Consultation outcome

Chapter 7 - Clinical Investigation and Performance Studies

Updated 26 June 2022

The consultation considered whether the UK medical devices regulations should include more detailed requirements for conducting and documenting a clinical evaluation. The objective of this would be to ensure that medical device manufacturers conduct effective, consistent and systematic clinical evaluations of their medical devices, taking into account all relevant clinical data, in order to demonstrate that a medical device is safe and performs as intended.

This would help ensure that medical devices are not placed on the UK market unless there is sufficient evidence of their safety and performance.

Section 31 – Clinical evaluation (general medical devices)

31.1 Proposals and feedback

Currently, manufacturers can use the clinical data arising from investigations of a similar ‘equivalent’ device as evidence that their own device is safe and performs as intended (due to the similarities between the devices). This can result in ‘product creep’ where new devices on the market in practice become very different from their ‘equivalent’ devices.

The MHRA consulted on proposals to introduce stricter requirements for claiming equivalence. These included requirements for an equivalent medical device to be ‘entirely equivalent’ to the manufacturer’s medical device and for appropriate contractual arrangements to be in place with the manufacturer of the predicate device. Of 218 respondents:

• 61% supported the proposals outlined in the consultation relating to claiming equivalence
• 35% were not in support of these proposals
• 4% did not know or had no opinion

Those who supported this proposal reasoned that industry, patients and other stakeholders need regulatory certainty and that requirements around entire equivalence would lead to improved patient and public safety.

Suggestions for additional requirements that could be introduced around claiming equivalence included:

• the contractual arrangements referred to above should cover adverse event data
• recalls of predicate devices should be extended to the chain of ‘equivalent’ devices
• it was also noted that the approach may cause issues for registering or listing legacy devices

Comments from those that did not support the proposal were mainly based on the concern that more stringent requirements for claiming equivalence could stifle innovation and would be burdensome on industry and resources. Some respondents considered that requirements around claiming equivalence should be balanced against the class and risk of the device. Others caveated their support and commented that we should align with the EU’s position on equivalence, rather than requiring that devices must be “entirely equivalent”.
We also invited views on equivalence from respondents to the abridged consultation (Chapter 17). Of the 56 respondents to this question:

• 80% were in favour of introducing stricter requirements for claiming equivalence
• 13% were not in favour
• 7% did not know or had no opinion

The abridged consultation also invited views from those who answered ‘yes’ to the previous question to indicate their preferred requirements for claiming equivalence. Out of 44 responses selected options as follows:

• the device the manufacturer is claiming equivalence to, should be “entirely equivalent” to the manufacturer’s medical device (on a biological, physical, and clinical basis) (39%)
• where a manufacturer does claim equivalence to another medical device, they must have a contract with the manufacturer of that medical device to allow them full access to the device’s necessary documentation (9%)
• manufacturers claiming equivalence must have post-market studies in place to collect their own data, once the device is on the market (27%)
• manufacturers of certain devices such as implantable and Class III devices cannot claim equivalence to other devices except in specific circumstances (14%)
• other (11%)

When asked to provide rationale for the answers on clinical evaluations in Chapter 17, some respondents suggested that requirements should align with EU and US approaches, while others noted that equivalent devices should either be the same as or similar to the predicate device. Other comments identified a need to consider equivalence of manufacturing techniques, while some noted a preference for a risk-based approach, with higher risk devices subject to more stringent requirements.

We invited views on whether manufacturers of products without an intended medical purpose should be required to perform clinical investigations or other pre-market studies involving human subjects/participants and that such products should be regulated under the UK medical devices regulations, unless reliance on existing clinical data from an entirely equivalent medical device is duly justified. Of 213 respondents:

• 61% supported the proposal
• 17% did not support the proposal
• 23% did not know or had no opinion

31.2 The government response

After careful consideration of consultation responses, the government intends to introduce requirements on entire equivalence on a biological, technical and clinical basis (please note that we have amended the wording from “physical” basis in the consultation document to “technical” basis in order to align with the recognised international terminology). This approach would take us beyond the equivalence requirements in the EU MDR. There was support for this among consultation respondents and we consider that this approach will lead to improvements in patient and public safety. The government recognises that there was also support among consultees for alignment with EU requirements. However, we consider that the proposed approach will help mitigate the risks of ‘product creep’ where new devices on the market in practice become very different from their ‘equivalent’ devices. In addition to making legislative changes in this area, the MHRA will provide clear and detailed guidance on this topic.

The government also intends to proceed with the proposal to introduce clinical investigation requirements for products with similar functions and risk profiles to medical devices that do not have an intended medical purpose. We will provide supplementary guidance on these requirements and will work with the Health Research Authority and the Devolved Administrations regarding any requirements for ethical review.

Section 32 – Performance evaluations (IVDs)

32.1 Proposals and feedback

We sought views on whether confirmation of conformity of an in vitro diagnostic device (IVD) within the UK medical devices regulations should be based on scientific validity, analytical and clinical performance data. Of 140 respondents:

• 86% supported the proposal
• 1% did not support the proposal
• 13% did not know or had no opinion

The consultation invited views on whether manufacturers should be required to produce a performance evaluation report as part of the technical documentation for the device. Of 139 respondents:

• 86% supported the proposal
• 1% did not support the proposal
• 13% did not know or had no opinion

We asked consultees whether manufacturers should be required to specify and justify the level of clinical evidence necessary to demonstrate conformity with the UK medical devices regulations. Of 137 respondents:

• 81% supported the proposal
• 4% were unsupportive
• 15% did not know or had no opinion

We invited views on whether the UK medical devices regulations should require manufacturers to rely on data from their own clinical performance studies unless they can justify reliance on other sources of clinical performance data. Of 138 respondents:

• 74% supported the proposal
• 14% did not support the proposal
• 12% did not know or had no opinion

Those in favour of introducing the above proposals suggested that the following factors could be included in the justification:

• proof of safety and functionality
• the device could be substantially rather than entirely equivalent to the predicate device
• published peer-reviewed literature / study data
• reliance on other sources (in addition to small scale studies) could get products to market more quickly
• clinical evidence could be derived from real world evidence
• clinical evidence could be derived from registries

Other respondents commented that alignment with the EU IVDR and with relevant standards would be beneficial.

We asked consultees whether the UK medical devices regulations should require that the performance evaluation is updated throughout the lifetime of the IVD, and that performance evaluation data should be used to update the summary of safety and clinical performance (SSCP) and the post-market performance follow-up report (PMPF). Of 137 respondents:

• 82% were in favour of the proposal
• 5% of did not support the proposal
• 13% did not know or had no opinion

When asked how the evaluation should be updated by the manufacturer and whether any other technical documentation should be updated, respondents made the following suggestions:

• requirements should be proportionate to device risk class (for example, more frequent updates for higher risk devices)
• updates should be made on a continuous basis, for example, when a manufacturer has new information on risks associated with a device or when the use case changes or when the design or function changes
• the documents should be updated to a regular schedule - for example, annually, biannually, every 5 years and product lifecycle should be considered
• manufacturers should inform users of issues with false results and the Yellow Card scheme could support this

Other comments provided on this topic included:

• there is a need to take account of Approved Body capacity in terms of validation of technical documents
• there is a need to avoid additional burdens, particularly for small and medium-sized enterprises (SMEs) and for well-established devices, and the requirements should be proportionate

32.2 The government response

Taking into account the high degree of support, it remains the government’s intention to introduce the proposals outlined in this section of the consultation. The government also intends to provide guidance regarding what the justification for reliance on other sources of clinical performance data should include. In developing the guidance, the MHRA will reflect on the points raised in the consultation, including the need for international alignment, the role of designated standards in demonstrating compliance, and the clinical performance data sources that can be used to support the justification.

Reflecting on consultation feedback, the government considers that the requirement should be that the SSCP and PMPF are updated on at least an annual basis. There would be nothing to preclude a manufacturer from updating these documents more frequently, for example, on a continuous basis or in response to changes in device design or function. This approach aligns with international practice. We consider that it is best practice for the manufacturer to regularly review available evidence on state of the art to ensure that they are keeping abreast of any new developments.

This approach is intended to support international alignment and consistency for manufacturers. The government is mindful of the need to avoid unnecessary manufacturer burden (particularly for SMEs) but considers that setting requirements for an annual review should not be overly onerous and is necessary for safety reasons. As noted above, this approach does not prevent manufacturers from updating more frequently where necessary and we would encourage this.

Section 33 - General requirements regarding clinical investigations (general medical devices)

33.1 Proposals and feedback

Requirements for clinical investigations

The consultation invited views on whether clinical investigations regulated under the UK medical devices regulations should be limited to those carried out for one of the purposes outlined in the consultation. 175 responses were received, of which:

• 75% were in support of the proposal
• 10% did not support the proposal
• 15% did not know or had no opinion

In regard to the proposal that in situations where the sponsor of a clinical investigation or performance study is based outside the UK, they should be required to appoint a legal representative in the UK, 177 responses were received, of which:

• 63% were in support of the proposal
• 16% did not support the proposal
• 21% did not know or had no opinion

The consultation invited views on whether the legal representative should be responsible for ensuring compliance with the clinical investigation sponsor’s obligations and be the addressee for all communications with the sponsor. Of the 175 responses received:

• 62% were in support of the proposal
• 16% were not in favour of the proposal
• 22% did not know or had no opinion

On the proposal that any communication with that legal representative should be deemed to be communication with the clinical investigation sponsor, 174 responses were received, of which:

• 63% supported the proposal
• 16% were not in favour of the proposal
• 21% did not know or had no opinion

The consultation invited views on whether the UK medical devices regulations should set out the sponsor obligations for a clinical investigation. 174 responses were received, of which:

• 76% were in support of the proposed approach
• 9% were not in favour of this approach
• 15% did not know or had no opinion

Suggestions of other requirements that respondents considered should be introduced for the sponsor of a clinical investigation included:

• requirement for the sponsor to publish the study summary
• requirements around the reporting of serious adverse incidents
• requirement to appoint an independent monitor
• requirement to appoint a UK Responsible Person

Some respondents raised concerns over additional burdens that may be associated with these requirements.

The consultation invited views on whether the UK medical devices regulations should set out the minimum requirements for the clinical investigation report, as set out in the consultation. Of the 177 responses:

• 87% were in favour of the proposal
• 6% were not in favour
• 7% did not know or had no opinion

Respondents made the following suggestions for other requirements which they considered should be introduced regarding the clinical investigation report:

• refer in the regulations to specific standards (for example, International Organization for Standardization (ISO) standard 14155, and ISO 20916) to ensure consistency
• an accessible report or summary, suitable for lay persons, should be published
• clarify timelines on notification of end of trial and submission of reports
• the report should include patient-related outcomes
• a template of the clinical investigation report should be provided in guidelines

Other respondents commented that alignment with the EU MDR/IVDR would be beneficial.

The consultation sought views on whether the UK medical devices regulations should require the sponsor to publish the clinical investigation report. 174 responses were received, of which:

• 61% were in support of this proposal
• 25% were not in support of the proposal
• 14% did not know or had no opinion

The consultation sought views on whether the UK medical devices regulations could be amended to further clarify and supplement the existing requirements relating to the methods for a clinical investigation. 175 responses were received, of which:

• 79% were in support of this proposal
• 12% were not in support
• 9% did not know or had no opinion

Respondents also outlined other requirements, relating to the methods for a clinical investigation, that they considered could be introduced - including:

• clinical investigation sites and investigator training should be strengthened and recorded
• we should require the recording of patient outcomes
• we should require long term follow-ups
• MHRA should provide a template for reports, with focus on endpoints and outcomes

Many respondents commented that alignment with the EU MDR and ISO 14155 would be beneficial and that there is a strong need for specific guidance to support the regulations. Others noted that more clarity is required on what is meant by ‘clinical benefit’.

The consultation invited views on whether the UK regulations should set out more detailed requirements for the clinical investigation plan, as outlined in the consultation. 176 responses were received, of which:

• 79% were in favour of the proposal
• 10% were not in favour of the proposal
• 11% did not know or had no opinion

Respondents also made the following comments in relation to requirements for the clinical investigation plan:

• there is a need to align with the EU MDR
• standards are sufficient and there is no need to add further requirements to the regulations
• it is not necessary to include financial arrangements in the clinical investigation plan

The MHRA consulted on proposals to expand the conditions that must be met when performing a clinical investigation and set out a number of possible requirements in the consultation. 174 responses were received, of which:

• 79% were in support of the proposal
• 10% did not support the proposal
• 11% did not know or had no opinion

The MHRA asked respondents to outline any other requirements that should be met when performing a clinical evaluation. Key points can be summarised as follows:

• requirements should align with the EU MDR and ISO 14155; or potentially with medicines clinical trials
• clinical Investigations should represent diverse populations, racial bias should be reduced where possible and we should consider using gender neutral terms, for example, refer to breastfeeding ‘people’ rather than ‘women’
• the proposed requirements may be overly stringent
• the requirement for a UK-based legal representative was challenged

The consultation invited views on whether the UK medical devices regulations should set out the rights of subjects/participants to withdraw from clinical investigations at any time without any resulting detriment and without having to provide any justification. 172 responses were received, of which:

• 83% were in favour of the proposal
• 5%were not in favour of the proposal
• 12% did not know or had no opinion

When asked for views on the introduction of qualification requirements for investigators of clinical investigations and personnel involved in clinical investigations as set out in the consultation, 173 responses were received, of which:

• 79% were in favour of the proposal
• 6% were not in favour of the proposal
• 15% did not know or had no opinion

Some respondents supported the consultation proposals and felt that no additional requirements beyond those proposed were needed for investigators of and personnel involved in clinical investigations, and many respondents proposed that aligning with EU MDR and IVDR would be beneficial.

Respondents suggested that the following requirements should be introduced for investigators of and personnel involved in clinical investigations:

• follow relevant standards
• follow Good Clinical Practice Guidelines
• be inclusive - for example, include nurses, clinical scientists and other health care professionals

There was disparity in views regarding the need for qualifications, with some respondents advocating that relevant experience was equally or more important than academic qualifications. Others considered that it would be important for the investigator and other personnel to hold relevant qualifications.

33.2 The government response

After careful consideration of responses to the proposals outlined in this section, it remains the government’s intention to proceed with all areas, for the reasons set out below.

Based on the consultation response we intend to set out in the regulations, the purposes for which clinical investigations shall be designed, authorised, conducted, recorded and reported in line with the consultation proposals – namely:

1. a. to establish and verify that, under normal conditions of use the medical device achieves the performance intended by its manufacturer
2. b. to establish and verify the clinical benefits of a medical device as specified by its manufacturer
3. c. to establish and verify the clinical safety of the medical device and to determine any undesirable side-effects, under normal conditions of use of the medical device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the medical device.

We consider that this approach will provide clarity and consistency for manufacturers and sponsors.

Based on the consultation response we intend to require non-UK-based sponsors of clinical investigations and performance studies to appoint a UK-based legal representative. This will ensure that the MHRA has a UK-based point of contact in relation to all clinical investigations, which will lead to more streamlined and efficient communications and will facilitate MHRA oversight.

The government considers that the sponsor obligations set out in the consultation are necessary to facilitate enforcement activities and therefore improve public and patient safety, and the proposals were supported by the majority of respondents. The MHRA will support manufacturers in transitioning to these changes, including through the provision of detailed guidance, covering aspects such as publication requirements and timings.

It remains the government’s intention to proceed with the proposal to set out the minimum requirements for the clinical investigation report, as detailed in the consultation. Reflecting on the consultation feedback, we will require that the clinical investigation report shall be accompanied by a publicly accessible lay person summary. The MHRA will clarify in the regulations, the time frame for publication. We will take international frameworks and standards into consideration as we take forward this work. Further guidance and templates will also be developed for the clinical investigation report. We will work with the Health Research Authority and the Devolved Administrations in developing this guidance.

The government intends to take forward the proposal to introduce additional detailed requirements for conducting clinical investigations relating to methods for a clinical investigation, as outlined in the consultation. The MHRA will take international frameworks and standards into account as we take forward this work. We will also develop guidance to set out further detail on the regulatory requirements, taking account of the consultation feedback.

It remains the government’s intention to proceed with the proposal for setting out the detailed requirements for the clinical investigation plan, including those outlined in the consultation.

The government intends to set out in the UK medical devices regulations, the requirements that must be met for performing a clinical investigation, including those outlined in the consultation. We consider the points raised around bias and diversity to be very important and will address them within the regulations and supplementary guidance. We will work with the Health Research Authority and the Devolved Administrations in developing this guidance. In addition, the MHRA will continue to support the review led by Dame Margaret Whitehead into identified inequities for medical devices announced on 4 February 2022: Government launches landmark reviews to tackle health disparities - GOV.UK (www.gov.uk).

Based on the consultation response it remains the government’s intention to set out in the regulations, the rights of participants to withdraw from a clinical investigation, as outlined in the consultation, so that this is clear for subjects/participants and sponsors.

It remains the government’s intention to proceed with the proposal to set out in the regulations, requirements for investigators of clinical investigations and personnel involved in clinical investigations, with supplementary guidance to provide additional detail. Reflecting on consultation feedback, our intention is to take a comprehensive approach here with regards to the relevant skills and qualifications that will be applicable.

Section 34 – General requirements regarding performance studies (IVDs)

34.1 Proposals and feedback

The MHRA consulted on introducing a requirement that, where appropriate, performance studies shall be performed in circumstances similar to the normal conditions of use of the medical device. 133 responses were received, of which:

• 83% were in favour of the proposal
• 5% were not in favour of the proposal
• 12% did not know or had no opinion

The consultation sought views on whether the UK medical devices regulations should set out in detail, the specific requirements for any performance study, as outlined in the consultation document. 131 responses were received, of which:

• 73% supported the proposal
• 5% were not in favour
• 22% did not know or had no opinion

Many respondents considered that aligning with the EU IVDR and ISO 20916 / 14155 standards would be beneficial. Others noted that these requirements should be set out in guidance rather than in legislation.

Respondents made the following suggestions for the specific requirements of a performance study:

• align with Clinical Trials of Investigational Medicinal Products (CTIMPs)
• such studies should be subject to ethical review and approval
• there is a need to define ‘invasive sampling’
• follow Good Clinical Practice (GCP) guidance, for example, on transparency and informed consent
• there should be an exemption for research only IVDs

The consultation proposed that the UK medical devices regulations could be amended to set out the obligations applicable to sponsors of performance studies, including a requirement to provide a publicly accessible summary of the study at the time of registration and on completion of the summary. Of 130 respondents:

• 78% were in favour of introducing the proposal
• 7% did not support the proposal
• 15% did not know or had no opinion.

A number of respondents considered that aligning with the EU IVDR and relevant standards would be beneficial. Others felt that these obligations should be set out in guidance rather than in legislation.

When invited to outline any other obligations that should apply to the sponsor of a performance study, respondents made the following comments:

• the study summary should not need to be made publicly available at all or at the point of registration

• there is a need to clarify how the study summary should be made publicly available and the types of study this obligation would apply to

On the proposal that sponsors should be required to implement a clinical performance study plan, 128 responses were received, of which:

• 78% were in favour of the proposal
• 7% were not in favour of the proposal
• 15% did not know or had no opinion

On whether detailed requirements for the clinical performance study plan should be set out in the UK medical devices regulations, 128 responses were received, of which:

• 74% were in favour of the proposal
• 11% were not in favour of the proposal
• 15% did not know or had no opinion

When invited to suggest possible requirements that could be put in place for the clinical performance study plan, respondents commented that:

• there should be a requirement to take account of patient feedback
• there should be different requirements for archived and left-over samples

A number of responses proposed that we align with the EU IVDR and ISO standards 20916 / 14155, and some noted that these proposals would be duplicative of existing practice (for example, ISO and United Kingdom Accreditation Service (UKAS)). Others considered that these obligations should be set out in guidance rather than in legislation.

The consultation invited views on whether these obligations should also extend to other types of performance study (other than clinical performance studies).128 responses were received, of which:

• 40% were in support of the proposal
• 28% were not in support of the proposal
• 32% were not sure or had no opinion

The consultation invited views on whether the UK medical devices regulations should set detailed requirements for performance studies, including purpose, methods, objectives and ethical considerations for a performance study. Of 129 respondents:

• 74% were in favour of the proposal
• 10% were not in favour of the proposal
• 16% did not know or had no opinion.

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU IVDR and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through the regulations.

On the proposal that sponsors should be required to provide a clinical performance study report, 128 responses were received, of which:

• 76% were in support of the proposal
• 9% were unsupportive of the proposal
• 15% did not know or had no opinion

The consultation invited views on whether the UK medical devices regulations should set out the minimum requirements for the clinical performance study report, as outlined in the consultation. Of 127 responses:

• 72% supported the proposal
• 13% did not support the proposal
• 15% did not know or had no opinion

Respondents made the following suggestions for requirements that could be put in place for the clinical performance study report:

• there should be a requirement to include a lay person summary
• requirements should be aligned with requirements for the clinical investigation report
• clarify how and where the report would be published and whether it would need to be peer reviewed
• suggestion that we should follow relevant reporting guidelines, for example, Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines
• there is a need to be mindful of commercial sensitivities
• there is a need to consider handling of bias

A number of respondents felt that the UK Regulations should align with international frameworks, such as the EU IVDR and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than regulations.

The consultation invited views on whether minimum requirements for the clinical performance study report should also extend to analytical performance studies. Of 126 responses:

• 48% supported the proposal
• 23% were not supportive
• 29% did not know or had no opinion

A number of respondents felt that the UK Regulations should align with international frameworks, such as the EU IVDR and relevant ISO standards. Some respondents also suggested that clear definitions on the scope and requirements of different types of study are required.

Suggestions for other types of performance study (other than clinical performance studies) that should be subject to a clinical performance study report were as follows:

• carry-over
• sample stability
• analytical performance studies

On the proposal that the UK medical devices regulations should require the clinical performance study report to be published, 124 responses were received, of which:

• 56% were in favour of the proposal
• 25% were not in support of the proposal
• 19% did not know or had no opinion

Regarding the proposal that all performance studies involving human samples should be subject to ethical review by an ethics committee, 130 responses were received, of which:

• 49% were in favour of introducing this requirement
• 35% were not in favour of introducing this requirement
• 16% did not know or had no opinion

On the proposal to introduce a requirement that performance studies involving companion diagnostics should be subject to the same requirements as all other performance studies, 128 responses were received, of which:

• 70% were in support of the proposal
• 27% did not support the proposal
• 2% did not know or had no opinion

In regard to the proposal that performance studies involving companion diagnostics using only left-over samples should not be subject to the same requirements as all other performance studies, 129 responses were received, of which:

• 39% were in favour of the proposal
• 24% were not in favour
• 37% did not know or had no opinion

The consultation invited views on the proposed introduction of the requirement that performance studies involving companion diagnostics using only left-over samples should be notified to the MHRA. Of 129 responses:

• 47% were in favour of the proposal
• 19% were not in favour
• 34% did not know or had no opinion

On the proposal that the conditions for conducting a performance study should be set out in the UK medical devices regulations, 130 responses were received, of which:

• 76% supported the proposal
• 12% were not in support of the proposal
• 12% did not know or had no opinion

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU IVDR and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through legislation.

Some respondents also suggested that GCP guidance should be used when conducting a performance study, and that there are existing frameworks that could also be utilised (for example, those provided by the Health Research Authority (HRA)).

In regard to setting out in the regulations, the rights of subjects to withdraw from a performance study at any time without any resulting detriment and without having to provide any justification, 130 responses were received, of which:

• 84% supported the proposal
• 3% were not in support of the proposal
• 13% did not know or had no opinion

The consultation invited views on whether the regulations should include requirements around the requisite skills and qualifications for the investigator of and other personnel involved in the performance study, as set out in the consultation. Of the 129 responses:

• 71% were in support of the proposal
• 6% were not in support of the proposal
• 23% did not know or had no opinion

Many respondents suggested that aligning with international approaches such as the EU IVDR and the use of relevant standards would be beneficial.

Other suggestions and comments included:

• guidelines on GCP should be followed
• there is a need to take an inclusive approach in terms of requisite skills and qualifications, so as to avoid excluding nurses, clinical scientists and other health care practitioners
• a need to avoid being overly prescriptive, which may risk excluding academics and SMEs, for example
• conversely some respondents felt that key personnel should be doctors or surgeons
• there is a need to define what is meant by ‘suitably qualified’ in relation to the requisite education, training or experience in the relevant medical field and in clinical research methodology (as set out in the consultation)

As with the corresponding questions on clinical investigations, there was a degree of disparity among respondents regarding the balance of relevant experience and formal qualifications. Some respondents considered relevant experience to be of greater value than academic qualifications, whereas others were of the view that qualification requirements should be set.

The consultation invited views on the proposal that the UK medical devices regulations should require that, where appropriate, the facilities where the performance study is to be conducted should be suitable for the conduct of the study. Of 126 responses:

• 82% were in support of the proposal
• 13% were not in support of the proposal
• 5% did not know or had no opinion

The consultation proposed that, where appropriate, the setting and users of the medical device in the clinical performance study should be similar to the intended setting and intended users of the medical device. Of the 126 responses received:

• 80% supported the proposal
• 6% were not in support of the proposal
• 14% did not know or had no opinion

Consultees were asked to provide any reasoning and supporting evidence for the answers given in this section. Respondents were broadly supportive, noting that performance studies should reflect real world use conditions and user populations as this approach would generate more accurate data.

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU IVDR and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations.

34.2 The government response

Having considered the views of respondents, the government intends to proceed with the proposals laid out in this section of the consultation, to provide clarity and ensure that performance studies are carried out in a consistent way.

The government intends to proceed with the proposal to set out in detail, the specific requirements for any performance study. We note the points raised around the need for guidance and intend to publish detailed guidance to accompany the regulatory requirements. This will cover concepts referred to in the legislation, such as ‘invasive sampling’.

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal to set out set out the obligations of the sponsor of a performance study, as outlined in the consultation. The government will provide supplementary guidance on the detailed requirements, in line with consultation feedback.

Having taken account of consultation feedback, the government intends to proceed with the proposal that sponsors should be required to implement a clinical performance study plan. We also intend to set out in legislation, the detailed requirements for the clinical performance study plan.

In addition, we intend to proceed with the proposal for extending the requirement for a clinical performance study plan to other types of performance studies (other than clinical performance studies). Although there was not an overall majority, the largest portion of respondents supported the proposal to extend the obligation and we consider this will create a more robust, consistent approach to conducting these studies.

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal that detailed requirements for the purpose, methods, objectives and ethical considerations for a performance study should be outlined in the regulations. In developing the regulations, the government will take account of international approaches. We recognise the importance of standards in this area – however we consider that setting out requirements in legislation will place them on a more robust footing and provide clarification for manufacturers and sponsors.

The government intends to take forward the proposal that sponsors should be required to provide a clinical performance study report. In developing the regulations, the government will take account of international approaches. As above, we recognise the importance of standards in promoting best practice but consider it necessary to set out requirements in legislation to facilitate a clear and consistent approach. Further consideration will be given to how we approach the handling of bias, including through guidance.

It also remains the government’s intention to proceed with the proposal to require analytical performance studies to have performance study reports. Although there was not an overall majority, the highest portion of those who responded were in favour of extending the obligation and the government considers that this approach will create a more robust, consistent approach to conducting these studies.

After careful consideration, the government intends to proceed with the proposal for requiring all performance studies involving human samples to be subject to ethical review by an ethics committee. Although there was not an overall majority, almost half of the respondents were in support of extending the obligation and the government considers that this approach will create a more robust, consistent approach to conducting these studies. We will work with the Health Research Authority and Devolved Administrations as we take forward this work.

Based on the consultation response, it remains the government’s intention to introduce the consultation proposals to require that performance studies involving companion diagnostics are subject to the same requirements as all other performance studies. This approach was supported by the majority of respondents, and we consider that it will create a more robust, consistent approach to conducting these studies.

It also remains the government’s intention to introduce the proposal that performance studies involving companion diagnostics using only left-over samples should not be subject to the same requirements as the types of performance studies outlined in Section 34.5 of the consultation. However, performance studies involving companion diagnostics using only left-over samples should be subject to the same requirements as all other performance studies using left-over samples.

The government also intends to introduce the proposal that performance studies involving companion diagnostics using only left-over samples should be notified to the MHRA. Although there was not an overall majority, almost half of the respondents were in favour of the proposal and, as above, the government considers that it will create a more robust, consistent approach to conducting these studies.

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal that the conditions for conducting a performance study, as outlined in the consultation, should be set out in the regulations. In developing the regulations, the government will take account of international approaches, including the IVDR.

Based on the consultation response, the government intends to set out in the regulations, provisions concerning the rights of subjects/participants to withdraw from a performance study. We consider that this would provide clarity to both sponsors and study subjects/participants so that they are aware of and able to exercise their rights. We will work with the Health Research Authority and the Devolved Administrations as we take forward this work.

Having considered the views of respondents, the government intends to proceed with the proposal to set out requirements for the investigator and other personnel involved in the performance study. We will set out the details of the requirements in supplementary guidance, taking account of the need to take an inclusive approach.

Based on the consultation response, we intend to introduce the proposals, as outlined in the consultation, for the settings, facilities and users for conducting performance studies. In developing the regulations, the government will take account of international approaches and the role of standards in promoting best practice.

Section 35 – Informed consent

35.1 Proposals and feedback

The consultation invited views on the proposed introduction of requirements for obtaining informed consent from individuals participating in a clinical investigation or performance study. Of the 173 responses received:

• 85% supported the proposal
• 8% were not in support of the proposal
• 7% did not know or had no opinion

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU MDR and IVDR, the U.S. Food and Drug Administration (FDA), and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations. In addition, some respondents felt that informed consent should fall within the remit of ethics committees.

Respondents also outlined additional considerations for obtaining informed consent, including:

• the approach should align with applicable medicines / clinical trials regulations
• the approach should align with the CTIMPs
• the approach should follow GCP and the Declaration of Helsinki
• the MHRA should work with the Health Research Authority on this matter
• the approach should consider the NHS Act 2005 s251
• involve patients and the public
• use plain English for consent forms
• risks and benefits should be explained
• de-identified surplus samples should be exempt from informed consent requirements
• the person obtaining consent should be required to sign relevant forms and paperwork in addition to the subject or participant

Respondents were asked to outline any circumstances under which they considered that the requirements for informed consent should be waived. Some respondents felt that informed consent requirements must never be waived. Others considered that informed consent is covered by other frameworks that the UK should align with and that there is no need for additional requirements to be set. Further comments considered that the UK regulations should align with international frameworks, such as the EU MDR and IVDR.

Other comments included:

• waive informed consent requirements for observational studies
• waive informed consent requirements for de-identified data and / or left-over samples
• waive informed consent requirements for life or death / emergency situations
• follow the Declaration of Helsinki
• there is a risk that de-identified samples can later be re-identified

Respondents were asked to provide any reasoning and supporting evidence for the answers given in response to Section 35 of the consultation.

A number of comments were similar to points raised above in response to pervious questions, including the need for international alignment, advocation of the use of standards and calls for guidance rather than regulation in this area.

Some respondents commented on their personal experiences of injuries caused by surgical mesh implants, noting that they had not been properly consented to their procedures - highlighting the need for clear and robust regulation in this area, rather than reliance on guidance.

35.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the introduction of requirements for obtaining informed consent from individuals participating in a clinical investigation or performance study.

In the consultation feedback, a number of respondents highlighted existing standards, legislation and guidance documents that outline best practice on obtaining informed consent. The government is mindful of the need to align with best practice and avoid duplication. However, we consider that, given the importance of this issue and the points raised by consultees, there is a need to set out clear requirements in legislation that align with and complement existing frameworks. This will provide clarity and consistency for both public and private sector entities. We will work closely with the Health Research Authority and the Devolved Administrations in developing the regulations and will supplement legislative provisions with clear guidance. In addition, we will reflect on need for alignment with requirements for medicines.

The government also intends to set out the circumstances in which requirements for informed consent might be waived, as outlined in the consultation. This may apply to studies using left over or archived specimens, where they have been sufficiently de-identified and/or prior informed consent has been provided in a generic form to cover the use of the specimens for such purposes. Any waiver of informed consent would require approval by a research ethics committee, in line with international standards and existing best practice.

Section 36 – Specific requirements for clinical investigations / performance studies

36.1 Proposals and feedback

The consultation sought views on whether additional requirements should apply to clinical investigations or performance studies on minors, as set out in the consultation. Of the 163 responses:

• 73% were in favour of this approach
• 12% were not in support of the proposal
• 15% did not know or had no opinion

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU MDR and IVDR, and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations.

Consultees were asked to suggest other requirements which could be introduced for clinical investigations or performance studies on minors. Responses can be summarised as follows:

• information provided to subjects/participants should be adapted accordingly
• we should consider the capacity of minors to consent and any safeguarding issues
• parental consent should be taken into account
• there should be no financial incentives offered for participation (other than compensation for expenses)
• there is a need to clarify how information pertaining to the health of the subject/participant should be communicated (including genetic information)
• consent should be sought later once the minor reaches the age of legal competence
• the subject’s/participant’s right to withdraw should be respected
• there is a need to clarify what is meant by ‘direct benefit’ (as set out in the consultation) – meaning whether this is a health-related or other type of benefit
• there is a need to clarify whether all or any of the requirements set out in the consultation would need to be met

The consultation sought views on whether additional requirements should apply to clinical investigations or performance studies on pregnant or breastfeeding women, as set out in the consultation. Of 160 respondents:

• 70% supported the introduction of additional requirements
• 13% were not in support of the proposal
• 17% did not know or had no opinion.

When asked to outline other requirements that should apply to such studies, some respondents felt that no additional requirements were needed beyond those set out in the consultation. A number of respondents considered that the UK regulations should align with international frameworks, such as the EU MDR and IVDR, the Declaration of Helsinki and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through Regulations.

Suggestions for other requirements which could be introduced for clinical investigations or performance studies on pregnant or breastfeeding women were as follows:

• there should be long-term post-natal follow up on babies in cases where their mothers had participated in a clinical investigation or performance study during pregnancy
• counselling should be provided for studies that involve pre-natal genetic testing
• no financial incentives should be offered (beyond compensation for expenses)
• there is a need for specific risk assessment
• relevant documentation should be retained long-term
• procedures should be in place for recalls and remedial action

Respondents were asked to provide any reasoning and supporting evidence for the answers given in Section 36 of the consultation.

A number of responses were similar to points raised in pervious questions, including the need for international and cross-UK alignment, as well as advocation for the use of standards and guidance rather than legislation.

Other responses highlighted the importance of not excluding these groups from clinical investigations or performance studies. Some respondents commented that studies on ‘difficult to study’ patient populations, such as pregnant women, should not be limited by the participant’s medical condition as this approach may miss opportunities to fill evidence gaps for these populations.

36.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal to introduce additional requirements for clinical investigations or performance studies on minors. The government considers that there is a need to set out these requirements in legislation to provide clarity to manufacturers and sponsors and so that a consistent approach applies to public and private sector entities.

The government is mindful of the need for the UK medical devices regulations to complement existing frameworks and the MHRA will work closely with the Health Research Authority and the Devolved Administrations as we develop the legislation.

In addition to the consultation proposals, respondents raised the need to adapt information about the study to the maturity of the subject/participant, to ensure that no financial incentives or inducements are offered (beyond compensation for expenses), that the right to withdraw should be respected and that explicit consent should be sought from the subject/participant once they reach the age of legal competence. The government intends to also include these provisions in the regulations.

The government will also publish supplementary guidance on these matters and others raised in the consultation – for example on the definition of ‘direct benefit’ and on the reporting of genetic information to subjects/participants.

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal to introduce additional requirements for clinical investigations or performance studies on pregnant or breastfeeding women.

In the consultation feedback, a number of respondents highlighted existing standards, legislation and guidance documents that outline best practice. The government considers that there is a need to set out in legislation, the requirements that apply to clinical investigations and performance studies on pregnant or breastfeeding women so that this is very clear to subjects/participants, manufacturers and sponsors and so that a consistent approach applies to public and private sector entities.

The government is mindful of the need to complement existing frameworks and avoid unnecessary duplication, and we will work closely with the Health Research Authority and the Devolved Administrations as we develop the legislation.

In addition to the points included in the consultation, respondents raised the need to ensure that there are no financial incentives or inducements for participation in clinical investigations and performance studies (beyond compensation for expenses). We will address these points in the regulations.

The government does not intend to omit the requirement for there to be an expectation that clinical investigations and performance studies on the above populations will produce a direct benefit to the minor / pregnant or breastfeeding woman, outweighing the risks and burdens involved. However, for pregnant or breastfeeding women, our intention is that the regulations will provide that sponsors should demonstrate that a study of comparable effectiveness cannot be carried out on women who are not pregnant or breastfeeding. We will require a risk assessment to be conducted to demonstrate that the clinical investigation or performance study poses a minimal risk to the subject/participant concerned, or their embryo, foetus or child after birth.

Section 37 – Clinical investigations / Performance studies in emergency situations

37.1 Proposals and feedback

The consultation invited views on whether the conditions should be set out in which informed consent to participate in a clinical investigation or performance study may be obtained or given after the decision to include the subject/participant in a clinical investigation or performance study due to an emergency situation. 144 responses were received, of which:

• 73% supported the proposal
• 5% were not in support of the proposal
• 22% did not know or had no opinion

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU MDR and IVDR, and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations.

Supporting evidence and comments for the responses given above can be summarised as follows:

• consent should always be sought
• delegated consent (for example from next of kin) is preferred
• there is a need to define what is meant by ‘emergency situation’
• CTIMPs provide a model here

The consultation proposed that systems should be put in place for compensation for any damage suffered by a subject/participant as a result of participating in a clinical investigation or performance study conducted in Great Britain. In the consultation we noted that this could be in the form of insurance, a guarantee or a similar arrangement, proportionate to the nature and extent of the risk. Of the 143 responses received:

• 76% were in support of the proposal
• 9% were not in support of the proposal
• 15% did not know or had no opinion

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU MDR and IVDR, and relevant ISO standards. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations.

Other supporting evidence and comments for the responses given in Section 37 can be summarised as follows:

• there is a need to confirm whether requirements would apply to both pre- and post-approval studies
• compensation requirements would help ensure manufacturer accountability
• this approach would deliver safety benefits
• insurance premiums can be cost-prohibitive, especially for the academic sector and SMEs, and the MHRA should liaise with the insurance sector on this matter
• the approach outlined in the consultation is bureaucratic - redress is already available
• we should put in place a collective or mutual insurance scheme

37.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal that the conditions should be set out in which informed consent to participate in a clinical investigation or performance study may be obtained or given after the decision to include the subject/participant in a clinical investigation or performance study due to an emergency situation.

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU IVDR and relevant ISO standards. In developing the regulations, the government will take into consideration international approaches, including relevant standards.

The government will publish detailed guidance to supplement the legislative requirements and will work with Health Research Authority and the Devolved Administrations to ensure that the legislative requirements complement wider frameworks. In addition, we will reflect on need for alignment with requirements for medicines.
Having considered the views of respondents, it remains the government’s intention to proceed with the proposal that systems should be put in place for compensation for any damage suffered by a subject/participant as a result of participating in a clinical investigation or performance study conducted in Great Britain.

On financial coverage / compensation requirements, it was noted that setting requirements out in the regulations would facilitate improved accountability and ultimately deliver patient safety benefits. The government will therefore set a requirement in the legislation so that compensation requirements apply to both clinical investigations and performance studies and will supplement this with guidance. The government is mindful of comments regarding impacts on SMEs and will work to minimise this impact.

Section 38 – Application for clinical investigations / performance studies

38.1 Proposals and feedback

The consultation proposed that the UK medical devices regulations could outline detailed requirements for the clinical investigation or performance study application form and the accompanying documentation, as set out in the consultation. Of 152 respondents:

• 80% were in favour of the proposal
• 9% did not support of the proposal
• 11% did not know or had no opinion

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU MDR and IVDR. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations.

The consultation proposed that the UK medical devices regulations should outline the relevant timescales that the applicant and the MHRA should conform to when an application for a clinical investigation or performance study is submitted to the MHRA, as set out in the consultation. Of the 148 responses received:

• 81% were in support of this proposal
• 5% were not in support of the proposal
• 14% did not know or had no opinion

Some of those in favour of this proposal suggested that timescales should be based on risk stratification. Respondents also suggested that timescales should align with the EU MDR and IVDR and should include a degree of flexibility for more complex applications.

Respondents were asked to provide any reasoning and supporting evidence for the answers given in Section 38 of the consultation. A number of comments covered points raised in response to pervious questions, including the need for international alignment, and advocation of the use of standards and guidance rather than regulation. Other responses again called for an approach based on risk stratification and suggested that relevant timelines should not be set out in legislation.

38.2 The government response

Having considered the views of respondents, the government intends to include in the regulations, requirements for the clinical investigation or performance study application form and the accompanying documentation. With regards to the application form specifically, and in light of consultation feedback, the government recognises the need for a degree of flexibility. We will therefore give further consideration to requests that the detailed requirements for the application form be set out in supplementary guidance as we take forward this work.

Having taken account of consultation feedback, the government intends to outline in the UK medical devices regulations, the relevant timescales that the applicant and the MHRA should conform to when an application for a clinical investigation or performance study is submitted to the MHRA. Having reflected on consultation feedback and given this matter further consideration, our intention is to retain the current 60 calendar day timescale for assessment for clinical investigations and we are considering further what an appropriate timescale would be for the assessment of performance studies. We consider that retaining the 60-day timescale for clinical investigations will be clearer and more straightforward for both applicants and the MHRA as it represents a continuation of current practice. We consider it important to set these requirements out in legislation to provide clarity and to support compliance. We will provide supplementary guidance to support manufacturers and sponsors.

Section 39 – Assessment of applications for clinical investigation/performance study by the MHRA

39.1 Proposals and feedback

The consultation sought views on whether the UK medical devices regulations should require that performance study applications be assessed by the MHRA (in addition to clinical investigation applications, which are already subject to MHRA assessment). Of 151 respondents:

• 60% were in favour of the proposal
• 15% were not in favour
• 25% did not know or had no opinion

The MHRA invited views on whether the detailed requirements for assessment of the application for clinical investigations or performance studies should be outlined by the MHRA, as outlined in the consultation. Of 153 responses:

• 75% supported the proposal
• 11% were not in support of the proposal
• 14% did not know or had no opinion

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU MDR and IVDR and the FDA, as well as relevant ISO standards, and noted the potential for a reduced level of assessment if approval has already been granted in other jurisdictions. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations.

Respondents were asked to provide any reasoning and supporting evidence for the answers given in Section 39 of the consultation. A number of comments were similar to points raised in response to previous questions, including the need for international alignment, and a preference for use of standards and guidance rather than regulation. Other responses highlighted that greater transparency and clarity is needed on any requirements and that additional burden in submissions, cost and time could affect access to experimental devices. Some respondents suggested that there should be a risk-based approach to review which could apply, for example, only to high-risk studies.

39.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the proposals that the MHRA should be required to assess applications for performance studies and that the detailed requirements for assessment of the application for clinical investigations or performance studies should be outlined in the regulations. There was support for this approach among consultees and we consider that it will add greater clarity and transparency to the application and assessment process.

Section 40 - Conduct of a clinical investigation / performance study

40.1 Proposals and feedback

The consultation invited views on whether the UK medical devices regulations should set out the requirements on sponsors and investigators for the conduct of a clinical investigation or performance study, as outlined in the consultation (including a requirement to have adequate processes in place to identify deviations from the clinical investigation plan, and record and report any such deviations immediately). Of the 152 respondents:

• 85% were in favour of the proposal
• 10% were not in support of the proposal
• 5% did not know or had no opinion

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU MDR and IVDR, as well as Good Clinical Practice guidelines and relevant ISO standards, or should align with requirements that apply to clinical trials for medicines. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations.

Some respondents felt that not all deviations should be reported, and that setting a requirement for immediate reporting would be too strict. It was also proposed that deviations should be assessed and rated as ‘critical’, ‘major’ or ‘minor’.

Some respondents suggested that timeframes for reporting deviations should be specified and potentially linked with the level of impact.

We invited views on whether the MHRA should be required to inspect, at an appropriate level, clinical investigation, or performance study site(s). 154 responses were received, of which:

• 60% were in favour of the proposal
• 18% were not in favour of the proposal
• 22% did not know or had no opinion

Supporting rationale for the responses given in Section 40 of the consultation can be summarised as follows:

• there should be alignment with the EU MDR and IVDR
• there should be consideration of the role of standards
• this approach would support compliance with relevant requirements
• there is a need to define ‘appropriate level’ of inspection
• the regulations should create a power rather than a duty to inspect
• a preference for a spot check rather than blanket inspection approach
• there should be a risk-based / randomised approach to inspection
• inspection obligations could create unnecessary bureaucracy, which could lead to delays and ultimately supply issues
• there is a need to consider impacts on health institutions and the National Health Service (NHS)
• there is a need to clarify who would be inspected, whether this would be the sponsor or the manufacturer
• clear guidance and timescale information would be needed
• follow Good Clinical Practice guidelines
• limit requirements to cases where there is intention to commercialise devices

40.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal that the regulations should set out the requirements for the conduct of a clinical investigation or performance study as set out in the consultation. We remain of the view that all deviations should be reported as soon as the sponsor becomes aware of them.

Taking account of consultation feedback, the government intends to proceed with the proposal that the MHRA should be able to inspect, at an appropriate level, clinical investigation, or performance study site(s). The approach taken here will differ slightly to that set out in the consultation as we intend to ensure the MHRA has the ability to inspect clinical investigation and performance study sites rather than make this a requirement.

We consider that this will allow the MHRA to take a pragmatic and flexible approach to inspection processes, which was broadly supported by consultees. The proposal will enable the MHRA to inspect clinical investigation and performance study sites at any time. As identified by consultation respondents, the government considers that enabling inspection will encourage compliance with the legislative requirements. We will give further consideration to the detailed approach and will provide supplementary guidance, addressing important points raised by respondents around the nature of inspections (randomised, risk-based etc.), entities to be inspected and relevant timings.

Section 41 – Clinical investigations / performance studies regarding devices bearing the UKCA marking

41.1 Proposals and feedback

The consultation invited views on whether, in certain cases, a sponsor should be required to notify the MHRA within a specified timeframe prior to the start of a study, in cases where a clinical investigation or performance study is to be conducted to further assess a device which is already UK Conformity Assessed (UKCA) marked according to its intended purpose. Of the 147 responses:

• 59% supported this proposal
• 22% were not in favour
• 19% did not know or had no opinion

Some respondents felt that a notification of a clinical investigation or performance study in the above circumstances should not be required due to additional bureaucracy. Other respondents considered that the UK medical devices regulations should align with international frameworks, such as the EU MDR and IVDR with a time period of 30 days for notification.

41.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the notification requirements, summarised above and outlined in the consultation, within a specified time period prior to the start of that clinical investigation or performance study. Our intention is to require that the notification is made at least 30 calendar days prior to the start of the study. This approach was supported by the majority consultees, is in line with international practice and a requirement would give the MHRA greater oversight of post-market clinical follow-up (PMCF) and post-market performance follow-up (PMPF) studies conducted on these devices.

Section 42 – Modifications to clinical investigations / performance studies

42.1 Proposals and feedback

We invited views on whether the UK medical devices regulations should set out the procedures for sponsors intending to introduce modifications to a clinical investigation or performance study that are likely to have an impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation/study, as set out in the consultation. Of 135 respondents:

• 85% were in favour of the proposal
• 5% were not in support of the proposal
• 10% did not know or had no opinion

When asked to provide suggestions for procedures, other than those set out in the consultation, which should be introduced and/or the associated timeframes for notifying the MHRA, feedback included:

• a significant number of responses suggested that we should align with the EU MDR / IVDR
• some respondents suggested that we should align with relevant standards
• there should be a requirement to notify modifications with likely impacts on safety or the robustness of data
• this would be an unnecessary requirement and could cause delays
• we should follow the CTIMPs model
• modifications to clinical investigations and performance studies should not be made
• proposed timescales for notifying the MHRA of modifications included: 1 week, 2 weeks, same timescale as initial notification, 30 days, 35 days, 38 days, and 30-60 days
• modifications that are needed for safety purposes should not need up-front notification or approval, however retrospective notification should be possible
• there should be a requirement to alert participants and allow them to withdraw

Supporting evidence for the responses given in Section 42 of the consultation can be summarised as follows:

• clarity is needed on the timescales for notifying the MHRA of modifications
• we should align with the EU MDR and IVDR and international models
• we should follow relevant standards
• requirements should be covered in guidance rather than legislation
• the requirement to notify MHRA could lead to delays in the clinical investigation
• the requirement could be resource intensive for both the MHRA and sponsors
• a risk-based approach is needed
• modifications should only be notified if they are in response to adverse incidents

42.2 The government response

Having considered the views of respondents, it remains the government’s intention to set out in the regulations, the procedures for sponsors intending to introduce modifications to a clinical investigation or performance study, as outlined in the consultation. The concerns raised regarding the approach potentially causing delays to clinical investigations and performance studies have been noted. We would like to clarify that all modifications and amendments to clinical investigations currently require review without any timescales associated with this. We therefore consider that the introduction of timescales will provide clarification and facilitate forward planning. In taking forward this work we will reflect upon feedback on the need for international alignment and the need for alignment with requirements for medicines.

Section 43 – Corrective measures to be taken by the MHRA in relation to a clinical investigation / performance study

43.1 Proposals and feedback

We invited views on whether the MHRA should be able to take corrective measures in cases where it is considered that the requirements of the UK medical devices regulations relating to a performance study have not been met, as set out in the consultation. This would align requirements for performance studies with the current measures applicable to clinical investigation studies. Of 141 respondents:

• 81% were in favour of the proposal
• 6% were not in support of the proposal
• 13% did not know or had no opinion

Suggestions for other measures that respondents considered should be introduced for either a clinical investigation or performance study were as follows:

• a significant number of responses said that no additional requirements were needed beyond those set out in the consultation
• a significant number of responses suggested that we align with EU IVDR and MDR
• some respondents noted that a risk stratification / risk-based approach is needed
• some respondents suggested that requirements could be set out in guidance rather than regulations
• some respondents proposed alignment with CTIMPs

The consultation proposed that, in cases where the MHRA has grounds for considering that the requirements for a performance study are not met and except where immediate action is required, the sponsor or the investigator or both should be asked for their opinion regarding the corrective measures. Of 136 respondents:

• 79% were in favour of the proposal
• 3% were not in support of the proposal
• 18% did not know or had no opinion

Suggestions for the specified time period for the sponsor or investigator to give their opinion ranged from 5 working days to 90 days, including timeframe grading according to case complexity.

The rationale provided for these suggestions included the need for alignment with the EU MDR and IVDR and a desire for a risk stratification approach.

43.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal that, where it is considered that the requirements of a performance study have not been met, the MHRA should be able to take certain corrective measures that would be laid out in the UK medical devices regulations, as set out in the consultation.

A number of respondents felt that the UK regulations should align with international frameworks, such as the EU IVDR and relevant ISO standards. In developing the legislation, the government will take account of international approaches and relevant standards.

In light of consultation responses, the government intends to proceed with the proposal that, except where immediate action is required, the sponsor or the investigator or both should be asked for their opinion regarding the corrective measures, as outlined in the consultation. Having considered the views of respondents, we intend to set a timeframe of seven calendar days for the sponsor or investigator to give their opinion except where immediate action is required.

Section 44 - Information from the sponsor at the end of a clinical investigation / performance study or in the event of a temporary halt or early termination

44.1 Proposals and feedback

The consultation proposed that the procedures which must be undertaken and the timeframes that should apply at the end of a clinical investigation or performance study, or in the event of a temporary halt or early termination, could be specified in the regulations. Of 133 respondents:

• 78% were in favour of this approach
• 5% were not in support
• 17% did not know or had no opinion

Responses to the follow-up question regarding appropriate notification timescales and procedures were limited, but where comments were provided, they suggested that the UK regulations should align with international frameworks, such as the EU MDR and IVDR. Some respondents also suggested that the detailed requirements could be covered by guidance rather than through regulations.

44.2 The government response

Having considered the views of respondents, it remains the government’s intention to clarify in the UK regulations, the procedures which must be undertaken and the timeframes which would apply at the end of a clinical investigation or performance study, or in the event of a temporary halt or early termination.

The government intends to introduce requirements that a notification should be made to the MHRA within 15 days of a temporary halt or early termination, unless this is on safety grounds, in which case notification shall be made within 24 hours, or within 15 days of the end of the clinical investigation (last visit of last subject/participant unless set as different in clinical investigation plan).

We also intend to set out obligations for the sponsor, who will be required to submit a report and summary to the MHRA within 1 year of the end of the clinical investigation or performance study unless the study was terminated early or temporarily halted - in which case the report will need to be submitted within 3 months.

Section 45 – Recording and reporting of adverse events that occur during clinical investigations / performance studies

45.1 Proposals and feedback

The MHRA sought views on whether sponsors of clinical investigations and performance studies should be required to fully record and provide information to the MHRA upon request on all of the following:

1. any adverse event of a type identified in the clinical investigation or performance study plan as being critical to the evaluation of the results of that clinical investigation or performance study
2. any serious adverse event
3. any medical device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate
4. any new findings in relation to any event referred to in points (a) to (c)

Of 153 respondents:

• 88% were in favour of the proposal
• 6% were not in support of the proposal
• 6% did not know or had no opinion

The consultation asked whether sponsors should be required to report adverse incidents, medical device deficiencies and new findings without delay to the MHRA. Of 152 respondents:

• 86% were in favour of the proposal
• 10% were not in support of the proposal
• 4% did not know or had no opinion

The consultation proposed that, where necessary, sponsors should be able to submit an initial report that is incomplete, followed up by a complete report. Of 153 respondents:

• 82% were in favour of the proposal
• 7% were not in support of the proposal
• 11% did not know or had no opinion

The MHRA invited views on whether the UK medical devices regulations should require sponsors to report to the MHRA, any event (referred to in points (a) to (c) below) that has occurred in a non-UK country in which a clinical investigation or performance study is performed under the same clinical investigation or performance study plan.

1. any serious adverse event
2. any medical device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate
3. any new findings in relation to any event referred to in points (a) and (b)

Of 153 respondents:

• 84% were in favour of the proposal
• 8% were not in support of the proposal
• 8% did not know or had no opinion

Respondents were next asked to provide any reasoning and supporting evidence for the answers given in Section 45 of the consultation.

A number of respondents noted that the proposals would deliver safety and transparency benefits, while others felt that the UK regulations should align with international frameworks, such as the EU MDR and IVDR or align with medicines requirements. Some respondents noted that the requirement for reporting all incidents could be burdensome - suggesting, for example, that only serious incidents with a causal relationship either to the device or procedure should be reported, and that other incidents could be reported via an annual/final report. Other comments referenced the need for clarification over timescales, a need to have a definition of ‘without delay’ and a request to have in place an efficient method for reporting events.

45.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the proposals laid out in Section 45 of the consultation. While noting that some responses suggested a requirement to report all incidents would be burdensome, it should be noted that this is already a requirement for serious adverse incidents in relation to clinical investigations and, given the observational nature of many IVD performance evaluations, the risk of adverse incidents is likely to be minimal. Where interventional performance evaluations are conducted, the reporting of adverse incidents is essential to determine the cause and solution. Guidance will be provided to support those carrying out clinical investigations and performance studies.

Section 46 – Types of clinical investigations / performance studies and exemptions / authorisations

46.1 Proposals and feedback

The consultation sought views on whether exemptions from some of the requirements of the regulations for certain types of clinical investigations and performance studies could apply. Examples could include cases where an academic institute is working with a health institution to conduct a proof of concept or early feasibility study on a medical device without any input from industry, and there is no intention to place the device on the market. However, all such studies would still need to be registered with the MHRA before taking place. 158 responses were received, of which:

• 61% were in favour of this proposal
• 15% were not in favour of this proposal
• 23% did not know or had no opinion

The MHRA invited consultees to outline what types of clinical investigations and performance studies they considered should be exempted. Comments included:

• further guidance and clarity would be needed to support this
• further clarity is needed on what is deemed to be a medical device in proof-of-concept investigations
• industry involvement should not matter
• there should be a risk-based approach (exemption for low risk)
• there should be no exemptions
• there should be a lighter-touch approach for registration/notification
• we should align with the EU MDR and IVDR
• there should be requirements set out for studies that fall within exemptions (for example, a requirement that such studies are still subject to Research Ethics Committee approval)

The consultation invited views on whether health institutions should be required to notify certain types of clinical investigations / performance studies to the MHRA for authorisation before proceeding. The consultation noted that this could include larger pivotal or confirmatory clinical investigation studies which are conducted to provide the information necessary to evaluate the clinical performance, effectiveness or safety of the investigational device. Of the 157 responses:

• 70% were in support of the proposal
• 6% were not in support of the proposal
• 24% did not know or had no opinion

The consultation next asked respondents to outline the types of clinical investigations and performance studies that should be required to meet the requirements of the UK medical devices regulations. Comments included:

• align health institution requirements with industry, as there is no difference in risk
• larger pivotal and / or confirmatory clinical investigation for evaluating clinical performance, effectiveness or safety should be notified to MHRA
• high risk and invasive devices should be treated with higher scrutiny
• concern was expressed regarding the financial burdens to health institutions of registering studies where there will be no commercialisation of the devices
• registration requirements for all clinical investigations and performance studies should be considered
• we should align with the EU MDR and IVDR
• we should align with approaches that apply to medicines
• Good Clinical Practice guidelines should be followed

Respondents were asked to provide any reasoning and supporting evidence for the answers given in Section 45 of the consultation. Feedback can be summarised as follows:

• concerns were raised as to why risks from studies conducted by health institutions should be treated differently to those conducted by commercial manufacturers
• concerns were raised regarding perceived barriers for early feasibility and concept studies in cases where it is too early for an academic start-up to be planning a route to market. It was noted that an exemption could help address this to improve innovation - but would need careful consideration
• it was noted that it can be difficult to pass early development stage without any commercial sponsor or funding
• references were made to taking a device class / risk-based approach, questioning whether low risk devices need a clinical investigation when the risk posed is low
• it was also suggested that there should be consideration of benchtop testing as an alternative option

46.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with the proposal that the UK medical devices regulations should allow for exemptions from some of the requirements of the regulations for certain types of clinical investigations and performance studies, as outlined in the consultation. We also intend to require that healthcare institutions should notify certain types of clinical investigation / performance studies to the MHRA before proceeding. We consider that this approach will help reduce barriers for certain organisations, such as academic institutions, that may wish to carry out certain types of clinical investigation or performance study and encourage innovation while continuing to protect patients.

Section 47 – Summary of safety and clinical performance

47.1 Proposals and feedback

The consultation invited views on whether the UK medical devices regulations should require manufacturers to produce a summary of safety and clinical performance (SSCP) for high-risk medical devices and IVDs. 190 responses were received, of which:

• 73% were in support of the proposal
• 13% were not in support of the proposal
• 14% did not know or had no opinion

Respondents were asked to outline the classes/types of medical devices that they considered should require an SSCP. The 119 responses can be summarised as follows:

• the requirement should also apply to Class IIa and IIb devices
• all devices should be required to have an SSCP
• an SSCP should be required for all devices other than Class I
• we should align requirements with the EU MDR
• the requirement should only apply to high-risk devices

The consultation also invited views in the abridged version of the consultation (Chapter 17) as to whether we should introduce a requirement for manufacturers to produce an SSCP. Of the 53 responses:

• 90% supported this approach
• 4% were not in favour
• 6% did not know or had no opinion

The abridged consultation (Chapter 17) also invited respondents to select the types / classes of medical device that should be subject to SSCP requirements. Of the 49 responses received, the following selections were made:

• all implantable medical devices (88%)
• highest risk (Class III) medical devices (55%)
• highest risk IVDs (47%)
• medium risk (Class IIb) medical devices (24%)
• medium risk IVDs (22%)
• other (8%)

In terms of further commentary, some respondents noted that this approach would support transparency and patient safety, while others considered that the SSCP should be accessible and written in plain English. A number of respondents reiterated that the SSCP requirements should extend to medium and low risk devices.

In Chapter 7 of the consultation, we sought views on whether the UK medical devices regulations should set out the minimum content of the SSCP. Of the 182 responses received:

• 72% supported the proposal
• 14% were not in support of the proposal
• 14% did not know or had no opinion

Respondents were next invited to outline any other content which they considered should be included in the SSCP for a medical device. Feedback can be summarised as follows:

• we should align with the EU MDR / IVDR
• we should accept SSCPs that have been approved by EU Notified Bodies
• the requirement should only apply to devices that do not have an SSCP under the EU MDR
• we should not have an SSCP requirement
• we should require that the SSCP includes specific information, including that relating to chemicals, metals and indicated users, and Information for patients should also be included

The consultation sought views on requirements for manufacturers to upload the full SSCP or a link to the SSCP (hosted externally) to the MHRA registration system. When asked to select one of the following options, the majority of respondents picked option ‘a’:

1. the manufacturer should upload the full SSCP to the MHRA registration system (46%)
2. the manufacturer should upload a link to the SSCP to the registration system (12%)
3. the manufacturer should not be required to upload the SSCP to the registration system (15%)
4. other – please specify (18%)
5. don’t know/no opinion (9%)

Responses for ‘other’ included:

• the Approved Body should upload the form
• this should be available on the Public Access Database for Medical Devices

The consultation sought views on whether an Approved Body should be required to validate the SSCP for a medical device prior to upload to the MHRA registration system. Of the 185 responses:

• 59% were in favour of the proposal
• 19% were not in support of the proposal
• 22% did not know or had no opinion

Respondents made a range of suggestions regarding how an Approved Body should validate the SSCP for a medical device, as follows:

• they should cross check the SSCP against previous studies
• we should align with global regulations / EU MDR / IVDR
• this should be done remotely against specified minimum criteria or there should be hybrid inspection: desk based combined with onsite visit
• this should be conducted by an independent body with no conflict of interest
• the process should involve appropriate clinical and other experts
• this should be conducted as part of conformity assessment

Respondents were asked to provide any reasoning and supporting evidence for the answers given in Section 47 of the consultation. Feedback can be summarised as follows:

• we should align with EU requirements
• the SSCP should be easily accessible for stakeholders and patients
• these requirements would be bureaucratic, burdensome and costly - and could risk stifling innovation
• the SSCP assessment should be risk proportionate
• there is a need for guidance and further public engagement

47.2 The government response

Having considered the views of respondents, it remains the government’s intention to proceed with all the proposals covered in Section 47. Based on consultation feedback, our intention is to require the manufacturer to upload the full SSCP to the MHRA registration system, and for it to be made publicly available. We have noted that some respondents requested that the SSCP requirements should apply to all device classes; however, our intention at this point, is to introduce this for high-risk devices only. We will keep our position under review and will give further consideration, as necessary, to the need to expand tthese requirements to lower risk devices.