Defining and measuring complex multimorbidity: a critical analysis

INTRODUCTION

As populations around the globe age, the prevalence of patients with multiple long- term conditions (multimorbidity) is on the rise, and research into this topic has increased exponentially in the last decade. The most commonly recommended definition of multimorbidity is the coexistence of two or more long-term conditions within an individual.^1,2 These can include physical non-communicable disease, infectious diseases of long duration (such as HIV), and mental health conditions. More recently, the concept of ‘complex multimorbidity’ has emerged, based on the idea that some types of multimorbidity may be more difficult to manage than others, by healthcare systems, practitioners, and patients themselves. In this article, we review the concept of complex multimorbidity, examine some of the definitions in common use, and critically analyse the strengths and weaknesses of these definitions and their implications for future research and the clinical management of the increasing numbers of patients with multimorbidity.

WHY IS MULTIMORBIDITY IMPORTANT?

Multimorbidity is important for many reasons. For the patient, increasing levels of multimorbidity reduce quality of life and increase mortality, and can place severe financial and other strains (such as treatment burden) on individuals and families.³ Healthcare practitioners often struggle to cope with the complex needs of multimorbid patients,³ and the evidence base for interventions in multimorbid patients is sparse.⁴ Multimorbidity places pressure on the healthcare system, with higher utilisation of care services.³ Multimorbidity increases in prevalence with age, and also with worsening socioeconomic status, with poorer patients developing multimorbidity at a much earlier age than the well- off.⁵ Multimorbidity is not only the norm rather than the exception in high-income countries, but is also of growing importance in low- and middle-income countries.⁶ Thus, understanding multimorbidity better and developing better ways to identify and treat the most vulnerable patients is of key concern globally.

WHAT IS COMPLEX MULTIMORBIDITY?

The widely accepted broad definition of multimorbidity as two or more conditions means that multimorbidity is very heterogeneous. Some patients will have conditions that have little or no impact on their health, whereas others will be severely affected. In order to prioritise those with higher needs, some researchers have proposed the concept of ‘complex multimorbidity’. Although the concept of complex multimorbidity is clearly important, there is no universally accepted ‘gold standard’ definition, and different stakeholders may have very different underlying assumptions as to what it means. For example, patients might frame it as the complex impact that living with multiple conditions can have on their health and wellbeing. Healthcare planners and managers may see it in terms of healthcare provision and the need for ‘complex’ patients to see numerous different specialists. Prescribers such as pharmacists may conceptualise it as extreme polypharmacy and the potential for adverse drug–drug and drug–tissue interactions. GPs working in deprived areas might conceptualise it as the mix of mental, physical, and social problems they commonly see in younger people, whereas GPs working in more affluent areas might see it in terms of frail older patients, living alone with cognitive decline and at risk of falls. Below we summarise some of the ways that complex multimorbidity has been defined in literature, critique each approach, and offer some ways forward.

Three conditions from three body systems

Harrison and colleagues⁷ define complex multimorbidity as three or more conditions from three or more body systems (3+ from 3+) based on their view that ‘conditions in different body systems are likely to compete for treatment, while the treatments of chronic conditions within the same system are more likely to be complementary’. They also propose that ‘counting the body systems affected also provides an estimate of the specialist types that may be involved in the care of the patient’, which could be important in healthcare planning. They thus define complexity in a way that speaks to healthcare planners and clinical prescribers. However, depending on disease severity, patients with physical multimorbidity across only one or two bodily systems could easily have a higher burden of illness, more complex management needs, and more polypharmacy, and more treatment burden, than others with mild disease across three bodily systems.

Mental‒physical multimorbidity

Other authors have argued that a combination of mental and physical conditions also represent complex multimorbidity.⁸ Mental–physical multimorbidity has a very different pattern across age groups from other definitions of complex multimorbidity (Figure 1), showing a much less steep association with increasing age.⁹ Mental– physical multimorbidity is over twice as common, and occurs at a much younger age in deprived areas than in affluent areas^5,9 — with those aged 40‒45 years in the most deprived areas showing the same prevalence as those aged 85–89 years in the most affluent areas.⁹ Using the 3+ from 3+ definition by Harrison and colleagues⁷ would substantially underestimate the scale of such complexity, as this definition showed a gap of only 10 years between affluent and deprived. Thus, the mental–physical definition may speak more to patients of low socioeconomic position and Deep End GPs, as well as to public health organisations concerned with health inequalities.

Figure 1.

Prevalence of multimorbidity by age using four different definitions. Multimorbidity 2+ = ≥2 long-term conditions (LTCs). Multimorbidity 3+ = ≥3 LTCs. Multimorbidity 3+ from 3+ = ≥3 LTCs from ≥3 bodily systems. Mental–physical multimorbidity = ≥2 LTCs where ≥1 mental health LTC and ≥1 physical health LTC. Source: MacRae et al.⁹

Other definitions of complex multimorbidity

Kingston and colleagues¹⁰ have defined complex multimorbidity in those aged over 65 years as being four or more conditions (including vision and hearing problems) on the basis of simulation modelling, which predicts that the percentage of people in the UK with 4+ conditions will double by 2035, and two-thirds of this group will have mental ill health. They do not explicitly explain why this equates to complexity, but the association with mental health problems, together with the large predicted increase in prevalence of this group, would seem to underlie their definition. This may be a useful definition for planning health and social care provision of the growing population of older people, though its utility to clinicians or patients themselves is unclear as yet.

There is also a growing focus on the use of advanced clustering techniques, including AI, to identify ‘complex clusters’ of conditions, and to relate these to outcomes such as mortality and healthcare utilisation.¹¹ However, there is at present no accepted gold standard approach to clustering, and different methods can produce different findings. It is also unclear at present whether identified clusters will significantly add to clinical knowledge or be helpful in the planning of services or treatments.

Other examples exist in the literature regarding complexity and multimorbidity. For example, premature multimorbidity is extremely common in people experiencing homelessness but purely biomedical concepts of multimorbidity are inadequate in capturing the overlapping complexities and vulnerabilities associated with such extreme health inequalities. The term ‘multiple complex needs’ embraces the co-occurring issues of homelessness, substance use, crime, and mental health problems.¹² This definition will therefore speak to a wide range of health and non- healthcare professionals and organisations involved with the issues of homelessness, as well as to those experiencing such problems.

HOW DO THE DIFFERENT DEFINITIONS OF COMPLEX MULTIMORBIDITY RELATE TO OUTCOMES?

Most existing studies of complex multimorbidity (however defined) and associated outcomes have been cross- sectional and thus provide limited evidence of likely causality. In a longitudinal study, Storeng and colleagues¹³ reported that complex multimorbidity, defined as 3+ from 3+, predicted the need for assistance in instrumental activities of daily living 11 years later, and moderately predicted mortality compared with people not meeting this criteria. However, there was no comparison with other definitions of complex multimorbidity, nor with different levels of ‘simple’ multimorbidity (such as increasing numbers of conditions irrespective of bodily systems). Further longitudinal research from the same group compared a range of measures of multimorbidity in predicting mortality including individual disease counts, organ-grouped disease counts, 3+ conditions, or 3+ from 3+, and found that all measures predicted mortality, with no clear differences between the measures.¹⁴ Similarly, Kato and colleagues in Japan examined the relationships between complex multimorbidity and mortality over a 6-year period in a propensity score- matched cohort study and found that the impact of complex multimorbidity based on 3+ from 3+ on mortality was no different from the impact of ‘simple’ multimorbidity (2+ conditions).¹⁵

Mental–physical multimorbidity is known to be associated, in cross-sectional studies, with higher rates of unplanned hospital admission, as well as large decreases in quality of life.¹⁶ A longitudinal study in China showed that both physical multimorbidity and depression had detrimental effects on work productivity, with mental– physical multimorbidity showing additive effects on disability, work loss, and social participation.¹⁷ Similarly, a national longitudinal study found that health-related quality of life decreased markedly with multimorbidity, which was exacerbated by having mental– physical multimorbidity.¹⁸ A longitudinal study from Singapore also showed that mental‒ physical multimorbidity exerted additive and multiplicative effects on functional disability and quality of life.¹⁹ However, whether these associations are larger than with ‘simple’ multimorbidity counts has not been examined. Given the above findings, there does not appear to be strong evidence that complex multimorbidity (however measured) is a better predictor of poor outcomes than simple multimorbidity counts. The relationships between the other definitions of complex multimorbidity discussed above have not been prospectively linked to outcomes as far as we are aware. Future longitudinal studies are thus required that compare different settings and definitions of complex multimorbidity, within the same study on a wide range of outcomes.

DOES COMPLEX MULTIMORBIDITY MATTER IN PRACTICE?

The National Institute for Health and Care Excellence (NICE) multimorbidity clinical guideline¹ considered this issue in terms of trying to identify people who would benefit from ‘an approach to care that takes account of multimorbidity’ (as opposed to usual care), and considered that this depended on the impact on the individual patient in terms of burden of disease and treatment burden (Figure 2). The guideline development group believed that higher disease burden and/or higher treatment burden made the need for such an approach to care more likely, but were unable to identify any structured way to measure this.

Figure 2.

An approach to care that accounts for multimorbidity. Adapted from National Institute for Health and Care Excellence Guideline NG56.¹ CHD = coronary heart disease. CKD = chronic kidney disease. COPD = chronic obstructive pulmonary disease. PVD = peripheral vascular disease. T2DM = type 2 diabetes mellitus.

From this perspective, most existing studies of complex multimorbidity have not examined associations with treatment burden, and have not demonstrated a clearly stronger association with outcomes related to disease burden. A limitation of the NICE approach, however, is that it fails to consider the social and environmental aspects of multimorbidity alluded to above in those patients with multiple complex needs, such as people experiencing homelessness or those living in areas of extreme deprivation.

It is also unclear what these different definitions of complex multimorbidity mean in clinical practice. Should GPs categorise patients with complex multimorbidity on a practice registrar and systematically deliver more intensive care such as holistic reviews in longer consultations? As discussed above, different definitions may differ in utility depending on the target population. Mental‒ physical may be the most appropriate way for GPs to target care for complex patients in deprived areas, whereas the 3+ from 3+ definition, or the 4+ definition, may help GPs target care for older patients with complex needs in more affluent areas. The views of patients are also lacking in this debate, and it is noteworthy that Ho and colleagues have recommended that ‘complex multimorbidity definitions should be co-developed with patients to ensure that these are relevant to their illness experience’.²⁰

In conclusion, the concept of complex multimorbidity is an important one but may mean different things to different stakeholders. The choice of definition therefore may depend on the purpose for which it is being used, the setting it is being used in, and the target group of interest. Further research is required to increase our understanding of complex multimorbidity and to help develop effective and cost-effective interventions. Given the importance of holistic care in patients with multimorbidity,¹ the vital role of the GP as the core expert generalist in the healthcare system will remain central.

Funding

This study was funded through a research grant from the Economic and Social Research Council (reference: ES/T014164/1).

Provenance

Freely submitted; externally peer reviewed.

Competing interests

The authors have declared no competing interests.