What elements does a study concept or study synopsis contain for a clinical investigation of medical devices or digital applications?

A study design for a clinical investigation or other clinical investigation according to the Medical Device Regulation (REGULATION (EU) 2017/745, MDR) and ISO 14155 includes several elements to be considered.

These elements are necessary in order to fulfil the legal and regulatory requirements and to ensure the safety and effectiveness of the medical appliances and ultimately to make the study a success through careful preparation. The procedure is similar, but with a different focus, for example when planning an observational study, systematic data analysis or case study.

Study design: From the idea to the preparation of study planning

Here are the most important elements of a study concept:

‍1. regulatory categorisation, objectives and quality requirements

Our experts support you in complying with all relevant regulatory requirements and implementing them in the appropriate or possible investigation procedure. We help you prepare the necessary documentation and, if necessary, the preparatory communication with the relevant authorities, opinion leaders and other stakeholders so that exactly the right project is chosen with the resulting decisions, with the objective that the investigation follows the necessary orientation, meets the quality requirements to be achieved and the subsequent results convince all decision-makers - so that the evidence generation methodology fits into your market entry strategy for optimal reimbursement.

In this confidence-building phase, we focus on you as a person and your personality.

2. study protocol

The study protocol is the central document of a clinical investigation or other prospective or retrospective study. Here, detailed information is recorded and documented in a structured manner for conducting, analysing and evaluating the study. It includes:

• Objectives of the study: Clear definition of the primary and secondary endpoints.
• Study design: Description of the study design (e.g. randomised, controlled, prospective, observational study, retrospective data analysis).
• Study population: description of the inclusion and exclusion criteria for the participants
• Treatment plan: details on the administration of the investigational medical device and the comparator treatment.
• Data collection plan: methods and timing of data collection, data security and data protection.
• Integration of all elements of a digital study centre (DTC-MED®): manufacturer-independent technical functionalities and services for completely digital or hybrid clinical studies
• Statistical plan: description of the statistical methods for data analysis.
• Organisation and logistics, including all necessary documents as appendices

‍3. time, resource and budget planning‍

A realistic timeline, clarification of the required and available resources and an iteratively increasingly detailed budget are crucial for the success of your clinical investigation or other project. We draw up a comprehensive project plan that takes into account all the necessary steps and milestones and ensure that the necessary framework conditions can be met within the available budget. Based on our many years of experience, we show where studies can be kept lean and which savings can lead to incalculable risks later on.

4. risk management

Regulatory requirements stipulate that the benefits of all contents of a clinical study must always outweigh all risks and that every effort must be made to ensure the dignity, well-being and safety of the study participants (DIN EN ISO 14155:2021-05 Chapter 6.2 and Annex H)

• Risk assessment: iterative and continuous identification, assessment and management of potential risks associated with the clinical investigation.
• Monitoring and mitigation of risks: strategies to minimise identified risks.

Furthermore, a clinical study can only succeed if all those involved are well trained and sensitised, and the corporate cultures of all those involved promote awareness and willingness to manage risk. The basis for this should be risk management systems that have been tried and tested in practice. The highest standards must be consistently adhered to in digitally conducted clinical studies.

5. quality management

Quality management includes the implementation of a quality assurance plan that contains measures to ensure compliance with regulatory requirements, data quality and adherence to study protocols. Depending on the risks identified, regular monitoring and audit processes are required on a risk-adapted basis to ensure the success of a clinical study and its informative value. This includes, among other things

• Quality assurance plan: Measures to ensure the quality and integrity of the study data.
• Monitoring plan: Monitoring of study activities to ensure compliance with the protocol and regulatory requirements.

6. data management

Data management in a clinical study is subdivided into systematic collection, processing, analysis, storage and backup to ensure its quality and integrity. It begins with the planning of data requirements and sources and continues with the development and use of standardised data collection tools such as electronic clinical trial questionnaires (eCRFs) or interfaces between different data sources. Data is cleansed, validated and verified by suitable measures after collection in order to minimise errors and ensure data quality.

• Data management plan: Central document for documenting the planned collection, storage and analysis of study data, describes processes and procedures for handling study data.
• Analysis: for prospective, in particular confirmatory projects, according to a predefined statistical analysis plan

After the inclusion of study participants, their diagnosis and treatment, data management is crucial to ensure the quality and reliability of the data in clinical studies and compliance with regulatory requirements. The guidelines from the data protection regulations and thus the GDPR apply to all European study participants.

7. Reporting and documentation

The reporting and documentation of a clinical study serves to report the results of the study transparently and comprehensively to the competent authorities in order to ensure compliance with regulatory requirements and to demonstrate the safety and effectiveness of the product under investigation. In addition, the publication of study results in scientific journals or at specialist conferences is important in order to inform the scientific community, discuss the results, gain access to the guidelines of specialist societies and expand the evidence base. Important reports are:

• Interim reports: either as regular reports on the progress of the study for larger, high-risk or longer-lasting studies or, for example, for a preliminary application for inclusion in the DiGA Directory.
• Final report: summarising the results and conclusions of the study.

In general, study participants have the right to know the results of the studies that they have supported with their participation. This information must therefore always be published in layman's language via the appropriate channels after the study has been completed.

The study concept or the concept for the clinical investigation or performance study will be based on the appropriate regulatory framework, the objectives or the quality standards that may be specified. Various structures are used here, such as ISO14155, Annex XV Regulation (EU) 2017/745 (MDR), Regulation (EU) 2017/746 (IVDR), the MPDG or the Declaration of Helsinki.

‍

* "Study" here includes "clinical investigation", "other clinical investigation", "clinical investigation after placing on the market", or from the DiGAV "comparative study", "systematic data analysis", "clinical study", "epidemiological study", "comparative study", randomised controlled trial" and others

For a study concept, we will listen to you carefully and guide you step by step through the design of the entire clinical investigation or study using checklists established in the reality of conducting fully digital or hybrid clinical trials. We will consult with you in such a way that you will be in a position to make qualified decisions at all times. Feel free tocontact us for an initial consultation!