How is a study design to be seen within a study concept?

A precise and well-structured study design is the basis of your clinical investigation or clinical study.

‍The study concept forms the strategic basis and comprises the overarching objectives and methodological approaches of the clinical investigation.

The study design, on the other hand, is the detailed operational implementation of this strategy, which includes all practical and methodological aspects of conducting and monitoring the clinical investigation. This applies equally to therapeutic or diagnostic clinical investigations or clinical studies of e.g. digital health applications (DiGA) and is independent of indications or study populations.

The study design must comply with current scientific and technical knowledge and be suitable for the specific objectives of the clinical investigation. It must have sufficient statistical power and validity to demonstrate the safety, performance and clinical benefits of the medical device. The choice of study design (e.g. randomised controlled, cohort study, case series) depends on factors such as the research question, the risk classification of the device and the purpose of the study. For certain high-risk medical devices, randomised controlled trials are required to provide robust evidence of clinical performance.

The compass for the road to success: core elements of the study design

The study design is an integral part of the clinical investigation plan, which must be approved by the competent authorities and ethics committees. Careful planning of the design is crucial to generate valid and meaningful data and to fulfil regulatory requirements. The MDCG has published specific guidelines on the content of the protocol that provide detailed guidance on study design. Manufacturers should work closely with subject matter experts and regulatory authorities to select a design that is appropriate for their product.

The core elements of the study design include

• clear formulation of the study objectives and endpoints
• Description of the study population via inclusion and exclusion criteria
• Specification of the sample size and statistical methods for data analysis
• Details of randomisation, blinding and control groups (if applicable)
• Description of data collection, follow-up and safety monitoring
• Definition of the study procedure and schedule

The elements to be considered in detail

Based on the Regulation (EU) 2017/745 (MDR) based on ISO 14155:2021 and the documents of the MDCG, a study design is developed by professionals on the following points for clinical investigations of medical devices or clinical studies of DiGAs:

1. study objectives and endpoints

• Clear formulation of the objectives to be achieved with the clinical investigation, e.g. proof of safety, performance or clinical benefits of the medical device
• Definition of the primary and secondary endpoints against which the study objectives are assessed, e.g. survival rate, complication rates, quality of life

2. study population

• Description of the target group for which the medical device is intended, e.g. patients with certain diseases or age groups
• Definition of the inclusion and exclusion criteria that participants must fulfil in order to be included in the study

3. study type and comparison groups

• Selection of the appropriate study type, e.g. randomised controlled trial, cohort study, case series.
• Description of the comparison groups, if applicable (e.g. control group with standard treatment or placebo).

4. randomisation and blinding

• Explanation of whether participants will be randomised to different treatment groups and how this will be done
• Whether the study is blinded (single-blind or double-blind) and how blinding is ensured

5. sample size and statistical analysis

• Calculation of the sample size required to obtain meaningful results
• Description of the statistical methods used to analyse the study data and handling of missing data

6. data collection and follow-up

• Determine the timing and methods for data collection during the study
• Description of processes for tracking study participants and handling dropouts

7. safety monitoring

• Implementation of a safety monitoring plan to identify, assess and report adverse events
• Definition of severity levels and deadlines for reporting incidents to authorities

8. ethical aspects and consent

• Description of measures to protect the rights, safety and privacy of study participants
• Processes for obtaining informed consent from participants before the start of the study

The knowledge and many years of in-depth experience of experts in this field are particularly important here to ensure that the evidence for the product to be tested is appropriate and that all elements of the study design are properly coordinated. Mistakes made here cannot be corrected later or can only be corrected at great expense.

For manufacturers, regulatory authorities and healthcare professionals alike, a carefully prepared study design is of crucial importance. This is the only way to fulfil strict regulatory requirements, demonstrate the safety and performance of innovative and relevant products and ultimately ensure optimal patient care.

At MEDIACC, we offer comprehensive support in writing study concepts and develop the necessary study designs closely tailored to your wishes and needs to ensure that all scientific, ethical and regulatory requirements are met. Contact us for an initial non-binding consultation!

(as of spring 2024)