The term clinical validation it is also often used in relation to medical devices. For example, the BMBF publishes a guideline on the topic “Clinical validation of innovative medical technological solutions”. The FDA also talks about it clinical validation.

What is clinical validation? How does it differ from a clinical evaluation and a clinical trial? Are clinical validations also necessary?

Here are the answers in compact form.

1. Definition and delimitation

a) Definition of “clinical validation”

There are many definitions of the term, but unfortunately there is no universally accepted one. Publications such as those by Shah et al. try it.

Useful definitions

The following definition is very useful:

This definition takes into account the generally accepted definition of the term validation, also used by ISO 14155-2021-05.

Clinical validation is therefore validation based on clinical data.

Less useful definitions

The following definitions are less common and appropriate:

b) Differentiation from “clinical evaluation”

Clinical validation is part of clinical evaluation: Clinical evaluation is also a process that includes planning and implementation of clinical validation.

The clinical evaluation evaluates the data coming from the verification and validation of the product. This may include clinical and non-clinical data.

Examples of clinical data include data from

Examples of non-clinical data are biocompatibility test results.

c) Differentiation of “clinical trial”

Clinical validation is based on clinical data. Clinical data is obtained in the context of the use of the medical device and consists of: data from clinical studies with the product or comparator products, published specialist literature on clinical experiences with the product or a comparator product or clinically relevant information from post-market surveillance.

Die clinical trial it can be part of the clinical validation of a medical device, with the aim of generating clinical data to demonstrate safety and performance. The term “validation” is often used in the context of clinical studies/trials. For example, the HTA Guidance on the Validity of Clinical Trials explicitly includes medical devices and IVDs.

To be considered “valid”, a clinical study must meet the following points:

• The clinical trial should ensure that the results are clinically relevant and scientifically valid with respect to the endpoints of the clinical trial and the risk/benefit profile of the investigational product.
• The design of the clinical trial should be chosen in such a way that it can be declared whether the product under investigation is suitable for the patient population intended by the manufacturer within its intended purpose specified by the manufacturer.

d) Differentiation from non-clinical validations

A non-clinical validation is a validation based on non-clinical data. Examples of this are the biocompatibility tests mentioned above and the validation of sterilization processes.

Non-clinical validation is usually carried out based on established (non-clinical) test methods described in the standards. Examples of such standards can be found in the ISO 10993 and IEC 60601 families of standards.

2. Legal requirements for clinical validations

a) Europe

Neither the MDR nor the IVDR uses the term “clinical validation.” They require a clinical evaluation (Article 61 MDR) or a performance evaluation (Article 56 IVDR).

Without prejudice to the exceptions referred to in Article 61(10), the evidence that the device meets the essential safety and performance requirements shall be based on clinical data assessed in the clinical evaluation. The collection of this clinical evidence corresponds to clinical validation.

b) United States

The FDA has numerous requirements for clinical evaluation. However, it almost only uses the term “clinical validation” for software as a medical device (SaMD).

In the guidance document Software as a Medical Device (SAMD): Clinical Evaluation, the FDA makes clear that it wants the term “clinical evaluation” to be understood in the same way as IVD (see Fig. 1). Consequently, clinical validation is proof that the (correct and precise) output of SaMD is suitable to actually achieve the intended purpose of the product in a clinical context.

The FDA describes it as follows:

Clinical validation measures the ability of a SaMD to produce clinically meaningful output associated with the target use of the SaMD output in the target health situation or condition identified in the SaMD definition statement.

This evidence should be based on clinical data (see chapter 1.b of this article).

3. Procedure for clinical validations

In the clinical evaluation plan, manufacturers must plan the clinical strategy for the clinical evaluation and then, if necessary, the collection of further data as part of the clinical validation.

First, an “inventory” of all existing clinical data on the product is created. Existing clinical data is evaluated and any data gaps that need to be filled as part of clinical validation are identified. Clinical validation can, but does not have to, take place in the context of a clinical trial.

Clinical validation occurs before approval as part of a clinical trial to generate clinical data for the conformity assessment procedure, or in the post-marketing phase, e.g. B. to confirm new clinical claims.

4. Conclusion and summary

The term “clinical validation” is not particularly useful when talking about medical devices and causes confusion. Medical device manufacturers should rather distinguish other terms:

• Clinical evaluation
• Clinical trial
• (Gather) clinical data

For IVD and SaMD manufacturers, however, proof of clinical validity is important. The process for providing this evidence can be described as: clinical validation designate.

Similar posts