Therapeutic innovation in high-prevalence chronic diseases: Challenges and opportunities for specialist care models

Abstract

Therapeutic innovation is expected to change if not disrupt present care models for several chronic diseases in the coming years, as suggested by recent clinical trials. New drugs that anticipate and possibly delay the full expression of a disease will likely face some common challenges, such as the need of designing and implementing large scale interventions; the necessary engagement of multiple specialties for both diagnosis and treatment; the shift from specialist to non-specialist interventions and secondary prevention. Building on the case of HCV and other innovation in hepatology, we discuss common challenges caused by disruptive change that other chronic conditions faced in the past. The recent history of hepatology shows interesting examples of disruptive innovations that completely reverted traditional treatment approaches. As we learned from the slow early diffusion of antiviral drugs, without a clear information and a prompt design of the appropriate delivery modalities, the effectiveness of new treatments is undermined and care risk to be postponed for long time. This implies the definition of (i) new service models diversified by care phases and patients’ target; (ii) horizontal integration: to go beyond the professional boundaries to build solid alliances; (iii) vertical integration between primary and secondary care.

Introduction: Definition of the Problem

Recent clinical trials suggest that therapeutic innovation could disrupt present care models for several chronic diseases in the coming years. This is the case of new drugs in the pipeline for intercepting and tackling the initial symptoms and early stages of common diseases such as Alzheimer’s disease (AD),^1,2 migraine,^3,4 and non-alcoholic steatohepatitis (NAFLD/NASH).^5,6

New drugs that anticipate and possibly delay the full expression of certain diseases, to the extent of possibly eradicating them, will likely face some common implementation challenges, such as:

1. The need to design and implement large scale interventions for diseases, such as AD, migraine and NASH, that affect large numbers of patients. Recent studies report the prevalence of AD is estimated at 5.08%. ⁷ Similarly, available data estimate that about 14.4% of adults all over the world develop some form of migraine over the course of life, ⁸ but according to recent studies, the number could be underestimated. ⁹ Finally, a recent meta-analysis showed that worldwide prevalence of NAFLD and NASH is increasing constantly over time, and is 25.25% for NAFLD and between 1.5% and 6.45% for NASH. ¹⁰

2. The necessary engagement of multiple specialties for both diagnosis and treatment, with technology often representing the point of contact between different professional groups orchestrating costly treatments.

3. The shift from specialist to non-specialist interventions and secondary prevention, in order to identify diseases before symptoms become serious.

If this kind of innovations are radically new in neurology, with yet no resolutive treatments for most chronic neurological diseases, the recent history of hepatology shows interesting examples of disruptive innovations that completely reverted traditional treatment approaches. This perspective paper is based on the observation of the different models of care (MoC) for Hepatitis C Virus (HCV) adopted by 7 Italian hospitals. We refer to MoC as setting-specific frameworks that address what services are provided, where, by whom and how they are integrated along the cascade of care. ¹¹ Italy has a universal regionalized healthcare system, ¹² and was at the forefront of HCV eradication programs with a dedicated 1.5 billion euros fund allocated in 2017. ¹³ This work aims at sharing lessons to be learnt for the management of other chronic conditions approaching similar technological disruption.

The example of HCV treatment

In 2014, the introduction of DAA (Direct-Acting Antiviral) regimens for the treatment of HCV dramatically changed the landscape and perspective of patient care. ¹⁴ Professionals, hospitals, and ultimately patients affected by HCV experienced a radical shift in treatment delivery and clinical outcomes, going from life-long disease management to three to 4-month curative antiviral treatments that are fast contributing to eliminate the disease, in harmony with the WHO Global Hepatitis Strategy 2016–2021. Being recommended for very large patient pools, the introduction of DAA-based therapies imposed on healthcare systems all the three types of challenges previously listed:

• Therapeutic innovation virtually allowed coverage for all infected persons (overall HCV prevalence was estimated at 1.4% worldwide, ¹⁵ including candidates traditionally labelled as “difficult to treat”, before the widespread diffusion of DAAs, and was higher overall in Italy ¹³ ). These individuals represented an untreatable group that can now access treatment, a key criterion for the definition of disruptive development. ¹⁶ In order to treat the whole population with HCV, the system had therefore to increase access to care and look proactively for the hidden pools of patients (‘unknown patients’) that could not reach services due to their socio-economic conditions or simply because of their unawareness.

• To treat such a high number of patients, multiple disciplines (i.e. gastroenterology, infectious disease, internal medicine) were brought together across different settings of care. Before the introduction of DAA therapies, HCV, as a chronic disease, used to be treated as one among many comorbidities and normally managed by the specialist who intercepted the patient by chance or due to the most serious condition. Diagnostic technologies, such as ultrasounds or liver elastography (e.g. Fibroscan), became connection nodes among different physicians typically belonging to different specialties and units, fostering treatment and process standardization over time.

• The introduction of new drugs required the formalized collaboration of different levels of care, and the definition of related competences, sometimes leading to a shift from specialist to non-specialist interventions. Indeed, the need to catch the disease at its early stage or to identify “difficult-to-reach” targets led to an attempted vertical integration of services, and to the creation of clinical networks. This is fundamental considering that the HCV prevalence, despite therapeutic advances, is still increasing in special populations such as people who inject drugs. ¹⁷ Integrated care pathways (ICPs) were developed across different settings, with responsibilities and duties distributed according to the specific phase of the patient journey. Hospitals focused on the second-level diagnosis and the treatment, while primary care worked on the identification and recruitment of patients, the first-level diagnosis, and the follow-up.

While all observed cases have had to address these challenges, MoC differed in terms of hospital and community care contribution, prevailing specialties, adoption of strategies for the identification of hidden cases and activation of dedicated clinical networks. Three different models of care were identified across the 7 hospitals in Italy, all still prevalently managed by specialists in hospitals: (i) a so-called ‘concentrated model’, where the entire care pathway is hospital-based with no formalized linkages with the community; (ii) a ‘hybrid model’, where a preliminary liaison with the community is initiated and includes active screening on high-risk populations; (iii) a ‘network model’, with a well-established integration between hospital and community care within broader networks.

Discussion: What can we learn to innovate the management of large and increasing numbers of patients

For a long time, healthcare systems were organized around the traditional split between the chronic care and the acute care models. According to these models, chronic conditions are better managed by primary care, and general practitioners (GPs), in outpatient settings, while acute and complex illnesses imply a highly specialized response that is concentrated in a defined time (the acute episode) and space (mainly the hospital and acute setting). In recent years, a new concept has been introduced: the “highly complex chronic condition” ¹⁸ , which is associated with multiple morbidities, requires the attention of multiple healthcare providers or facilities, and displays needs not necessarily linked to hospitalization episodes but where specialist competences and expertise still play an essential role. The management of AD, migraine and NAFLD/NASH, as highly prevalent chronic diseases with a possibly incoming therapeutic innovation, can be paradigmatic examples of the new challenges posed by these complex conditions. To successfully address these challenges implies the definition of (i) new service models diversified by care phase and patient subgroup; (ii) horizontal integration, to go beyond professional boundaries and build solid alliances; (iii) vertical integration between primary and secondary care. Hereafter a description of these challenges.

New service models diversified by care phases and patient subgroup

The management of a large and increasing number of highly complex chronic patients requires the design of new MoC across all possible settings. This is particularly complex in cases where patients with the same chronic disease, pending the introduction of new technological innovation, are currently treated by several different organizational units and related disciplines.

In particular, the introduction of new pharmaceutical drugs could trigger two recurring problems in chronic care models. ¹⁹ First, different actors will tend to persist in developing different service models, due to discipline-specific values and beliefs. Thus, an orchestration of the delivery modalities will be needed to ensure an equitable diffusion of the new treatments and avoid multiple service models for the same disease/therapy. Second, the radical increase in the number of patients treated will require a sharp acceleration in the development of a vertical integration between primary and secondary care (which is further discussed below).

New service delivery models could be developed following two different approaches. In some cases, it will be appropriate to design integrated pathways in which different care settings or organizational units are responsible for different phases of care. Hospitals will likely remain the focus of diagnostic activities, with centralization of high-level services in a few highly specialized centres, but less intensive phases of care could be better addressed in less intensive and less specialized settings. In all cases, however, it will be fundamental to develop ad-hoc MoC for vulnerable targets of patients based on clinical or socio-economic factors. ²⁰ Once again, the HCV case is very illustrative, with a variety of organizational models observed across hospitals and regions, with only recent changes to assign the responsibility over diagnosis and follow-ups to GPs and other local actors. ²¹

Horizontal integration: beyond professional boundaries to build solid alliances

Large scale interventions require multi-professional collaborations^22,23 in order to trigger the necessary actions at different institutional levels (e.g. new policies, new hospital and medical practices), to avoid duplications and other inefficiencies, and build solid alliances across organizations and communities of practice. This translates into defining clear roles and responsibilities among various disciplines that equally and complimentary contribute to the management of specific conditions.

New curative pharmaceutical drugs could radically modify the patient care pathway, suggesting either an increasing concentration of cases in acute settings at the hospital level, or opening new routes for more out-of-hospital home-based care. When hospital care is preferable, multiple units that in the pre-drug era were competing for patients will have to collaborate or rediscuss how to allocate resources and specialize. For some chronic conditions, concentration in one unit/discipline might be recommended, but, considering the increasing demand, it is unlikely that patients will be assigned to one discipline only, thus fostering the adoption of cross-discipline collaboration and multi-disciplinary teams.

Prescription power, that is the right and legal authorization to prescribe innovative treatments, has typically been the main driver for patient allocation across different care centres or units, as in the case of HCV. With proper training, it has now been confirmed that treatment prescription can competently go beyond specialists in tertiary care centres. ¹¹ In the near future, we foresee that to better manage care networks fewer but more diffuse nodes might be responsible for prescriptions, while others will focus on organizing and delivering care and follow-ups.

Vertical integration between primary and secondary care

Regardless of the availability of new therapeutic innovations, the early detection of complex diseases represents a cornerstone of effective disease management and necessarily requires multi-level collaboration with primary care and GPs,^24,25 who are in a privileged position given the high number of patients they see. Primary and secondary care have a new opportunity to coordinate healthcare services by complementing each other and thus fulfilling patients’ needs on various levels. Coordination models and respective duties have to be flexible and prone to change. GPs should at first be key in detecting early symptoms and guiding patients to specialist follow-ups, especially for diseases in which unknown cases are copious (e.g. HCV, NAFLD), but in the future, with simplified and controlled treatment plans, they could possibly support or substitute specialists in prescribing and delivering the treatments.

Nevertheless, GPs will not be the only channel to identify early signs of disease, especially considering the escalating care needs. Self-diagnosis, for certain diseases, could also spread in the next future, thanks to the continuous development and simplification of diagnostic technologies. Furthermore, nurses, social workers and other community professionals must all contribute to this multidisciplinary effort, particularly for vulnerable targets that could be better treated where they are already accessing other services. Pharma companies will also play a pivotal role in this ecosystem accelerating the production and diffusion of evidence.

In general, the knowledge about emerging diseases or early stages of well-known diseases will need to be developed and further diffused by multiple actors to ensure appropriate measures are taken to identify and catch unknown cases, but also to prevent new ones. Equally, proper surveillance measures must be implemented after treatment provision for people in need. Healthy people should be informed in order to take, for instance, the necessary precautions and adopt healthy lifestyles associated with a lower incidence of the ‘new diseases’. Clinical networks in which GPs closely collaborate with specialist centres could boost information diffusion and ensure scientific evidence to inform policy and organizational choices.

As we learned from the slow early diffusion of antiviral drugs in the case of HCV, without clear information and a prompt design of the appropriate delivery modalities, the effectiveness of new treatments is undermined and care risks to be postponed for a long time. New treatments with high effectiveness and good tolerability do provide meaningful opportunities to reshape the treatment of several chronic diseases, but only through sustained focus on strengthened diagnosis procedures, streamlined patient pathways and robust integration models this potential can turn into actual reality. The observation of HCV MoC still prevalently rooted in earlier paradigms confirms that therapeutic innovation does not immediately translate into equivalent organizational innovation.

Conclusion

The HCV example is predictive of what can happen to other diseases (at the moment AD, migraine and NAFLD/NASH) managed by specialists, usually in a single discipline, in case of new drugs suited for initial symptoms and early stages of disease.

The history of HCV therapies helps to know the impacts of new therapies on MoCs and to organize them timely and appropriately. In fact, the three different MoC for HCV identified across the 7 hospitals in Italy, could be arranged to manage other health conditions.