Inclisiran: testing a population health management methodology to implement a novel lipid treatment

Br J Cardiol 2021;28(suppl 2):S19–S22doi:10.5837/bjc.2021.s09 Leave a comment
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This sponsored supplement was initiated and funded by Novartis Pharmaceuticals UK Ltd. Editorial control was retained by the authors and editors, however, Novartis reviewed the supplement for technical accuracy and compliance with relevant regulatory requirements. Leqvio® (inclisiran) prescribing information is available on the Novartis website: https://www.health.novartis.co.uk/sites/health.novartis.co.uk/files/inclisiran-pi.pdf

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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via uk.patientsafety@novartis.com or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com

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Job code: 133819
Date of preparation: September 2021

Cardiovascular disease (CVD) is an area that places a large burden on both the NHS and society, and is one of the health conditions most strongly associated with health inequalities. This has been recognised by the NHS Long Term Plan and identified as a clinical priority.

Within the context of the Long Term Plan and CVD prevention strategies, Novartis Pharmaceuticals announced plans to collaborate with NHS England to tackle the burden of CVD in the UK. The focus of this collaboration is to provide inclisiran, a novel treatment for dyslipidaemia, for secondary prevention atherosclerotic cardiovascular disease (ASCVD) patients in primary care through a population-level agreement.

Population health management represents a proactive approach to managing the health and wellbeing of a population and aims to incorporate the total care needs, costs and outcomes of the population. It is a move away from the provision of reactive, demand-led care, and it is recognised that primary care has a clear role to play within population health management strategies.

A population health model should be implemented in primary care to access an entire population locally. To test a proposed population health model of system delivery for inclisiran, Novartis and Health Innovation Manchester are running the VICTORION-SPIRIT study – which uses implementation research methodology – with 900 patients recruited across Greater Manchester general practices. The study aims to understand healthcare system challenges and enablers for implementation. It will assess the proposed implementation processes together with the efficacy and safety of inclisiran in a primary care setting.

Implementation research provides appropriate methodology to assess the implementation of inclisiran in a primary care setting as part of a population health management approach. The outcomes of this research can be used to elucidate appropriate patient identification approaches, system barriers and enablers and the efficacy and safety of inclisiran in a primary care setting in the UK.

Introduction

Cardiovascular disease (CVD) affects around seven million people in the UK. It is a significant cause of disability and is responsible for one in four premature deaths – accounting for the largest gap in health life-expectancy. It is also an area where there are significant health inequalities, with those in the most deprived 10% of the population almost twice as likely to die as a result of CVD, than those in the least deprived 10% of the population.1

Box 1. Five major practical changes to the NHS service model2

  1. We will boost ‘out-of-hospital’ care, and finally dissolve the historic divide between primary and community health services
  2. The NHS will redesign and reduce pressure on emergency hospital services
  3. People will get more control over their own health, and more personalised care when they need it
  4. Digitally-enabled primary and outpatient care will go mainstream across the NHS
  5. Local NHS organisations will increasingly focus on population health and local partnerships with local authority-funded services, through new Integrated Care Systems (ICSs) everywhere

The National Health Service (NHS) Long Term Plan2 identifies CVD as a clinical priority and “the single biggest condition where lives can be saved by the NHS over the next 10 years.”1 In addition, the Long Term Plan sets out five major practical changes to the NHS service model that can help to bring about change over the next 5 years (box 1).

These practical service model changes aim to focus patient care in local neighbourhoods, through Primary Care Networks of 30–50,000 patients, and also pave the way for an increasing focus on population health through new integrated care systems (ICSs).

As a result of the Long Term Plan, the National CVD Prevention programme has been set up to develop targeted interventions that optimise care by maximising diagnosis and treatment, in order to minimise both individual risk factors, and population risk. The Programme is developing a clear approach to meet the Long Term Plan goals by working with a wide range of partners, including the British Heart Foundation, the Stroke Association, Academic Health Science Networks, Public Health England, and other arm’s length bodies and third-sector organisations to deliver the national programme of work.1

Together with the focus on local care and population health, the National CVD Prevention Programme provides the opportunity for more effective lipid management in primary care.

Collaboration in practice

Within the context of the Long Term Plan and CVD prevention strategies, Novartis Pharmaceuticals announced plans to collaborate with NHS England to tackle the burden of CVD in the UK.3 The focus of this collaboration is to provide inclisiran, a novel treatment for dyslipidaemia (reviewed elsewhere in this supplement), for secondary prevention atherosclerotic cardiovascular disease (ASCVD) patients in primary care through a population-level agreement. Inclisiran is licensed for lowering low-density lipoprotein cholesterol (LDL-C). The effect of inclisiran on cardiovascular morbidity and mortality has not yet been determined.

Box 2. Accelerated Access Collaborative (AAC)

The AAC ambition is to help make the UK one of the most pro-innovation health systems in the world through bringing decision-makers from across the health service together with innovators from industry to accelerate impactful and cost-effective products in a way that hasn’t happened before.

  • For patients: this means access to new technologies and treatments
  • For clinicians: access to cutting-edge innovations that will help you deliver excellent care
  • For industry: help you understand the needs of patients and clinicians, and champion great solutions
  • For investors: innovations that meet NHS needs will receive greater support, from proof of concept to national commissioning
https://www.england.nhs.uk/aac/about-us/

The collaboration between Novartis, NHS England & Improvement, the National Institute for Health Research, and the Nuffield Department of Population Health at Oxford University, represents an innovative approach to tackling a major public health issue.3,4 To achieve a positive impact on national cholesterol management, the collaboration proposes that inclisiran initiation and management be carried out within primary care, where, predominantly, this patient population is located. To this end, a novel population health management (PHM) approach to tackle a large at-risk patient population with ASCVD is being developed in collaboration with the Accelerated Access Collaborative (AAC) (box 2).

Population health management

Critical to the success of this strategy is the application of principles of population health management. This represents a proactive approach to managing the health and wellbeing of a population and aims to incorporate the total care needs, costs and outcomes of the population. It is a move away from the provision of reactive, demand-led care, and it is recognised that primary care has a clear role to play within population health management strategies.5

There are three fundamental steps to consider for the proactive management of the health and wellbeing of a population:5

  • Know your population’s health needs.
    There are various methods – working with the community to understand the needs of different population groups, gathering population-level data and analysing detailed patient-level data that map journeys across sectors and providers. This is an ongoing process and there are different levels of analysis that can be carried out.
  • Engage with your population.
    It is wide engagement across the community that will ensure the success of a population health management approach. Services should be co-designed with patients and all stakeholders involved to ensure they make a positive difference to the groups you have defined.
    An engagement strategy should be developed and implemented.
  • Manage your population.
    After designing services in collaboration, this is the implementation of a multi-disciplinary approach to meet the needs of the different population groups.
    Work towards a culture of collaboration and retain a sense of belonging for patients and staff. Measuring against a defined baseline is key to success.

When developing PHM strategies, implementation research provides an opportunity to assess key aspects of the implementation approach.

Implementation research

Implementation research is a growing field of health research that can contribute to more effective public health and clinical policies and programmes. It is defined as the scientific inquiry into questions concerning implementation – the act of carrying an intention into effect – which in health research can be policies, programmes, or individual practices (collectively called interventions).6

The field provides a methodology to address the ‘know-do’ gap, between what we know from research to what we do in clinical practice, with particular reference to the uptake and adoption of new innovations.7 This systematic approach to identifying, understanding and addressing health system challenges from policy to practice, is important for the appropriate implementation of research into healthcare practice.8

As implementation research is particularly focused on the users of the technology being investigated (the patients, healthcare professionals, system decision makers and policy makers),6 it is ideally suited for the inclusion of patient-reported outcome measures and patient assessments of healthcare service engagement and satisfaction. These assessments enable patients to capture their health status and beliefs around the management of their condition, thus, informing the healthcare system on approaches related to patient empowerment and engagement in this context.9,10

The NHS presents an ideal framework within which to assess implementation strategies for new health technologies. This is due to the primary-care focused management of patients with chronic conditions, the increasing robustness and interconnectivity of electronic medical records, and the potential to reduce costs by identifying patient populations through health records. This enables clear commissioning processes and goals aligned to the NHS Long Term Plan regarding the optimisation of service delivery to patients within their locality.

Running an implementation research study in the Greater Manchester area presents an ideal test-bed opportunity to assess the implementation of inclisiran with a population health approach utilising a primary-care model of delivery. This is due to the cohesion of the primary and secondary care electronic medical record in Greater Manchester, their established use of implementation research approaches to assess new interventions and their established primary care networks.

The VICTORION-SPIRIT study

To research and inform the proposed primary care model of delivery for inclisiran, Novartis and Health Innovation Manchester are collaborating to run a UK implementation research study called VICTORION-SPIRIT.11 The study aims to understand the healthcare system barriers and enablers for implementation, utilising the Consolidated Framework of Implementation Research (CFIR),12,13 while also assessing the efficacy and safety of inclisiran in a primary-care setting within a type 1 hybrid study design.14

The study is based on the following principles:

  • Setting. It is run in the setting where inclisiran is intended to be implemented in clinical practice, with the intention of understanding the effects of innovations within the conditions of everyday clinical practice. The clinicians administering inclisiran will be the practice staff (GP, nurse or pharmacist) and not research staff.
  • Patients. The patient population will be aligned to the licensed population for inclisiran, with the intention of working with populations that will be affected by the intervention in clinical practice, rather than selecting patients who are suitable for a standard clinical trial.
  • System. Health delivery context: taking account of institutional and health system contexts – including the viewpoints of various stakeholders including commissioners, system managers and clinicians.
Inclisiran supplement - article 4: Figure 1. VICTORION-SPIRIT study design
Figure 1. VICTORION-SPIRIT study design

The study will recruit 900 patients across GP practices in Greater Manchester and randomise patients to one of three groups (figure 1):

  • inclisiran in addition to lipid-lowering background therapy, with access to a behavioural support programme
  • inclisiran in addition to lipid-lowering background therapy, without access to a behavioural support programme
  • Lipid-lowering background therapy with access to a behavioural support programme.

Patients will receive treatment for nine months, during which time changes in their lipid profile (LDL-C, total cholesterol and non-high-density lipoprotein [non-HDL] cholesterol) and safety outcomes will be assessed. System barriers and enablers will be explored through a healthcare service process evaluation using the CFIR, and measures of patient satisfaction, activation and empowerment will be recorded.

Patient recruitment methodology for the trial will be used to inform the wider healthcare system on appropriate patient identification approaches – including coding, system search criteria and proportion of patients meeting these criteria. In addition, electronic medical records will be used to provide observational follow-up during the trial.

The focus of this study is implementation and ‘transactability’ – how to organise, deliver and maintain an innovative treatment for LDL-C management in a primary-care setting in a sustainable way. This information will be used to inform the implementation of inclisiran into primary care, as well as future implementation efforts in the NHS and beyond.

Conclusion

Implementation research provides an appropriate methodology to assess the implementation of inclisiran in a primary-care setting as part of a PHM approach. The outcomes of this research can be used to elucidate appropriate patient identification approaches, system barriers and enablers, and the efficacy and safety of inclisiran in a primary-care setting in the UK.

Key messages

  • Cardiovascular disease (CVD) places a huge burden on the NHS and society, and is a condition strongly associated with health inequalities
  • The NHS Long Term Plan identifies CVD as a clinical priority
  • An innovative collaboration between Novartis, life sciences and healthcare systems, hopes to offer the lipid-lowering therapy inclisiran to at-risk patients, at scale, using a population health management (PHM) approach
  • The VICTORION-SPIRIT study has been set up to test this population health approach, and is set to provide and assess evidence for the implementation of inclisiran within a primary-care setting in the NHS

Conflicts of interest

SD and LR are employees of Novartis Pharmaceuticals. TV: none declared.

Funding

Novartis Pharmaceuticals UK Ltd has provided funding for the VICTORION-SPIRIT study.

Study approval

The VICTORION-SPIRIT study has received Research Ethics Committee approval.

Acknowledgements

The authors acknowledge the help of the British Journal of Cardiology in writing this article, and the collaboration with Health Innovation Manchester (HiM), NorthWest EHealth (NWEH), Applied Research Collaboration (ARC) Greater Manchester, and Manchester University in the development of the VICTORION-SPIRIT protocol.

Samantha Dixon
Therapy Area Head, Cardiovascular, Renal, Metabolism & Respiratory

Novartis Pharmaceuticals UK Limited, 2nd Floor The Westworks Building, White City Place, 195 Wood Lane, London W12 7FQ

(samantha.dixon@novartis.com)

Linda Rootkin
Region Head, Strategic Partnerships and Implementation Science

Novartis Latin America Services, Inc., 5200 Blue Lagoon Drive, Suite 650, Miami, Florida 33126, USA

Tracey Vell
General Practitioner, and Medical Director

Health Innovation Manchester, Citylabs 1.0, Nelson Street, Manchester, M13 9NQ

Articles in this supplement

Cardiovascular disease: the state of the nation, and the NHS Long Term Plan

Conversations on cholesterol: evaluating the role of LDL-cholesterol reduction in ASCVD

New opportunity for cholesterol lowering: inclisiran

References

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2. NHS. The NHS long term plan. London: NHS, January 2019. Available from: https://www.longtermplan.nhs.uk/

3. Gov.uk. Press release. New heart disease drug to be made available for NHS patients. Published 13 January 2020. Available at: https://www.gov.uk/government/news/new-heart-disease-drug-to-be-made-available-for-nhs-patients [accessed 8 June 2021].

4. University of Oxford. News: New heart disease drug to be made available to NHS patients through ground breaking collaboaration. Published 14 January 2020. Available at: https://www.ox.ac.uk/news/2020-01-14-new-heart-disease-drug-be-made-available-nhs-patients-through-ground-breaking [accessed 8 June 2020].

5. National Association of Primary Care (NAPC). Primary care home: population health management. London: NAPC, 2019. Available from: https://napc.co.uk/wp-content/uploads/2019/08/NAPC-Population-heath-guide-web.pdf

6. Peters DH, Adam T, Alonge A, Aku Agyepong I, Tran N. Implementation research, what is it and how to do it. BMJ 2013;347:1–7. https://doi.org/10.1136/bmj.f6753

7. University of Washington. What is implementation science. Available at: https://impsciuw.org/implementation-science/learn/implementation-science-overview/ [accessed 8 June 2021].

8. Spyridonidis D, Hendy J, Barlow J. Leadership for knowledge translation: the case of CLAHRCs. Qual Health Res 2015;25:1492–505. https://doi.org/10.1177/1049732315583268

9. Larsen DL, Attkisson CC, Hargreaves WA, Nguyen TD. Assessment of client/patient satisfaction: development of a general scale. Eval Program Plann 1979;2:197–207. https://doi.org/10.1016/0149-7189(79)90094-6

10. Hibbard J, Stockard J, Mahoney E, Tusler M. Development of the patient activation measure (PAM): conceptualizing and measuring activation in patients and consumers. Health Serv Res 2004;39:1005–26. https://doi.org/10.1111/j.1475-6773.2004.00269.x

11. US National Library of Medicine. Clinicaltrials.gov. Study in primary care evaluating inclisiran delivery implementation + enhanced support (SPIRIT). Available at: https://clinicaltrials.gov/ct2/show/NCT04807400 [accessed 8 June 2021].

12. Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci 2009;4:50. https://doi.org/10.1186/1748-5908-4-50

13. Consolidated Framework for Implementation Research. https://cfirguide.org/

14. Curran GM, Bauer M, Mittman B, Pyne JM, Stetler C. Effectiveness-implementation hybrid designs. Med Care 2012;50:217–26. https://doi.org/10.1097/MLR.0b013e3182408812

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