Study types in the study design of clinical investigations of medical devices

The following section takes a closer look at the study types as a core criterion of study design that can be used in clinical or other clinical investigations of medical devices.

Study types in clinical investigations: The right choice for meaningful results

The choice of study type is made not only on the basis of necessary scientific criteria, but also taking into account the requirements and possibilities arising from the regulatory framework, available resources, capacities and feasibility. The quality of the study is later determined by the careful preparatory work. The evaluability of the results, the significance of a medical study and thus the success of the entire project depend largely on this.
Different types of studies are used in clinical investigations, each with specific objectives and methodological approaches. The selection is made before the start of the study and is of decisive importance for its success.

Literature review versus clinical studies

As part of the conformity assessment procedure for medical devices, the results are usually compiled through a systematic literature review and summary based on secondary data as part of a clinical evaluation. In contrast, research on primary data, which includes clinical or other clinical investigations of medical devices, is the opposite of the results compiled as part of a clinical evaluation. In the investigation of primary data, a distinction is made between experimental (basic research), clinical and epidemiological study types. There may also be overlaps and mixed forms.

Important: a wrong decision about the study type cannot be corrected later!

We list the most important study types here so that you can get an initial overview and also show you which evidence levels* (also evidence level or evidence class) can be achieved with different study types according to scientific criteria.

In order to achieve the different levels of evidence, external reviews always take into account other factors from the study design as part of the study conception in addition to the study type and the extent to which the specifications laid down in the study protocol have been implemented and are suitable for the selected research question.

Interventional versus non-interventional study types

Clinical studies or clinical investigations with medical devices can be conducted both interventional and non-interventional. In an interventional study type, a study-related intervention is carried out on study participants, whereas this is not the case in a non-interventional study.
Regulation (EU) 2017/745 on medical devices(MDR) does not formally differentiate between interventional and non-interventional clinical or other clinical investigations. There is also no such distinction in the Medical Devices Implementation Act(MPDG). Interventional clinical performance studies with in vitro diagnostic medical devices are only mentioned in the requirements for designation as the head of a performance study in Regulation (EU) 2027/746 on in vitro diagnostic medical devices(IVDR). The term clinical investigations of therapeutic medical devices is usually used in the sense of interventional studies

Prospective versus retrospective study types

‍In addition, a further fundamental distinction is made between forward-looking (prospective) and retrospective studies. The informative value of prospective studies is greater than that of retrospective studies due to their higher quality.

This can be explained by the prior planning as part of the study design, in which the research question is formulated and the study design is subsequently optimised.

The quality characteristics of prospective studies include the exclusion of random correlations, statistical planning, ensuring a sufficiently long observation period, case number planning, the selection of a suitable, validated measurement method, a representative study population, avoidance of bias, quality assurance measures including monitoring of protocol-compliant implementation and the identification of unmet medical needs. Randomised, controlled and blinded clinical investigations with case number planning are considered the gold standard for clinical investigations.

This contrasts with retrospective studies, in which the safety, effectiveness or benefit of a medical procedure, therapy or performance of an in vitro diagnostic medical device is empirically investigated using existing data. Here too, the validity of the study can be increased by using careful methodology, for example in a case-control study. This type of study is particularly suitable for uncovering the causes of very rare diseases over long periods of time.

Important: What all study forms have in common is that they should be conducted in accordance with the binding international rules of "good clinical practice" as per ISO14155 and that all study participants must have given their informed consent.

Study types and levels of evidence

Here are examples of some of the most important study types used in clinical research, especially for medical devices in the therapeutic area:

1. randomised controlled trial (RCT):

The study is planned into the future, with participants randomly assigned to a so-called intervention group (receives the investigational medical device) or a control group (contains only the standard therapy, possibly a placebo or no therapy). It is advisable to have an idea in advance of what results are to be presented and how many patients should be included in the study.

• Objective: To compare the performance, effectiveness, benefit and/or safety of a medical device with a control treatment and to exclude so-called confounding factors from the study results in order to minimise their influence on the study results. Conducting an RCT requires attention to a number of special features, which are explained below.
• Complexity: An RCT is relatively complex and requires specially qualified personnel to conduct it.
• Use and best possible evidence level*: An RCT is the gold standard for a clinical investigation, especially if, for example, the final inclusion of an innovative product in the DiGA Directory is being sought. Evidence level Ib can be achieved.

2. cohort study

Longitudinal observational study over a defined period of time in which a group of patients exposed to the medical device (exposure cohort) is followed over a certain period of time and compared with a non-exposed group (comparison cohort). This type of study can be both forward-looking (prospective) and backward-looking (retrospective). Data is usually collected at several points in time.

• Objective: To investigate the long-term effects or the risk or occurrence of certain diseases.
• Complexity: A cohort study is relatively complex and is usually conducted by specially qualified personnel.
• Use and best possible level of evidence*: A cohort study is used, for example, to investigate the risk or benefit over a longer period of time. Evidence level IIb (with a prospective approach or if all diagnostic parameters for test accuracy are available) can be achieved.

3. case-control study

Retrospective observational study in which patients with a certain outcome (cases) are compared with patients without this outcome (controls) in order to identify possible exposure factors, a form of epidemiological study.

• Objective: to uncover causes of diseases that occur very rarely or over long periods of time
• Complexity: low complexity, but possibly long observation periods on large numbers of patients, high demands on statistics
• Use and best possible level of evidence*: Investigation of the influence of smoking on lung cancer. Evidence level III.

4. case series, observational studies, retrospective analyses and other non-comparative studies

Non-interventional study, description of a group of patients who have received a specific medical device, but without a control group.

• Objective: To gather initial evidence on the safety and effectiveness of the medical device.
• Complexity: low, can also be carried out by non-specialists under guidance/supervision
• Use and best possible evidence level*: initial descriptions of new therapies, symptoms and diseases, evidence level IV‍

5. case studies, individual case reports, descriptive accounts

Observational studies in which data are collected from a group of patients at a specific point in time, no use of specific treatments for those observed.

• Objective: to assess the prevalence of a condition or disease in relation to the use of the medical device.
• Complexity: low
• Use and evidence level*: initial descriptions of new therapies, symptoms and diseases, evidence level V

* There are currently (2024) several international hierarchy systems for classifying the significance (value) of medical research projects. Based on the classification of the Joint Federal Committee (G-BA) and the Federal Institute for Drugs and Medical Devices (BfArM) in the fast-track procedure for digital health applications (DiGA), we use the term evidence levels here.

Other study types also include so-called "cross-over" studies, in which patients alternately receive the investigational medical device under investigation and, if applicable, the standard therapy. Combinations of prospective and retrospective elements (so-called hybrid studies) are also possible.

Each study design has specific advantages and disadvantages and is suitable depending on the research question, objectives and development status of the medical device. The choice of the appropriate study design is crucial to generate valid and reliable data that meet the requirements of Regulation (EU) 2017/745, (EU) 2027/746, the MPDG or the Digital Care Act (DiGAV) or other laws or regulations and contribute to the safe and effective scientific evaluation of medical devices.

At MEDIACC, we offer comprehensive support in developing the appropriate study type. Pleasecontact us for an initial non-binding discussion!

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