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Specific rules for medical devices

Medical devices are in the EU regulated by two categories that follow different regulations:

  • For medical devices, the EU Regulation on Medical Devices (MDR) applies. New rules apply within the EU from 26 May 2021, additional rules apply in Sweden from 15 July 2021.
  • For in vitro diagnostic medical devices, the EU Regulation 2017/746 on in vitro diagnostic medical devices (IVDR) applies. New rules apply within the EU from 26 May 2022.

Medical devices, EU regulation MDR

Design of a medical device study
The design of a medical device study shall be based on the research question or hypothesis to be answered or tested. The study should be planned in such a way that the data collected is of good quality and can be used to answer the question involved. The question and study design can vary depending on what the purpose of the study is, but also depending on the development stage the medical device is at. You can read more about different study designs and statistical aspects in ISO14155:2020 Annex I and on the page Analysis on this website.

Information about the structure of the research question or hypothesis on the page Idea

Standard ISO 14155:2020, SIS website (login required) External link.

Information about study design and statistical aspects on the page Analysis on this website

In addition to considering scientific aspects, you also need to ensure that the design that is best from a purely scientific viewpoint is also ethically and practically feasible. It is also a good idea to consider how the study design impacts on the quality of the data collected. A complex study design may require greater educational efforts for users and personnel, or a comprehensive plan for monitoring, to avoid failings in data quality compared to a design that largely follows the normal healthcare procedures.

Medical device aspects on ethical review
In addition to the requirements set by the Ethical Review Authority on the written information to be given to study participants, there are specific requirements in EU regulation on medical devices and in ISO14155:2020on what information to be given to the participants in a medical device study.

EU regulation on medical devices External link.

Standard ISO 14155:2020, SIS website (login required) External link.

When it comes to insurance for study participants, there are also circumstances that are specific for studies involving medical devices. If the studies are conducted as part of the healthcare principals activities, the patient insurance the healthcare principal is obliged to have is valid. On the other hand, there is no equivalent to the Medicinal Products Act (SFS 1992:859) covering medical devices.

Should the study be reviewed by the Swedish Medical Products Agency?
Medical technical clinical trials must be notified or applied to to the Swedish Medical Product Agency. Clinical investigation of medical devices which:

  • is CE-marked, where the product is used for the intended purpose, requires a notification to the Swedish Medical Products Agency at least 30 days before the trial is to begin
  • are not CE-marked or where the product is used outside the intended purpose for the CE-marking, requires an application to the Swedish Medical Products Agency

If the product is a class I or a non-invasive product in class IIa or IIb, a validation notice from the Swedish Medical Products Agency must be awaited.

If the product is invasive in class IIa or IIb or a product in class III, a permit from the Swedish Medical Products Agency must be awaited.

You can find up to date and more detailed information on authorization procedures on the Swedish Medical Product Agency´s website.

Contact the Swedish Medical Product Agency for advice if needed.

Notification or application, the Medical Products Agency's website External link.

Medical device studies abroad
If you plan to conduct a clinical study involving medical devices in another country, you must inform yourself about the applicable legislation in that country. The European Clinical Research Infrastructure Network, ECRIN, has summarised information on regulatory requirements for many European countries. The US Food and Drug Administration is the regulatory authority for medical devices in USA, and China Food and Drug Administration is the Chinese equivalent, just to mention some.

Compiled information on regulatory requirements for many European countries External link.

Regulatory Authority for Medical Devices in the United States External link.

Regulatory Authority for Medical Devices in China External link.

An adapted clinical investigation plan is needed for notification to the Swedish Medical Products Agency
If you will conduct a medical technical clinical trial you will need to adapt your research protocol. The research protocol for a clinical trial involving medical devices is called a clinical investigation plan, or CIP. The demands on the content of a clinical investigation plan are more comprehensive than the Ethical Review Authority's specification of what is to be included in a research plan. In the EU regulation on medical devices and in ISO 14155:2020you can find detailed information on what it needs to include. Important parts of the clinical investigation plan are the description of the data to be collected, which statistical considerations form the basis for the study design, and how data is to be analysed. Other important parts are a description of the study population, the procedures the study participants are expected to undergo, how informed consent is obtained, and a risk-benefit assessment relating to study participation.

In addition to the clinical investigation plan, a number of further appendices shall also be included in the documentation sent the Swedish Medical Products Agency. Read more about on the page Application on this website.

Content of the clinical research plan according to the EU regulation on medical devices products External link.

Content for clinical research plan according to standard, ISO 14155: 2020, SIS website (login required) External link.

Information about the clinical trial plan and appendices on the page Application

Constructing a data collection tool
For a clinical investigation of medical devices, there must be a CRF, either in paper format or as an electronic system. An electronic CRF (e-CRF) can form the foundation for a database created for analyses, while a paper CRF needs to be converted into electronic data at a later stage. Irrespective of format, a CRF shall be constructed as a number of questions or tick-boxes that the study personnel fill in as the study participants answer questions or undergoes various investigations that generate measurement values. Data from the patient notes can also be filled in in a CRF. Annex C of ISO 14155:2020 has an example of what a CRF may include.

If you use an e-CRF, there are specific requirements for system functionality and security. For example, an e-CRF must have a “logging function” to register who makes any changes to input data. The requirements on electronic systems in a studying involving medical devices are shown in ISO 14155:2020. You are also responsible for how the electronic processing of sensitive personal data is done, and you must know whether the electronic system entails personal data being processed abroad, or in any other operation than that of the research principal.

Remember that all the data collected in a CRF must be described in the clinical investigation plan, which must be approved by both a ethical review board and by the Medical Products Agency. No other data may be collected.

Proposed content in CRF according to standard, ISO 14155: 2020, SIS website (login required) External link.

Allocating roles and responsibilities
According to ISO 14155:2020, there are a number of roles with varying responsibility to allocate when planning to carry out a clinical investigation of medical devices.

The manufacturer is the person responsible for construction, manufacture, marking, instructions, packaging and who states the designated purpose of a medical device, and who thereafter releases the device on the market in their own name. It is the manufacturer who shall CE-mark the product, irrespective of who has carried out the practical manufacture.

The sponsor is the individual or organisation responsible for starting and implementing a clinical study requiring a permit. It is common for the sponsor to also be the manufacturer of the medical device, but it is not a requirement.

The sponsor has overall responsibility for the implementation of the study, and is responsible for issues such as:

  • planning and implementation of the clinical study
  • communication with regulatory authorities
  • quality assurance and control
  • any contracting of subcontractors for tasks and functions

A full description of the sponsor’s role and responsibility is available in ISO 14155:2020.

The principal investigator is the person responsible for the implementation of a clinical study at a clinic. If the study is conducted at several clinics, there shall be a principal investigator at each site. The principal investigator shall have documented education and experience within the area the medical device is to be used in. The competence needs for the principal investigator shall be assessed based on the area of use of the device.

The full description of the role of the responsible examiner can be found in ISO 14155: 2020.

The principal investigator’s tasks include:

  • leading the work on the study at the clinic
  • ensuring that informed consent is obtained from study participants according to applicable rules and the clinical investigation plan
  • ensuring that the study is conducted according to the clinical investigation plan
  • being responsible for ensuring the study participants receive the medical care necessary during and after the implementation of the study
  • implementing safety reporting
  • ensuring that reliable data are generated

The principal investigator has overall responsibility for the study at the clinic, but may delegate tasks on condition that the delegation is done in writing to a person with suitable education and experience. A signature and delegation list must be drawn up and kept updated in the event of any personnel changes during the course of the study. A task must first be delegated before it may be executed by any person other than the principal investigator.

The monitor is a person appointed by the sponsor, whose responsibility it is to make independent checks that the study is conducted according to the clinical investigation plan and other applicable regulations. The monitor shall carry out the checks by visiting the clinics participating in the study, scrutinising the work and informing about recommended measures to improve the work on the study. After the visit, the monitor shall write a report to the sponsor.

In order to enable the monitor to monitor a study, he or she needs to have scientific and/or clinical prior knowledge, and also knowledge about:

  • ISO 14155:2020
  • the device being tested and how it is to be used
  • the clinical investigation plan
  • the approved procedure for obtaining informed consent
  • the sponsor’s procedures
  • regulatory requirements

A full description of the monitor’s role and responsibility is available in ISO 14155:2020.

Collaboration between business, universities and healthcare
Clinical studies can be carried out at the initiative of healthcare, but it is also common for a company or an academic researcher to have an idea for a new or changed medical device.

When the medical device sector and healthcare collaborate in the development of medical devices, for example by conducting a clinical study together, the collaboration rules shall be complied with.

Collaboration rules between health care and the medical device sector (in Swedish) External link.

When planning a clinical study in collaboration with healthcare, you should be aware that specific roles with a certain type of competence must be appointed. Read more about roles and liabilities in the section above. In addition to the competence that has to be recruited to fulfil the requirements of ISO 14155:2020, the main rule is also that the person listed as the researcher responsible in an ethical review application shall have a doctoral degree.

For help with contacting clinic that may be interested in implementing your planned study, you can use the service for coordinated feasibilities at the regional nodes.

Drawing up contracts and managing financial agreements
If the clinical study is implemented as commissioned research, that is to say some principal other than healthcare takes the initiative for the study, then a contract shall always be drawn up between the sponsor and the clinic or operation conducting the study. The contract shall regulate the allocation of responsibility for the study and any financial agreements. The healthcare principal will often require compensation for the additional costs the implementation of the study will entail for the operation. Financial agreements relating to commissioned research shall also be reported in the ethical review application.

If the healthcare principal takes the initiative for the clinical study, it is still recommended that a written agreement between the researcher and the operational manager is drawn up, governing aspects such as how additional costs to the clinic shall be financed.

Further agreements may need to be signed, for example if the study requires any X-ray or pathology input or a sample handling procedure via a central laboratory.

Medical devices for in vitro diagnostics, EU regulation IVDR


Definition of performance studies and purpose according to IVDR

IVDR defines performance studies as studies performed to determine or confirm the analytical or clinical performance of a product. The purpose of clinical performance studies is to establish or confirm aspects of product performance that cannot be determined through analytical performance studies, literature studies, and / or previous experience from routine diagnostic testing.

The structure of the clinical performance study
The sponsor must perform a risk analysis before the clinical performance study starts and risks that are identified must be documented and written into the clinical performance study plan.

The design of a performance study is based on the research question or hypothesis that is to be answered or tested. The study should be planned so that the data collected is of good quality and can be used to answer the current question. Questions and study approaches can vary depending on the purpose of the study.

Information about the structure of the research question or hypothesis on the page Idea

Standard ISO20916: 2019, SIS website External link.

Information about study design and statistical aspects on the page Analysis

In addition to taking into account scientific aspects, it is necessary to ensure that the approach that is best scientifically is also ethically and practically feasible. It can also be good to consider how the study design affects the quality of collected data. A complex study approach may require major training efforts for users and staff or a comprehensive monitoring plan to avoid shortcomings in data quality compared with an approach that largely follows the normal routines of care.

Informed consent
In addition to the requirements that the Swedish Ethics Review Authority places on the written information to be provided to the study participant, there are in IVDR and in ISO 20916: 2019, specific recommendations regarding the information to the participants in a clinical performance study.

When it comes to insurance for study participants, there are also circumstances that are specific to performance studies. If the studies are carried out in the healthcare healthcare provider's operations, the patient insurance that the healthcare healthcare provider is obliged to have applies. However, there is no equivalent to the Pharmaceutical Insurance for medical devices for in vitro diagnostics.

EU regulation on in vitro diagnostic medical devices External link.

Standard ISO 20916: 2019, SIS website External link.

Should the study be reviewed by the Swedish Medical Products Agency?
For intervention studies of clinical performance and other performance studies that involve risks for the subjects in the studies, the study must be reviewed by the Swedish Medical Products Agency.

Current and detailed information about the permit procedures, the Swedish Medical Products Agency's website External link.

Information about the application and registration for clinical performance studies can also be found on the Application page

Compile a clinical performance study plan
If you are going to do a clinical performance study of an in vitro diagnostic product, you need to write a clinical performance study protocol (CPSP). This document shall, among other things. a contain a justification for why the performance study needs to be done and a description of the performance study's objectives, design, method, monitoring, statistical considerations, organization and implementation. IVDR and ISO 20916: 2019 contain detailed information on what should be included.

In addition to the clinical performance study plan, a number of additional appendices in accordance with Chapter I of Appendix XIV of IVDR shall be included in the documents sent to the Swedish Medical Products Agency.

EU regulation on in vitro diagnostic medical devices External link.

ISO 20916: 2019, SIS website External link.

Construct a data collection tool
In an intervention study of clinical performance and other performance studies that involve risks to the subjects in the studies, there must be a CRF, either in paper format or as an electronic system. Electronic CRF (e-CRF) can form the basis of a database created for analysis, while paper CRF needs to be converted to electronic data at a later time. Regardless of format, a CRF is constructed as a number of questions or check boxes that the study staff fills in as the study participant answers questions or undergoes various surveys that generate measured values. Data from the patient record can also be filled in a CRF.

If you use an e-CRF, there are special requirements for the system's functionality and security. For example, an e-CRF must have a so-called logging function to register who may have made changes to the entered data. You must also take responsibility for how the electronic handling of sensitive personal data is carried out and you must know whether the electronic system means that personal data will be handled abroad or in an activity other than the research principal's.

Keep in mind that all data collected in a CRF must be described in the clinical performance study plan that must be approved by both the Ethical Review Authority and the Medical Products Agency. No other data may be collected.

Allocate roles and responsibilities
In accordance with IVDR and ISO 20916: 2019, there are a number of roles with different responsibilities to allocate when planning to conduct a clinical performance study.

The manufacturer is responsible for the design, manufacture, labeling, instructions for use, packaging and states the intended purpose of a medical device for in vitro diagnostics, and then places the product on the market in its own name. It is the manufacturer who must CE mark the product, regardless of who has carried out the tangible production.

The sponsor is the individual or organization responsible for initiating and conducting a clinical performance study. It is common for the sponsor to also be a manufacturer of the in vitro diagnostic product, but this is not a requirement.

The sponsor has the overall responsibility for the implementation of the study and is responsible for, among other things:

  • planning and conducting the clinical study
  • communication with regulatory authorities
  • quality assurance and control
  • possible subcontracting of tasks and functions.

The full description of the sponsor's role and responsibilities can be found in ISO 20916: 2019.

The investigator in charge is the person responsible for conducting a clinical performance study at a trial site. If the study is carried out at several test sites, there must be a responsible investigator at each site. The responsible investigator must have documented training and experience in the field in which the in vitro diagnostic product is to be used. The need for the competence of the responsible tester must be assessed on the basis of the product's area of use.

The full description of the role of the responsible investigator can be found in ISO 20916: 2019.

The tasks of the responsible investigator include:

  • lead the work with the study at the examination site
  • ensure that informed consent from study participants is obtained in accordance with applicable rules and the clinical performance study plan
  • ensure that the study is conducted according to the clinical performance study plan
  • be responsible for ensuring that the study participants receive the medical care that is necessary during and after the completion of the study
  • carry out safety reporting
  • ensure that reliable data is generated.

The investigator has the overall responsibility for the study at the examination site, but may delegate tasks provided that the delegation is made in writing to a person with appropriate education and experience. A signature and delegation list must be established and updated if there are staff changes during the course of the study. In order for a task to be performed by a person other than the investigator, the task must first be delegated.

The monitor is a person appointed by the sponsor and whose responsibility is to make independent checks that the study is carried out in accordance with the clinical performance study plan and the regulations in general. The monitor performs the control by visiting the test sites that participate in the study, reviewing the work and informing about recommended measures to improve the work with the study. After the visit, the monitor writes a report to the sponsor.

In order for the monitor to be able to monitor a study, he or she must, in addition to having scientific and / or clinical prior knowledge, have knowledge of:

  • ISO 20916: 2019
  • the product being tested and how it will be used
  • the clinical performance study plan
  • approved procedure for obtaining informed consent
  • sponsor routines
  • regulatory requirements

The complete description of the monitor's role and responsibilities can be found in ISO 20916: 2019.

Collaboration between business, universities and healthcare
Clinical studies can be performed on one's own initiative by the healthcare system, but it is also common for a company or an academic researcher to have the idea for a new or changed medical device for in vitro diagnostics.

When the medical technology industry and healthcare collaborate on the development of in vitro diagnostic products, for example by conducting a clinical performance study together, the collaboration rules must be followed.

Collaboration rules between health care and the medical technology industry (in Swedish) External link.

When the sponsor plans a clinical performance study in collaboration with the healthcare system, he or she should be aware that specific roles with a certain type of competence must be filled. Read more about roles and responsibilities in the paragraph above. In addition to the competencies that must be recruited to meet the requirements of ISO 20916: 2019, the main rule is that the person who is the responsible researcher in an ethics application must have a PhD.

To get help with contacting clinics that may be interested in conducting your planned performance study, you can use the regional nodes' initiative regarding coordinated study requests.

Establish agreements and manage financial agreements
If the clinical performance study is carried out as contract research, ie that it is another principal than the health service who is the initiator of the study, then an agreement must always be drawn up between the sponsor and the clinic or activity that carries out the study. The agreement shall handle the division of responsibilities in the study and any financial agreements. The healthcare principal often demands compensation for the additional costs that the implementation of the study entails for the business. Financial agreements in contract research must also be reported in the ethics application.

If it is the health care principal himself who is the initiator of the clinical study, it is recommended that a written agreement is made between the researcher and the head of operations about, for example, how additional costs for the clinic are to be financed.

Additional agreements may need to be signed if the study, for example, requires X-rays, pathology or a sample management procedure via a central laboratory.