinical testing are important components of today's research and development process in medical technology. They improve the efficiency and quality of data collection, analysis and reporting. However, digitalization goes even further and has a significant influence on quality management.

It also brings with it numerous advantages: It improves the efficiency of processes, thereby increasing the quality of medical devices and enabling better traceability and documentation. It also enables more efficient management of QMS. This is crucial to comply with ISO 13485 and MDR requirements.

A digitized QMS enables seamless and centralized document management, more efficient and transparent auditing, and improved risk and process management. All of these aspects are of crucial importance in order to ensure not only the requirements but also the high quality of the medical products.

3.2 orgavision and the digitalization of quality management

In the rapidly changing world of medical technology, digitalization of quality management is more than just an option - it is a necessity. With the right tools, medical device manufacturers can make their processes more efficient, improve compliance and ultimately deliver better products for patients.

An example of a tool for digitizing quality management is orgavision . This tool offers a wide range of features that contribute to the digitalization of quality management systems.

With orgavision, companies can digitize and automate their quality management, leading to improved compliance and ultimately higher quality medical products.

orgavision is a good example of a tool that supports the digitalization of quality management systems. The functions of orgavision range from integrated digital document management to a comprehensive event management system (e.g. customer feedback, complaints, corrective and preventive measures).

Orgavision's automation function is particularly noteworthy. An example of this is the automatic update of process names. If the name of a process is changed in orgavision, this name is automatically updated when explicitly linked in all documents in which the process is mentioned. This avoids inconsistencies and misinformation and improves the accuracy and reliability of documentation.

orgavision also offers efficient audit management. Audits can be planned, conducted and monitored, and the results can be easily integrated into the system and analyzed. This facilitates compliance with regulatory requirements and improves the efficiency of the auditing process.

orgavision is therefore a groundbreaking software solution that was developed specifically for the digitization and automation of the quality management system (QMS) in the medical sector. It offers a variety of functions that support the entire QMS process and help increase efficiency. Additional features of orgavision are highlighted below:

Change management: orgavision enables efficient change management by offering a structured process for processing change requests, approvals and implementations. By digitizing this process, changes are quickly captured, tracked and documented, improving control and efficiency.

Complaint management: The tool offers functions for effectively handling customer complaints. This includes collecting, categorizing and handling complaints as well as tracking corrective actions. By digitizing complaint management, companies can respond more quickly to customer feedback, process complaints efficiently and ensure continuous improvement in product quality.

Training: With the help of orgavision, training processes can be efficiently digitized and thus optimized. The training matrix provides a comprehensive overview of the training requirements and the current training status of all employees. You can include individual training elements, such as: B. Set training events, courses or webinars for different employees or employee groups.

Let us now present this example in more detail:

Fig. 2 Orgavision training matrix

Each training can be linked to corresponding competencies, departments or defined roles. This makes it possible to identify exactly which training courses are required for which employees and in which cycle. This systematic and structured approach ensures that no employee misses out on needed training and that all employees always have the necessary knowledge and skills.

orgavision also offers the option of linking and managing training certificates directly in the system. After training has been completed, relevant evidence, such as certificates or confirmations, can be uploaded directly to the system and assigned to the relevant employees.

This evidence can then be accessed at any time and can be exported from the system if necessary. Linking training records not only makes it easier to document and manage training courses, but also to check the training status of individual employees or entire teams.

4. Conclusion

The overall advantages of digitalization are obvious:

• more efficient work
• Target-oriented use of capacities
• Elimination of inefficiencies in the creation, maintenance and change of contents of technical documentation, clinical assessment and literature searches as well as in the area of ​​quality management
• Avoidance of redundantly managed information/documents
• long-term reduction in care costs

By using digital tools like orgavision, companies can improve their quality management processes while ensuring compliance.

The above-mentioned functions of orgavision enable comprehensive digitalization and automation of the QMS. This results in improved efficiency, accuracy and compliance. The central management of documents, the automation of workflows and processes as well as the digitalization of change management, complaint management and supplier management help to optimize quality management processes and meet the requirements of ISO 13485 and MDR.

In summary, it can be said that digitalization in quality management creates simplifications in the course of digitalization, solves redundancies and is therefore an absolute necessity in the long term. With the right tools and strategies, digitizing quality management can lead to more efficient processes, better compliance and ultimately higher quality products.

5. What we can do for you

If a clinical trial is to be carried out, basic safety and performance requirements must first be met and essential technical documentation must therefore be created.

In addition, all medical device manufacturers require a QMS, including when developing Class I products.

The clinical trial leads to the clinical evaluation, which in turn forms the basis for PMCF activities (including a PMCF study).

We therefore support you throughout your entire project with your medical device with primary reference to the clinical data on the product: from start to finish.

6. How we can help you

At medXteam we clarify whether and if so which clinical trial needs to be carried out under what conditions and according to what requirements during the pre-study phase: In 3 steps we determine the correct and cost-effective strategy in relation to the clinical trial required in your case Data collection.

We also provide support in the areas of development strategy, technical documentation and quality management.

Do you already have some initial questions?

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

The blog series continues this year during Advent with our three-part “Advent Special”. We would like to provide you with comprehensive information about the important interfaces between the various types of clinical trials and the technical documentation and the relevant documents.

The special thing about our campaign is that the contribution is spread over the first three weeks of Advent. Each week, one type of clinical trial and the respective interfaces are examined in detail. The topic of risk management in clinical trials will continue in January.  

The first part of our blog special dealt with the interfaces in the “approval study” (clinical trials in accordance with Article 62 of the MDR). This second part 2 now highlights the PMCF studies (Article 74 of the MDR, MPDG, ISO 14155). The third and final part will explain the interfaces in DiGA studies next week .

Abbreviations.

BOB (higher federal authority)

EK (Ethics Commission)

KP (clinical examination)

MDR (medical device regulation; Regulation 2017/745)

MPEUAnpG (the Medical Devices EU Adaptation Act was passed as law by the Bundestag on May 25, 2020. This MPAnpG-EU describes the Medical Devices Implementation Act (MPDG) in Article 1)

MPDG (the MPDG will gradually replace the Medical Devices Act (MPG) from May 26, 2021 and will be legally binding for all manufacturers and operators of medical devices in Germany).

Part 2: Interfaces to technical documentation in PMCF studies and connection to MDR

1 Introduction

The correct term for a clinical trial involving medical devices is “clinical trial”.

A distinction is made between the following types of clinical trials:

• Basic research: other clinical trials (MDR Article 82)
• Pilot study/approval study: clinical trials to demonstrate the conformity of products (MDR Article 62)
• PMCF study: clinical trials related to products bearing the CE marking (MDR Article 74)

In addition, there is now the so-called DiGA study, especially in Germany:

• Study with a digital health application (DiGA) to demonstrate positive care effects in order to obtain reimbursement status.
• d. R. with CE marked medical device: PMCF study
• If planned into the approval process, an approval study is also possible

(Sources: DiGAV, DVG, DiGA guidelines)

Fig. 1: Types of clinical trials

These different types differ in terms of the respective regulatory requirements and thus in terms of the different interfaces to the technical documentation of the medical device to be examined.

Special feature of PMCF studies:

A PMCF study that takes place with a CE-marked medical device within the scope of its intended purpose and without stressful examinations represents an exception to Article 74 of the MDR:

Figure 4: Article 74 of the MDR (Source: presentation slides, BfArM event, https://www.bfarm.de/DE/Service/Events/Dialogveranstaltungen/2021/210505-klinische_Pruefungen_von_MP.html )

Regardless of this, the documents according to Annex XV Chapter II and Articles 80ff of the MDR are still binding.

2. Documents to be submitted in PMCF studies

The following documents must be created for clinical trials involving a CE-marked product. Depending on whether Article 74 of the MDR applies, it will be submitted to the EC for a vote and to BfArM. If Article 74 does not apply, all that is required is professional advice from the responsible ethics committee in accordance with Section 15 of the Professional Code of Conduct for Doctors (BO). No matter which application is submitted, the following documents must be created and these are related to the technical documentation:

• Test plan - attachments according to appendix XV chapter. II 3 MDR.
• Clinical Investigator's Handbook - Appendices as per Annex XV Chapter. II 2 MDR.

The following documents are required from the technical documentation:

• clinical assessment - in accordance with Article 61 of the MDR.
• Instructions for use
• Biological safety test results
• How MP works/information about the MP (how MP works)
• How it works and further information about the medical device.
• Risk analysis and assessment including residual risks
• List basic security and performance requirements
• If necessary, suitable processing or sterilization processes
• Proof of CE marking (Required if the test product bears a CE marking.)

2.1 Interfaces to technical documentation

The following table lists the above-mentioned documents to be submitted as well as the elements contained therein and the respective correspondence in the technical documentation:

Table 1: Clinical trial documents and technical documentation

Since this is a CE-marked product, all of these documents are already present in the technical documentation and are particularly included in the test plan and the clinical examiner's manual.

The CE-marked medical device is therefore the test product tested in the PMCF study for which the clinical data is collected. I.e. the documents and results must refer to exactly this product and not to an earlier version!

Technical Documentation:

• Product description
• Intended use
• product specification
• Final clinical assessment with state of the art chapters and literature and risk-benefit assessment
• Risk management documentation according to ISO 14971: PHA, risk analysis, risk management report
• Instructions for use
• Classification
• Checklist of basic performance and security requirements
• List of standards
• Verification test reports
• Biosafety report (if applicable)
• Sterilization process documentation (if applicable)

2.2 Synergies

If you look at the list above, you will notice that this is almost all of the technical documentation.

A good example of using synergies when creating documents is the test plan. Many sections contain the same content as in other technical documentation documents. The intended purpose, the product description, etc. are just a few examples. In addition, the final clinical assessment includes state-of-the-art clinical data, which can also be used for the protocol and the clinical investigator's manual.

And here the digitalization of clinical trials plays a role again:

With the close integration of the clinical trial not only with the process of literature search and thus with the clinical assessment as reported in the penultimate blog post, but also with the technical documentation, digitalization of the essential documents of the clinical trial such as: b.

• Clinical trial plan (Appendix XV, Chapter II, Section 3 of the MDR)
• Clinical Investigator's Manual (Appendix XV, Chapter II, Section 2 of the MDR)
• clinical evaluation

possible.

The advantages of digitalization are obvious:

• more efficient work
• Target-oriented use of capacities
• Elimination of inefficiencies in the creation, maintenance and modification of technical documentation content, clinical evaluation and literature searches
• long-term reduction in care costs

Using the “Polarion” software application, interfaces such as purpose, risk management, usability, clinical evaluation, clinical testing can be assigned to projects and reused if necessary. The creation and maintenance of documents is thus significantly simplified and accelerated. In addition, redundancies and inconsistencies are avoided.

3. Outlook

our “ Advent special ” will focus on the interfaces to technical documentation in DiGA studies.

4. How we can help you

At medXteam we clarify whether and if so which clinical trial needs to be carried out under what conditions and according to what requirements during the pre-study phase: In 3 steps we determine the correct and cost-effective strategy in relation to the clinical trial required in your case Data collection.

Do you already have some initial questions?

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

The blog series continues this year during Advent with our three-part “Advent Special”. We would like to provide you with comprehensive information about the important interfaces between the various types of clinical trials and the technical documentation and the relevant documents.

The special thing about our campaign is that the contribution is spread over the first three weeks of Advent. Each week, one type of clinical trial and the respective interfaces are examined in detail. The topic of risk management in clinical trials will continue in January.  

The first part of our blog special dealt with the interfaces in the “approval study” (clinical trials in accordance with Article 62 of the MDR). The second part 2 now examines the PMCF studies (Article 74 of the MDR, MPDG, ISO 14155). This third and final part now explains the interfaces in DiGA studies .

Abbreviations.

BOB (higher federal authority)

EK (Ethics Commission)

KP (clinical examination)

MDR (medical device regulation; Regulation 2017/745)

MPEUAnpG (the Medical Devices EU Adaptation Act was passed as law by the Bundestag on May 25, 2020. This MPAnpG-EU describes the Medical Devices Implementation Act (MPDG) in Article 1)

MPDG (the MPDG will gradually replace the Medical Devices Act (MPG) from May 26, 2021 and will be legally binding for all manufacturers and operators of medical devices in Germany).

Part 2: Interfaces to technical documentation in PMCF studies and connection to MDR

1 Introduction

The correct term for a clinical trial involving medical devices is “clinical trial”.

A distinction is made between the following types of clinical trials:

• Basic research: other clinical trials (MDR Article 82)
• Pilot study/approval study: clinical trials to demonstrate the conformity of products (MDR Article 62)
• PMCF study: clinical trials related to products bearing the CE marking (MDR Article 74)

In addition, there is now the so-called DiGA study, especially in Germany:

• Study with a digital health application (DiGA) to demonstrate positive care effects in order to obtain reimbursement status.
• d. R. with CE marked medical device: PMCF study
• If planned into the approval process, an approval study is also possible

(Sources: DiGAV, DVG, DiGA guidelines)

Fig. 1: Types of clinical trials

These different types differ in terms of the respective regulatory requirements and thus in terms of the different interfaces to the technical documentation of the medical device to be examined.

A DiGA study is a PMCF study. That's why the same special features apply here:

A DiGA and thus PMCF study that takes place with a CE-marked medical device within the scope of its intended purpose and without stressful examinations represents an exception to Article 74 of the MDR:

Figure 4: Article 74 of the MDR (Source: presentation slides, BfArM event, https://www.bfarm.de/DE/Service/Events/Dialogveranstaltungen/2021/210505-klinische_Pruefungen_von_MP.html )

Regardless of this, the documents according to Annex XV Chapter II and Articles 80ff of the MDR are still binding.

2. Documents to be submitted for DiGA studies

The additional phase in a DiGA study includes the creation of the evaluation concept based on a systematic literature search, data collection with the DiGA itself on the user and the systematic evaluation of this data.

The clinical assessment - and in this case ideally the most recent one - serves as essential input. It lists the various claims for the medical device and it is important to find the right ones for the DiGA concept: The claims for clinical performance, safety and clinical benefit required for the clinical evaluation have already been included in the plan for the clinical evaluation defined and then documented with data in the clinical assessment report.

Note: This is exactly where it is recommended to use the interface on the DiGA topic of “medical benefits” or patient-relevant structural and procedural improvements, because this data can then be used to update the clinical assessment after the DiGA study.

We have already reported on this in detail in our blog post on the evaluation concept this year.

And then after creating the evaluation concept and finding the appropriate endpoints for the DiGA study, it's time to create the study documents. As with the PMCF study, the following documents must also be created for DiGA studies. Depending on whether Article 74 of the MDR applies, it will be submitted to the EC for a vote and to BfArM. If Article 74 does not apply, all that is required is professional advice from the responsible ethics committee in accordance with Section 15 of the Professional Code of Conduct for Doctors (BO). No matter which application is submitted, the following documents must be created and these are related to the technical documentation:

• Test plan - attachments according to appendix XV chapter. II 3 MDR.
• Clinical Investigator's Handbook - Appendices as per Annex XV Chapter. II 2 MDR.

The following documents are required from the technical documentation:

• clinical assessment - in accordance with Article 61 of the MDR.
• Instructions for use
• Biological safety test results
• How MP works/information about the MP (how MP works)
• How it works and further information about the medical device.
• Risk analysis and assessment including residual risks
• List basic security and performance requirements
• If necessary, suitable processing or sterilization processes
• Proof of CE marking (Required if the test product bears a CE marking.)

2.1 Interfaces to technical documentation

The following table lists the above-mentioned documents to be submitted as well as the elements contained therein and the respective correspondence in the technical documentation:

Table 1: Clinical trial documents and technical documentation

Since this is a CE-marked product, all of these documents are already present in the technical documentation and are particularly included in the test plan and the clinical examiner's manual.

The CE-marked medical device is therefore the test product tested in the PMCF study for which the clinical data is collected. I.e. the documents and results must refer to exactly this product and not to an earlier version!

Technical Documentation:

• Product description
• Intended use
• product specification
• Final clinical assessment with state of the art chapters and literature and risk-benefit assessment
• Risk management documentation according to ISO 14971: PHA, risk analysis, risk management report
• Instructions for use
• Classification
• Checklist of basic performance and security requirements
• List of standards
• Verification test reports
• Biosafety report (if applicable)
• Sterilization process documentation (if applicable)

2.2 Synergies

If you look at the list above, you will notice that this is almost all of the technical documentation.

A good example of using synergies when creating documents is the test plan. Many sections contain the same content as in other technical documentation documents. The intended purpose, the product description, etc. are just a few examples. In addition, the final clinical assessment includes state-of-the-art clinical data, which can also be used for the protocol and the clinical investigator's manual.

And here the digitalization of clinical trials plays a role again:

With the close integration of the clinical trial not only with the process of literature search and thus with the clinical assessment as reported in the penultimate blog post, but also with the technical documentation, digitalization of the essential documents of the clinical trial such as: b.

• Clinical trial plan (Appendix XV, Chapter II, Section 3 of the MDR)
• Clinical Investigator's Manual (Appendix XV, Chapter II, Section 2 of the MDR)
• clinical evaluation

possible.

The advantages of digitalization are obvious:

• more efficient work
• Target-oriented use of capacities
• Elimination of inefficiencies in the creation, maintenance and modification of technical documentation content, clinical evaluation and literature searches
• long-term reduction in care costs

Using the “Polarion” software application, interfaces such as purpose, risk management, usability, clinical evaluation, clinical testing can be assigned to projects and reused if necessary. The creation and maintenance of documents is thus significantly simplified and accelerated. In addition, redundancies and inconsistencies are avoided.

3. Outlook

Our “ Advent special ” is now over. We wish all readers a peaceful and relaxing Christmas ahead and plenty of time to do something other than deal with medical devices.

In the new year we will start again with the topic of “risk management in clinical trials”.

4. How we can help you

At medXteam we clarify whether and if so which clinical trial needs to be carried out under what conditions and according to what requirements during the pre-study phase: In 3 steps we determine the correct and cost-effective strategy in relation to the clinical trial required in your case Data collection.

Do you already have some initial questions?

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