STRENGTHS AND LIMITATIONS OF THIS STUDY

Process evaluation places the patient voice at the heart of the study and places value on the opinions of healthcare providers.

This analysis follows a validated, standardised, systematic approach that has been implemented across a range of studies.

The inclusion criteria for VICTORION-Spirit were broader than National Institute for Health and Care Excellence guideline recommendations and do not account for the lack of long-term data on cardiovascular outcomes.

Although it could be considered a limitation that the study was conducted in only one region, the merits of conducting the study in Greater Manchester are described.

Introduction

Elevated low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk of cardiovascular disease (CVD), including coronary heart disease and atherosclerotic CVD (ASCVD).1 2 Preventing CVD, which is responsible for >1 74 000 deaths annually in the UK, has been identified as a clinical priority for the National Health Service (NHS).3 4 Among a broad range of commitments, a national CVD prevention programme aims to ensure the routine awareness of cholesterol levels in the general population and to improve the effectiveness of approaches to rapidly treat those with high LDL-C.3

In England, the NHS’s lipid management pathway recommends statins for the primary prevention of CVD in five categories of adults with elevated LDL-C and without CVD, and for the prevention of secondary CVD in adults with coronary heart disease, angina, acute coronary syndrome, revascularisation, stroke or transient ischaemic attack or symptomatic peripheral arterial disease.5 Statins are prescribed in tablet form and slow the hepatic production of LDL-C by inhibiting the enzyme HMG-CoA reductase and ultimately lowering blood cholesterol levels.6 Although the benefits of statins for lowering cholesterol have been well demonstrated in clinical practice,7 some patients do not experience an adequate reduction in cholesterol with statins alone and require additional cholesterol-lowering therapies.8 9

Inclisiran (Novartis AG, Basel, Switzerland), a first-in-class small interfering RNA treatment, was developed as an injectable cholesterol-lowering therapy with twice-yearly dosing (after initial doses at baseline and 3 months).10 Inclisiran is indicated as an option for adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet, who have elevated LDL-C despite treatment with a statin or who are intolerant to statins.9 10 Within this patient group, the NHS lipid management pathway recommends inclisiran for patients with LDL-C levels≥2.6 mmol/L despite receiving the maximum tolerated statin dose.5 To date, the efficacy of inclisiran has been demonstrated in three key phase III trials in patients with ASCVD, ASCVD-risk equivalents and/or familial hypercholesterolaemia.9 11

The VICTORION-Spirit study was designed to assess the efficacy of inclisiran in patients managed at primary care practices in England.12 The study used a type 1 hybrid design, combining components of clinical effectiveness and implementation research to gather evidence on the performance of inclisiran in a clinical setting that is similar to real-world practice, alongside gaining insights on the contextual factors that could affect its delivery in primary care.12 The study had two main components: (1) a prospective phase IIIb trial in a primary care population to assess the efficacy of inclisiran, with or without behavioural support, compared with statins and/or other lipid-lowering therapies (ie, the standard of care (SOC)) with behavioural support; and (2) a process evaluation to ascertain the views of patients and healthcare providers about inclisiran and the potential ‘implementability’ of the intervention. Research nurses managed patient screening and injection appointments, and primary care professionals delivered the inclisiran injections.

This manuscript focuses on the process evaluation component of VICTORION-Spirit. Process evaluation provides a detailed understanding of how a therapy is implemented under real-world conditions and identifies active and dynamic factors that may act as barriers or facilitators, including finances, policies and laws, local attitudes and external pressures.13 14 The aims of the qualitative process evaluation in VICTORION-Spirit were to explore the process of implementing the delivery of inclisiran in primary care and to evaluate the implementability of its delivery by interviewing key stakeholders.

Here, we present the interim findings from the process evaluation in VICTORION-Spirit, including patient and healthcare provider perceptions of the acceptability of inclisiran, and identify key barriers to the successful implementation of inclisiran in primary care.

MethodsStudy design

VICTORION-Spirit was a pragmatic, type 1, hybrid, effectiveness–implementation research study that used a population-based approach and implementation science to assess the deliverability of a novel treatment in primary care. This phase IIIb, multicentre, open-label, randomised, controlled study assessed the delivery of inclisiran across 17 general practice centres in Greater Manchester, UK, to patients with elevated LDL-C who were on established lipid-lowering medication or who had been recommended lipid-lowering therapy but were unable to tolerate treatment. The primary objective of VICTORION-Spirit was to demonstrate the superiority of inclisiran with or without behavioural support compared with an enhanced care control group receiving SOC (eg, statin and/or other lipid-lowering therapies) with behavioural support in a primary care setting, as demonstrated by the percentage reduction in LDL-C from baseline to day 270. The study randomised 900 participants across three treatment groups (1:1:1): SOC plus behavioural support; SOC plus subcutaneous inclisiran sodium 300 mg and SOC plus subcutaneous inclisiran sodium 300 mg plus behavioural support (figure 1).15 We used the Feasibility Assessment and Recruitment System for Improving Trial Efficiency software tool (NorthWest EHealth, Manchester, UK) to search and identify potentially eligible patients for inclusion, and general practitioners (GPs) at the participating practices reviewed the results. Only the GP providing direct care to the patient was able to decide whether to invite that individual to participate in the study.

Figure 1

VICTORION-Spirit study design.15 aPatients will receive SOC (statin and/or other lipid-lowering therapies) as background therapy. bThe behavioural support service provided to patients will consist of a monthly, telephone-based, lifestyle intervention to motivate and support patients to make effective choices for improving self-management through behaviour change, goal setting and empowerment. cSubcutaneous inclisiran sodium 300 mg. dThe superiority of inclisiran without behavioural support (treatment group 2) compared with SOC with behavioural support (treatment group 1) on percentage reduction in LDL-C from baseline to day 270 in a primary care setting will be assessed. eThe superiority of inclisiran with behavioural support (treatment group 3) compared with SOC with behavioural support (treatment group 1) on percentage reduction in LDL-C from baseline to day 270 in a primary care setting will be assessed. fOther assessments will include: patient satisfaction with the services they have received or are currently receiving; patient activation and empowerment to evaluate the confidence of patients in managing their own health; adherence to treatment; SAE profile and adverse events leading to treatment discontinuation; a process evaluation to ascertain the views of patients and healthcare providers about the service they have received or provided and its potential implementability across the NHS. LDL-C, low-density lipoprotein cholesterol; NHS, National Health Service; SAE, serious adverse event; SOC, standard of care.

Health advisors trained in motivational interviewing and coaching techniques delivered behavioural support each month via telephone, with the aim of supporting patients to make effective self-management choices through behaviour change, goal setting and empowerment.16–18 Lifestyle factors, including diet, physical activity and smoking, have been shown to influence the risk of developing CVD and, despite receiving cholesterol-lowering medications such as statins, many patients do not achieve guideline standards for the secondary prevention of CVD through lifestyle management.19 In this study, inclisiran was delivered both with and without behavioural support, to understand the potential impact of enhanced care on the effectiveness of the intervention.

Overview of the process evaluation methodology

The Consolidated Framework for Implementation Research (CFIR) was used to identify the actions needed to support the implementation of inclisiran in real-world clinical practice.20 The CFIR is a widely used, standardised, determinant framework that includes five domains likely to influence the implementation of complex interventions.13 20 21 By facilitating the collation and analysis of stakeholder views on the acceptability, feasibility and sustainability of implementation processes, the CFIR provides a systematic analysis approach to identify the key factors that could influence the adoption of inclisiran into primary care.

Informed by the CFIR domains, the VICTORION-Spirit process evaluation comprised semistructured interviews with patients receiving inclisiran (online supplemental file 1) and with healthcare providers (Supplementary File 2). Two researchers, RE, PhD and AM, PhD, a Research Fellow and a Research Associate, respectively, at The University of Manchester, conducted telephone interviews between August 2021 and April 2022. All participants received an information sheet detailing the purpose of the research. Researchers verbally explained the interview process and how the data would be used; participants were informed that the researchers are from the University of Manchester and independent of the clinical trial team. Both researchers are trained and experienced qualitative researchers with a background in healthcare research and had no other contact with participants outside the interview.

A purposive sample of patients from the two groups receiving inclisiran (with or without behavioural support) from VICTORION-Spirit was recruited to participate in interviews, using a semistructured topic guide, relating to their experiences of managing high cholesterol (including taking statins), participating in the trial, receiving inclisiran injections and attending appointments and of the behavioural support received (the SOC plus inclisiran plus behavioural support group only). Interviews with patients took place between day 1 and day 90 of the trial. Each patient participated in one interview; interviews were arranged as soon as possible after the first inclisiran injection. Group 3 patient interviews were designed to be undertaken in two parts; first, after the initial injection, and second, soon after they had begun attending the behavioural support.

A purposive sample of healthcare providers provided insights into the structures, resources and processes required to embed inclisiran into routine general practice. Those interviewed included principal investigators, subinvestigators and nurses from participating practices, with a target recruitment of at least one professional from each practice. Healthcare providers were interviewed once, towards the end of the study.

Health advisors and research nurses were also interviewed about their role in VICTORION-Spirit and the support provided to practices, challenges to implementing inclisiran, the impact of inclisiran delivery on practice staff and patients, patients’ responses to inclisiran, perceptions of the behavioural support process and future provision of inclisiran.

To ensure that all relevant issues associated with the delivery of inclisiran in primary care were adequately captured in the data collected, the topic guides for interviews were iteratively reviewed and updated if required. Verbal, informed consent was confirmed and audio-recorded from all interviewees before participating in the study. There were no repeat interviews and transcripts were not returned to participants for comment or correction. Interviews continued until data saturation was reached.

Analysis

To support the need to inform real-time policy decision-making and national implementation, we used rapid analysis. We developed a rapid analysis technique based on Gale et al’s adaption of Hamilton’s rapid qualitative analysis approach.22 23 Our approach incorporated the CFIR and involved: (1) creating a summary template—one for each participant group—based on the five CFIR domains, with space provided for other observations, unexpected findings and key quotations; (2) reviewing the summary template as a team and independently testing, refining and finalising the template; (3) completing the summary template with participants’ responses following each interview, using field notes from the interviewer, noting if a question was not asked or an answer not given; (4) discussing the analysis and debriefing as a research team once a week to identify potential themes and areas to explore in subsequent interviews and (5) transferring the summary templates to a matrix. The matrix output provided a structure for analysing and interpreting the summarised data and facilitated comparisons between different interviewees across key issues.24 Subsequent theme refinement was deductive and guided by the CFIR.20 A detailed description of the rapid analysis technique and tool we developed and used has been published elsewhere.25

Interviews were audio-recorded and transcribed verbatim. Further thematic analysis, following the framework method,24 was applied to the transcripts; the research team read the transcripts and added condensed data extracts to the matrix, refined and amended codes and categories. Theme refinement was theoretically informed, drawing on the CFIR; it was both deductive and data-informed (as it drew on the data).

The researcher wrote field notes immediately following each interview. Participants were referred to by a unique identifier; the key to the identifier and respondent details were stored electronically on a secure server, separate to the deidentified data. NVivo software (QSR International, Burlington, MA, USA) was used to manage the data collected.

The research team met regularly to discuss analysis, ensure that summary templates were completed consistently and identify areas to explore in subsequent interviews. An audit trail of the process evaluation data was also maintained to enhance the credibility of the data analysis process.26 The data collection and analysis processes were iterative. Analysis started with populating the summary templates soon after each interview was complete and continued through further identification and refinement of the themes.

Patient and public involvement

Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

ResultsParticipants

Two participants declined to participate; no participants withdrew. Interviews were conducted with 84 participants, including patients, relevant staff members across participating general practices, research nurses and an administrator (table 1). Interviews were conducted with 56 patients across 17 participating general practices. The mean age of patient interviewees was 63 years, 52% were male and 82% were white; there was some variation in age profile by ethnic group. The mean length of patient interview was 16 min and 34 min in the inclisiran and inclisiran+behavioural support group, respectively; interviews in the latter group were longer on average due to the additional questions asked regarding the behavioural support they received (table 1). Provider interview mean lengths are shown in table 1.

Table 1

Participant demographics

The remainder of this section presents our findings in terms of patient and provider experiences and identifies key enablers and barriers to the implementation of inclisiran. Table 2 summarises these and sets out the constructs from the CFIR that were most salient.

Table 2

Barriers and enablers to implementing inclisiran in primary care

Patient experiencesLiving with elevated cholesterol

Patients were aware of their elevated cholesterol levels, which had usually been identified during routine health checks, but many reported that this knowledge did not usually have a notable impact on their daily life. However, while some patients reported little concern, others expressed fears that their high cholesterol could have health implications, with some sharing experiences from their family of illness or premature death due to CVD.

Most patients had elevated LDL-C despite taking statins. Some patients had previously switched statins due to intolerance, with some saying they had tried several different medications, but few side effects were reported with their current treatment. Patients quoted the ‘bad press’ associated with statins as contributing to adherence issues, and some said they occasionally forgot to take doses. Some patients disliked taking tablet medication generally, particularly if they were taking several daily medications.

Receiving Inclisiran

Patients generally found the process of arranging and attending appointments ‘easy’ and ‘straightforward’, and general practice was considered a convenient location to receive inclisiran. Several noted a preference for receiving inclisiran in their general practice compared with travelling elsewhere (eg, a hospital clinic), and patients were often familiar with the prescribing healthcare providers. Patients’ barriers to implementing inclisiran largely related to the context of the trial, including consent processes and the wait for and length of appointments.

Behavioural support

The behavioural support provided to patients in the inclisiran plus behavioural support group was generally viewed as favourable, and the motivational approach was novel for most. Patients were generally content to receive support via telephone, noting that the virtual nature permitted them to be open with the health advisors, although some reported that in-person ‘weigh-ins’ could provide beneficial external validation of weight loss. Many patients were aware of the impact that lifestyle, including diet, can have on cholesterol levels but had not received coaching on such factors. The content of the sessions and supporting materials (eg, booklets) was communicated in an easily digestible format for most; however, some patients said they felt disengaged after receiving generalised information with potentially unrealistic expectations. Most patients praised the social skills and knowledge of the health advisors.

Future provision

Most patients expressed a desire to continue inclisiran treatment after this open-label study, with many reporting a reduction in LDL-C after 90 days of treatment. There was a consensus that general practice was the best place to receive inclisiran and that a nurse-provided service would be acceptable, ideally fitting into existing annual or 6-monthly health reviews.

Some patients weighed a desire to continue receiving a beneficial medication against concerns about the cost of inclisiran to the NHS.

Healthcare provider experiencesCurrent management strategies for elevated cholesterol

Healthcare providers reported that most patients with elevated cholesterol are managed in general practice, with statins the most common treatment type (table 3). Some GPs said they wanted to encourage patients to make positive lifestyle changes, ideally before prescribing lipid-lowering medications, but noted the difficulty in providing behavioural support within the time constraints of a GP appointment.

Table 3

Themes and quotes from healthcare provider interviews

Several healthcare providers noted ongoing problems with non-compliance, resistance and intolerance related to statin treatments. They said that overcoming a hesitancy to take statins in some patients—which was linked to ‘bad press’ and ‘misinformation’ surrounding the medication class—required multiple consultations over several years.

Views on the delivery of inclisiran

Inclisiran was generally viewed as a useful addition to existing lipid-lowering therapies (table 3). The study design of VICTORION-Spirit required inclisiran to be administered by healthcare providers who were trained in and compliant with Good Clinical Practice; this meant administration was mostly undertaken by GPs.

Most GPs viewed the inclisiran injection as familiar, simple, effective and generally well tolerated. Several healthcare providers had previous experience with inclisiran as part of the ORION trials,9 11 27 28 which increased their competence and confidence in the medication. All GPs felt comfortable with their patients receiving inclisiran throughout the trial, and the reductions in LDL-C observed at day 90 in many of the GPs’ patients contributed to GPs’ positive feelings about inclisiran.

The trial protocol was amended to permit inclisiran to be administered in the arm or thigh instead of the abdomen, which was the original preferred site. Several GPs noted that their patients felt more comfortable receiving the injection in their arm due to familiarity and ease of access.

Views on sustainability

Healthcare providers agreed that inclisiran could partially address the unmet needs of patients with elevated LDL-C who require treatment beyond statins but highlighted several barriers to its implementation. Most concerns were associated with the limited resources of general practices, the potential implications for other services (Anything new that is introduced is at the expense of something else) and costs, relating to both the price of inclisiran and the costs associated with the delivery of extra appointments or clinics. Several healthcare providers said they will be guided by decisions from their local Medicines Management Group on the future local use of inclisiran (table 3).

Some GPs felt comfortable n prescribing inclisiran beyond the study but noted that training and education would be required to raise the knowledge and confidence of healthcare providers who had not participated in the programme, including colleagues within participating practices. It was suggested that such support and advice should come from lipidologists.

Primary care was viewed as ‘the right place’ for prescribing and delivering inclisiran. Healthcare providers felt that delivery of inclisiran within general practice was feasible and would be convenient for patients. For implementation to be sustainable in terms of time and resources, GPs thought that inclisiran should be administered by healthcare providers other than GPs; practice nurses were the most common suggestion, although healthcare assistants and assistant practitioners were also mentioned. Suggested approaches included dedicated nurse-provided clinics or incorporating inclisiran delivery into patients’ annual reviews, the latter of which may require minimal additional resources. There was variation in views around whether nurses or doctors should administer inclisiran, and caution was expressed around nurse capacity.

Barriers to implementation

Both patients and healthcare providers raised several barriers to the implementation of inclisiran in primary care (table 2). Healthcare providers discussed the time and resource pressure on primary care workforces that is associated with the delivery of a new initiative and advised this could lead to staff or appointment shortages and ultimately delay the delivery of inclisiran. In relation to the wider delivery of inclisiran, healthcare providers raised concerns regarding the lack of long-term data on cardiovascular outcomes for inclisiran and noted that the inclusion criteria for VICTORION-Spirit were broader than the National Institute of Health and Care Excellence (NICE) guideline recommendations.29 There may be a need, therefore, for the narrowing of future practice prescribing to reflect the population parameters recommended and supported by NICE. A lack of endorsement from key stakeholders was also raised as a barrier, meaning that remarks from key stakeholders, for example relating to the lack of long-term data on inclisiran, will likely have to be addressed in the future.30

Discussion

This process evaluation for VICTORION-Spirit highlights for the first time the implementability of inclisiran delivery in a primary care setting for patients with elevated LDL-C for whom statins are insufficient or intolerable. Patients cited the convenience of receiving injections at their local centre, and healthcare providers noted that administration was feasible in general practice as delivering inclisiran was straightforward, simple and effective. Patients and healthcare providers agreed that a nurse-provided inclisiran service would be preferred and, for patients, this would ideally align with their existing annual or 6-monthly reviews.

Our analysis was informed by the CFIR; the framework was a good fit with the data and all domains were relevant. table 2 summarises the enablers and barriers alongside the CFIR constructs most salient.

Implementing an intervention in practice is a lengthy process. According to a study published by the Health Economics Research Group and others in 2008,31 there is a 17-year gap between CVD scientific research and translation into meaningful clinical impact in the UK. This is somewhat reflected in the implementation timeline of statins; research into lipid-lowering therapies led to their development in the early 1980s, but the treatment class was not widely available until the end of that decade.32–34 The hybrid design of VICTORION-Spirit aimed to shorten the time lag between research and the realisation of innovations by concurrently gaining insights into the effectiveness of inclisiran in real-world practice and the ‘implementability’ of the intervention. Blending clinical effectiveness studies with implementation research can result in more rapid translational gains, enhance implementation strategies and potentially provide a wealth of useful information for researchers and key decision-makers.35 36

These interim findings suggest that while the delivery of inclisiran in primary care is feasible, there are several barriers to consider. The importance of training and education for healthcare providers was highlighted, with some GPs reporting healthcare providers may lack confidence in delivering inclisiran in general practice and suggesting that support from lipidologists could be valuable. Also, both patients and healthcare providers raised concerns about the associated costs of inclisiran to the NHS, with GPs recommending incentivisation via Direct Enhanced Services. Another key barrier identified during the process evaluation was the potential impact of an inclisiran service on the resources of general practices, many of which are experiencing additional strain following the COVID-19 pandemic.37–39 While the lasting implications of the pandemic on primary care are not fully understood, the VICTORION-Spirit process evaluation has highlighted the importance of considering the ‘postpandemic’ context when introducing innovation into general practice.

VICTORION-Spirit has several strengths and limitations. By incorporating the CFIR, this analysis has used a validated, standardised, systematic approach that has been implemented across a range of studies.21 24 Furthermore, engagement and insights from key stakeholders, who will influence the future implementation of inclisiran in primary care, were gained during the process evaluation. Centring the patient voice—which can sometimes be viewed as secondary to opinions from healthcare providers and other stakeholders in implementation research—is critical when considering the implications of establishing an inclisiran service in general practice. Many patients in the study spontaneously expressed uncertainty about taking statins, citing their bad press and undesirable side effects and healthcare providers also recognised the issue of statin hesitancy in their patients.

In 2014, Manchester was termed the ‘heart disease capital’ of England after data from the British Heart Foundation revealed the city had the second highest rate of premature deaths due to heart disease in the UK.40 Manchester remained high on the UK league table for 2018–2020, with an annual rate of premature death due to CVD for adults aged<75 years of 122 per 100 000 people.4 Greater Manchester, therefore, represented an ideal location for testing a population health approach that uses a primary care model of delivery to patients who could benefit from treatment with inclisiran. Furthermore, the Greater Manchester population is comparable with the wider UK population in terms of ethnicity, age distribution, sex (stratified by age) and prevalence of chronic disease,41–43 and implementation science approaches have been previously demonstrated in local primary care networks.44 Additionally, general practice works to a core national contract; therefore, implementation would be the same across all other areas of the UK.

Some limitations associated with the study design include a lack of clarity on the potential impact of health inequalities, which may influence the types of patient groups who agree to participate in research, and a relatively short follow-up period (270 days).15 Although it could be considered a limitation that the study was conducted in only one region, the merits of conducting the study in Greater Manchester, in a population that is generalisable to the wider patient population, have been described. GPs highlighted that the inclusion criteria for VICTORION-Spirit were broader than NICE guideline recommendations29 and do not account for the lack of long-term data on cardiovascular outcomes. It is well-established that lowering LDL-C levels improves cardiovascular outcomes. The recent ORION-3 trial demonstrated that inclisiran provided sustained LDL-C reductions over 4 years.28 Mean cumulative exposure to inclisiran in ORION-8 was 3.7 years, with a maximum of 6.8 years of exposure.45 Of the 3274 patients followed up, nearly 80% of those with ASCVD achieved the 1.8 mmol/L LDL-C target. Cardiovascular outcome trials such as ORION-4, VICTORION-1 PREVENT and VICTORION-2 PREVENT are ongoing. Furthermore, a relatively small number of patients, in particular those receiving secondary prevention interventions, were included in the study. As highlighted by some GPs, higher numbers of patients may be eligible for receiving inclisiran in the general population, and a higher throughput could affect the feasibility of delivery in practice. Several healthcare providers had experience of delivering inclisiran as part of the ORION trials, which may have introduced some bias to the process evaluation. Inclisiran was most commonly administered by GPs in VICTORION-Spirit, due to the requirement in the trial that the treatment was administered by a person certified in Good Clinical Practice. In real-world (non-trial) primary care, injections can be administered by any appropriately trained healthcare provider. Indeed, a nurse-provided inclisiran service was the preferred model identified by the patients and professionals interviewed. Furthermore, all patients and providers in our sample had ‘buy-in’ to the trial design and treatment and their views may not be representative of others who were not providing the treatment or taking part in the trial. Finally, while the use of an enhanced control group to explore the wider impacts of behavioural support on patient adherence and empowerment is a strength of VICTORION-Spirit, this also raises implications for wider implementation. If this study demonstrates clear benefits for providing a behavioural support service, resource and cost implications should be considered in terms of wider implementation efforts.

The determinants framework CFIR was used to explore the feasibility and acceptability of inclisiran delivery from the perspectives of patients and providers and to explore the wider ‘transactability’ of the delivery model tested in the trial. While determinant frameworks do not specify the mechanisms of change, they do surface key factors likely to influence implementation effort that would need to be targeted in any effort to promote wider adoption and spread. table 2 highlights that the CFIR had utility in surfacing a number of micro, meso and macro factors. Traditionally, determinant frameworks are deployed in the final step in the research translation process and in the context of interventions of established effectiveness. However, this study suggests that questions on how best to implement innovations in practice can be addressed much earlier in the translational pathway. More upstream consideration of implementation issues could ensure that the essential ingredients for implementation are understood much earlier and that real-world efforts to implement high-value innovations are appropriately planned, potential barriers mitigated and the chance of success maximised.

Conclusion

In conclusion, the process evaluation of VICTORION-Spirit demonstrated that patients and healthcare providers support the implementation of inclisiran in primary care for patients with elevated LDL-C for whom statins are not sufficient or tolerable. Receiving inclisiran in general practice was convenient for patients, and most healthcare providers felt inclisiran was a useful addition to existing lipid-lowering prescribing options. Several areas for improved implementation were highlighted during the process evaluation, including investment in population health delivery.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Per normal practice for qualitative analyses, the raw data for this analysis will not be made available.

Ethics statementsPatient consent for publication

Not applicable.

Ethics approval

The VICTORION-Spirit study conforms to the Declaration of Helsinki. The study protocol was approved by South Central—Berkshire B Research Ethics Committee (21/SC/0040) and all patients were required to provide written, informed consent before participating in the study.

Acknowledgments

The authors acknowledge the collaboration between Health Innovation Manchester, NorthWest EHealth, National Institute for Health Research (NIHR) Applied Research Collaboration Greater Manchester, The University of Manchester and Novartis Pharmaceuticals UK Limited in the development of the VICTORION-Spirit protocol. Medical writing and editorial support were provided by Iona Linford, MEng and Hilary Dean, BSc, from Complete HealthVizion, IPG Health Medical Communications, funded by Novartis Pharmaceuticals UK. The views expressed in this article are those of the authors and do not necessarily reflect those of Novartis, NIHR, NHS England, the Department of Health, arm’s-length bodies or other government departments.