Key findings

  • We developed a novel intervention for people with multimorbidity through an iterative and comprehensive process following the Medical Research Council framework. This included several reviews, cohort studies and interviews with people with multimorbidity and several stakeholders.

  • The detailed reporting of the development of the intervention can serve as a model for future development papers to increase transparency and reduce research waste.

  • We focused on people with specific combinations of long-term chronic conditions (i.e., multimorbidity), therefore, this intervention is tailored for this population.

  • The intervention has been developed to be delivered in person, therefore, delivering this intervention using other delivery modalities (e.g., digitally) may require amendments.

Background

Living with two or more chronic conditions (i.e., multimorbidity) is common among people of all ages [1, 2]. Worldwide, approximately one-third of the population lives with one or more chronic conditions [3]. People living with multimorbidity have poorer physical and psychosocial health, a higher risk of hospitalisation and of dying prematurely [4,5,6,7]. The complexity of multimorbidity challenges the single-disease approach generally used by healthcare sectors, where patients use several healthcare services to manage each of their long-term conditions separately [8, 9], which is inefficient and burdensome for the patient [10]. Furthermore, available evidence for effective interventions of multimorbidity is limited [11]. A possible solution to deal with the complexity of managing multimorbidity is to focus on specific combinations of conditions, linked by common risk factors [12,13,14]. This approach may also help improve care and treatment effects for this population [11].

Osteoarthritis (of the knee or hip), type 2 diabetes, depression, heart disease (heart failure or ischemic heart disease), hypertension, and chronic obstructive pulmonary disease [15,16,17,18,19,20,21,22], are among the leading causes of global disability, affect hundreds of millions of people around the world [23], and often coexist linked via systemic inflammation and physical inactivity [24, 25]. Treatment guidelines, while encouraging clinicians to recommend a healthy lifestyle (including exercise therapy and self-management) for people with multimorbidity, focus on pharmacology [26]. However, to our knowledge, there is no intervention which includes personalised exercise therapy and self-management support for people with multimorbidity, although these interventions may be as effective as for people with single chronic conditions [27,28,29].

Therefore, the aim of this paper is to describe the development of a novel intervention (MOBILIZE) which includes personalised exercise therapy and self-management for people with multimorbidity.

Methods

The development of the MOBILIZE intervention is reported following the GUIDance for the rEporting of intervention Development (GUIDED) recommendations (S1 Table) [30]. We followed the newest version of the Medical Research Council Framework [31] to develop the intervention supplemented with crucial elements from the Bleijenberg et al. [32] and O'Cathain et al. guidance [33]. This was done to improve the likelihood of developing an intervention feasible to deliver and accepted by patients living with multimorbidity to ultimately enhance the fit with clinical practice [31,32,33]. Overall, the development of the intervention can be summarised in four phases: (I) “evidence synthesis and registry-based studies” where we summarised the available evidence regarding the effect of exercise therapy and self-management for people with multimorbidity and identified predictors of health outcomes in such interventions, (II) “qualitative analyses” where we explored the perspectives of patients living with multimorbidity, health care professionals, relatives, and patient advocates in relation to self-management with a particular focus on exercise behaviour, (III) theories and mechanism of action for developing the intervention, where we hypothesised the potential mechanisms of action and created a logic model, and finally (IV) mixed-methods feasibility testing of the developed intervention. The full results of the feasibility study are reported elsewhere [34].

Patient and Public Involvement

The development of the MOBILIZE intervention included feedback from several stakeholders, that is, people living with multimorbidity and their carers, patient advocates, physiotherapists and occupational therapists who are routinely working with patients with chronic conditions, a dietician, medical doctors specialised in the chronic conditions of interest, researchers with different backgrounds (physiotherapists, an exercise physiologist, and a health psychologist). All the stakeholders were informed about the different stages of the development and asked to provide feedback when deemed relevant. To determine how the body of evidence generated from the four phases of intervention development could be integrated into the intervention, the research team (AB, MJ, and STS) presented an initial program (based on the evidence gathered in phases (I) and (II)), to the physiotherapists (MD, HR, MN, JRP, GZ, and KHA), the patient advocates and carers, and medical doctors. The structure of the programme was discussed, including the exercises proposed, progression/regression levels, and self-management themes. This approach was also used throughout the development of the intervention, including during the feasibility study, and helped inform the final version of the intervention that is being tested in a randomised controlled trial (RCT) (https://clinicaltrials.gov/ct2/show/NCT04645732). This approach strengthens the internal and external validity, minimises research waste, and adds value to health care research [31,32,33]. The following sections describe the development process of the intervention and how the intervention was adapted after qualitative and quantitative data on the feasibility study were gathered.

Results

Overall, we performed one scoping review [35], five systematic reviews [27, 36,37,38,39,40], two registry-based studies [41, 42], one qualitative interview study [43], and a mixed-methods feasibility study [34], to identify knowledge gaps and develop an exercise therapy and self-management intervention for people with multimorbidity (Table 1) and Fig. 1.

Table 1 Studies conducted in the MOBILIZE project to identify knowledge gaps in the design and conduct of exercise therapy and self-management trial in people with multimorbidity
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Fig. 1
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Infographic of the development process

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Evidence synthesis

The reviews performed used the following Population, Intervention, Comparator and Outcome characteristics:

Population

Multimorbidity was defined as people reporting two or more of the following conditions: osteoarthritis (of the knee or hip), type 2 diabetes, depression, heart disease (heart failure or ischemic heart disease), hypertension, and chronic obstructive pulmonary disease. These conditions are linked by a common risk factor (physical inactivity) and pathogenesis (systemic low-grade inflammation), resulting in a cascade of reactions resulting in a ‘vicious cycle’ of chronic diseases and poor outcomes [44, 45]. For two systematic reviews, we included studies reporting at least 80% of the patients with multimorbidity (as defined above) [27, 40]. This pragmatic approach was pre-specified [37], and adopted to capture all the studies which included people with multimorbidity, given the expected inconsistency of reporting of the conditions across trials.

Interventions

Interventions that included exercise therapy and self-management support, either alone or in combination. We did not apply restrictions to the mode of delivery of the interventions (e.g., digitally, face-to-face) and setting (e.g., municipality/community, hospital).

Comparators

Usual care, for instance, advice from their health care provider.

Outcomes

The outcomes of interest included physical (e.g. endurance), psychosocial (e.g. health-related quality of life) and behavioural health (e.g. physical activity). The rationale for including these outcomes follows the guidance of a consensus study [14], which identified outcomes for multimorbidity intervention studies, and the patient partners of MOBILIZE.

Registry-based studies

Additionally, two registry-based studies were conducted to investigate the impact of comorbidities on health outcomes and to identify prognostic factors for health outcomes following an 8-week exercise and education programme in people with knee or hip osteoarthritis [41, 42]. How the results of these studies informed the development of the intervention are summarised in Table 1.

Qualitative analyses

A qualitative approach is particularly useful in capturing how people are affected by a problem and their perspectives on it [33]. Therefore, the qualitative study we conducted aimed to explore the perspectives of people living with multimorbidity, health care professionals, relatives, and patient advocates concerning self-management with a particular focus on exercise behaviour [43]. We conducted 17 interviews (nine focus groups; eight key informants) with 48 informants from four groups (22 people living with multimorbidity, 17 health care professionals, five relatives, and five patient advocates). The interviews were carried out online, informed consent was provided by the participants; the interviews were audio recorded and then transcribed verbatim. For the qualitative and feasibility study [34], patients and relatives were recruited by healthcare professionals from one psychiatric hospital and four hospital departments in Region Zealand (one of five health care regions in Denmark) or via self-referral on the basis of a poster and flyers placed in the hospitals’ waiting rooms or through posts on the hospitals’ and patient organizations’ Facebook pages [43]. The focus groups and interviews were audio-recorded, transcribed verbatim and analysed in an inductive-deductive process using Framework Analysis [46] and the Capability Opportunity and Motivation-Behaviour (COM-B) profile [47]. ,We found that people with multimorbidity identified several barriers related to exercise behaviour (i.e., pain, fatigue, breathlessness, lack of motivation, financial issues, accessibility, transportation, and decreased social support). Relatives' perspectives illustrated an uncertainty concerning their role in supporting self-management while simultaneously showing that they often take over responsibilities, which may represent a burden on their own wellbeing. Therefore, strategies for overcoming barriers to exercise and the participation of relatives in the self-management sessions, as part of usual care, were included in the programme (Table 2). Furthermore, patient advocates emphasised a need for more resources, such as establishing new collaborations and initiatives for people with multimorbidity and the lack of a 'burning platform' for multimorbidity (i.e., lack of urgency and prioritization of multimorbidity in the society) . Hence, this was included in the self-management session by informing the patients about activities, events, and organisations they could join (Table 2). Finally, health care professionals recognised these challenges while sharing their own challenges of empowering people with multimorbidity to change their behaviour given the limited resources. Therefore, this implied we instructed the physiotherapists delivering the intervention to prioritise strategies (i.e., behaviour change techniques) shown to be associated with better health outcomes in people with multimorbidity (Table 1) [38]. Overall, this knowledge, together with the self-management support framework [48], served to identify the core element of the 24 themes of the self-management sessions as well as the specific content of the sessions (Table 2). The core elements of the self-management sessions were proposed by the author team to the patients and physiotherapists delivering the intervention, and this format was deemed acceptable and feasible by them.

Table 2 Self-management themes of the 24, 30 minute sessions of the MOBILIZE intervention. Since participants are enrolled on a rolling basis, they might receive the sessions in a different order
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Mechanism of action and theory to inform the development of the intervention

In this section, we report the possible mechanisms of action of the MOBILIZE intervention, which are summarised in Fig. 2. Overall, we hypothesised that personalised exercise therapy and self-management support in addition to usual care (for instance, advice from their health care provider or any other treatment prescribed as standard care) will improve health-related quality of life more than usual care alone when measured at 12 months with concurrent positive effects on secondary outcomes. Furthermore, we hypothesised those improvements will occur immediately after the programme with concurrent positive effects on secondary outcomes and that the programme will be cost-effective at 12 months. We, therefore, aimed to develop an intervention that may potentially generate these effects Fig. 2. The knowledge gained from the four phases of intervention development guided us in identifying the core components of the exercise therapy and self-management intervention, as summarised in Table 1.

Fig. 2
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Logic model for the MOBILIZE intervention

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Anti-inflammatory and physiological factors

The anti-inflammatory effects of exercise therapy at cellular, tissue and organ level [44], as well as its positive physiological effects such as increase in muscle strength, improved blood pressure regulation and insulin sensitivity [49], highlight its potential role in improving health by reducing systemic inflammation.

Psychosocial factors

Providing education about long-term chronic conditions, providing psychological and social support to adjust to life with chronic conditions, encouraging adherence to multiple treatments, and supporting activities of daily living and physical functioning may improve psychosocial wellbeing [50, 51]. This can be achieved both through exercise therapy amd self-management sessions and as result of the psychological and social benefits associated with participation in group-based activities [51].

Contextual factors and expectations

Contextual factors, including the setting of the intervention [52], facilitator, patient and treatment features, as well as the patient-facilitator relationship [53], can influence health outcomes positively or negatively. Therefore, much attention is given to ensuring such factors are addressed when delivering the intervention. The complete list of contextual factors and how they are considered in the MOBILIZE intervention can be found in the S3 Table. Furthermore, expectations are a large determinant of the placebo and nocebo effect [54]. A feasible strategy to increase patients’ realistic expectations is making sure the patients are aware of the health benefits of exercise therapy and self-management. We have therefore instructed the facilitators delivering the intervention to use strategies to set realistic expectations [54]. For instance, via adapting an authentic and empathic communication style when communicating and via educating patients on how to cope with possible adverse effects (e.g. muscle pain, fatigue, and shortness of breath), regularly assess and address patients’ anxieties, concerns, and treatment expectations, and provide adequate information regarding diseases, diagnoses, and treatments [54]. Taken together, the contextual factors and expectations offer an opportunity to integrate strategies which may stimulate placebo effects and prevent nocebo effects [53].

Behavioural factors

Engaging in a healthier lifestyle is associated with up to 6.3 years longer life expectancy for men and 7.6 years for women highlighting the role of a healthy lifestyle as a contributing factor to health [55]. Therefore, we included various Behaviour Change Techniques (BCTs) [56] in the intervention (Table 3). BCTs are defined as observable, replicable, and irreducible components of an intervention designed to alter or redirect causal processes that regulate behaviour. The rationale for using specific BCTs is based on the evidence synthesis results focusing on people with multimorbidity (Table 1) and previous literature investigating this topic given the low-certainty of the evidence for the association between BCTs and people with multimorbidity. For example, BCTs such as ‘Action planning’, ‘Self-monitoring’ and ‘Goal setting’ [56], are strongly associated with improved health behaviours in people without chronic conditions [57], and in people with one condition [55, 58,59,60].

Table 3 Behaviour Change Techniques (BCTs) used in the MOBILIZE intervention and examples of their use
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In line with the BCT taxonomy instructions, we have only included the ‘active ingredients of the intervention’. That is, the observable, replicable components aimed at changing a behaviour.

Personalisation of the MOBILIZE intervention

Prescribing the right treatment at the right time to the right patient is key to eliciting benefits and minimising harms. The exercise therapy and self-management content of the intervention has been developed to be personalised. The personalisation of the programme is set during a one-to-one session prior to initiating the programme, lasting 60 minutes between each patient and a physiotherapist. The one-to-one session includes the following phases: (I) Presentation of the exercise therapy programme to the patient and selection of the appropriate starting exercise levels, (II) Presentation of the criteria for progression or regression of the exercises (e.g., the OMNI scale [61], and the Borg scale [62], and how sets and repetitions are progressed are presented so that the patient can indicate the degree of exertion of the exercises) and instructions on how to fill in the intervention diary to record the exertion of the exercises, (III) setting of a Specific, Measurable, Attainable, Relevant, and Timely (SMART) goal (e.g., being able to walk the stairs without discomfort).

Preference and the content of the MOBILIZE intervention

Adherence to treatment is key to its effectiveness [63]. For people with multimorbidity, this is particularly challenging due to the high treatment burden they experience [64]. Having the option to receive treatments based on patient preferences may improve adherence to the treatment and ultimately improve health [65]. Therefore, the MOBILIZE intervention allows patients to choose the type of exercise therapy (aerobic training, strength training, or functional exercises) to perform (Table 4). This decision was supported by the fact that people with multimorbidity seem to benefit from exercise therapy interventions regardless of the type of exercise therapy [27], in line with the WHO guidelines for physical activity for general health [66].

Table 4 Details of the MOBILIZE intervention: Personalised exercise therapy and self-management support programme
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Safety concerns

Behavioural interventions, including exercise therapy, are safe [68]. Although, in general, the risk of non-serious adverse events (according to the FDA definition [69], including short-lasting muscle pain and fatigue) may increase (19%), they do not increase the risk of serious adverse events such as hospitalisation and death [68]. Indeed, in people with multimorbidity they seem to reduce the risk of any serious adverse events by 38% [37]. However, the certainty of these findings in people with multimorbidity is low, mainly due to too few studies investigating this and the heterogeneous reporting of adverse events. Therefore, when developing the intervention, we tried to identify the possible adverse events associated with exercise therapy by looking at systematic reviews of exercise therapy for single chronic conditions [15, 18,19,20, 22, 29, 49, 68], national clinical guidelines [70], and by regular meetings with medical doctors specialised in the single chronic conditions. Overall, in people with one or more stable medical chronic conditions, it is contraindicated to exercise if they experience chest pain, uncontrolled hypertension or diabetes, irregular heartbeat, dizziness or sudden vision change [49]. We have instructed the facilitators delivering the intervention to check these contraindications before initiating any new exercise therapy session.

The prototype of the intervention and amendments

Based on the evidence gathered and feedback from relevant stakeholders (listed in the patient and public involvement paragraph), we developed an intervention consisting of 18 (60 minutes) sessions of personalised, group-based supervised exercise therapy, six sessions of 90 minutes of group-based self-management support and six sessions of home-based unsupervised exercise therapy. The programme was designed to be delivered twice a week for 12 weeks and was tested in a mixed-methods feasibility study [34]. Briefly, the feasibility study showed the intervention was feasible and acceptable in people with multimorbidity in terms of recruitment rate, retention of outcomes at follow-up, outcome burden, adverse events, and qualitative feedback. Adherence to the home-based unsupervised exercise therapy, however, was low and a few barriers were identified in the interviews suggesting that some amendments were needed before proceeding to the RCT. For example, home-based exercise sessions were deemed challenging to complete by the patients, given the lack of supervision. Additionally, we discussed the option of splitting the self-management sessions into shorter but more frequent sessions to facilitate the uptake of the delivered information. Therefore, together with the physiotherapists, patient partners, project managers, and researchers of the MOBILIZE team, we amended the intervention by increasing the number of the group-based supervised exercise therapy sessions to 24 and the number of the group-based self-management sessions to 24.

Overall, each session of the intervention, which will be tested in a randomised controlled trial, lasts 90 minutes and includes 30 minutes of self-management support followed by 60 minutes of supervised group-based exercise therapy delivered by a physiotherapist. The material will be made publicly available in the randomised controlled trial paper. The overall content of the intervention is presented in Table 4 following the Template for the TIDieR (Template for Intervention Description and Replication) [71], incorporating the CERT (Consensus on Exercise Reporting Template) items [67], and S2 Table, including the mechano-biological descriptors of strengthening exercise therapy proposed by Toigo & Boutellier [72].

Discussion

This paper summarises the development of the MOBILIZE intervention, which includes personalised exercise therapy and self-management support for people with multimorbidity. We followed the newest version Medical Research Council framework to develop the intervention [31], which targets people with multimorbidity and can be delivered in different settings at a relatively low cost as it uses material available in most gyms of hospitals, municipalities, and private physiotherapy clinics.

The evidence-based approach used to develop the MOBILIZE intervention together with the input from relevant stakeholders, resulted in an intervention for people with multimorbidity which includes components aimed to elicit physiological, psychosocial, and behavioural effects, considering contextual factors ultimately leading to improved health. This is novel for people with multimorbidity who are usually treated pharmacologically [26].

The iterative process used to develop and feasibility test the intervention helped us identify several challenges that could be addressed before the randomised controlled trial tests the effectiveness of the intervention. This is a key step in reducing waste in research [73].

The continuous interaction with key stakeholders to develop the MOBILZIE intervention in addition to improving the design of the intervention, aims to facilitate its implementation in clinical practice. While this approach has been acknowledged to be time-consuming, it is required when developing complex interventions aiming at improving people’s health behaviours [74].

Limitations

The limited quality of evidence (few studies with inconsistent results) supporting the use of exercise therapy and self-management in people with multimorbidity meant that many decisions taken regarding the type, duration, and intensity of the intervention were taken from evidence of research for people with single chronic conditions. However, the extensive qualitative work conducted as part of the development of the intervention and the constant feedback from the stakeholders helped to adapt this knowledge to people with multimorbidity. This will also improve the translation of our research into clinical practice if the MOBILIZE intervention is shown to be superior to usual care in the randomised controlled trial.

Conclusions

In this paper, we detail the development of a novel intervention for people with multimorbidity. The MOBILIZE intervention, is currently being tested for its safety and effectiveness in a randomised controlled trial. The intervention includes personalised exercise therapy and self-management support to improve health-related quality of life and physical function by eliciting physiological, psychosocial, contextual, and behavioural factors. The development of the MOBILIZE intervention has highlighted the importance of using an iterative process supported by the involvement of several stakeholders to identify solutions to the challenges of developing complex interventions.