Medtech Online Guide

Medical Technologies A Guide to the Maze for SMEs Route Map

Is it a medical device?

Clinical Investigation

Early Engagement

Glossary

Clinical investigation Early engagement CE marking Is it a medical device?

Directly diagnoses, prevents or monitors a medical condition or disease Treats or alleviates a disease, injury or handicap Is an accessory, software or hardware for a categorical medical device The principal mechanism of action is not pharmacological, nor immunological or metabolic Controls conception Replaces or investigates an anatomical part

NIHR CRN Wessex: Clinical feedback to SMEs on NHS treatment pathways and feasibility to integrate your innovation

Notify MHRA before you start a clinical investigation (60 day assessment time)

WAHSN: Health Innovation Surgeries SME guidance and advice on business models, scalability and NHS payers Wessex Technology Support Programme Support in building research collaborations and studies

IVDs can be CE marked on the basis of their analytical performance (non-clinical)

Determine your specific CE-mark requirements

Research study costings NIHR CRN provides commercial & non-commercial costing templates, and cost validations

WAHSN: Funding support service Horizon scanning for funding streams & support with writing grant applications

Analysis & Evaluation For interventional studies incorporate patient reporting (e.g. SF-12/36)

Trial Design

▪ Define the research question ▪ Determine lead site & investigator criteria selection ▪ Develop the protocol

Classify your device by type and risk

Design modifications?

Non-sterile & non-measuring Class I devices can be selfcertified

Data Analysis

Post-market surveillance

Funding Proposal ▪ You’ll need to include the research proposal (trial summary) + trial costings

Protocol Peer Review & PPI feedback ▪ Once funding is approved, finalise protocol through reviews

NIHR CRN Portfolio Adoption Apply to a notified body or compile Declaration of Conformity

▪ Where eligible, for trial staffing & set-up support, plus trial performance monitoring

Publishing outcomes in a peer-reviewed journal

Health Economics (HE) Produce a formal evaluation including ICER, QALYs, modelling or forecasting Resources: o Hospital Episodes Statistics o NHS Reference costs o Condition-based NICE guidelines o Unit Costs of Health & Social care o NHS market forces factor o Google Scholar o Patient advocate reports o Office for National Statistics o BNF (for combination devices)

Appraisals IRAS & Ethics Submission

Produce the Technical documentation

Deliver your protocol statistical plan either independently or as part of your contract with your lead trial site

▪ Ensure you have completed a risk assessment for trial conduct

NHS adoption schemes For low-cost devices: o ITP programme For high-cost devices: o HCTED programme

o NICE submission o NIHR HTA o NHS Test Beds

Is it a medical device?

Device Legislation

Medical Device (MD) •

Includes medical hardware, from plasters to implantable devices

•

Includes medical software, that may be uncompiled, open-source, apps or functional documents (e.g. with script enabled functions)

•

Includes standalone medical software

•

From 26/5/20, cosmetic products (See Annex XVI) will also classify as MDs.

MDR EU2017/745

MD

IVDR EU2017/746

IVD In Vitro Diagnostic (IVD) • • •

IVDs are inherently medical devices, but simply fall into a focused set of regulatory rules (IVDR) Includes bench-top, point of care and self-testing diagnostic devices

•

The new EU regulation for Medical Devices (MDR) was introduced on the 25/5/17

•

Applicants can CE mark using either the MDR OR the old regulation, MDD, until 25/5/20 after which the MDR will strictly apply.

•

Any CE certificates issued before 25/5/20 using the old regulation will be valid for up to 4 years.

•

MDs are classified by the level of risk they pose, into I, IIa, IIb or III.

Diagnostics Legislation •

The new EU regulation for In Vitro Diagnostics (IVDR) was introduced on 25/5/17

•

Any CE certificates issued before 25/5/2022, using the old regulation (IVDD) will be valid for up to 2 years. However, after 26/5/22 the IVDR becomes the only route.

•

IVDs are risk-classified into A, B, C, or D.

Includes medical software that works directly with in vitro data.

Is it a medical device? – Software IT Health systems • • •

•

Software that serves to enter, record, transmit or store health data, or for administrative use, are not medical devices.

Thus, a CE mark is not required Required to demonstrate compliance with Information Governance and Clinical Risk Management.

Consider interoperability and cloud hosting.

Processing • • •

e.g. Patient Health Records

e.g. Ann’s IVF drug schedule

Any software that performs a calculation to determine or automate personalised drug regime or treatment pathway, is a medical device Also a MD if it derives clinical measurements (e.g. vital signs) CE marking is required; supporting data must demonstrate software verification & validation in a simulated or actual user environment.

Inform, Simple Monitoring & Communications

e.g. Back pain physio

•

Any standalone app that helps track wellbeing, enables virtual communication with GP or peers, or provides non-personalised health content such as tips and educational information, is not a medical device.

• Endorsement is required by a relevant professional body.

Consider gaining approval through the NHS Apps Library or ORCHA

Self-manage

/

e.g. HeLP Diabetes

•

Facilitates self-management through behavioural change by: • Providing health plans and goal setting (e.g. exercise, alcohol-reduction) and provides feedback • Providing coping strategies for mental health

•

Critical that you comply with Data Protection Rules & Initial Code of Conduct for Data-Driven Health & Care Technology.

Is it a medical device? – The Minimum Effectiveness Evidence Standard for your MEDICAL DEVICE Performance of its intended function within a relevant care pathway in the UK

Medical Devices Promoting health equality by not creating an inequality

Minimum Evidence Standard

Reliability or reproducibility of its function

Co-development or cotesting with relevant health professionals, within the UK health system

User satisfaction or acceptability demonstrating tested perceptions of relevant user groups

For Digital Health check out our Summary of the Evidence Tiers

Early engagement – Overview NHS Supply Chain

ADOPTION SCHEMES

TRL 8 - 9

SCALE-UP Patient & Public Involvement Research governance

PATHWAY/ SERVICE EVALUATION

CLINICAL TRIAL FEASIBILITY STUDY

ECONOMIC CASE

NEEDS GUIDANCE

Market feasibility

TRL 5 - 7

Technology Readiness Level (TRL ≥5)

PROCUREMENT

Early engagement Some examples within Wessex:

PROCUREMENT ADOPTION SCHEMES

TRL 8 - 9

SCALE-UP Patient & Public Involvement Research governance

FEASIBILITY STUDY

PATHWAY/ SERVICE EVALUATION

CLINICAL TRIAL ECONOMIC CASE

NEEDS GUIDANCE

TRL 5 - 7

Technology Readiness Level (TRL ≥ 5)

NHS Supply Chain

✓ Needs assessment ✓ Treatment pathway identification ✓ Gap analysis of the evidence base ✓ Defining product strategy

Market feasibility

✓ Stakeholder introductions

Early engagement Some examples within Wessex:

PROCUREMENT ADOPTION SCHEMES

TRL 8 - 9

SCALE-UP Patient & Public Involvement Research governance

FEASIBILITY STUDY

PATHWAY/ SERVICE EVALUATION

CLINICAL TRIAL ECONOMIC CASE

NEEDS GUIDANCE

TRL 5 - 7

Technology Readiness Level (TRL ≥ 5)

NHS Supply Chain

✓ Bespoke research study support service ✓ Support with preparing study costings ✓ Study protocol peer review by CRN clinical leads across a range of specialty areas ✓ Advance counsel on regulatory submission’s requirements for clinical investigations

Market feasibility

✓ Research ethics approval through the HRA

Early engagement Some examples within Wessex:

PROCUREMENT ADOPTION SCHEMES

TRL 8 - 9

SCALE-UP Patient & Public Involvement Research governance

FEASIBILITY STUDY

PATHWAY/ SERVICE EVALUATION

CLINICAL TRIAL ECONOMIC CASE

NEEDS GUIDANCE

TRL 5 - 7

Technology Readiness Level (TRL ≥ 5)

NHS Supply Chain

✓ Technology trial design & co-development ✓ Grants identification & proposal endorsement ✓ Trial site intelligence and contract agreements ✓ Trial performance monitoring ✓ PPI engagement and representation

Market feasibility

✓ Links with MHRA to ensure regulatory compliance

Early engagement Some examples within Wessex:

PROCUREMENT ADOPTION SCHEMES

TRL 8 - 9

SCALE-UP Patient & Public Involvement Research governance

FEASIBILITY STUDY

PATHWAY/ SERVICE EVALUATION

CLINICAL TRIAL ECONOMIC CASE

NEEDS GUIDANCE

Market feasibility

TRL 5 - 7

Technology Readiness Level (TRL ≥ 5)

NHS Supply Chain

✓ NIHR Innovation Observatory provides 10year innovation tracking insights & trends; alongside early notification to NICE for topic selection and technology appraisals ✓ Southampton Health Technology Assessment Centre (SHTAC) provides expertise and courses in health economics

Early engagement

PROCUREMENT ADOPTION SCHEMES

TRL 8 - 9

SCALE-UP Patient & Public Involvement Research governance

FEASIBILITY STUDY

PATHWAY/ SERVICE EVALUATION

CLINICAL TRIAL ECONOMIC CASE

NEEDS GUIDANCE

Market feasibility

TRL 5 - 7

Technology Readiness Level (TRL ≥ 5)

NHS Supply Chain

✓ Conducts treatment pathway/service evaluations for the implementation of specific innovations in care settings

✓ Works with local CCGs/STPs/public health bodies to support service pilots

Early engagement Some examples within Wessex:

PROCUREMENT ADOPTION SCHEMES

TRL 8 - 9

SCALE-UP Patient & Public Involvement Research governance

FEASIBILITY STUDY

PATHWAY/ SERVICE EVALUATION

CLINICAL TRIAL ECONOMIC CASE

NEEDS GUIDANCE

TRL 5 - 7

Technology Readiness Level (TRL ≥ 5)

NHS Supply Chain

✓ Scale-up guidance and bespoke signposting ✓ Access to experts in the fields of commercialisation and market entry ✓ Intensive course for innovators who wish to grow their business.

Market feasibility

Early engagement

PROCUREMENT ADOPTION SCHEMES

TRL 8 - 9

SCALE-UP Patient & Public Involvement Research governance

FEASIBILITY STUDY

✓ Provides a comprehensive landscape of adopters/payers for innovators to make contact with.

PATHWAY/ SERVICE EVALUATION

CLINICAL TRIAL ECONOMIC CASE

NEEDS GUIDANCE

TRL 5 - 7

Technology Readiness Level (TRL ≥ 5)

NHS Supply Chain

✓ Innovation forums to foster a levelled understanding of the innovation journey ✓ Leads on the Innovation and Technology Payment (ITP) to enable first-time adoption of medical devices ✓ Continually builds on best practice knowledge in adoption and procurement

Market feasibility

Clinical investigation Generally applies to:

Clinical evaluation or investigation?

Evaluations are procedures to collect, appraise and analyse pertinent clinical data, and to assess the quality and quantity of clinical evidence on a device.

Investigations test the safety and performance of MDs in ≥1 human subjects.

As such, they answer scientific hypotheses by generating new and transferable clinical data

Responsible for: ▪ The financial sponsorship of the study (i.e. securing the finance) ▪ The legal sponsorship of the study (i.e. obtaining MHRA & HRA approvals to cover the risk of the product and its study conduct) ▪ The design, methodology and management of the study

▪ ▪

▪

▪

▪

Requires:

Low risk devices Devices that are equivalent to existing (marketed) devices For all other MDs, evaluations form the next step following clinical investigations.

All MDs where: no/limited evidence exists in the intended clinical setting specification/use modifications have been made.

SME +/contracted evaluators

SME + clinical investigators

Responsible for: ▪ Conducting the study in accordance with GCP ▪ Accurately adhering to the study protocol ▪ Safekeep of study-generated documentations and collected data

Study participants Study team

Responsible for: ▪ Making an informed decision to partake in a study

Clinical investigation – the critical path Determine requirements…

▪

SME + clinical investigators

For either pre-market or post-market clinical investigation based on your type & risk classification

Methods ▪

▪

Formulate the primary objective/s that will generate the required evidence Develop the study design into a protocol

Study documents

Trial end:

Apply for Funding

Prepare: - Participant information sheet (PIS) - Patient consent form - Synopsis of protocol

Declaration of end

Trial progress:

Trial commence:

Safety and performance monitoring

Patient recruitment, taking informed consent

▪ ▪

Site intelligence ▪

Contact the NIHR CRN to determine study feasibility and site/s, based on your study design (e.g. patient size & characteristics)

Agreements Prepare: - Study costings at selected site/s - MoU with site/s on IP, confidentiality, roles & indemnity

Final trial documentation

Public Funders Private Funders ▪ Charities

Secured Establish contracts SME and trial site/s to agree & sign the contracts, including the financing terms

Legal ▪

Now notify MHRA of your investigation plan ▪ Fill IRAS application for: - governance & legal compliance (HRA approval) - ethics (REC approval)

Approved

Questions/feedback?

Please e-mail them to: industry.crnwessex@nihr.ac.uk Author: Dr Sandra Nwokeoha, DPhil

Glossary

CCG

Clinical Commissioning Group In England, health and care services are bought and commissioned by CCGs spread across the country to deliver these services to their local populations. CCGs cover secondary care (elective and non-elective) rehabilitation care, most community services, mental health and learning disability services. For more information click here.

GCP

Good Clinical Practice GCP is the international ethical, scientific and practical standard to which all clinical research is conducted and compliance is mandatory. The clinical study team must be GCP trained before they can interact with study participants. This provides public assurance that the rights, safety and wellbeing of research participants are protected. The NIHR CRN runs continuous GCP training. For more information click here.

HCTED

High-Cost Tariff-Excluded Devices In England, specialised medical devices are to be bought and supplied under the HCTED framework, which has been running since April 2016. In this framework, Trusts no longer need to pay HCTED suppliers to make purchases, and later seek reimbursement by NHS England. Trusts can now place their orders directly with NHS Supply Chain who then invoices NHS England. Consequently, the purchase of HCTEDs is rationalised by reducing pricing variations among Specialised Services. The programme also involves Device Working Groups (DWGs) who will scan the horizon for new devices with proven added value.

Glossary

HRA

Health Research Authority A non-departmental public body of the Department of Health & Social Care, responsible for ensuring that research conducted in the NHS is ethical and compliant with governance requirements. HRA approval is mandatory for clinical investigations that will be conducted in NHS organisations and/or independent contractor primary care services.

HTA

Health Technology Assessment The HTA is part of the NIHR, and is both a funding programme and a research journal. Typically referring to the former, it aims to evaluate the clinical effectiveness and cost savings of a technology to the NHS, compared to the current best alternative. It forms part of a device’s appraisal, as the programme does not fund its translation or research & development.

ICER

Incremental cost-effectiveness ratio It calculates the total costs and total health benefits for an intervention versus a comparator. ICER is used in costeffectiveness analyses to combine data on treatment effects and costs for alternative treatments.

IP

Intellectual Property IP is by definition the novel or previously undescribed tangible output of any intellectual activity. It has an owner and can be bought, sold or licensed and must be adequately protected. It can include inventions, industrial processes, software, data, written works, designs and images.

Glossary

IRAS

Integrated Research Application System Is a single system for applying for permission to conduct health, social or community care research in the UK. It is through IRAS that you apply for Ethics and HRA approval – a mandatory step for the initiation of a clinical investigation.

ITP

Innovation and Technology Payment A competitive programme led by NHS England and supported by the AHSNs. In this programme, low cost medical devices and digital technologies are selected for scaled adoption (having already proven clinical effectiveness) by covering the cost of acquisition and implementation.

IVD

In vitro diagnostic IVDs are medical devices that enable tests on biological samples to be made to detect disease or other medical conditions. For more information click here.

MD

Medical Device Any product, hardware or software that imparts a change to a medical condition or determines a medical status.

Glossary

MHRA

Medicines and Healthcare products Regulatory Agency MHRA is an executive agency sponsored by the Department of Health & Social Care. It holds a highly significant role in the regulation of medical devices as well as pharmaceutical products. MHRA is the gateway to CE-marking as all MD developers need to comply with the appropriate regulatory Essential Requirements, and register their products with the MHRA. It is also responsible for conducting inspections of clinical investigations involving MDs and postmarket surveillance.

MoU

Memorandum of Understanding An agreement made between two parties, that is not legally binding but carries enough weight in setting the terms for the partnership or collaboration. At the appropriate time, a legal contract may follow.

NICE

National Institute for Health and Care Excellence NICE is a non-departmental body of the Department of Health & Social Care. It provides clinical guidelines for an exhaustive range of medical procedures, with the aim to standardise best clinical practice across the UK. Secondly, they evaluate technologies through the lens of the NHS (thus, with an emphasis on cost benefits). Such evaluations are published by NICE and are often referred to as NICE “recommendations�, which assist in opening doors into reimbursement programmes such as the ITP. However, the only NICE programme that mandates the NHS to fund and procure NICE-evaluated MDs is the Technology Appraisal programme.

Glossary

NIHR

National Institute for Health Research The NIHR is funded by the Department of Health & Social Care, and is effectively a clinical research funder. It is composed of 1. funding programmes that launch frequent nationwide grant competitions and are managed by dedicated programme teams; 2. the Clinical Research Network which significantly funds the research workforce (e.g. clinical advisors and research nurses) and whose remit is to administratively manage the setup and performance of clinical studies conducted in NHS settings (the public sector equivalent of Contract Research Organisations); 3. services and centres designed to assist the translation of research into clinical trials.

PPI

Patient and Public Involvement PPI represents a mechanism in which patients and lay people can influence the conduct of a relevant clinical study, by providing the investigator team with feedback on the importance (or lack thereof) and acceptability of the study objectives, and thus better shape the research outcomes. This activity is favourable in ethics and legal compliance approvals.

QALY

Quality-adjusted Life Years QALY is a metric used in economic evaluations to weigh up the effects of quantity of life (e.g. time spent in a health state) combined with the quality of life (at its best: ‘perfect health’, at its worst: death).

Glossary

REC

Research Ethics Committee REC provides the Health Research Authority (HRA) with an independent opinion in question of the ethics surrounding a new clinical investigation. REC approval forms part of the HRA approval process, through a single IRAS application.

SHTAC

Southampton Health Technology Assessments Centre It is one of the centres of excellence for health technology assessment contracted to the National Institute for Health Research (NIHR). Customers for SHTAC’s research include the National Institute for Health and Care Excellence (NICE) and the Department of Health Policy Research Programme, the National Clinical Directors, the NIHR Health Technology Assessment (HTA) and the Cochrane Collaboration.

SF-12/36

Short Form 12 / Short Form 36 SFs are self-reporting questionnaires on health-related quality of life, for patients who may have been/or currently are involved in interventional studies. SF-12 contains 12 selected questions from the SF-36 Health Survey which lists 36 questions.

Glossary

SME

Small and Medium-sized Enterprise SMEs are businesses, that could be either private or public, have an employee headcount between 50-250 and an annual turnover not exceeding 50 million euros.

STP

Sustainability and Transformation Partnership/Plan A STP is a partnership or plan between the NHS and local councils to improve the co-ordination and integration of care. There are 44 STPs across England that deliver proposals for local care. For more information click here.

TRL

Technology Readiness Level The TRL constitutes a method of estimating the maturity of a technology through aggregation into activity levels. There are 9 technology readiness levels. The first level (TRL 1) represents technologies at the stage of discovery and basic science research, while the last level (TRL 9) represents technologies that are fully integrated into their intended systems and ready for launch.