UPDATE
In our last blog post before our summer break, coinciding with the first medXevent, we're discussing the product registry within the framework of post-market clinical follow-up (PMCF). Under the Medical Device Regulation (MDR), manufacturers of medical devices are obligated to use various general and specific methods and procedures for post-market clinical follow-up (PMCF). A registry offers a highly proactive method for gathering your own clinical data from routine clinical practice. In this blog post, we'll explain what a registry is and how you can use it for your medical device within your PMCF framework.
Abbreviations
MDR (medical device regulation; EU Regulation 2017/745)
PMCF (Post-Market Clinical Follow-up)
RCT (Randomized Controlled Trial)
1 Introduction
The MDR, within the framework of the PMCF (Product Lifecycle Compliance Framework), requires the continuous collection of clinical data on the clinical performance, clinical benefit, and safety of medical devices throughout their entire product lifecycle. A registry can be established and used, in particular, to collect efficacy data from the routine clinical use of the product and is therefore suitable for demonstrating its effectiveness in everyday healthcare practice.
Within the framework of the MDR, the registry is therefore considered one of the proactive activities of post-market clinical follow-up (PMCF). The evaluation of the registry is referred to as a review of the registry data, which is generally designed to be retrospective.
Fig. 1 Integration of the registry into the market surveillance process according to the 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, Whitepaper)
2. Definition of the register
2.1 Definition 1
"A register is a data collection process that is as active and standardized as possible, based on observational units and addresses predefined but expandable questions, for which a precise reference to the source population can be transparently demonstrated."
(Source: German Institute for Vascular Health Research)
2.2 Definition 2
"An organized system that uses observational study methods to collect uniform data (clinical and other) to evaluate specific outcomes for a population defined by a particular disease, condition or exposure, and that serves one or more predetermined scientific, clinical or policy purposes."
(Source: Gliklich RE et al., 2010)
3. Product Register
In general, medical registries are useful and beneficial because they generate necessary medical care data under everyday conditions
- They create the conditions for safe medical operations and continuous quality improvement,
- They create market observation knowledge and generate important product information for medical device manufacturers, as well as knowledge for their market research and new developments
- offer the chance of an "early warning system" to detect anomalies early and avoid recurring damage,
- provide answers to the questions:
- Where and why did this incident occur?
- What role do the product, the doctor, and the patient play?
- Where can we learn more?
- What conclusions can we draw from this regarding quality improvements for the product in terms of its safety and performance/effectiveness?
Furthermore, effects from registry data can provide an indication of or evidence of clinical benefit and are therefore an important contribution to post-market clinical follow-up (PMCF).
3.1 Regulatory requirements
Annex XIV Part B of the MDR: Clinical Follow-up requires, within the framework of the PMCF, the continuous collection of clinical data on the clinical performance, clinical benefit and safety of medical devices throughout the entire product lifecycle:
"Post-market clinical follow-up is to be understood as an ongoing process for updating the clinical evaluation in accordance with Article 61 and Part A of this Annex and is addressed in the manufacturer's post-market surveillance plan. In post-market clinical follow-up, the manufacturer proactively collects and evaluates clinical data arising from the use in or on the human body of a CE-marked product that has been placed on the market or put into service within the scope of its intended purpose in accordance with the relevant conformity assessment procedure, in order to confirm the safety and performance during the expected lifetime of the product, to ensure the continuing acceptability of the identified risks, and to identify emerging risks based on 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 involve the immutability of the chosen endpoints throughout the study and, in addition to a time limit, usually also have a quantitative limitation with regard to the population. Furthermore, they operate within a defined framework (endpoints, inclusion and exclusion criteria, etc.). If one wants to collect data from the routine clinical use of a medical device, as is possible with a registry, no such framework can prevail, as this would, for example, render the collection of off-label use data absurd. Yet this is precisely what a registry makes possible.
A registry thus collects unrestricted data (i.e., without inclusion and exclusion criteria) from routine clinical practice, without following a restricted and defined study structure.
A registry study, as a non-interventional study, thus forms a complementary approach to a randomized clinical trial (RCT).
Table 1: Registry study versus RCT (Source: Novustat, https://novustat.com/statistik-blog/registerstudien-professionell-auswerten-die-essentials.html)
Compared to registries, RCTs are often criticized for their lack of representativeness of everyday healthcare due to a severely limited population and artificial intervention scenarios. And this is, of course, one of the advantages of a registry, particularly in meeting the PMCF requirements of the MDR:
3.3 Advantages of a register
Because registries collect data from routine clinical practice, they do not take place within the strictly regulated and controlled framework of a PMCF study and can therefore provide manufacturers with important insights into the actual use of the product in the market. Further advantages include:
- scientific and empirical evidence
- Valid representation of trends from application observation
- All commonly used forms of therapy and interventions are depicted
- No patient consent is required, only a data privacy statement and consent to the use of the data
3.4 Data collection using registers
A product registry collects data on specific clinical questions and, if necessary, data gaps (parameters) in a completely anonymized manner, both prospectively and retrospectively.
To make valid statements, the registries must be carefully planned and implemented. This planning is carried out using a registry plan. This plan includes specifications for the parameters to be collected as well as their evaluation (including frequency). Based on this plan, a specific registry database is built. The data are entered into this database, which should be as independent as possible, completely anonymized, and initially validated for completeness and plausibility. Ideally, the entries in the registry database are validated by trained and qualified external experts. The validation and verification of completeness and compliance with exclusion criteria are monitored and documented by a data manager.
Furthermore, GCP and ICH guidelines must be followed, as well as data protection regulations. Patients must be informed via patient information and must consent to the data collection.
The data should not only be collected but also statistically analyzed. When analyzing registry studies, methods are used to ensure the comparability of patients or patient groups. This allows, for example, matched-pair analyses. Analyses based on propensity scores are also used in registry studies. Based on predefined criteria, suitable comparison partners can be found. Adjustment procedures for different characteristics, such as disease severity, can be useful.
(Source: Novustat, https://novustat.com/statistik-blog/registerstudien-professionell-auswerten-die-essentials.html . Accessed on 25.06.2021)
Users of such a registry include, on the one hand, those who enter data into the registry database in medical practices, clinics, or during the use of the medical device. Other users are data managers who statistically analyze and process the data. And, of course, the manufacturer, who can then use this data for the PMCF (Medical Device Competence Framework).
Fig. 3: Cycle of data collection, analysis and use
3.4 What characterizes a good register?
The quality of the register is of primary importance here:
The systematic and appropriate nature of the data collection within the framework of the register is important.
The validity
- the sampling process,
- data collection and
- the statistical analyses and reports
These are further quality characteristics. Likewise, further overarching quality requirements. These include:
- Dealing with limiting framework conditions
- Acceptance among reporters and patients
- Efficiency
- Transparency and scientific independence
- Flexibility and adaptability
- Timeliness
Standardization is also a crucial aspect if valid and evidentiary clinical data are to be collected via this method. This includes, for example:
- the establishment of standards in procedural instructions
- the training/review of data collection/recording
Registries provide a nearly complete picture of the entire population and thus data from routine clinical practice. They therefore offer the following advantages:
- Demonstration of effectiveness in everyday care
- large number of patients with baseline data
- heterogeneous study population
- Direct comparison for benefit assessment of different forms of therapy is possible
- potential use as a QM tool for benchmarking in long-term observation
- High case numbers can be achieved
(Source: Neugebauer, 2013. Development of a registry for registries. Institute for Research in Operative Medicine (IFOM))
Instead of a PMCF study, manufacturers can thus 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-quality data. Professional support is also recommended with regard to medical statistics, analysis, and the selection of appropriate methods.
4. What we can do for you
We function as a scientific, manufacturer-independent institution (CRO). As such, we work with you to determine how we can best close any existing data gaps within the PMCF framework or continuously collect clinical data on your medical device.
One option here is the product register. This was also presented in detail at our first free medXevent on July 1, 2021. The recording available on our YouTube channel.
With this first live event, we're now taking a summer break from blogging and events. Our second medXevent, focusing on DiGA studies, is planned for September. The next blog post will also be published then, introducing our brand-new GCP-MDR training courses for investigators.
5. How we can help you
Whether a clinical trial is necessary at all, and if so, which one, under what conditions and according to which requirements, is clarified by us at medXteam during the pre-study phase: In 3 steps, we determine the right and cost-effective strategy regarding the clinical data collection required in your case. This also applies to your registry!
Do you already have some initial questions?
You can get a free initial consultation here: free initial consultation