UPDATE

 

In keeping with the first medXevent, the last blog post before our summer break is about the product register as part of the PMCF. Manufacturers of medical devices are obliged under the MDR to use various general and special methods and procedures as well as specific clinical follow-up during clinical follow-up (PMCF). The register is a very proactive method for obtaining your own clinical data from routine clinical practice. In this blog post we will show you what a register is and how you can use it for your medical device as part of your PMCF.

Abbreviations

MDR (medical device regulation; EU regulation 2017/745)

PMCF (Post-Market Clinical Follow-up)

RCT (Randomized Controlled Trial)

1 Introduction

As part of the PMCF, the MDR requires the continuous collection of clinical data on the clinical performance, clinical benefit and safety of medical devices throughout the entire product life cycle. A register can be set up and used here in particular to record effectiveness data in the routine clinical use of the product and is therefore suitable for displaying the effectiveness in everyday care.

As part of the MDR, the registry is one of the proactive clinical follow-up activities (Post-Market Clinical Follow-up, PMCF). The evaluation of the register is referred to as a review of the register data, which is usually retrospective.

 

Fig. 1 Integration of the register into the market surveillance process according to MDR (source: General methods and procedures of PMS and PMCF (source: Keene A. Leveraging Post-Market Surveillance and Post-Market Clinical Follow-Up Data to Support EU Medical Device Regulation (MDR) compliance, white paper)

2. Definition of the register

2.1 Definition 1 

“A register is the most active, standardized data collection possible from observation units on predetermined but expandable questions, for which a precise reference to the source population can be transparently presented.”

(Source: German Institute for Vascular Health Research)

2.2 Definition 2

“An organized system that uses observational study methods to collect consistent data (clinical and other) to evaluate specific outcomes for a population defined by a particular disease, condition, or exposure, and one or more predetermined scientific, clinical, or policy Serves a purpose.”

(Source: Gliklich RE et al., 2010)

3. Product register

In principle, medical registers are sensible and useful because they generate necessary medical care data under everyday conditions. register

• create the conditions for safe medical operations and continuous quality improvement,
• create market observation knowledge and generate important product information for medical device manufacturers and knowledge for their market research and new developments,
• offer the opportunity of an “early warning system” to detect abnormalities at an early stage and avoid repeat damage,
• provide answers to the questions:
  • Where and why did the incident occur?
  • What role do the product, doctor and patient play?
  • Where can we learn about this?
  • What conclusions do we draw from this for quality improvements for the product in terms of its safety and performance/effectiveness?

In addition, effects from registry data can provide evidence of or evidence of clinical benefit and are therefore an important contribution to clinical follow-up (post-market clinical follow-up, PMCF).

3.1 Regulatory requirement

In Annex

“Post-marketing clinical follow-up shall be understood as an ongoing process to update the clinical assessment in accordance with Article 61 and Part A of this Annex and shall be addressed in the manufacturer's post-marketing surveillance plan. During post-market clinical follow-up, the manufacturer proactively collects and assesses clinical data resulting from the use in or on humans of a CE-marked product placed on the market or put into service in accordance with the relevant conformity assessment procedure for its intended purpose Body to confirm the safety and performance over the expected life of the product, to ensure the continued acceptability of the identified risks and to identify emerging risks on the basis of relevant evidence."

(MDR, Annex XIV Part B)

3.2 Differentiation from PMCF studies

The occasionally used term “registry study” should actually be avoided. Studies can have very different designs, but generally always include the immutability of the selected endpoints over the course of the study and, in addition to a time limit, usually also have a quantitative limit in relation to the population. In addition, you run within a defined framework (endpoints, inclusion and exclusion criteria, etc.). If you want to collect data from the routine clinical practice of a medical device, as is possible with a register, no framework conditions can prevail, since this can be done, for example. B. collecting off-label use data would lead to absurdity. But that is exactly what is possible with a register.

A registry therefore collects data from routine clinical practice without restrictions (ie without inclusion or exclusion criteria) without following a restricted and defined study structure.

A registry study as a non-interventional study therefore forms a complementary approach to a randomized clinical trial (RCT).

Table 1: Register study versus RCT (Source: Novustat, https://novustat.com/statistics-blog/registerstudien-professional-auswerte-die-essentials.html) 

In comparison to the registry, RCTs are often criticized for the lack of representativeness of everyday care due to a severely restricted population and artificial intervention scenarios. And of course this is one of the advantages of a register in order to comply with the PMCF requirements of the MDR:

3.3 Advantages of a register

Since registries collect data from routine clinical practice, they do not take place in the strictly regulated and controlled context of a PMCF study and can therefore also provide the manufacturer with important insights into the actual application of the product on the market. Other advantages include:

• scientific and empirical evidence
• Valid representation of trends from application observation
• All actually common forms of therapy and interventions are depicted
• No patient consent required, just privacy policy and consent to use the data

3.4 Data collection using registers 

A product register is used to collect data on specific clinical questions and, if applicable, data gaps (parameters) in a completely anonymized manner, both prospectively and retrospectively.

However, in order to make valid statements, the registers must be carefully planned and implemented. This planning is done via a register plan. This contains specifications for the parameters to be collected as well as their evaluation (also in terms of frequency). Based on this, a specific register database is built. The data is entered into this database, which is as independent as possible, completely anonymously and is first validated there with regard to completeness and plausibility. The entries in the register database are ideally validated by trained and trained external specialists. The validation and checking for completeness and compliance with the exclusion conditions is monitored and documented by a data manager.

GCP and ICH must also be adhered to, as well as the issue of data protection. Patients must be informed using patient information and must consent to data collection.

The data should not only be collected, but also statistically evaluated. When evaluating registry studies, methods are used that ensure the comparability of patients or patient groups. This allows, for example, matched pairs evaluations to be carried out. But evaluations based on the propensity score are also used in register studies. Matching comparison partners can be found based on defined criteria. Adjustment procedures with regard to different characteristics, e.g. B. the severity of an illness can be useful.

(Source: Novustat, https://novustat.com/statistics-blog/registerstudien-professional-auswerte-die-essentials.html . Accessed on June 25, 2021)

On the one hand, users of such a register are those who enter data into the register database in practices, clinics or when using the medical device. Other users are data managers who statistically evaluate and process the data. And of course the manufacturer, who can then use this data for the PMCF.

Fig. 3: Cycle of data collection, evaluation and use

3.4 What characterizes a good register?

What matters most here is the quality of the register:

What is important is the systematic and appropriate nature of data collection within the register.

The validity

• the sampling,
• data collection and
• statistical analyzes and reports

are further quality features. Likewise, other overarching quality requirements. These include:

• Dealing with limiting conditions
• Acceptance among reporters and patients
• Efficiency
• Transparency and scientific independence
• Flexibility and adaptability
• Actuality

Standardization is also an essential aspect if valid and evident clinical data is to be collected in this way. These include, for example:

• the establishment of standards in procedural instructions
• the training/review of data collection/capture

Registries provide an almost complete picture of the entire population and thus data from routine clinical practice. You therefore have the following advantages:

• Presentation of effectiveness in everyday care
• high number of patients with basic data
• heterogeneous study population
• Direct comparison to assess the benefits of different forms of therapy is possible
• possible use as a QM tool for benchmarking in long-term observation
• high case numbers can be achieved

(Source: Neugebauer, 2013. Establishment of a register for registers. Institute for Research in Operative Medicine (IFOM))

Instead of a PMCF study, manufacturers can generate long-term data on the safety, performance and benefits of their specific product as part of clinical follow-up.

Professional approaches to data collection and recording ensure high data quality. Professional support is also recommended with regard to medical statistics, analysis and the selection of suitable procedures.

4. What we can do for you

We act as a scientific, manufacturer-independent institution (CRO). As such, we will work with you to consider how we can best close any existing data gaps within the PMCF or continuously collect clinical data on your medical device.

One option here is the product register. This was also presented in detail in our first free medXevent on July 1st, 2021. recording is now available on our YouTube channel.

With this first live event we are going into the summer break in terms of blogs and events. Our second medX event on the topic of DiGA studies is planned for September. The next blog post will also appear. In this we will introduce our brand new GCP MDR training for auditors.

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. This also applies to your register!

Do you already have some initial questions?

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