From data to insights: trend reports and the requirements of the MDR

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. This is where the topic of trends in accordance with Article 88 of the MDR comes into play: data must also be collected and evaluated for this purpose. That's exactly what this blog post is about.  

Abbreviations

MDR Medical Device Regulation;
EU Regulation 2017/745 PMS Post-Market Surveillance

Underlying regulations

EU Regulation 2017/745 (MDR)

1 Introduction

In the world of medical devices, safety and effectiveness are paramount, making it crucial to identify trends early and respond appropriately.

A trend report in accordance with Article 88 of the Medical Device Regulation (MDR) may be required if statistically significant negative trends are identified in the data collected. Provided that the criterion defined in Article 88 of the MDR is met, manufacturers of medical devices are obliged to prepare regular trend reports and, if necessary, take measures to minimize potential risks and ensure the safety of their products.

2. Trend reports

2.1 What is a trend report?

A trend report can be a part of the post-market surveillance (PMS) report.
The PMS plan and PMS report are based on Articles 84 and 85 of the MDR. The trend report is a tool for the early identification of trends and developments related to the safety and performance of medical devices. This report is intended to identify and assess potential risks or safety concerns associated with a medical device. According to Article 88 of the MDR, a trend report is required when a statistically significant increase in the frequency or severity of non-serious incidents or expected adverse reactions is identified that could have an impact on the benefit-risk analysis and result in risks to the health or safety of Lead or may lead to patients, users or others that is unacceptable in light of the intended use.

2.2 Importance of Trend Reports

Trend reports are critical to medical device manufacturers for several reasons:

• Early identification of risks: By regularly analyzing trends, potential risks or safety concerns can be identified early and appropriate measures taken to ensure patient safety.
• Informed decision making: Manufacturers can make informed decisions based on trend reports, both in terms of product development and ongoing monitoring of products already on the market.
• Compliance with legal requirements: Article 88 of the MDR makes the creation of trend reports a legal requirement. Compliance with this provision is therefore essential for manufacturers to meet regulatory requirements and maintain marketing authorization for their products.

3. Implementation of trend reports in accordance with Article 88 of the MDR

The implementation of trend reports in accordance with Article 88 of the MDR requires a structured and systematic approach.

3.1 Data analysis

As part of the data analysis, the data collected is evaluated with regard to its development over time using a suitable statistical method. The following points, among others, are taken into account:

3.2 Data collection and analysis

Manufacturers must continually collect and analyze data that reflects relevant trends and developments related to their products. This may include evaluation of clinical trials, user feedback, post-market surveillance data and regulatory updates.

• • The collected data is evaluated and first checked for a statistically significant increase in frequency or severity to evaluate whether further analysis of the trend and a resulting trend report are necessary.
  • Statistical significance occurs when an observed effect or difference in data is highly unlikely to be due to chance, but rather indicates an actual connection or difference between the variables examined. This is typically expressed by a p-value, where a p-value smaller than the specified significance level indicates that the observed results are statistically significant.
  • An observed trend in the data may or may not be a causal connection to the use of the product being evaluated. The existence of a causal relationship will be checked in the further course of the evaluation of a significant trend.
  • A trend is determined by evaluating the data from the individual survey times and thus analyzing the development over time in more detail.
  • For this purpose, various statistical methods can be used to evaluate the data collected over time and to adequately check for statistical significance.
    Which statistical method is suitable in a specific case depends on several factors. This includes, among other things, the type of data collected, the size and structure of the sample and the underlying assumptions about the distribution of the data.
  • As part of data analysis, trends are also graphically represented using diagrams or graphics as an effective means of making complex statistical results more understandable and clear.

3.3 Documentation

The results of data analysis must be documented in the form of trend reports as part of the post-market surveillance reports or separately. These results reports should be clearly structured and contain relevant information on identified trends, their root cause analysis and potential impacts, as well as the proposed risk mitigation measures:

• Description of the trend:
  A clear description of the identified trend including its potential impact on the safety and performance of the medical device.
• Root cause analysis:
  An analysis of the causes or factors that could contribute to the development of the trend, including possible technical, clinical or regulatory aspects.
• Impact Assessment:
  An assessment of the potential impact of the trend on the safety and performance of the medical device, as well as on users and patients.
• Suggested actions:
  Suggestions of appropriate actions to minimize or eliminate potential risks, including updates to the risk management plan, changes to product design or instructions for use, and user training.
• Action Plan:
  A plan to implement the proposed actions, including timelines and responsibilities.

4. Review and Update

Trend reports must be reviewed regularly and updated as necessary to ensure they reflect current trends and developments.

5. Application example

To illustrate the concepts and processes associated with trend reports in accordance with Article 88 of the MDR, we consider fictitious data on sales figures and complaints from a medical device manufacturer (Table 1).

Table 1: Number of sales and complaints over time

The collected data on sales and complaints can now be checked for a trend and a significant change using suitable statistical methods (Table 2).

Table 2: Results of the statistical analysis of the data collected

At a defined significance level of 0.05, the number of sales from year 1 to year 11 is a significantly positive increase with a p-value of 0.0126. For complaints with a p-value of 0.8205, which is greater than the significance level of 0.05, the change cannot be demonstrated to be statistically significant.

Since the results of the evaluations do not represent negative, statistically significant trends, a root cause analysis and the consideration of further measures are not necessary.

However, if there is a negative, statistically significant trend, this trend is analyzed thoroughly. The data collected is evaluated in detail with regard to a causal connection to the use of the product, the causes and the effects of the trend. This also includes a thorough examination of the complaints, their distribution in the complaint categories and their influence on the identified trend for the derivation of measures and, if necessary, adjustments to the risk analysis. The results of these evaluations and appropriate measures to be taken are documented as part of the post-market surveillance report or separately.

6. Conclusion

Trend reports in accordance with Article 88 of the MDR play a crucial role in ensuring the safety and performance of medical devices. By systematically analyzing trends, manufacturers can identify potential risks early and take appropriate measures to ensure the safety of patients, users and third parties. Compliance with this legal requirement is therefore essential for all manufacturers who want to sell medical devices on the European market.

7. How we can help you

Our statisticians accompany you from data collection through analysis to documentation, the trend report! Be safe!

Clinical trials:

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.

If a clinical trial is to be carried out, basic safety and performance requirements must first be met. The data from the clinical trial then feed into the clinical evaluation, which in turn forms the basis for post-market clinical follow-up (PMCF) activities (including a PMCF study).

In addition, all medical device manufacturers require a quality management system (QMS), including when developing Class I products.

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 implementation through to technical documentation - always with primary reference to the clinical data on the product: from the beginning to the end End.

Do you already have some initial questions?

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

Literature search for medical devices

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. The literature search plays an important role in this context. Because it is not only essential in connection with the clinical evaluation of medical devices. This blog post shows when, where and why you need a literature search in other situations.

Abbreviations

MDR Medical Device Regulation; EU Regulation 2017/745

DiGA Digital Health Application

PMCF Post-Market Clinical Follow-up, clinical follow-up

QMS quality management system

Underlying regulations

EU Regulation 2017/745 (MDR)
Medical Device Implementation Act (MPDG)
ISO 14155

1 Introduction

In the regulatory environment of medical devices, the literature search is an elementary process that takes place in different phases of the life cycle. It is relevant not only in clinical assessment, but also in context

• the clinical strategy,
• the development strategy,
• of risk management
• in connection with clinical trials, PMCF studies
• at DiGAs with regard to systematic data collection

This article therefore first answers the question: When do I carry out a literature search for medical devices? The different contextual situations and the design of the search in the respective situation are discussed.

In addition, we also show how to conduct an effective literature search and offer practical examples for designing the search strategy in different situations.

2. Literature search and clinical data

When it comes to the topic of “literature search”, clinical data obviously plays an important role. Clinical data is the heart of medical research and refers to the collection of information about the product when used on humans. They include a wide range of information obtained from clinical studies, patient observations, research results and other medical sources. This data is essential for assessing the effectiveness, safety and quality of medical devices. They form the basis for regulatory decisions and make a significant contribution to the development of innovative medical solutions.

Clinical data is defined in connection with medical devices in the MDR in Art. 2 as follows:

“Clinical data” means safety or performance information obtained through the use of a product from the following sources:

• clinical trial(s) of the product in question,
• clinical trial(s) or other studies reported in the scientific literature on a product whose similarity to the product in question can be demonstrated,
• in peer-reviewed scientific literature published reports of other clinical experience either with the device in question or with a device whose similarity to the device in question can be demonstrated,
• clinically relevant information from post-marketing surveillance, in particular from post-marketing clinical follow-up."

The literature search is therefore the process of finding clinical data. This leads us into the world of medical databases. The most important sources include PubMed, the Cochrane Library and EMBASE. These databases provide access to a variety of publications, journals, conference proceedings and systematic reviews, meta-analyses, guidelines and much more.

The literature search process takes place in several steps and is the same in every regulatory situation:

Fig. 1: Literature search process

Defining the search strategy : The first step is to carefully plan the search strategy. Relevant keywords and search terms are defined that form the framework of the research.

Choosing the right databases : Because of the wealth of information, choosing the right databases is crucial. Each database has its own strengths and specializations that need to be taken into account.

Carrying out the search : The databases are systematically searched using the defined keywords. This phase requires patience and care to ensure that no relevant information is missed.

Analysis and selection of data : After collecting the information, the results are critically evaluated. The most relevant and well-founded studies and reports are selected that help answer the question.

A possible technique that can be used in this process is e.g. B. the PICO technique: It helps to make search queries more precise and more effective. PICO stands for Population, Intervention, Comparison and Outcome. This method makes it possible to focus the research on the most important aspects, thereby providing more precise and relevant results.

This technology is used in particular in the context of

• Patient care
• Treatment

and for determination

• the accuracy of diagnostic tests
• prognostic factors

used.

3. Literature search in practice

The literature search enables well-founded decisions to be made, in this context we also speak of “evidence-based” decisions. It is therefore an indispensable part of the development and evaluation of medical devices because it

• provides a structured basis for decision-making and
• which ensures the quality, clinical performance and safety of medical devices.

There are various situations in the product life cycle of a medical device in which a literature search is necessary. Each has specific goals and foci:

• Context Clinical Assessment: Plan, Report
• Context Clinical strategy, development strategy, risk management
• Context Clinical trial, PMCF study, systematic data collection

These are discussed in detail below.

3.1 The literature search in the context of clinical evaluation

The clinical evaluation of medical devices (Article 61 of EU Regulation 2017/745 (MDR)) is a core element of technical documentation and, as part of the validation of clinical data, confirms the safety of the medical device, its clinical performance and its benefit-risk ratio. The literature search is an integral part of providing this information. The process of "assessing" clinical data is a defined sequence of actions to analyze the various sources, including clinical trials, not only in terms of content but also methodologically. Evaluation criteria include the relevance of the publication, the quality and scientific validity as well as the weighting of the data with regard to the clinical evaluation.

The analysis of “state of the art” data captures the current state of the art. In contrast, the data of the product being evaluated is provided to substantiate the claimed clinical performance and safety of the product.

The literature search includes four steps:

Fig. 2: Literature search step by step

The aim of the clinical evaluation is to create a sound basis for market approval and to ensure the quality, safety and effectiveness of the medical device. This requires careful documentation of the entire process, including literature search plan, protocol and report, to ensure transparency and traceability for audits and regulatory reviews.

3.2 Context clinical strategy, development strategy, risk management

Clinical strategy:

In these areas, literature searches facilitate the identification of potential risks and the development of risk mitigation strategies. It also supports the formulation of a long-term clinical and development strategy based on current research and existing data. It thus lays the foundation for the clinical evaluation route and sets the course for the entire planning of the development process in terms of costs and time.

Risk management:

Risk management is the systematic application of management strategies to identify and control product risks. There is a close interface between risk management and clinical assessment, especially when incorporating the current medical and technological state of the art.

The literature search in the context of the clinical strategy is also carried out in four steps (see Figure 2).

A focus is on searching for similar products to assess equivalence, identify side effects and incorporate market data. The product's intended use is also examined, including the prevalence and incidence of relevant conditions or diseases, alternative forms of use, and current medical guidelines.

3.3 Context clinical trial, PMCF study, systematic data collection

Clinical test:

The clinical trial is designed in the project planning phase and carried out with the final product as part of product validation. The collected data flows into the Clinical Evaluation Report (CER) and is crucial for the product's market entry. It is carried out in accordance with legal requirements such as MDR and ISO 14155.

The literature search in the context of clinical testing is again carried out in four steps (see Figure 2). The focus here is on identifying relevant endpoints on the basis of which the research question should be answered. Furthermore, ideas for a potential study design should be collected.

DiGA:

For digital health applications (DiGAs), a literature search for the "minimally important difference/change" (MCID) is crucial for the systematic data collection and evaluation of the data collected on the product in order to assess the clinical significance of the data and classify it accordingly. But the DiGA guidelines require a systematic literature search, particularly for the evaluation concept: it should provide evidence of the positive care effect.

4. Digital literature search

We have seen how important and central the literature search is in connection with medical devices, across the entire product life cycle.

medXteam specializes in the collection and evaluation of clinical data: our focus is on literature searches. The execution of objective research in Pubmed and Pubmed Central can be partially automated with digital software solutions to ensure comprehensible and reproducible research documentation and to reduce the effort required for documenting the research results. The solution used (Polarion with avaPubmed extension) offers a direct, validated interface to Pubmed and Pubmed Central.

4.1 Digitized literature search via Polarion

Literature search is the core process of clinical evaluation.

When searching for literature via Polarion, a direct connection is established to the database sources (e.g. directly to PubMed).

The literature search is carried out and documented in the form of the following documents:

• Literature Search and Review Plan

The literature search and review plan describes the objective search and describes the identification of publications. It includes:

• Sources of publications
• Search terms
• defined filters
• Assessment criteria and process for identified publications
• Process for analyzing the relevant publications
• Literature Search Execution Protocol

The implementation protocol provides details of the research carried out and an overview of the history of the research. It includes:

• Search queries and results used
• Deviations from the literature search and review plan
• Overview of searches carried out and search results
• Literature Review Report

The report contains a summary of the search carried out, as well as the evaluation and analysis. It includes:

• Summary of objective search execution and results
• conducted search and selection procedures for identification by other means
• Evaluation of the identified publications
• Analysis of the relevant publications (see following section)

4.2 Documentation of the analysis

The full text of each potentially relevant publication is read and analyzed with regard to the scope of the literature search and the relevant clinical assessment topics in the respective clinical assessment plan. The extracted statements about safety, performance, benefits, demands or state of the art are documented.

The analysis of a single "publication" is documented in the form of a single "publication evaluation" (see diagram below): The "publication" is linked to the "publication evaluation" and the evaluation is linked to the respective "clinical evaluation object" linked in the clinical evaluation plan. The following graphic explains the connection between the individual work item types:

Fig. 3: Analysis

4.3 Report on the literature search

The literature search report provides an overview and summary of the analysis:

For each clinical assessment topic, it is listed which publication was identified as being relevant to this topic and which specific statements were extracted in the publication assessment.

Based on these results, it is analyzed whether the relevant data sets as a whole show evidence for the respective clinical evaluation subject (the respective claim, see figure above). The aim is to look for consistency of results across specific clinical assessment topics. If different results are observed across datasets, it is helpful to determine the reason for these differences.

The following graphic visualizes the connection between the documents and the digital content they contain in the form of work items:

Fig. 4 Interfaces and work items

4.4 Digitalized clinical assessment

Digitalization is of course particularly effective here:

The core of the clinical assessment is the literature search, which can be carried out digitally (see above). Embedded in Polarion as a subsystem, it can also be digitized itself. The following figure provides an overview of the content of the clinical assessment documents

• CEP,
• CERIUM,
• Literature search documents – plan, minutes, report

embedded as a subsystem in the overall technical documentation system:

4.5 Advantages of digitalization

The digitalization of technical documentation for medical devices and thus clinical evaluation and literature search is the future!

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

Via Polarion, interfaces such as purpose, risk management, usability, clinical evaluation, clinical trial 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.

5. Conclusion

According to MDR Art. 2, clinical data includes information on safety and performance derived from clinical trials, specialist literature, clinical experience reports and post-market surveillance. These data sources are crucial for an effective literature search. Searching the literature where we find clinical data and the importance of this data to various aspects of medical device development illustrates how fundamental literature searching is to the entire development process.

The literature search for medical devices is more than just a step in the development process; it is a continuous process that has a decisive influence on the quality and safety of medical devices. It enables manufacturers, researchers and clinical experts to make informed decisions based on the latest scientific evidence. In an ever-evolving industry, literature searches remain an essential part of ensuring innovative and safe medical devices.

A literature search is essential for all medical devices over the entire product life cycle, namely: To obtain clinical data!

6. How we can help you

Due to high demand, we have produced a special online training:

This training is designed to provide medical device professionals with comprehensive guidance on effective literature searches in various settings with a focus on clinical evaluation. The training is divided into four lessons, which include both theoretical basics and practical application examples.

Lesson 1: Literature search and clinical data

Lesson 2: Literature search in practice

Lesson 3: Getting started in practice: First practical example

Lesson 4: More practical examples

Clinical trials:

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.

If a clinical trial is to be carried out, basic safety and performance requirements must first be met. The data from the clinical trial then feed into the clinical evaluation, which in turn forms the basis for post-market clinical follow-up (PMCF) activities (including a PMCF study).

In addition, all medical device manufacturers require a quality management system (QMS), including when developing Class I products.

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 implementation through to technical documentation - always with primary reference to the clinical data on the product: from the beginning to the end End.

Do you already have some initial questions?

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

The undetected trap? The black box of the new DiGA requirements

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. This time the topic of the DiGA is again in this context. Data is also collected here. But this time the focus is on the question: What potential challenges lie behind the DiGA requirements for manufacturers?

Abbreviations

BSI Federal Office for Information Security

DiGA Digital Health Application

ePA Electronic patient record

KBV National Association of Statutory Health Insurance Physicians

MDR Medical Device Regulation; EU Regulation 2017/745

QMS quality management system

Underlying regulations

EU Regulation 2017/745 (MDR)
Medical Device Implementation Act (MPDG)
ISO 14155
ISO 27001
DiGA Guide V3.4
Digital Supply and Care Modernization Act (DVPMG)
EU Regulation 2016/679 (GDPR)
Technical Guideline TR -03161

1 Introduction

DiGAs (Digital Health Applications) have become increasingly important as digital applications in healthcare in recent years. They can help improve medical care and facilitate access to healthcare services. They provide patients with the ability to monitor their health and manage disease while providing doctors with valuable data to make better decisions.

However, in addition to the opportunities for patients and medical staff, the regulatory context of DiGAs also presents challenges for the manufacturers of these products. Numerous requirements have already been defined, which must be implemented by manufacturers within certain deadlines and documented with appropriate evidence. Due to these requirements, which we will examine in more detail in this article, manufacturers are faced with, among other things, the key question of classifying their medical software product. While most DiGAs are currently classified as Class I products, a higher classification may result from the implementation of the new requirements. This is not just a fundamentally regulatory issue, the certification of the quality management system (QMS), the resulting cost and time issues as well as the argument to investors also form important pillars of this consideration.

If we take into account the debate in our last blog post about why doctors are primarily reluctant to prescribe DiGAs, the question arises as to how the immense challenges will relate to the potential benefits of digital applications in the future.

2. Regulatory requirements for DiGA manufacturers

As a DiGA manufacturer, it is currently necessary to implement some requirements as part of product development and internal company processes. The following chapter highlights both the current requirements and those to be implemented in the future, which are largely based on the DiGA guidelines.

2.1 Applicable Requirements

All manufacturers currently need an information security management system. Both establishment/implementation and certification are required as proof. There are two options: according to ISO 27001 or “ISO 27001 based on IT-Grundschutz (BSI standard 200-2: IT-Grundschutz methodology)”.

The Digital Supply and Care Modernization Act (DVPMG) also states that a penetration test must be carried out for all components, regardless of the protection requirements of the DiGA. Penetration tests are one of the “basic requirements that apply to all digital health applications” in Appendix 1. The BSI implementation concept for penetration tests and the current OWASP top 10 security risks must be used as the basis for the test concept. Upon request, the BfArM must be presented with proof that the relevant tests have been carried out.

2.2 What’s new and when?

The secure authentication of insured persons via digital identity must be implemented January 1, 2024 Originally, this requirement was supposed to have been implemented by January 1, 2023. However, the health insurance companies have until January 1st, 2024 to create the digital identity:

"Social Code (SGB) Fifth Book (V) - Statutory health insurance - (Article 1 of the law of December 20, 1988, BGBl. I p. 2477)
§ 291 Electronic health card:
(8) From January 1, 2024 at the latest In addition to the electronic health card, health insurance companies can, upon request, provide the insured with a secure, barrier-free digital identity for the healthcare system that meets the requirements of paragraph 2 numbers 1 and 2 and enables the health insurance companies to provide data in accordance with Section 291a paragraphs 2 and 3."

From January 1st, 2024, a regular, automated export of the data collected by the DiGA into the electronic patient file (ePA) must be guaranteed. The National Association of Statutory Health Insurance Physicians (KBV) defines the corresponding requirements for semantic and syntactic interoperability.

Proof in the form of a certificate in accordance with Article 42 GDPR (Regulation (EU) 2016/679) of compliance with data protection requirements must be available August 1st, 2024

"Social Code (SGB) Fifth Book (V) - Statutory Health Insurance - (Article 1 of the law of December 20, 1988, Federal Law Gazette I p. 2477)
§ 139e Directory for digital health applications; Authorization to issue regulations:
(11) The Federal Institute for Medicines and Medical Devices, in agreement with the Federal Commissioner for Data Protection and Freedom of Information and in consultation with the Federal Office for Information Security, shall, for the first time by March 31, 2022 and then generally annually, specify the testing criteria for the requirements to be demonstrated by digital health applications Data protection in accordance with paragraph 2 sentence 2 number 2. From August 1, 2024, proof of compliance with the data protection requirements by the manufacturer must be provided by submitting a certificate in accordance with Article 42 of Regulation (EU) 2016/ 679 to lead."

The technical guideline TR-03161 includes the requirements for applications in the healthcare sector defined by the Federal Office for Information Security (BSI) and is part of the data security requirements of a DiGA according to Section 139e Paragraph 10 SGB V. From January 1st, 2025 there is a corresponding one Certificate to be presented.

"Social Code (SGB) Fifth Book (V) - Statutory Health Insurance - (Article 1 of the law of December 20, 1988, BGBl. I p. 2477)
§ 139e Directory for digital health applications; Authorization to issue regulations:
(10) The Federal Office for Security in of Information Technology, in agreement with the Federal Institute for Drugs and Medical Devices and in consultation with the Federal Commissioner for Data Protection and Freedom of Information, lays down the data security requirements to be demonstrated by digital health applications in accordance with paragraph for the first time by January 1, 2024 and then generally annually 2 sentence 2 number 2. From June 1, 2024, the Federal Office for Information Security will offer procedures for checking compliance with the requirements according to sentence 1 as well as procedures for confirming compliance with the requirements according to sentence 1 through appropriate certificates Fulfillment of the data security requirements by the manufacturer must be carried out by presenting a certificate in accordance with sentence 2 from January 1, 2025 at the latest."

3. Other requirements

In principle, all regulatory requirements that generally apply to all medical devices also apply to digital health applications. Technical documentation must also be created for a digital health application, which is used to demonstrate compliance with the basic security and performance requirements of the MDR. Every manufacturer of a medical device needs a QMS based on ISO 13485 based on the applicable regulations. Since the MDR came into force, this also applies to manufacturers of Class I products.

But the spectrum of requirements in the digital environment continues to grow. For example, there is now the additional issue of whether a form of 14-day right of return should be introduced for patients after the initial prescription of the DiGA.

4. Consequences of these new requirements

What consequences might these additional requirements bring? It should be said that the deadlines currently lie in the future, which is why the actual handling of possible consequences for manufacturers is still a hypothetical space. Realistic experience will only be available in the coming months. Nevertheless, one aspect in particular appears particularly sensitive when considering the requirements: classification . The classification of software is generally based on the classification rules from Appendix VIII of the MDR. However, there are also valid guidance documents that can be used for support. Rule 11 states that “ software intended to provide information used to make decisions for diagnostic or therapeutic purposes belongs to Class IIa ”.

Now imagine the following hypothetical scenario: You as a manufacturer have successfully implemented all required export functionalities and interoperability requirements. It is now possible to carry out a regular and automated export of the data collected with your DiGA into the individual's ePA, as well as to export certain information from the DiGA as a patient. Your DiGA concept includes, among other things, the provision of material for exercises that patients should do at home. Now let's assume that Ms. Müller is prescribed her DiGA and then uses it diligently. The data collected is sent to Ms. Müller's ePA, so her treating doctor has access to this data. In addition, Ms. Müller exports the generic content provided by you as the manufacturer, which also contains data on Ms. Müller's individual application. At Ms. Müller's next doctor's visit, the use of the DiGA is discussed (both Ms. Müller's export and the data in the ePA are available), whereupon her treating doctor suggests that she no longer do exercise No. 5 in her explicit case of illness to carry out. So, according to Rule 11, in theory we ended up in a scenario in which the DiGA provided information that led the doctor to make treatment recommendations to Ms. Müller. The result of the scenario: a Class I product became a Class IIa product through the implementation of the requirements.

The possible consequences of such a classification are considered in detail in the following chapters.

4.1 Certification

We have already explained that since the MDR came into force, every manufacturer of a medical device must have a QMS. However, it is only for manufacturers with a Class IIa product or more that this QMS must also be certified. For Class I manufacturers, setting up and living such a process structure is sufficient. If the requirements result in a higher classification, your QMS must be certified so that you as a manufacturer continue to comply with the applicable regulations. Given the deadlines for the MDR transition, this aspect is probably one of the most time-critical factors and requires immediate consideration of possible classification consequences for your product .

4.2 Cost question/investors

The current requirements already entail high costs for manufacturers. It is not only important to complete a successful audit of the implementation of the information security management system (ISMS), the path from data collection to successful DiGA listing is also a long and costly one. Due to the additional requirements to be implemented, manufacturers now face an additional cost block, which from an economic point of view often depends on the willingness of their investors.

4.3 Technical documentation

The technical documentation is the basis of every medical product as proof of compliance with the basic safety and performance requirements of the MDR. Essential components of this technical documentation include, among other things, risk management and the usability file with the corresponding tests for the use of the product. In the case of software, the software file also forms a large component of the documentation. This includes both the definition of the requirements and the actual implementation in the form of the architecture as well as other relevant process documentation to verify and validate the successful development. The level of detail of this technical documentation, particularly with regard to the software file, depends, among other things, on the classification of the software product. If this results in a higher classification, the technical documentation must also be revised accordingly, which entails costs and may temporarily tie up resources in the company. In addition, this must then also be certified by a notified body; the manufacturer can no longer issue the EU declaration of conformity itself.

5. Relation to the last blog post

Our last blog post took a closer look at doctors' reluctance to prescribe DiGAs. Despite the numerous advantages of DiGAs, many doctors are hesitant to prescribe them. One reason for this is that they are not sure whether DiGAs are actually effective. There are also concerns about the security of DiGAs as well as data security. Another factor is the lack of time and resources to support patients in the use of DiGAs. Additionally, many physicians are concerned about the additional burden of prescribing and monitoring DiGAs. And last but not least, there is the concern as to whether the health insurance companies will really cover the costs or whether a corresponding prescription can lead to recourse.

The previously described requirements for DiGAs largely relate to the security and, above all, the data security of the applications placed on the market, which would address at least one aspect of reluctance to prescribe. However, the implementation of the requirements also results in a major entrepreneurial risk for the manufacturers. If you look at the additional costs for the implementation of all these aspects and also take into account the fact that the prescription of the successfully listed DiGA might only progress slowly, the break-even point slips further and further into the distance and the economic viability of the development Such DiGAs must be seriously questioned.

6. Conclusion/Conclusion

DiGAs have the potential to improve medical care and make it easier for patients to access digital health applications. However, the enormous opportunities offered by these products are offset by immense challenges, especially for manufacturers.

As a significant consequence of the implementation of the highlighted requirements, we were able to identify the question of the resulting classification of the DiGA. This affects both manufacturers who are still in the initial development of their product and those who have already achieved a provisional or final listing for their DiGA. The possible resulting higher classification has far-reaching consequences - this affects both the certification of the quality management system and the technical documentation as well as all business aspects (e.g. costs, time, investors). Manufacturers should therefore first address this question of the correct future classification of their medical device in order to be able to initiate further steps.

The question posed at the beginning of how the immense challenges will relate to the potential benefits of digital applications in the future cannot be answered conclusively. The requirements must only be implemented by the defined deadlines, so that the resulting consequences for manufacturers will only become clear in the coming months. However, looking at the multitude of requirements clearly shows that the strong regulation of this particular type of medical software product should be urgently questioned. Ultimately, it is important to provide the patient with added value and to support and accompany them in everyday life in dealing with their illnesses.

7. How we can help you

We would be happy to support you in successfully listing your DiGA by means of an early evaluation of the product classification based on your planned features.

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.

If a clinical trial is to be carried out, basic safety and performance requirements must first be met. The data from the clinical trial then feed into the clinical evaluation, which in turn forms the basis for post-market clinical follow-up (PMCF) activities (including a PMCF study).

In addition, all medical device manufacturers require a quality management system (QMS), including when developing Class I products.

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 implementation through to technical documentation - always with primary reference to the clinical data on the product: from the beginning to the end End.

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. 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. This time the topic in this context is the DiGA. Data is also collected here. But this time the focus is on the question: Why are doctors holding back on prescribing DiGAs? In the following blog post, Dr. med. Gisela Knopf contributed. As a general practitioner, she has already had extensive experience in this area.

Since October 2023, the previous month's blog post has also been published as a podcast ( medXteam Kompakt ). This article appears as an interview with Dr. med. Gisela Knopf will then be available as a podcast in December 2023.

Abbreviations

DiGA Digital Health Application

KV Association of Statutory Health Insurance Physicians

Underlying regulations

Digital Healthcare Act (DVG)
Digital Health Applications Ordinance (DiGAV)
DiGA Guide

1 Introduction

DiGAs (Digital Health Applications) have become increasingly important as digital applications in healthcare in recent years. They can help improve medical care and facilitate access to healthcare services. They provide patients with the ability to monitor their health and manage disease while providing doctors with valuable data to make better decisions.

Despite this, many physicians appear hesitant to prescribe DiGAs. This article examines this situation and the perspectives of doctors and health insurance companies. It also examines the reasons for this reluctance and suggests ways in which physicians can be encouraged to prescribe DiGAs.

2. Introduction to the DiGAs

DiGAs are medical applications that are reimbursed by health insurance companies and can be prescribed by doctors at the expense of the health insurance companies. They are intended to improve medical care, for example by helping to diagnose diseases or support the monitoring of patients. DiGAs can be used, for example, in the treatment of diabetes, mental illnesses or for smoking cessation. The applications are usually easy to use and can be downloaded to smartphones or tablets.

3. Case studies of successful implementation of DiGAs

DiGAs have become more important in recent years. They include a variety of applications, from fitness trackers to specialized health apps. Many of these applications were developed by medical professionals and provide evidence-based solutions to improve health. Nevertheless, DiGAs are often not formulated or used.

One reason for this problem is the lack of awareness and training among doctors. Many doctors are either not aware that DiGAs are approved as medical aids or they do not have sufficient knowledge of the benefits and possible uses. This means that they do not prescribe DiGAs or are hesitant to recommend them.

There are already some successful examples of the implementation of DiGAs in medical care. One example is the formulation of DiGAs for the treatment of diabetes. Applications can be used here to monitor blood sugar levels and support self-management of the disease. Another example is the use of DiGAs to treat anxiety disorders and depression. Appropriate applications can be used here to support psychotherapeutic treatment.

4. Prescription of DiGAs

Physicians have various concerns and challenges when it comes to prescribing DiGAs. On the one hand, they are concerned about the quality and effectiveness of the applications. You want to be sure that the DiGAs are evidence-based and actually help patients. On the other hand, doctors have limited time during patient consultations and do not want to have to recommend or prescribe too many different applications.

To address these challenges, better training and education for physicians is needed. They need to be informed about the latest developments in the field of DiGAs and learn how to effectively integrate them into their practice. In addition, criteria and guidelines should be developed to ensure the quality and effectiveness of DiGAs or, ideally, the DIGAs should be integrated into the existing guidelines.

4.1 The role of the doctor in prescribing DiGAs

Prescribing DiGAs is the responsibility of physicians. They must decide which applications are best for their patients, what benefits they can provide, and whether they are cost-effective. Doctors must also ensure that the applications are safe and effective and that they are funded by health insurance companies. This requires a certain level of expertise and experience in relation to DiGAs.

Doctors and psychotherapists can issue a prescription (sample 16) for a DiGA if the prescription is medically necessary. Economic efficiency must always be taken into account.

The cost-effectiveness principle also applies to apps: The DiGA regulation also applies to the cost-effectiveness requirement, according to which the service must be sufficient, appropriate and economical (Section 12 SGB V).

(Source: Apps on Recipe , accessed on November 3rd, 2023)

4.2. Factors contributing to physicians' reluctance to prescribe DiGAs

Despite the benefits of DiGAs, many doctors are hesitant to prescribe them. One reason for this is that they are not sure whether DiGAs are actually effective. There are also concerns about the security of DiGAs and data security. Another factor is the lack of time and resources to support patients in the use of DiGAs. Additionally, many physicians are concerned about the additional burden of prescribing and monitoring DiGAs. And last but not least, there is the concern as to whether the health insurance companies will really cover the costs or whether a corresponding prescription can lead to recourse.

Added to this is the already very complicated billing and prescription system used by statutory health insurance physicians. Especially with the constantly hovering sword of Damocles of the risk of recourse (see also the following section). Recourse means that a doctor who makes a “mistake” (according to the KV specifications) in prescribing a health insurance service can and often actually is asked to pay for this service. In the case of DIGAs, this means becoming the prescribing doctor The costs of € 300 - 500 may be billed personally. And in order to correctly carry out a DIGA prescription, a few points are required that are set by the Association of Statutory Health Insurance Physicians, which also differ from DIGA to DIGA if, for example, this is changed from “provisional” to “permanent” or from “provisional” to “no longer available on the list”. And how should the KV requirement of “economic efficiency” be met? Perhaps the DIGA will ultimately be compared with a medication that costs a few cents per day for therapy? What the KV understands by economic efficiency is unfortunately usually not defined in detail for the individual case and is the big black box when it comes to the risk of recourse. Unfortunately, it is well known that apples are often compared with oranges without the medical profession having any influence.

4.3 Impact of budget constraints on the prescription of DiGAs

Another important factor that can contribute to doctors' reluctance to prescribe DiGAs is the very special and sometimes difficult to understand billing systems of statutory health insurance physicians, including budget restrictions. The health insurance companies provide limited resources for financing DiGAs and so there are major concerns among the medical profession as to whether and under what conditions DIGAs will be reimbursed by statutory (and private) health insurance companies. Doctors are under constant pressure to work cost-effectively, combined with the ever-present time pressure in practice. Just dealing with the matter of when which DIGA can be prescribed and under what conditions requires a lot of time.

In addition, there is the Sword of Damocles already mentioned above, that if one of the specified conditions was (inadvertently) not met, the health insurance company or the Association of Statutory Health Insurance Physicians will generally refuse to cover the costs and the doctor will be billed for the costs of the DIGA in the form of recourse be provided. This risk is avoided if the doctor does not prescribe DIGA at all or recommends that the patient get a corresponding app themselves.

4.4 Addressing physician concerns regarding DiGAs

To encourage physicians to prescribe DiGAs, their concerns and concerns must be addressed. One way to do this is to provide training and education to improve physicians' knowledge and understanding of DiGAs. It may also be helpful to emphasize the benefits of DiGAs, such as improving patient care and reducing costs. Another option is to give doctors the opportunity to try DiGAs and test them themselves to assess their effectiveness and safety.

5. Health insurance companies’ perspective

Health insurance companies also play an important role in the prescription of DiGAs. They must ensure that the applications they reimburse actually provide patient benefit and are cost-effective. For this reason, they often conduct their own assessments and studies to verify the effectiveness of DiGAs.

Another problem that health insurance companies have is the large number of DiGAs available. They have to decide which applications they will reimburse and which they will not. This requires careful evaluation and selection to offer patients the best options.

6. Overcoming barriers to prescribing DiGAs

To promote the prescription of DiGAs, barriers to the adoption and use of DiGAs must be overcome. This includes providing sufficient resources and training for doctors and patients. With regard to doctors, the prescription modalities in particular must be trained or, better yet, significantly simplified, which then also fits with the topic of digitalization.

It may also be helpful to encourage collaboration between physicians and developers of DiGAs to ensure that the applications meet patients' needs. In addition, health insurance companies for DiGAs can create meaningful incentives for the prescription of DiGAs in order to promote acceptance and use. The health insurance companies already have these incentives, but obtaining them is so complicated and confusing that the ratio of profit to effort is not worth it for most doctors.

6.1 The future of DiGAs in healthcare

The future of DiGAs in healthcare is promising. They can help improve medical care and facilitate access to healthcare services. DiGAs can also help reduce healthcare costs by reducing the need for expensive follow-up medical costs. The demand for DiGAs is expected to continue to increase in the coming years as more and more people have access to digital technologies.

6.2 Resources for physicians to learn more about DiGAs

A number of resources are available for physicians interested in learning more about DiGAs. This includes training and education, specialist magazines and online resources. It can also be helpful to exchange ideas with colleagues who already have experience with the regulation of DiGAs. Although all of this is available, the effort required to obtain information must remain manageable; the prescription of DIGAs is ultimately only a very small part of the medical field of application.

7. Conclusion

DiGAs have the potential to improve medical care and make it easier for patients to access digital health applications.

There are a number of reasons for physician reluctance to prescribe, with concerns about the effectiveness and safety of DiGAs likely outweighed by the risk of recourse and lack of time.

In this respect, doctors simply hesitate to prescribe a form of therapy in the three-digit price range for the reasons mentioned above, which the manufacturers are probably not aware of. The fact that patients can sometimes receive the DIGAs directly from the health insurance company without a doctor's prescription seems to be a good approach here.

To promote the prescription of DiGAs, barriers must be overcome and physicians must be encouraged to become familiar with DiGAs. For example, better training and education for doctors as well as clear and, above all, uniform criteria and guidelines for DiGAs are required. In addition, health insurance companies may need to improve their evaluation processes to select the best DiGAs.

5. 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.

If a clinical trial is to be carried out, basic safety and performance requirements must first be met. The data from the clinical trial then feed into the clinical evaluation, which in turn forms the basis for post-market clinical follow-up (PMCF) activities (including a PMCF study).

In addition, all medical device manufacturers require a quality management system (QMS), including when developing Class I products.

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 implementation through to technical documentation - always with primary reference to the clinical data on the product: from the beginning to the end End.

Do you already have some initial questions?

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