Digital Features for this article can be found at https://doi.org/10.6084/m9.figshare.13653563

FormalPara Key Points

Clinical freedom and consideration of patient choice and preference are vital for individualised care. The increasing availability of new biologics and biosimilars adds cost-based complexity to prescribing decisions for patients who may require these drugs. Clinical freedom should be exercised within a value framework that forms the backbone of rigorous, transparent evidence reports to include available evidence and clinical experience.

Although UK National Institute for Health and Care Excellence (NICE) clinical guidance theoretically allows a degree of clinical freedom, local variations in interpretation occur, with a resulting impact on equity of patient access to treatments. The clinical freedom within UK NICE clinical guidelines could therefore be harmonised across local services to ensure equity of patient access to treatments.

Communication and collaboration between clinicians and commissioners can foster optimal pathway development for better value, access and patient outcomes.

1 Introduction

Biologics are a core part of treatment for many patients with moderate-to-severe immune-mediated inflammatory diseases (IMIDs), such as psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA) and inflammatory bowel diseases (IBDs; Crohn’s disease and ulcerative colitis) [1,2,3,4]. These diseases have a number of commonalities in terms of pathophysiological mechanisms, overlap in patient population and management strategies [5,6,7,8]. In addition to potential synergies, this presents a number of shared challenges, of which, the balance between clinical freedom and equitable distribution of biologics is key.

Clinical practice guidelines increasingly acknowledge the benefits that biologics can offer patients [1, 9, 10]. Yet, although biologics demonstrate superior efficacy over conventional therapies, particularly in patients with moderate-to-severe IMIDs, they are notably more expensive. The recent availability of biosimilar agents for tumour necrosis factor inhibitors (TNFi) has relieved some aspects of cost pressures on healthcare systems [11,12,13]. However, biosimilar availability has coincided with the introduction of a number of biologics with novel modes of action, including inhibitors of interleukin (IL)-12/23, IL-23, IL-17 and anti-integrins, which have different efficacy and safety profiles. In certain therapy areas, some of these novel biologics have demonstrated improved clinical outcomes versus TNFi in direct head-to-head clinical trials (see the Table in the electronic supplementary material [ESM]), meta-analyses and real-world observational studies in terms of short- and long-term efficacy, durability, safety and longevity [9, 10, 14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31].

Clinical freedom, or a physician’s right and duty to do what they regard as the best for their individual patient, is a key concept in choosing treatments together with patients through shared decision making [32]. Interlinked with this concept is clinical judgement, or the physician’s ability to combine clinical experience and expertise with the best available evidence and resources to choose the appropriate treatment [33]. Both clinical freedom and clinical judgement are becoming increasingly important as the choice of available biologics continues to grow. The UK National Institute for Health and Care Excellence (NICE) guidelines are generally phrased to allow a degree of interpretation [34,35,36,37], which enables a physician to exercise some clinical freedom. Yet, within healthcare systems with finite resources, understandable onus is placed on decision makers to opt for the most cost-effective choice [11]. Emerging data show that this is translating into variations in biologic use across England due to local commissioning decisions and mandated clinical pathways [38]. There are likely multiple reasons behind this variability, including local expertise and historical patterns of use, which can leave patients subjected to an inequitable ‘postcode lottery’ of available treatments [38].

Across the three specialty areas, local, regional and national harmonisation of commissioning and prescribing services is required to permit synergies in NICE guideline interpretation and ensure equity of patient access to biologics through shared decision making. The Delphi process, which is a structured, egalitarian method for incorporating multiple expert views, can help to establish and document recommendations in instances such as this in which evidence is lacking and issues are difficult to define [39,40,41,42]. In this report, we aimed to use a modified Delphi process to generate an integrated consensus on clinical freedom and equitable use of biologics in England. We also offer practical strategies to optimise patient access to biologics and to enhance existing guidance and excellence in clinical outcomes for patients with IMIDs by balancing treatment choice with value for the English National Health Service (NHS).

2 Methodology

The panel consisted of invited representatives of specialties from across England, representing dermatology (n = 3), rheumatology (n = 2) and gastroenterology (n = 3).

A modified Delphi process was used to reach consensus, consisting of an e-survey and a group meeting in January 2020. A literature review of 144 unique references was conducted to inform the e-survey content, using PubMed Central and the European, UK national and NICE clinical guidelines. Details of the search strategy and the full list of articles identified are presented in the ESM.

Consensus statements were voted on in the e-survey and using an anonymous mobile application during the meeting. E-surveys and meeting voting were programmed, administered and collated by OPEN Health Medical Communications to maintain blinded voting. Consensus statements assessed the level of agreement using the terms ‘strongly disagree’, ‘disagree’, ‘agree’ or ‘strongly agree’. Consensus was defined as achievement of at least 75% ‘agree’ or ‘strongly agree’. Results are reported as n/N voting ‘agree’ or ‘strongly agree’ (e.g. 7/8 indicates seven of eight panellists voting ‘agree’ or ‘strongly agree’). Additional comments and discussions were recorded to supplement specific statements.

Following analysis of results and development of the manuscript, representatives from three UK patient advisory groups (National Rheumatoid Arthritis Society, Crohn’s & Colitis UK and the Psoriasis Association) were asked to comment on this manuscript and the relevance of its recommendations for patients with IMIDs in England.

3 Results

3.1 Defining the Principle of Clinical Freedom and its Role in Clinical Choice

3.1.1 Expert Consensus

  1. (i)

    Clinical freedom enables a physician to select the best treatment option in partnership with each individual patient (8/8 [100%]).

  2. (ii)

    Clinical freedom should be exercised within a value framework, utilising all available evidence (8/8 [100%]).

  3. (iii)

    In the UK, factors affecting the degree to which clinicians can exercise clinical freedom include geographical location and disease specialty (8/8 [100%]).

  4. (iv)

    Clinical judgement involves the interpretation of all available sources of information to formulate a recommended management plan for a patient (8/8 [100%]).

  5. (v)

    Clinical guidelines provide a useful framework for how treatment options may be used at a population level. However, when determining an individualised treatment plan, the exercise of clinical judgement remains vital (8/8 [100%]).

    • The panel reached consensus on factors that should be considered when deviating from a population pathway, which are summarised in Table 1.

      Table 1 Factors that should be considered when deviating from a population pathway and that impact the choice of biologic prescription and influencing switching decisions, by consensus
      Full size table
  6. (vi)

    In order to optimise care for both individual patients and the larger population, it is important for clinical guidelines and commissioning groups to strike a balance between clinical freedom and restrictions that support equitable resource distribution (8/8 [100%]).

3.1.2 Additional Comments

Debate on the exercising of clinical freedom and healthcare system resourcing practices is ongoing. Clinical judgement and clinical freedom are interlinked with patient choice and preference, and all play a role in appropriate prescribing for individual patients in a given value framework. Value frameworks, such as that devised by the Institute for Clinical and Economic Review, aim to provide sustainable access to high-value care for all patients. They offer a conceptual framework to assess an intervention’s long-term value for money through its incremental cost effectiveness—including additional benefits, disbenefits and potential cost offsets for new treatments over a patient’s lifetime—to inform decisions both at the patient/physician level and at the population level [43,44,45]. Clinical practice decisions are based on available evidence and experience; individual patients require tailored treatment according to the physician’s judgement, and decisions should only be made after discussion with the patient [32]. Indeed, many clinicians argue that primary focus on the individual patient is the basis of clinical freedom [46], meaning that clinical freedom is a significant facilitator to the practice of personalised care. Table 1, which shows factors to consider when deviating from a population pathway, could be construed as suggesting that cost is not a consideration. Rather, it is intended that cost should not be the sole consideration, unless all other factors listed are equal.

In the specific case of the English healthcare system, a balance between clinical freedom and equitable resource distribution would continue to ensure fair implementation of NICE guidance.

3.2 The Value of Biologics

3.2.1 Expert Consensus

  1. (i)

    Interpretation of drug value is hampered by a lack of available evidence relating to long-term impact across a range of outcome measures of importance to patients, the healthcare system and society (8/8 [100%]).

    • The panel reached consensus on factors that are encompassed by a drug’s value, which are shown in Table 2.

      Table 2 Factors encompassed in the concept of a drug’s value, by consensus
      Full size table
  2. (ii)

    Lack of transparency on drug pricing, regional variations, cost fluctuations and complex contracting arrangements present additional challenges to physicians’ abilities to assess value (8/8 [100%]).

3.2.2 Additional Comments

The term ‘drug value’ can often be misunderstood or improperly used. This may present a challenge to the freedom of clinical choice and appropriate prescribing decisions that allow the practice of holistic and personalised medicine.

Efficacy was agreed to be a factor encompassed by a drug’s value and that should impact choice of biologic prescription or the decision to switch between agents. However, efficacy is a composite of several aspects, including short- and long-term clinical scores (e.g. Psoriasis Area and Severity Index response, American College of Rheumatology response, Crohn’s Disease Activity Index), speed of response, durability and patient-reported outcome measures. Clinical trial data suggest that novel biologics appear to offer additional value for particular patients over older agents or conventional non-biologics. The evidence base for drug impact across a range of clinical outcomes is limited but growing. For example, there is now evidence showing reductions in the incidence of cardiovascular disease in patients receiving adalimumab for RA [47], whilst there is increasing evidence and guidance to state that some TNFi (adalimumab, certolizumab pegol, golimumab, infliximab) may be possible treatment options during pregnancy in certain patients for whom the benefit of staying on treatment outweighs any potential risk to the foetus [9, 10, 48,49,50,51,52,53]. Yet, most registration study data are short term in nature, typically demonstrating outcomes of no longer than 1 year and with primary focus on clinical scores [35, 54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71]. This highlights the continued lack of published evidence to demonstrate a drug’s value.

It has been argued that clinical freedom may be limited by proscriptive treatment and resourcing mandates or reimbursement practices [72]. However, the authors argue that a lack of evidence to demonstrate value can also be a limiting factor. In the absence of unlimited resources, medical care must be restricted to interventions of proven value. Therefore, some suggest that, without evidence of efficacy and safety, resources should not be allocated to a particular treatment [73,74,75]. Although biologics have revolutionised the management of many IMIDs, there remains interpatient variability in clinical and safety responses to therapies [76], and some published literature from randomised controlled trials (RCTs) is not always applicable to a certain patient’s situation. Therefore, the clinician’s experience should be included among available evidence to be used within the value framework, enabling them to choose from multiple agents or classes of agents, and to optimise outcomes for each patient.

3.3 Equitable Use of Biologics in the English Healthcare System

3.3.1 Expert Consensus

  1. (i)

    Clinical freedom to prescribe across all available treatment modalities is important to offer personalised care to patients (8/8 [100%]).

    • Consensus was reached on a number of factors that can impact choice of biologic prescription and influence the decision to switch from one biologic class to another (Table 1).

  2. (ii)

    Local pathways can help commissioners and clinicians reach a shared understanding of how national guidelines may impact upon their patient populations. However, variable interpretations and setting of additional barriers and targets create inequity of patient access (8/8 [100%]).

  3. (iii)

    Effective development, implementation and updating of current pathways requires close cooperation between clinicians and local commissioners. It is vital that these two groups maintain ongoing, open and transparent dialogue (8/8 [100%]).

3.3.2 Additional Comments

The availability of newer biologic options has expanded therapeutic options for patients with IMIDs; however, it should be noted that their availability in IBD has so far been slower than in psoriasis and PsA, which is mirrored by a slower rate of change in NICE guidelines and treatment choice availability for biologic-eligible patients in clinical practice.

In psoriasis and PsA, novel biologics may be considered over TNFi, especially for patients with specific disease characteristics such as those with a more aggressive disease course, involvement of vulnerable areas (e.g. genitals), a worse phenotype, or other comorbidities, all of which may increase impact on quality of life [1, 9]. In addition to potential improvements in efficacy, access to drugs with better safety profiles is particularly important for certain patient subgroups [9, 10, 20, 23, 77]. Clinicians may have a choice of biologic classes and will therefore need to consider variations in a patient’s disease presentation, disease severity and comorbidities when deciding which drug to use. For example, in patients presenting with multiple IMIDs, it may be logical to select an agent that is effective across disease areas and that would not otherwise be first choice. TNFi biosimilars have an important role in clinical practice by reducing direct drug costs. However, as with any biologic, biosimilar use must be exercised within a framework that considers clinical value as far as evidence is available. This includes the growing literature base assessing factors beyond direct costs such as tolerability issues (e.g. injection site reactions with citrate-containing agents), efficacy (e.g. the nocebo effect) and indirect costs (e.g. the administrative costs or increased healthcare utilisation associated with non-medical switching) [78,79,80,81,82,83,84,85]. Of note, although these recommendations were made with a specific focus on biologics, the concept can be extrapolated to other drugs with a high unit cost, e.g. targeted systemic small molecule inhibitors such as Janus kinase (JAK) and phosphodiesterase E4 (PDE4) inhibitors.

3.4 Practical Strategies to Optimise Patient Access

3.4.1 Improving Dialogue

Enhanced communication between clinician and commissioner is critical to improve equity of access that aligns with the principles of NICE guidelines and permits clinical freedom. Commissioners should understand the commonalities and differences between IMIDs. Although recommendations for one may not necessarily transfer to others, there are significant overlaps in the specialties. Similarly, understanding the pricing factors involved in commissioning decisions would aid physicians in assessing a drug’s value, which cannot be complete without knowledge of cost. Some clinical commissioning groups (CCGs) or clinician pathway groups use tables that group biologics by cost bands to aid decision making. These may be beneficial if implemented more widely across England.

Clinicians are best placed to shift the focus from resources and costs to health outcomes, quality of life and patient satisfaction. Hence, medical participation in management, as well as perhaps commissioning decisions around it, is imperative [74]. Understanding decision making by clinicians helps clinical leaders and policy makers to determine resource allocation, which then allows clinicians to make appropriate treatment selections [86].

A good relationship between commissioners and clinicians is key to good communication; conversely, the lack of such a relationship can present challenges to current practices. Strategies for improving communication could help resolve the majority of disagreements around commissioning decisions (see Box 1). In rare circumstances, it may be necessary to consider formal proceedings such as a letter to the medical director outlining the grounds of concern and invoking the formal complaint process. In this instance, we regard it as good practice to copy the patient into correspondence so they can be fully aware of ongoing discussions regarding their care.

Box 1 Methods for improving physician–commissioner communication
Full size table

3.4.2 Aligning Clinical Judgment and Commissioning Decisions

Ideally, collaboration between physicians and commissioning groups should foster the development of suitable pathways and protocols that reflect the clinical freedom permitted by NICE guidelines, which not only respect the physician’s ability to select management strategies for individual patients but also eliminate geographical variations in care. Improved dialogue between specialties would additionally benefit pathway development due to differences in clinical outcomes: the effectiveness of a specific biologic in one disease may be suboptimal in another, knowledge of which can be improved through interactive working and cross-specialty dialogue.

In some cases, it may be necessary to challenge a commissioning decision, such as where the clinician believes a particular CCG pathway mandates limits and targets for certain agents to the detriment of a patient. Improved communication and informal discussion between clinicians and commissioners should be the first port of call to reach a solution or compromise. Figure 1 depicts a process and resource bank that aims to support physicians and patients to resolve a misalignment between clinical judgement, as per NICE guidelines and a CCG pathway.

Fig. 1
figure 1

Process and resources for reaching a solution in the event of misalignment between clinical judgement as per NICE guidelines and a CCG pathway. BAD British Association of Dermatologists, BSG British Society of Gastroenterologists, BSR British Society for Rheumatology, CCG Clinical Commissioning Group, CD Crohn’s disease, IFR individual/independent funding request, NICE National Institute for Health and Care Excellence, TA treatment appraisal, UC ulcerative colitis

Full size image

Independent/individual funding requests (IFRs) may also be a route to funding of a drug that is not supported in a CCG pathway or by the English NHS. They are submitted when the clinician believes that an individual patient has an ‘exceptional health need’ and are considered by a panel of clinicians, health experts and laypeople on the basis of evidence for clinical and cost effectiveness, as well as equity for the whole population [87, 88]. IFRs are not appropriate where a drug is NICE approved and when proposed use is within the relevant NICE technology appraisal guidance. The authors express variable sentiments towards IFRs, which is likely reflective of local CCG variations. Some feel that they are not a pragmatic way to reach a solution, due to the demand for specific, robust outcome and economic evidence, despite the fact that the patient’s case is exceptional and is therefore unlikely to align with evidence published in RCTs. Others have successfully argued that a lack of evidence does not mean a lack of efficacy and have used published case reports or phase II studies to support an application.

Clinicians and commissioners should be aware that the NHS has a duty to fund and resource medicines and treatments recommended by NICE’s technology appraisals. Patients have the right to drugs and treatments that have been recommended by NICE for use in the NHS if their doctor believes they are clinically appropriate [89]. Although this may not currently be the case in certain CCGs, the authors emphasise that ongoing communication can optimise development of sufficiently flexible pathways that can account for a variety of patient situations and minimise the need for a physician to challenge them.

4 Discussion

The panel has discussed clinical freedom and clinical judgement, which are two related concepts in the context of biologics prescribing in England. Although both play a part in treatment decisions, clinical judgement is broader and goes beyond just treatment selection, considering situational factors such as those imposed by the healthcare system. The consensus reached shows that it is vital for physicians to be able to make clinical choices to best serve the variety of patients that they treat.

NHS working groups have already set out the importance of a collaborative approach in the commissioning of biologics, including biosimilars, and offered some guidance as to how this could be achieved in the current climate of cost pressures and evidence gaps [11, 90]. We endeavour to enhance these processes by defining important concepts of clinical freedom, clinical judgement and drug value in the context of biologic prescribing.

In a variety of therapy areas, clinical guidance or decision-making tools have been shown to correlate with expert clinical judgement and to improve patient outcomes [39, 91,92,93,94]. It has been demonstrated that improvements in available clinical tools and better knowledge thereof can alter clinical judgement [88]. Guidelines must therefore help to define treatment standards while accurately reflecting areas of uncertainty to avoid limiting innovative practices in clinical care [72]. Treatment guidelines increasingly advocate that patient preference should factor into treatment decisions, thus permitting practice of personalised medicine to optimise patient adherence and treatment outcomes [1, 9, 10, 34, 36, 37, 95, 96]. Furthermore, there will always be patients who fall outside of the available evidence and require expert interpretation for their treatment. For this reason, our proposals are intended to help re-align clinical judgement and commissioning decisions and to include the patient, who is directly impacted, in these discussions.

The debate on how best to balance competing demands when prescribing within a finite budget is ongoing. The quality-adjusted life-year (QALY) measure accounts for life length and quality and was designed to standardise healthcare funding decisions across diseases based on the degree of a treatment’s health benefit [45, 97,98,99]. The QALY is a cornerstone of NICE health technology appraisals and is seen as an important tool for ensuring maximum benefits when healthcare budgets are limited [97]. However, the QALY also remains problematic for applying a uni-dimensional measure to the multi-dimensional nature of health effects without recognising non-health benefits [45, 97,98,99]. There are limitations to assessing a treatment based on the QALY, including false limitation of clinical freedom and potential hindrance of patient outcomes. Such limitations are likely to be exacerbated by personalised medicine [99]. Particularly pertinent to our recommendations are the ethical issues, wherein the QALY is unable to discriminate between individual patients or situational factors that may have a considerable impact on the patient [97, 99]. In the UK, QALYs are usually based on general quality-of-life instruments that are not sufficiently sensitive to account for small but meaningful health status changes in specific patient subgroups or the disease-specific experience [97, 99]. Examples include the individual with RA unable to type because of hand pain and stiffness, someone whose mobility and hand function are limited by palmoplantar psoriasis, or the person living with Crohn’s disease who misses appointments because of the need to remain close to a toilet, thus escaping incorporation into health technology assessments.

Our consensus recommendations align with the views of other groups: there can be advantages to incorporating additional attributes of benefit into analytical frameworks to support explicit and transparent decision making [45]. Yet, whilst there is a need for empirical assessment to support funding decisions and establish appropriate overall expenditure [45], the evidence is usually based on efficacy from strict RCT populations. For the majority of patients, access to medicines falls within QALY remits and calculations; it is for those who sit outside the norm, and who might typically be the subject of an IFR, that readjustment and harmonisation of services across England can be improved. Here, value frameworks could assist with value judgements and support transparency around prescribing decisions. An expanded-value framework has been proposed, incorporating a wider range of elements beyond the core of health gain and offset of cost savings, including productivity, reduction in uncertainty of response to treatment and value of hope [98]. In line with our own recommendations and commentary from patient groups, the importance of including patients in discussions around value has also been highlighted [100]. This would be further enhanced by additional data for both health- and non-health benefits, spanning more complex, real-world cohorts as well as stringent RCT populations. Such elements may not be the most important in definition of value, or the easiest to incorporate, and the relevant data may not yet exist [98, 99]. Yet, without consideration of these elements, patients may be subjected to inappropriate access decisions and the potential exists for suboptimal spending on healthcare [98, 99].

By way of enhancing the current situation, we have supplemented the consensus on clinical freedom and biologics prescribing in England by suggesting practical ways to improve communication between clinicians and commissioners. We have attempted to enhance the existing decision-making processes by offering recommendations for collaboration, communication and resource sharing to facilitate solutions for patients with IMIDs, while considering the economic sustainability of the healthcare system. Finally, input from three relevant expert patient organisations indicates the applicability of these recommendations to the patients who are ultimately affected by any decisions (Box 2). As a future step, it would be valuable to gain perspective from commissioners from multiple CCGs and specialties to further understand the processes and relative differences in commissioning decisions across England.

Box 2 Real-life applicability of these recommendations for patients—statement from the National Rheumatoid Arthritis Society, Crohn’s & Colitis UK, and the Psoriasis Association
Full size table

4.1 Strengths and Limitations of These Recommendations

A Delphi process is affected by the number and representativeness of its participants, which will affect the range of discussion and quantity of data [41]. The project’s main limitation is the small number of participants in the Delphi process. No guideline on the standard number of participants or the criteria against which an appropriate number of participants could be judged yet exist [101, 102]. Although Delphi panels most frequently consist of 10–100 participants [101, 102], it has been suggested that confidence in the results could still be maintained with a smaller Delphi panel if participants had similar training, knowledge and understanding of the field [101]. Our panellists were all from academic centres; the drugs discussed here are typically prescribed in secondary care, so physicians in academic centres are likely to have the greatest experience and understanding of their use, benefits and drawbacks in patients with complex needs. As a future step, there could be value in expanding the consensus statements defined and voted upon here to a wider group of physicians, to understand the applicability to the general population of biologic-eligible patients.

A key strength of this project is its cross-specialty focus. Inclusion of both specialist physicians and feedback from multiple patient groups highlight the broad scope of the issues discussed. Each panellist represented a different CCG; although some may be geographically close, such as those in London, there are discrepancies even within neighbouring boroughs of the capital, which further highlight the issue under discussion. The commentary from patients in particular indicates the relevance of these issues to those ultimately affected. Given the interlinked nature of many IMIDs, in both their manifestation and their management, these practical recommendations have the potential to benefit a greater number of patients than if they were to address just one disease.

5 Conclusions

This consensus highlights that clinicians must be able to exercise clinical freedom in order to best serve patients; however, this is necessarily limited by the funding restrictions of a healthcare system. Striking a balance between clinical freedom and short-term cost restrictions is vital to support equitable resource distribution. Consideration of these recommendations may help to harmonise local, regional and national services through a multi-stakeholder approach involving policy and patient groups as well as physicians and commissioners, improve data generation to support value-based prescribing decisions, and ultimately ensure equity of patient access to biologic treatments.