A patient-centred care model for patients with complicated multimorbidity: Protocol for a pilot cluster randomised trial in general practice, municipalities, and hospitals

Sanne Lykke Lundstrøm; Nina Kamstrup-Larsen; Barbara Ann Barrett; Louise Marie Bidstrup Jørgensen; Solvej Skriver Hansen; John Sahl Andersen; Bolette Friderichsen; Anders Stockmarr; Anne Frølich

doi:10.1371/journal.pone.0310697

. 2024 Dec 4;19(12):e0310697. doi: 10.1371/journal.pone.0310697

A patient-centred care model for patients with complicated multimorbidity: Protocol for a pilot cluster randomised trial in general practice, municipalities, and hospitals

Sanne Lykke Lundstrøm ^1,^2,^*, Nina Kamstrup-Larsen ^1,³, Barbara Ann Barrett ^1,³, Louise Marie Bidstrup Jørgensen ³, Solvej Skriver Hansen ³, John Sahl Andersen ³, Bolette Friderichsen ⁴, Anders Stockmarr ⁵, Anne Frølich ^1,³

Editor: Kathleen Finlayson⁶

PMCID: PMC11616888 PMID: 39630823

Abstract

Introduction

Current care is inadequate for patients with complicated multimorbidity, and frequently results in fragmented care. There is no widely agreed-upon optimal organisation of healthcare services for this patient group. By drawing upon existing literature and prior studies, we developed a patient-centred complex intervention for multimorbidity (CIM) and subsequently refined it into CIM version 2 (CIM2). This paper describes the study protocol for a pilot cluster randomised control trail (RCT) evaluating the effectiveness of a general practice-based intervention.

Methods

CIM2 aims to support integrated care for patients with complicated multimorbidity. CIM2 comprises five elements: 1) Training healthcare professionals, 2) an extended overview consultation in general practice, 3) a nurse care coordinator in general practice supporting the planning of the patient trajectory, 4) follow-up care services in general practice, and 5) improving the integration of care between general practice, municipality, and hospital. The pilot cluster RCT involve 350 patients with complicated multimorbidity across 14 general practices in Region Zealand and The Capital Region of Denmark. Patients are randomly assigned to either the intervention group or the usual care group. The primary outcome measure is the patients experience of quality of care measured by the Patient Assessment Chronic Illness Care Questionnaire (PACIC). Secondary outcomes include the patient’s health-related quality of life, measured by the EuroQol-5 Domain questionnaire (EQ-5D-5L) and the treatment burden measured by the Multimorbidity Treatment Burden Questionnaire (MTBQ). Data on chronic conditions, healthcare utilization, and demographic information such as sex, age, and educational attainment will be collected from national registries. The outcome measures will be recorded before, during, and after implementing the intervention. Qualitative evaluation will include semi-structured interviews with healthcare professionals across various sectors as well as patients. The cost-effectiveness and Incremental Cost Effectiveness Ratio (ICER) of the CIM2 will be assessed using Diagnose Related Group rates.

Trial registration

ClinicalTrials.gov Identifier: NCT05406193. https://clinicaltrials.gov/study/NCT05406193.

Introduction

The increasing prevalence of multimorbidity–driven by the ageing population, and advanced diagnostic health technologies—represents a major challenge for the healthcare system and society [1–4]. Multimorbidity is commonly defined as the coexistence of two or more chronic conditions in the same person [5,6]. In the Capital Region of Denmark and Region Zealand, approximately 21% and 37% of the citizens aged 16 years and older suffer from multimorbidity [7,8]. Around 10% of people in Denmark with multimorbidity have complicated multimorbidity characterized by a severe symptom complex caused by more concomitant chronic conditions [9]. Other researchers have proposed different definitions of complicated multimorbidity such as the severity of conditions and perception of illness [10,11]. Patients with complicated multimorbidity often experience reduced health-related quality of life [12–14], high treatment burden, polypharmacy, reduced ability to work, and increased mortality [9].

In this study, we define multimorbidity as complicated when the patient has two or more of three chronic conditions (diabetes, chronic obstructive pulmonary disease, or chronic heart conditions) [15], has been hospitalised, or visited an outpatient clinic due to their chronic condition(s) during the previous year [16], and take at least five different prescription drugs assessed from the Shared Medicine Record (SMR) in general practice [17].

Care pathways for patients with complicated multimorbidity are often complex with multiple appointments, frequent ambulatory visits, hospital admission, and use of other healthcare services. The siloed organization of healthcare around single diseases, the lack of guidelines and incompatible IT systems can be a barrier to effective care for patients with complicated multimorbidity. [18].

While the above challenges described are widely recognized [19] and some consensus exists regarding key components for enhancing care [20], knowledge of the most effective organizational structure for healthcare services to deliver patient-centred, high-quality integrated care for patients with complicated multimorbidity remains limited [21,22].

In Denmark, general practice is the key organisational setting in terms of offering people with complicated multimorbidity integrated, patient-centred care. To improve care for patients with complicated multimorbidity in general practice, we developed a complex intervention care model, “A patient-centred complex intervention for multimorbidity” (CIM) [16]. The model was developed based on the Chronic Care Model [23,24], models of care for multimorbidity [21,22,25] and results from our studies in multimorbidity [15,26,27].

Based on the results from the feasibility study, we developed an improved version of the CIM model named “A patient-centred complex intervention for multimorbidity version 2” (CIM2) [16,28]. The new CIM2 model includes improved training of healthcare professionals, strengthened identification of patients with complicated multimorbidity, adjustment of the extended consultation according to the consultation model of The Danish College of General Practitioners (DSAM), improved medical treatment, and strengthened integration of care services between healthcare organisations [16,29]. The development of the CIM2 model relies on the Medical Research Council (MRC) framework for complex interventions [30,31]. The MRC framework consists of four phases: 1) development or identification of an intervention, 2) assessment of the feasibility of the intervention and evaluation design, 3) evaluation of the interventions, and 4) impactful implementation.

The development of the extended overview consultation in the feasibility study of CIM model [16] caught the attention of the Danish Regions Organisation and The Danish Organization of General Practitioners. The collective agreement accepted in 2022 for general practice introduced a fee-for-service covering an extended overview consultation for people with complex multimorbidity [32]. The CIM2 pilot study is expected to improve and strengthen the CIM2 model, and the results will be used to inform further interventions.

Objective

This paper describes the protocol for a pilot cluster randomised controlled trial to determine the effectiveness of a general practice-based intervention aimed at improving treatment and care for patients with complicated multimorbidity.

Methods

Study design

This study is a 1:1 pilot cluster RCT (Fig 1). The study will include 14 general practices, of which seven will be randomized to the intervention group and seven to the control group, providing usual care. Each practice will recruit 25 patients, amounting to 350 patients in total. At the time of recruitment, and respectively at 6 and 12 months of the intervention period, the patient’s assessment of perceived patient-centred integrated care, health-related quality of life, and treatment burden will be measured in both groups. The patients in the intervention group will receive an extended overview consultation after recruitment and again after 12 months.

Study setting

The study will take place in Region Zealand and the Capital Region of Denmark, in general practices, healthcare centres in municipalities, and hospital outpatient clinics during the 3^rd quarter of 2022 through the 4^th quarter of 2024. The general practices should have a minimum of 4,500 patients registered to ensure that the number of patients with complicated multimorbidity reaches the needed number of 25 patients per practice. The municipalities will be selected based on the rank of sociodemographic groups I-IV. Groups III and IV, the lowest sociodemographic groups, will be chosen as the prevalence of patients with complicated multimorbidity is expected to be higher [8]. The possible benefits of the CIM2 model are expected to be larger in patients from municipalities characterized as belonging to lower sociodemographic groups.

Sample size

The primary outcome measure of the study is the Patients Assessment Chronic Illness Care (PACIC) questionnaire [33,34]. The difference of interest between the intervention and the control group is Δ = 0.36, with a mean value of 2.86, and with an expected standard deviation SD = 1, based on results from earlier studies [35,36]. The power calculations take a potential Intraclass Correlation Coefficient (ICC) of 0.1 into account. With patients being allocated to clinics with 25 patients per clinic, and a random loss to follow up on 30% [37], we base ourselves on the following random effects model for those not lost to follow up:

Y_{i} = α_{G r o u p (i)} + Z_{C l i n i c (i)} + ε_{i}, i = 1,2 \dots, n

(1)

so that the outcome Y consists of a group-specific level α (intervention/control), a clinic-specific random effect Z, allowing for intra-clinic correlation, and an individual noise term ε. Simulating the above model for 10,000 times per choice of the number of clinics in each group, with individually evaluated random loss to follow up, yields a power of 78%, and 84% for 6 and 7 clinics in each group, respectively, based on a two-sided test at the level α = 0.05. The uncertainty of these powers is found to be less the 1 percentage point, using the binomial formula. Thus, to obtain a power of 80% for detecting the specified difference Δ from the random effects modelling, 7 clinics of 25 patients, i.e., 175 patients are needed in the intervention and control group.

As a consequence of an anticipated attrition rate (or drop-out rate) of approximately 30% due to mortality or other unforeseen circumstances, we plan to include 183 patients in each group.

Randomization and blinding

General practices in the designated municipalities are contacted with an invitation to participate in the study. If they accept the invitation, they will receive detailed study information. The 14 participating general practices will be randomised into either the intervention group providing care as described in the CIM2 model or the control group, providing usual care. The general practices will be randomly allocated, at an allocation rate of 1:1, by a computer program. To ensure the concealment of allocation, a data manager from another organisation will provide the information on the randomization to the general practice and will be responsible for a randomization list, which will be available to the investigator. Due to the nature of the study, the general practices and the patients cannot be blinded.

Eligibility criteria

Healthcare professionals in general practice included in the study identify eligible patients. We use the following inclusion criteria:

The patient has two or more of three common chronic conditions (diabetes, chronic obstructive pulmonary disease, chronic heart condition) [15].
The patient has been hospitalised or visited an outpatient clinic due to their chronic conditions during the previous year [16].
The patient takes at least five different prescription drugs assessed from SMR in the general practice [17].

Patients accepting to become part of the study get an invitation with a link to the project database in the Research Electronic Data Capture (REDCap) [38], a web-based application developed to capture data for clinical research. In the invitation from REDCap patients receive information about the project and are asked to 1) provide informed consent to participate in the study and 2) complete the baseline questionnaires. Patients will receive up to 2 reminders if they do not fill in the questionnaires. The patients will receive the questionnaires again at 6 and 12 months after inclusion and again up to 2 reminders for non-responders.

Patients, who are unable to speak Danish, have a life expectancy of less than 12 months, or cannot give their informed consent, for example people with dementia, will be excluded from the study.

Control general practices

Healthcare professionals working in general practices allocated to the control group will receive the same information about the project concerning the recruitment of patients, collection of patient data including informed consent and patient questionnaires and the use of REDCap. Patients will receive usual care according to the Danish Health Authority’s National Clinical Guideline. Any changes in the intervention period affecting the usual care or activities for the control group will be recorded.

Intervention general practices

The elements of the CIM2 model are described in the following and is illustrated in Fig 2.

The teaching program will be developed in collaboration with The Danish College of General Practitioners. Healthcare professionals from general practice, nurses and physiotherapists from the municipalities, and healthcare professionals from the outpatient clinics participate in the training program. It will include topics on multimorbidity, project content, and methods to recruit and include patients (including informed consent). Further, the training program will offer training in the collection of patient data comprising the use of REDCap software for patient questionnaires.

The patient intervention in general practice starts with an extended consultation, lasting 45 minutes, with the GP, the patient and possibly a relative, and the nurse care coordinator. The consultation is based on the guidance for a patient-centred overview status for patients with multimorbidity published by The Danish College of General Practitioners [39]. The aim is to obtain an overview of the patient’s conditions, problems, needs, and potential beneficial changes in treatment. The patient’s goals, preferences, and needs are identified, and the medical treatment of the patient’s conditions is prioritized. An individual care plan is developed, covering activities in the three sectors that will take place within the 12-month intervention period.

The individual care plans include 6 themes [39]: 1) Listing of important diagnoses, 2) Overview of the patient’s prescription drugs, 3) Prioritising the patients’ treatment goals (using shared decision-making), 4) Development of a coordinated individual care plan with telephone follow-up and future visits, 5) To lower burden of treatment, the GP will identify outpatient visits at hospitals which could be reduced or replaced by a GP visit if the patient and the specialist agree, and 6) Referral to community-based rehabilitation programs if there is clinical indication and the patient is motivated [40].

The individual care plan is printed for the patient and can be shared with the municipality and outpatient clinic based on an IT standard (MedCom). The GPs is reimbursed with 137 US dollars for the extended overview consultations.

General practice coordinates the planned patient care between general practice, the municipality, and the hospital, and follow-up on the execution of planned healthcare activities. The care coordinator function might be undertaken by the GP or the nurse in the practice. The practice plans the division of responsibilities and tasks in the project between the GP and the nurse.

The follow-up activities include telephone calls to the patient by the care coordinator at relevant time intervals according to the severity of conditions and planned activities. A second extended overview consultation takes place after 12 months.

As mentioned earlier, the individual care plan is shared electronically with the healthcare centre in the municipality and with the outpatient clinics using the national standard IT communication tool MedCom.

Ethics

The study was notified to the Danish Data Protection Agency (protocol: REG-161-2020) and the National Committee on Health Research Ethics in Region Zealand (protocol no.: EMN-2020-37129). The study is registered at ClinicalTrials.gov, identifier: NCT05406193.

The study will be conducted in line with ethical principles for medical research as described in the Declaration of Helsinki [41]. Personal identification is encrypted, and data will be kept in accordance with the requirements of the Danish Data Protection Agency. All results will be reported in the anonymity of respondents and participating general practices.

Informed consent will be obtained from all participants before entering the study. Before signing the consent forms, participants will be informed that participation is voluntary and that they can withdraw anytime.

Outcomes

Primary outcome is the quality of care assessed by the PACIC questionnaire. The twenty-item PACIC questionnaire with five dimensions considers whether patients receive patient-centred care measuring aspects of care most important to patients; patient activation, organisation of treatment/decision-support, goal setting/individual adaptation, problem-solving/context, and follow-up/coordination. The PACIC questionnaire has been validated and translated into Danish [33–35].

Secondary outcomes include the patients’ health-related quality of life, measured by the EuroQol-5 Domain questionnaire (EQ-5D-5L). EQ-5D-5L is a generic instrument comprised of five questions covering mobility, self-care, everyday activities, pain, discomfort, anxiety, and depression, each item on a five-point scale from no problems to extreme problems. The EQ-5D-5L has been validated and translated into Danish [11,42]. The treatment burden is measured by the Multimorbidity Treatment Burden Questionnaire (MTBQ), which has been validated and translated into Danish [43]. The utilization of health care services (number of admissions), bed days, visits to emergency departments, outpatient visits, GP visits, out-of-hour GP visits, yearly control visits in general practice and specialist visits are assessed from national register data [26]. The cost-effectiveness and Incremental Cost Effectiveness Ratio (ICER) of the CIM2 will be calculated based on Diagnose Related Group rates [44,45].

Qualitative evaluation

The qualitative evaluation consists of semi-structured interviews with health professionals representing all three sectors, as well as patients. Semi-structured interviews will be conducted with:

General practitioners and nurses from the seven intervention practices.
Health professionals from municipalities and hospitals involved in cross-sectoral collaboration.
patients with a cross-sectorial course of treatment.

The semi-structured interviews with health professionals will be guided by an interview guide, which covers the following subjects: the content and relevance of the extended consultation, patient-centeredness of the care pathway, the individual care plan, referral to rehabilitation, and the content of the rehabilitation program in the community. Furthermore, semi-structured interviews with patients will explore how patients experience the extended overview consultations.

The interviews will assess the interviewees’ experiences with the model, their assessment of potentials and challenges applying the model and their potential input for improving the model. One focus will be the sharing of the individual care plan and communication with patients. Interviews will be conducted once participants are familiarised with the model. All interviews will be audio-recorded, transcribed and analysed using Nvivo software.

Semi-structured interviews will be complemented with cross-sectorial focus group interviews with patients in the intervention group to assess how the CIM2, and the cross-sectorial elements associated with it, are experienced by the patients in the study. Additionally, focus group interviews will be conducted with healthcare professionals from the three sectors to gather their perspectives on the CIM2. The interviews are supported by an interview guide, which covers the following topics:

Teaching program for healthcare professionals: Assessing the effectiveness and comprehensiveness of the training provided to healthcare professionals prior to implementing the CIM2.
Structure of Extended Consultations: Evaluating the structure and organization of extended consultations in general practice settings, including their duration, format, and participant roles.
Integration of Care: Exploring the extent to which the CIM2 facilitates and promotes integrated care, examining collaboration and communication among healthcare providers from different sectors.
Information Sharing: Assessing the effectiveness of information sharing mechanisms between the three sectors, identifying potential barriers and facilitators to seamless information exchange.
Referral to Rehabilitation: Evaluating the process of identifying patients who require rehabilitation services and the appropriateness of referral criteria.
Content of Community Rehabilitation Programs: Assessing the relevance and effectiveness of community-based rehabilitation programs, ensuring alignment with patient needs and goals.

Monitoring

As the content of the intervention does not increase risks of adverse effects on the participants, a data monitoring committee is not needed nor is a plan for stopping the intervention in case of adverse events.

Data management

All data will be secured in a closed folder on the Region Zealand server with personal login access authorized by the primary investigator. The primary investigator has access to the full data set and the conversion key. Co-investigators will be given access when needed. The quantitative data is secured in the project database in REDCap during the intervention [38]. A data management agreement and a collaboration contract have been mutually accepted by all involved parties.

Analyses

Descriptive data are reported as mean (SD) or median (Interquartile range) for continuous variables depending on the distribution, and as numbers and percentages for categorical variables. Descriptive statistics for demographic data will be used to describe the population in the intervention and the control groups, as well as for the populations in each of the general practices.

The primary analysis will investigate the effectiveness of the CIM2 model from the PACIC scores in the two groups. To our knowledge, no minimal important difference, which provides a ‘measure of the smallest change in the patient-reported outcome of interest that patients perceive as important, either beneficial or harmful, and that would lead the patient or clinician to consider a change in management’ [46], has been defined for the PACIC score. We expect a relevant change in the PACIC score to be 0.36 [35]. The analysis will be based on an intention-to-treat focus, including all participants regardless of study adherence and drop-out. To create a dataset with maximum information, missing values in the PACIC scheme will be imputed using multiple imputations if the study subject has answered at least 50% of the PACIC scheme. A linear mixed model, see Eq (1), will be used for the analysis as this model can handle the clustered observations within general practice. The variance structure will be chosen as the most suitable structure concerning the data assessed. If there is a difference between the groups at the time of randomisation, a sensitivity analysis including factors that vary between the two groups will be conducted. A comparative analysis without multiple imputations will be performed as another element of the sensitivity analysis. In addition to the intention-to-treat analysis, we will also perform a per-protocol analysis. To handle possible issues with clustered observations, the project will work with differences in the PACIC score post and before intervention. It is presumed however that this effect will be small, 0,01 to negligible in the survey population. The secondary analyses will compare scores of the EQ-5D-5L and MTBQ in the intervention group and the control group using the same methods as described.

Cost-effectiveness will be assessed by the estimation of an ICER. The ICER defines the price for an increase in quality of life (QALY) when investing in CIM2 [47]. The cost will constitute training costs, cost for the extended visits as well as the costs associated with all health care utilization in both primary and secondary care. The latter will reveal any potential effect of CIM2 on the use of health care in other sectors. QALY will be based on EQ-5D-5L measures. The time horizon will be the twelve months that the intervention lasts–hence no time discounting will be needed. The perspective will be that of the healthcare sector and the sensitivity of the ICER will be based on 95% confidence intervals estimated by probabilistic sensitivity analyses and illustrated by Cost-Effectiveness Acceptability Curves (CEACs) [48].

The qualitative interviews with patients will be analysed thematically [49] with a focus on themes related to the outcomes of the intervention, i.e., health-related quality of life and everyday experiences of living with multimorbidity. The analysis will include a focus on patients’ experiences with the new consultation in general practice and will focus on the patient’s experiences of integrated care.

Thematic analysis of qualitative interviews [49] with health professionals in all three sectors will identify 1) the acceptability of the intervention and 2) their experiences of possibilities and hindrances in cross-sectorial collaboration. The analyses will add to the quantitative analyses and contribute to an integral assessment of the CIM2 models’ success in providing improved integrated care to patients with multimorbidity.

Discussion

This paper describes the protocol for a pilot cluster randomised controlled trial designed to evaluate the integrated care intervention, with a focus on general practice, aimed at improving care for patients with complicated multimorbidity. The CIM2 study will contribute novel and valuable insights into multicomponent interventions targeting an expanding population.

Earlier studies have shown that GPs provided slightly fewer chronic care services than expected in practices where many patients with multimorbidity and low socioeconomic status were clustered, suggesting the inverse care law mechanisms [50]. Furthermore, providing care to patients with complicated multimorbidity in general practice in geographical areas with higher rates of patients with multimorbidity seems to increase the risk of burnout among GPs [51]. If the CIM2 model was integrated as part of usual care, it could contribute to all patients with multimorbidity were offered and received all the chronic care services they could benefit from.

Furthermore, an implementation of CIM2 could also benefit general practitioners by possibly reducing the risk of burnout [51]. A Danish study showed that a high crude rate of patient with multimorbidity increase GP’s likelihood of burnout. The study concluded that general practices with a high number of patients with multimorbidity need support to prevent suboptimal care and GP burnout [49]. By implementing an extended consultation overview for patients with multimorbidity it is possible to compensate GPs economically in the existing combined fee-for-service and capitation reward system and supposedly decrease the stress levels GPs often experience caring for patients with complex care needs [50].

Limitations

Studies on multimorbidity define multimorbidity as very heterogeneous and rarely include the severity of the conditions [5,6,52,53]. One study reported that a majority of authors using "multimorbidity" fail to provide a clear definition in their publications [52]. This makes it difficult to compare different multimorbidity studies. As mentioned earlier in this paper, we defined multimorbidity as the coexistence of two or more chronic conditions in the same person, which is one of the more common definitions [5,6]. We anticipate that this approach should facilitate comparison with previous studies.

Firstly, the study design, being a pilot cluster RCT, may have inherent limitations in terms of generalizability to broader populations. The inclusion of specific geographical regions and general practices may introduce selections bias and limit the extrapolation of findings to different healthcare settings. Additionally, the use of specific chronic conditions (diabetes, chronic obstructive pulmonary disease, chronic heart condition) as criteria for complicated multimorbidity might not cover the full spectrum of conditions affecting patients, possibly influencing the generalizability of our results.

Furthermore, the nature of the intervention, although evidence-based and informed by prior feasibility studies, may present challenges in implementation across diverse healthcare context. Factors such as variations in healthcare infrastructure, healthcare professionals, and patient populations could impact the effectiveness of the CIM2 model in different settings.

From a clinical perspective, the PACIC questionnaire, though validated, might not fully capture the complexity of patient experiences in the context of complicated multimorbidity. We use a qualitative evaluation, such as in-depth interviews, to gain a deeper understanding of patient experiences.

Source of potential bias

A recurring challenge when conducting pilot cluster RCT studies is recruitment. There is a risk of bias during both the recruitment of general practices and patients. General practices with a high patient burden may be less likely to participate. To minimize the differences in patient burden between the general practices, we will solely recruit from municipalities with similarly low socioeconomic status. Patients recruited by their GP be more likely to participate when asked by a familiar healthcare professional whom they trust. However, there might still be a potential bias since the most vulnerable and sick patients will be less likely to participate in the study.

Dissemination

The scientific dissemination will consist of publication in peer-reviewed scientific journals and presented at national and international conferences. The results from the study will be presented at a seminar, inviting patients, relatives, and professionals from all three sectors included in the study. Short reports on recommendations for organisational cross-sectoral and cross-disciplinary collaboration on complicated multimorbidity will be made to the ensure dissemination of key findings and implications for practice to relevant stakeholders at the regional and national levels.

Conclusion

A successful pilot cluster RCT will yield valuable insights into recruitment strategies, how to get CIM2 implemented in general practice, municipalities, and out-patient clinics, how to improve the effectiveness and quality of the CIM2, sample size estimates for future studies and cross-sectorial collaboration. The qualitative findings will shed light on the experiences of patients and healthcare professionals with the CIM2, potentially identifying areas for improvement and informing its application in future studies.

Supporting information

S1 Checklist. SPIRIT 2013 checklist: Recommended items to address in a clinical trial protocol and related documents*.

(DOC)

pone.0310697.s001.doc^{(128KB, doc)}

S1 Protocol

(PDF)

pone.0310697.s002.pdf^{(636.8KB, pdf)}

Acknowledgments

We would like to thank general practitioners Berit Lassen and Janne Unkerskov for sharing their knowledge and experience with patients with multimorbidity, and for contributing to the discussion during the development of the CIM2.

Data Availability

No datasets were generated or analysed during the current study. Data in the pilot study cannot be shared publicly because of restrictions on data availability according to Danish registration. The participants in the study have not given consent to make these data publicly available. Authorized scientific institutions can request access to this data from Statistics Denmark for individual researchers within or outside the country. Requests should be directed to Statistics Denmark at: https://www.dst.dk/en.

Funding Statement

This work was supported by: Den forskningsfremmende pulje i Region Sjælland (ID); Region Sjælland Sundhedsvidenskabelige Forskningsfond (R22-A649; R37-A1598); KEU Region Sjælland; KEU Capital Region of Denmark, Helsefonden (21-B-0422), and Den lokale forskningspulje for NSR (A1315; A1098). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

1.Bahler C, Huber CA, Brungger B, Reich O. Multimorbidity, health care utilization and costs in an elderly community-dwelling population: a claims data based observational study.(Report). BMC Health Serv Res. 2015;15: 23. doi: 10.1186/s12913-015-0698-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Souza DLB, Oliveras-Fabregas A, Minobes-Molina E, de Camargo Cancela M, Galbany-Estragués P, Jerez-Roig J. Trends of multimorbidity in 15 European countries: a population-based study in community-dwelling adults aged 50 and over. BMC Public Health. 2021;21: 76–76. doi: 10.1186/s12889-020-10084-x [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Smith SM, Wallace E, O’Dowd T, Fortin M. Interventions for improving outcomes in patients with multimorbidity in primary care and community settings. Cochrane Database Syst Rev. 2021;1: CD006560–CD006560. doi: 10.1002/14651858.CD006560.pub4 [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Tran PB, Kazibwe J, Nikolaidis GF, Linnosmaa I, Rijken M, van Olmen J. Costs of multimorbidity: a systematic review and meta-analyses. BMC Med. 2022;20: 1–234. doi: 10.1186/s12916-022-02427-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
5.van Den Akker M, Buntinx F, Knottnerus JA. Comorbidity or multimorbidity: what’s in a name? A review of literature. Eur J Gen Pract. 1996;2: 65–70. doi: 10.3109/13814789609162146 [DOI] [Google Scholar]
6.Willadsen TG, Bebe A, Køster-Rasmussen R, Jarbøl DE, Guassora AD, Waldorff FB, et al. The role of diseases, risk factors and symptoms in the definition of multimorbidity—a systematic review. Scand J Prim Health Care. 2016;34: 112–121. doi: 10.3109/02813432.2016.1153242 [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Blaakilde AL, Eiriksson S, Hansen B, Olesen L, Wingstrand A. Sundhedsprofil 2017 for Region Sjælland og kommuner– »Hvordan har du det?« [Health profile 2017 for Region Zealand and municipalities—“How are you?”]. Region Sjælland: Produktion, Forskning og Inniovation; 2018. [Google Scholar]
8.Nanna Borup Johansen Maja Bülow Lykke, Maj Bekker-Jeppesen Lone Prip Buhelt, Karen Allesøe Anne Helms Andreasen, et al. Sundhedsprofil for Region Hovedstaden og kommuner 2017 –Kronisk sygdom [Health profile for the Capital Region and municipalities 2017 –Chronic disease]. Center for Klinisk Forskning og Forebyggelse, Bispebjerg og Frederiksberg Hospital, Region Hovedstaden; 2018. [Google Scholar]
9.Willadsen T, Siersma V, Nicolaisdóttir D, Køster-Rasmussen R, Jarbøl D, Reventlow S, et al. Multimorbidity and mortality: A 15-year longitudinal registry-based nationwide Danish population study. J Comorbidity. 2018;8. doi: 10.1177/2235042X18804063 [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Rijken M, Valderas JM, Heins M, Schellevis F, Korevaar J. Identifying high-need patients with multimorbidity from their illness perceptions and personal resources to manage their health and care: A longitudinal study. BMC Fam Pract. 2020;21: 75–75. doi: 10.1186/s12875-020-01148-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
11.Heins M, Korevaar J, Schellevis F, Rijken M. Identifying multimorbid patients with high care needs—A study based on electronic medical record data. Eur J Gen Pract. 2020;26: 189–195. doi: 10.1080/13814788.2020.1854719 [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Fortin M, Lapointe L, Hudon C, Vanasse A, Ntetu A, Maltais D. Multimorbidity and quality of life in primary care: a systematic review. Health Qual Life Outcomes. 2004;2: 51. doi: 10.1186/1477-7525-2-51 [DOI] [PMC free article] [PubMed] [Google Scholar]
13.Makovski TT, Schmitz S, Zeegers MP, Stranges S, van Den Akker M. Multimorbidity and quality of life: Systematic literature review and meta-analysis. Ageing Res Rev. 2019;53: 100903–100903. doi: 10.1016/j.arr.2019.04.005 [DOI] [PubMed] [Google Scholar]
14.Eriksen CU, Kamstrup–Larsen N, Birke H, Helding SAL, Ghith N, Andersen JS, et al. Models of care for improving health-related quality of life, mental health, or mortality in persons with multimorbidity: A systematic review of randomized controlled trials. J Multimorb Comorbidity. 2022;12. doi: 10.1177/26335565221134017 [DOI] [PMC free article] [PubMed] [Google Scholar]
15.Schiøtz ML, Stockmarr A, Høst D, Glümer C, Frølich A. Social disparities in the prevalence of multimorbidity–A register-based population study. BMC Public Health. 2017;17. doi: 10.1186/s12889-017-4314-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Birke H, Jacobsen R, Jønsson AB, Guassora ADK, Walther M, Saxild T, et al. A complex intervention for multimorbidity in primary care: A feasibility study. J Comorbidity. 2020;10. doi: 10.1177/2235042X20935312 [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Brilleman SL, Salisbury C. Comparing measures of multimorbidity to predict outcomes in primary care: a cross sectional study. Fam Pract. 2012;30: 172–178. doi: 10.1093/fampra/cms060 [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Mads Aage Toft Kristensen, Tina Drud Due, Bibi Hølge-Hazelton, Ann Dorrit Guassora, Frans Boch Waldorff “More constricting than inspiring”—GPs find chronic care programmes of limited clinical utility. A qualitative study. 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Wolff JL. Prevalence, expenditures, and complications of multiple chronic conditions in the elderly.(Archives of Internal Medicine). JAMA J Am Med Assoc. 2003;289: 824. [DOI] [PubMed] [Google Scholar]
20.World Health Assembly 69. Framework on integrated, people-centred health services: report by the Secretariat. 2016. [cited 30 Jun 2021]. Available: https://apps.who.int/iris/handle/10665/252698. [Google Scholar]
21.Smith SM, Wallace E, O’Dowd T, Fortin M. Interventions for improving outcomes in patients with multimorbidity in primary care and community settings. Cochrane Database Syst Rev. 2016;3: CD006560–CD006560. doi: 10.1002/14651858.CD006560.pub3 [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Smith SM, Soubhi H, Fortin M, Hudon C, O’dowd T. Managing patients with multimorbidity: systematic review of interventions in primary care and community settings. BMJ. 2012;345: e5205. doi: 10.1136/bmj.e5205 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Wagner EH. Chronic disease management: what will it take to improve care for chronic illness? Eff Clin Pract. 1998; 2–4. [PubMed] [Google Scholar]
24.Bodenheimer T, Wagner EH, Grumbach K. Improving Primary Care for Patients With Chronic Illness: The Chronic Care Model, Part 2. JAMA J Am Med Assoc. 2002;288: 1909–1914. doi: 10.1001/jama.288.15.1909 [DOI] [PubMed] [Google Scholar]
25.Leijten FRM, Struckmann V, van Ginneken E, Czypionka T, Kraus M, Reiss M, et al. The SELFIE framework for integrated care for multi-morbidity: Development and description. Health Policy. 2018;122: 12–22. doi: 10.1016/j.healthpol.2017.06.002 [DOI] [PubMed] [Google Scholar]
26.Frølich A, Ghith N, Schiøtz M, Jacobsen R, Stockmarr A. Multimorbidity, healthcare utilization and socioeconomic status: A register-based study in Denmark. Kwon YD, editor. PLOS ONE. 2019;14: e0214183. doi: 10.1371/journal.pone.0214183 [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Schiøtz ML, Høst D, Christensen MB, Domínguez H, Hamid Y, Almind M, et al. Quality of care for people with multimorbidity–a case series. BMC Health Serv Res. 2017;17. doi: 10.1186/s12913-017-2724-z [DOI] [PMC free article] [PubMed] [Google Scholar]
28.Rozing M P Jønsson A, Koster-Rasmussen R, Due T D, Brodersen J, Bissenbakker K H. The SOFIA pilot trial—a cluster-randomized trial of coordinated, co-produced care to reduce mortality and improve quality of life in people with severe mental illness in the general practice setting. Pilot Feasibility Stud. 2021; 1–158. [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Webmaster. Overblikskonsultation. Københavns Universitet; 16 Apr 2018. [cited 9 Mar 2023]. Available: https://overblikskonsultation.ku.dk/. [Google Scholar]
30.Skivington K, Matthews L, Simpson SA, Craig P, Baird J, Blazeby JM, et al. A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. BMJ Online. 2021;374: n2061–n2061. doi: 10.1136/bmj.n2061 [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Craig P, Dieppe P, Macintyre S, Michie S, Nazareth I, Petticrew M. Developing and evaluating complex interventions: the new Medical Research Council guidance. BMJ. 2008;337: a1655–983. doi: 10.1136/bmj.a1655 [DOI] [PMC free article] [PubMed] [Google Scholar]
32.OK22 | læger.dk. [cited 10 Mar 2022]. Available: https://www.laeger.dk/PLO/OK22.
33.Glasgow E, Wagner H, Schaefer D, Mahoney J, Reid M, Greene M. Development and Validation of the Patient Assessment of Chronic Illness Care (PACIC). Med Care. 2005;43: 436–444. doi: 10.1097/01.mlr.0000160375.47920.8c [DOI] [PubMed] [Google Scholar]
34.Maindal HT, Sokolowski I, Vedsted P. Adaptation, data quality and confirmatory factor analysis of the Danish version of the PACIC questionnaire. Eur J Public Health. 2012;22: 31–36. doi: 10.1093/eurpub/ckq188 [DOI] [PubMed] [Google Scholar]
35.Salisbury C, Man M-S, Bower P, Guthrie B, Chaplin K, Gaunt DM, et al. Management of multimorbidity using a patient-centred care model: a pragmatic cluster-randomised trial of the 3D approach. The Lancet. 2018;392: 41–50. doi: 10.1016/S0140-6736(18)31308-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
36.Szecsenyi J, Rosemann T, Joos S, Peters-Klimm F, Miksch A. German diabetes disease management programs are appropriate for restructuring care according to the chronic care model: an evaluation with the patient assessment of chronic illness care instrument. Diabetes Care. 2008;31: 1150–1154. doi: 10.2337/dc07-2104 [DOI] [PubMed] [Google Scholar]
37.Bell ML, Kenward MG, Fairclough DL, Horton NJ. Differential dropout and bias in randomised controlled trials: when it matters and when it may not. BMJ Online. 2013;346: e8668–e8668. doi: 10.1136/bmj.e8668 [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42: 377–381. doi: 10.1016/j.jbi.2008.08.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
39.overbliksstatus-og-rsstatus.pdf. [cited 30 Jun 2021]. Available: https://vejledninger.dsam.dk/media/files/21/overbliksstatus-og-rsstatus.pdf.
40.Freund KS, Guassora AD, Hegelund T, Hvas L, Lous J. Resources in vulnerable young adults: self-assessments during preventive consultation with their general practitioner in Denmark. Health Promot Int. 2020;35: 1180–1189. doi: 10.1093/heapro/daz114 [DOI] [PMC free article] [PubMed] [Google Scholar]
41.Williams J. The Declaration of Helsinki and public health. Bull World Health Organ. 2008;86: 650–651. doi: 10.2471/blt.08.050955 [DOI] [PMC free article] [PubMed] [Google Scholar]
42.Herdman M, Gudex C, Lloyd A, Janssen B, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20: 1727–1736. doi: 10.1007/s11136-011-9903-x [DOI] [PMC free article] [PubMed] [Google Scholar]
43.Duncan P, Murphy M, Mei-See M, Chaplin K, Gaunt D, Salisbury C. Development and validation of the Multimorbidity Treatment Burden Questionnaire (MTBQ). BMJ Open. 2018;8: e019413. doi: 10.1136/bmjopen-2017-019413 [DOI] [PMC free article] [PubMed] [Google Scholar]
44.Bang H, Zhao H. Median-Based Incremental Cost-Effectiveness Ratio (ICER). J Stat Theory Pract. 2012;6: 428–442. doi: 10.1080/15598608.2012.695571 [DOI] [PMC free article] [PubMed] [Google Scholar]
45.DRG-takster 2019—Sundhedsdatastyrelsen. [cited 27 Feb 2020]. Available: https://sundhedsdatastyrelsen.dk/da/afregning-og-finansiering/takster-drg/takster-2019.
46.Schünemann HJ, Guyatt GH. Commentary—Goodbye M(C)ID! Hello MID, Where Do You Come From? Health Serv Res. 2005;40: 593–597. doi: 10.1111/j.1475-6773.2005.00374.x [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Drummond MF. Methods for the economic evaluation of health care programmes. 2. ed., reprint. Oxford: University Press; 1997. [Google Scholar]
48.Fenwick E O’Brien BJ, Briggs A. Cost-effectiveness acceptability curves–facts, fallacies and frequently asked questions. Health Econ. 2004;13: 405–415. doi: 10.1002/hec.903 [DOI] [PubMed] [Google Scholar]
49.Lochmiller C. Conducting Thematic Analysis with Qualitative Data. Qual Rep. 2021;26: 2029–2044. doi: 10.46743/2160-3715/2021.5008 [DOI] [Google Scholar]
50.Prior A, Vestergaard CH, Ribe AR, Sandbæk A, Bro F, Vedsted P, et al. Chronic care services and variation between Danish general practices: a nationwide cohort study. Br J Gen Pract. 2021; BJGP.2021.0419-. doi: 10.3399/BJGP.2021.0419 [DOI] [PMC free article] [PubMed] [Google Scholar]
51.Pedersen AF, Nørøxe KB, Vedsted P. Influence of patient multimorbidity on GP burnout: a survey and register-based study in Danish general practice. Br J Gen Pract. 2020;70: e95–e101. doi: 10.3399/bjgp20X707837 [DOI] [PMC free article] [PubMed] [Google Scholar]
52.Almirall J, Fortin M. The coexistence of terms to describe the presence of multiple concurrent diseases. J Comorbidity. 2013;3: 4–9. doi: 10.15256/joc.2013.3.22 [DOI] [PMC free article] [PubMed] [Google Scholar]
53.Islam MM, Valderas JM, Yen L, Dawda P, Jowsey T, McRae IS. Multimorbidity and Comorbidity of Chronic Diseases among the Senior Australians: Prevalence and Patterns. Laks J, editor. PLoS ONE. 2014;9: e83783. doi: 10.1371/journal.pone.0083783 [DOI] [PMC free article] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0310697.r001

Decision Letter 0

Kathleen Finlayson

13 Nov 2023

PONE-D-23-28616A patient-centred care model for patients with complicated multimorbidity: Protocol for a cluster randomised trial in general practice, municipalities, and hospitalsPLOS ONE

Dear Dr. Lundstrøm,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. The protocol describes a study of significance in today's global ageing population. Please consider the reviewers' feedback and queries, particularly addressing the need for more detail on the rationale for the study, to report the protocol according to the SPIRIT guideline, confusion re a pilot study or full randomised trial, and consideration of appropriate analysis tests for your outcome variables.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Partly

Reviewer #2: Partly

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Partly

Reviewer #2: Partly

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: No

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the opportunity to read and review this protocol manuscript. Overall, I find the protocol relevant and feasible.

I do however, have some suggestions for improvement.

Abstract: overall, I find the language in the abstract inconsistent and in need for revision by a native English speaker.

Especially the Introduction (in the abstract) need a re-writing regarding coherence and language. Consider not to use "often" (also in the manuscript) as it is unspecific tending to appraising.

I find the sentence "There remains limited understanding..." both clumsy and arrogant - what do you know about peoples' understanding? I know, it hasn't been the intention but nevertheless, it is the signal. CIM should be explained (or not used) in the abstract. I struggle a bit to understand the choice of the word "effects" in the aim - are you sure that this is the correct word to use here? or is it rather "impact" or "effectiveness"?

First line in the Methods (in the abstract): should it be: ".. integrated care for patients..."?

Should "patient's" be plural (patients')?

In the last 4-5 lines of the abstract you write in the past tense (were collected, were recorded, assessments involved...) - should this be the present tense or have these actions been carried out?

Introduction

Unless it is due to journal guidelines, please, gather consecutive references in one bracket.

Consider to decrease the use of "often"

The literature used to argue for a recent empirical situation (here: the organisation of healthcare, the number of persons suffering from multi-morbidity and so on) should be recent and not from e.g., 2015, 1996, 2016.

Line 5 regarding the amount of people with complicated multi-morbidity - where is this? still in Denmark?

The coherence between some of the sections in the Introduction is poor - for example the description of the secondary healthcare sector appears a bit out of context.

Reference 15 has not publication year presented in the Reference list.

Line 8 from the bottom of the section: what is a critical potential? please, clarify.

Consider moving the sentences describing that both studies run simultaneously to tie Limitations - it is a bit weird to have this information here.

Aim: this aim corroborates better with the study design and the chosen outcomes - but why does it differ substantially from the aim in the abstract? Please align.

Methods

It is stated that the study will take place in the 3rd quarter of2022 - does this mean that the study is completed? before the protocol is published?

Regarding the sample size - why do you think that 30% will dropout? Please, provide a reference for this.

Data

What is meant by "Patient outcome"? should this term be mentioned in the design..?

And why have you chosen to interview 15 patients?

Analyses

In this section, quite new terms are introduced: comparability, health economic evaluation and process evaluation - they should be introduced earlier. Please, align terms in Abstract, Methods, Data and Analyses.

References

The reference list should be scrutinized regarding Danish titles (should be presented in English in square brackets) - for example no4, 5, 25, 42 - and lack of information - for example no 15 without publication year.

Reviewer #2: Important note: This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ [like medical importance, relevance of the study, ‘clinical significance and implication(s)’ of the whole study, etc.] are to be evaluated [should be assessed] separately/independently. Further please note that any ‘statistical review’ is generally done under the assumption that (such) study specific methodological [as well as execution] issues are perfectly taken care of by the investigator(s). This review is not an exception to that and so does not cover clinical aspects {however, seldom comments are made only if those issues are intimately / scientifically related & intermingle with ‘statistical aspects’ of the study}. Agreed that ‘statistical methods’ are used as just tools here, however, they are vital part of methodology [and so should be given due importance]. I look at the manuscript in/with statistical view point, other reviewer(s) look(s) at it with different angle so that in totality the review is very comprehensive. However, there should be efforts from authors side to improve (may be by taking clues from reviewer’s comments). Therefore, please do not limit the revision only (with respect) to comments made here.

COMMENTS: There are a few issues about which I have different opinion and such observations/concerns are given below (since the study is at ‘Protocol’ stage, it is possible to incorporate agreed ones):

In ‘Aim of the pilot study’ section [end of ‘Introduction’, page 5] it is stated that “This paper describes the protocol for a pilot cluster randomised controlled trial to determine the effectiveness of a general practice-based intervention aimed at improving treatment and care for patients with complicated multimorbidity”. Is this a protocol for a pilot cluster randomised controlled trial? I wonder, why (in that case) the word PILOT has not appeared in ‘title’ of the study (then)? In my opinion that is expected. Later in ‘Development of the CIM2 intervention’ section you state that “The study described in this protocol is the execution of phase 3 of the MRC framework for complex interventions”, and accordingly [according to ‘MRC framework’ described by you described in this section] a full-fledged clinical trial is expected. Then why this ‘PILOT’? Actually, the present one seems to be a full-fledged clinical trial.

In ‘Abstract - methods’ section, it is stated that “The primary outcome measure is the patient’s experience of quality of care measured by the Patient Assessment Chronic Illness Care Questionnaire (PACIC). Secondary outcomes include the patient’s health-related quality of life, measured by the EuroQol-5 Domain questionnaire (EQ-5D-5L) and the treatment burden measured by the Multimorbidity Treatment Burden Questionnaire (MTBQ).”. Note that though the measures/tools used are appropriate, all of them are likely to yield data that are in ‘ordinal’ level of measurement [and not in ratio level of measurement {as the score two times higher does not indicate presence of that parameter/phenomenon as double (for example, a Visual Analogue Scales VAS score or say ‘depression’ score)}]. Then application of suitable non-parametric (or distribution free) test(s) is/are indicated/advisable [even if distribution may be ‘Gaussian’ (also called ‘normal’)].

Agreed that there is/are no non-parametric test(s)/technique(s) available to be used as alternative in all situation(s), but should be used whenever/wherever they are available. Therefore, in short use suitable non-parametric test(s)/technique(s) while dealing with data that are in ‘ordinal’ level of measurement even if [despite that] the distribution may be ‘Gaussian’.

In ‘Analyses - Analyses of comparability’ section use of any non-parametric test/technique is/are not proposed. Instead, it is said that “A linear mixed model, will be used for the analysis”. Using mixed-model regression is not wrong at all, but note that this technique [in fact any regression technique(s) for that matter] is/are not originally developed for testing the ‘Group difference(s)’. Head-to-head comparison is expected, as through regression is an indirect/secondary/by-product testing, in my opinion. {Section ‘Analyses of comparability’ mentions that “The secondary analyses will compare scores of the EQ-5D-5L and MTBQ in the intervention group and the control group using the same methods as described.”}

Sample size estimation used is described in ‘Sample size’ section seems to be alright but is little complicated (since not usual). In this (‘Sample size’) section for few assumptions refences are given [example: The difference of interest between the intervention and the control group is Δ=0.36, with a mean value of 2.86, and with an expected standard deviation SD = 1, based on results from earlier studies [33], [34].] but the other important assumption is without any relevant refence(s) [example: The power calculations take a potential Intraclass Correlation Coefficient (ICC) of 0.1 into account.], whereas the sample size estimate depends on all [and so is very much affected due to assumed values without any relevant refence(s)]. Your sample size estimation may be correct, however, raises doubt in mind of most readers. Further, kindly confirm whether the procedure used here, takes care of (i.e., incorporates) ‘30% dropouts assumed’? Otherwise, mind you that 30% (of 175) is 53 and so needed sample size is 228.

The ‘Limitations’ section includes only defining term multimorbidity and this makeing it difficult to compare different multimorbidity studies. Does that mean {according to authors} there are none other(s)? As pointed out in ‘important note’ above “This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ should be assessed separately/independently [one should carefully consider/look at the clinical implications of the study].

In my opinion, to make this article acceptable (which is quite possible), a small amount of re-vision (re-drafting) may be needed. However, please do not limit the revision only (with respect) to comments made here. More improvement is expected. The respected ‘Editor’ may consider accepting/further processing only if found ‘clinical implications’ valuable [i.e., add(s) to clinical knowledge or positively influence clinical practice]. ‘Minor revision’ is recommended.

Important note: This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ [like medical importance, relevance of the study, ‘clinical significance and implication(s)’ of the whole study, etc.] are to be evaluated [should be assessed] separately/independently. Further please note that any ‘statistical review’ is generally done under the assumption that (such) study specific methodological [as well as execution] issues are perfectly taken care of by the investigator(s). This review is not an exception to that and so does not cover clinical aspects {however, seldom comments are made only if those issues are intimately / scientifically related & intermingle with ‘statistical aspects’ of the study}. Agreed that ‘statistical methods’ are used as just tools here, however, they are vital part of methodology [and so should be given due importance]. I look at the manuscript in/with statistical view point, other reviewer(s) look(s) at it with different angle so that in totality the review is very comprehensive. However, there should be efforts from authors side to improve (may be by taking clues from reviewer’s comments). Therefore, please do not limit the revision only (with respect) to comments made here.

The ‘Limitations’ section includes only defining term multimorbidity and this making it difficult to compare different multimorbidity studies. Does that mean {according to authors} there are none other(s)? As pointed out in ‘important note’ above “This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ should be assessed separately/independently [one should carefully consider/look at the clinical implications of the study].

**********

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Reviewer #2: No

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PLoS One. 2024 Dec 4;19(12):e0310697. doi: 10.1371/journal.pone.0310697.r002

Author response to Decision Letter 0

22 Dec 2023

Authors replies in red

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REPLY (also stated in the above cover letter to editor)

There are legal restrictions, but data from the pilot study may be accessed if an application to access the data is approved by government agencies. Hence, “upon request refers” to submitting a formal application to the Danish authorities. We have made the following changes:

Data Availability Statement

No datasets were generated or analysed during the current study. The European General Data Protection Regulation will safeguard the sharing of data in the pilot study. In compliance with patient privacy and Danish data protection law restrictions, the aggregated dataset utilized in the pilot study will only be accessible through Statistics Denmark, a trusted third party that manages and governs the data. Authorized scientific institutions based in Denmark can request access to this data from Statistics Denmark for individual researchers within or outside the country. Requests for accessing the data should be directed to Statistics Denmark at: https://www.dst.dk/en

3. Please include a caption for figure 2.

We have included a caption for Figure 2: Figure 2. An overview of the patient-centred care model for patients with complicated multimorbidity (CIM2).

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REPLY (also stated in the above cover letter to editor)

We have updated the Cover Letter and indicated that we would like to have the manuscript considered as a Study Protocol. We also confirm that neither recruitment nor data collection had been completed in September 2023, when the manuscript were submitted. We are still recruiting patients and data collection will continue until spring 2025.

Comments to the Author

Reviewers #1 Comments Authors Response

ABSTRACT:

Especially the Introduction (in the abstract) need a re-writing regarding coherence and language. Consider not to use "often" (also in the manuscript) as it is unspecific tending to appraising. We have re-written the abstract:

Introduction

Methods

CIM should be explained (or not used) in the abstract. We made sure that the CIM is explained in the abstract

. I struggle a bit to understand the choice of the word "effects" in the aim - are you sure that this is the correct word to use here? or is it rather "impact" or "effectiveness"?

We have changed the word effects to effectiveness.

First line in the Methods (in the abstract): should it be: ".. integrated care for patients..."? Yes, thank you. We have now changed it.

Should "patient's" be plural (patients')? It is changed to plural – patients. Thank you.

In the last 4-5 lines of the abstract you write in the past tense (were collected, were recorded, assessments involved...) - should this be the present tense or have these actions been carried out? We have changed the last lines in the abstract from past tense to present continuous tense.

INTRODUCTION:

Unless it is due to journal guidelines, please, gather consecutive references in one bracket. We have made changes in the document preferences, so consecutive references are shown in one bracket.

Consider to decrease the use of "often" We have decreased the use of often in the introduction.

Jerez-Roig J. Trends of multimorbidity in 15 European countries: a population-based study in community-dwelling adults aged 50 and over. BMC Public Health. 2021;21: 76–76. doi:10.1186/s12889-020-10084-x

3. Smith SM, Wallace E, O’Dowd T, Fortin M. Interventions for improving outcomes in patients with multimorbidity in primary care and community settings. Cochrane Database Syst Rev. 2021;1: CD006560–CD006560. doi:10.1002/14651858.CD006560.pub4

4. Tran PB, Kazibwe J, Nikolaidis GF, Linnosmaa I, Rijken M, van Olmen J. Costs of multimorbidity: a systematic review and meta-analyses. BMC Med. 2022;20: 1–234. doi:10.1186/s12916-022-02427-9

Line 5 regarding the amount of people with complicated multi-morbidity - where is this? still in Denmark? Yes, we have specified in the manuscript that this is in Denmark

The coherence between some of the sections in the Introduction is poor - for example the description of the secondary healthcare sector appears a bit out of context. Thank you to the reviewer for giving us the opportunity to revise the introduction to make the sections more coherent.

Reference 15 has not publication year presented in the Reference list. We have changed it to the following:

19. Wolff JL. Prevalence, expenditures, and complications of multiple chronic conditions in the elderly. (Archives of Internal Medicine). JAMA J Am Med Assoc. 2003;289: 824-.

Line 8 from the bottom of the section: what is a critical potential? please, clarify. We have clarified it in the manuscript:

This has created an opportunity for a large-scale testing of the elements from the CIM2 model at a national level

Consider moving the sentences describing that both studies run simultaneously to tie Limitations - it is a bit weird to have this information here.

After careful consideration have, we chosen to take part of this section out of the manuscript and re-written this section in the introduction:

The development of the extended overview consultation in the feasibility study of CIM model[18] caught the attention of the Danish Regions Organisation and The Danish Organization of General Practitioners. The collective agreement accepted in 2022 for general practice introduced a fee-for-service covering an extended overview consultation for people with complex multimorbidity[34]. The CIM2 pilot study is expected to improve and strengthen the CIM2 model, and the results will be used to inform further interventions.

Aim: this aim corroborates better with the study design and the chosen outcomes - but why does it differ substantially from the aim in the abstract? Please align. We have rephrased the aim in the abstract: This paper describes the study protocol for a pilot randomised controlled trial (RCT) evaluating the effectiveness of a general practice-based intervention.

METHODS:

I wonder why you do not describe that the protocol is guided by the SPIRIT - I would have recommended that but noticed by the end of the manuscript that you have... I do however, then wonder why you haven't followed the guideline? your structure differ completely from the structure recommended by the guideline. Our research protocol adheres to SPIRIT guidelines. In crafting our protocol article, we meticulously selected elements from SPIRIT that were pertinent to our study's framework. To align more closely with these guidelines, we have modified certain subheadings and restructured sections of the protocol article for enhanced coherence with SPIRIT's principles.

It is stated that the study will take place in the 3rd quarter of2022 - does this mean that the study is completed? before the protocol is published? We find this questions confusion as it is written in the manuscript that: The study will take place in Region Zealand and the Capital Region of Denmark, in general practices, healthcare centres in municipalities, and hospital outpatient clinics during the 3rd quarter of 2022 through the 4th quarter of 2024.

To clarify, the study is not completed before the protocol was submitted and will probably also not be completed before the protocol is published – depending on when it is published. The first general practices began recruiting patients in the 3rd quarter of 2022 and have continued recruiting during 2023. The extended overview consultations will continue during 2024 and maybe also during the 1st quarter of 2025.

Regarding the sample size - why do you think that 30% will dropout? Please, provide a reference for this. We have added a reference [37]

DATA:

What is meant by "Patient outcome"? should this term be mentioned in the design..? To not creating any confusion, we have changed it to outcome.

And why have you chosen to interview 15 patients? In this qualitative part of the study, we have prioritized in-depth exploration of individual experiences, and we estimate that approximately 15 interviews will be appropriate to achieve a rich understanding of the phenomenon under investigation.

ANALYSES:

In this section, quite new terms are introduced: comparabi

PLoS One. doi: 10.1371/journal.pone.0310697.r003

Decision Letter 1

Kathleen Finlayson

13 Mar 2024

PONE-D-23-28616R1A patient-centred care model for patients with complicated multimorbidity: Protocol for a cluster randomised trial in general practice, municipalities, and hospitalsPLOS ONE

Dear Dr. Lundstrøm,

In particular, please consider the reviewers' comments below on addressing justification for the study in the introduction and background, and the need for further details of the methods for the interviews and recruitment.

Please submit your revised manuscript by Apr 27 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Kathleen Finlayson

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #3: No

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #3: No

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #3: Yes

**********

6. Review Comments to the Author

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: Annotation Summary of PONE-D-23-28616.pdf.

Note [page 15]: Abstract

Introduction: correct spelling of trail to trial

Methods: Change to “Diagnosis- Related” rather than "Diagnose"

Note [page 16]: Introduction

To make this more readable, I suggest that you put the definitions of morbidity followed by the stats, then the definition of complicated multi morbidity, then describe the situation in Denmark - with 10% having… etc.

The first 2 paras do not read well in the current format.

Later in the introduction, please state that you are in phase 3 of the MRC framework - if this is the case.

It is important that the introduction correlates with the outcomes of the study. The outcome of your study is a patient reported measure (at least your primary outcome). Therefore, when you comment on the current state of care for multi-morbid patients, please make reference to the literature which shows that existing patient reported outcomes are poor in this group.

Your other comments in the introduction regarding the ‘silo-ing’ of care or the lack of "effective care" are probably true, but this protocol is not designed to improve any of that. The primary outcome the study measures is the effect on patient reported outcomes.

I also think the introduction can be rewritten to improve flow and readability.

Note [page 22]: Methods - Qualitative Evaluation

There is repetition here regarding the guide for semistructured interviews. Please streamline, and mention the inclusions in your guide one place only. Articulate clearly the interviews that you will conduct as part of the qualitative process. Under each type of the interviews, list the questions you will consider in the semistructured interview. In its present form, there is a series of interviews mentioned and multiple "guides to interview" descriptions.

You also need to specify whether you will interview patients / HCPs who have been randomly allocated to standard care. Do you think this will be necessary so that you can draw good comparisons to your intervention group?

Note [page 22]: Outcomes.

Please see my earlier comment regarding writing an introduction that matches to the outcomes that you are studying in the current protocol. We need to show that the current literature demonstrates that patient reported outcomes are poor with the current models of care.

Note [page 25]: Discussion

Returning to my earlier comments, it is important that you mention in the discussion that the study seeks to improve patient experiences in particular. In its current form, you have spoken, generally about "improving care for patients" or "reducing burnout for GPs “. While both are laudable aims, the purpose of your study to improve patient-reported outcomes and you must talk about this in your discussion.

Note [page 27]: Source of potential bias

Please clarify this sentence: Patients recruited by their GP be more likely to participate when asked by a familiar healthcare professional whom they trust.

Principles of good clinical practice in research suggest that recruitment should not be undertaken by practitioners involved in the treatment of patients. Therefore, it would be wrong for patients to be asked to participate by a healthcare professional whom they are familiar with or trust.

All requests for participation in a clinical studies should be made by people who are not connected to the care of the patient so as to not introduce any unwanted pressure to participate. You are right in saying this is also a potential for bias.

I am sure you are aware of this but your sentence is misleading and needs to be clarified.

If, on the other hand, you do plan to recruit patients by invitations from their own health professionals, you must change this as it is not acceptable practice.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: Yes: Assoc Prof Rajesh Raj

**********

PLoS One. 2024 Dec 4;19(12):e0310697. doi: 10.1371/journal.pone.0310697.r004

Author response to Decision Letter 1

8 Aug 2024

Authors replies in red

Journal Requirements:

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #3: No

________________________________________

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

Reviewer #3: Yes

________________________________________

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #3: No

________________________________________

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

Reviewer #3: Yes

________________________________________

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #3: Yes

________________________________________

6. Review Comments to the Author

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: Annotation Summary of PONE-D-23-28616.pdf.

Note [page 15]: Abstract

Introduction: correct spelling of trail to trial

We appreciate the reviewer's attentive eye in identifying the typographical error in the Introduction section of our manuscript. The incorrect spelling of "trail" has been corrected to "trial" as suggested.

Methods: Change to “Diagnosis- Related” rather than "Diagnose"

Thank you for your insightful suggestion regarding the terminology used in the Methods section of our manuscript. We have made the recommended change to ensure the manuscript's precision and readability

Note [page 16]: Introduction

The first 2 paras do not read well in the current format.

Later in the introduction, please state that you are in phase 3 of the MRC framework - if this is the case.

I also think the introduction can be rewritten to improve flow and readability.

Thank you for your detailed feedback and constructive suggestions for improving the introduction of our manuscript. Your input is invaluable in helping us refine our presentation and ensuring that it accurately reflects the study's scope and objectives. Here is the revised introduction that incorporates your recommendations:

Introduction

Multimorbidity is commonly defined as the coexistence of two or more chronic conditions in the same person [1,2]. The increasing prevalence of multimorbidity is largely driven by the ageing population, and advanced diagnostic health technologies, presenting a major challenge for the healthcare system and society [3–6]. In the Capital Region of Denmark and Region Zealand, approximately 21% and 37% of the citizens aged 16 years and older suffer from multimorbidity [7,8].

Complicated multimorbidity, a subset of the diagnosis multimorbidity is characterized by a severe symptom complex caused by more concomitant chronic conditions, and affects about 10% of people with multimorbidity in Denmark [9]. Definitions of complicated multimorbidity vary, encompassing aspects such as the severity of conditions and patients’ perceptions of their illness [10,11].

Due to the single disease focus, current care models for patients with multimorbidity are often fragmented and fail to provide integrated, patient-centered care. This is particularly evident from patient-reported outcomes, which consistently reveal dissatisfaction among this group. Studies have highlighted that patients with multimorbidity frequently experience poor health related quality of life, high treatment burdens, and a sense of being underserved by the healthcare systems [12–14]. These outcomes underscore the urgent need for revised care models that prioritize the patient experience and improve the overall management of multiple chronic conditions.

In this study, we define multimorbidity as complicated when the patient has two or more of three specific chronic conditions (diabetes, chronic obstructive pulmonary disease, or chronic heart conditions) [15], has been in contact with the hospital during the previous year or visited an outpatient clinic due to their chronic condition(s) during the previous year [16], and take at least five different prescription drugs assessed from the Shared Medicine Record (SMR) [17].

Care pathways for patients with complicated multimorbidity are often complex with multiple appointments, frequent ambulatory visits, hospital admission, and use of other healthcare services. The siloed organization of healthcare around single diseases, the lack of guidelines for multimorbidity and incompatible IT systems can be a barrier to effective care for those patients [18].

Based on the results from the feasibility study, we developed an improved version of the CIM model named “A patient-centred complex intervention for multimorbidity version 2” (CIM2) [16,28]. The new CIM2 model includes improved training of healthcare professionals, strengthened identification of patients with complicated multimorbidity, adjustment of the extended consultation according to the consultation model of The Danish College of General Practitioners (DSAM), improved medical treatment, and strengthened integration of care services between healthcare organisations [16,29]. The development of the CIM2 model relies on the Medical Research Council (MRC) framework for complex interventions [30,31], confirming that this study is in phase 3, focusing on the evaluation of interventions.

The development of the extended overview consultation in the feasibility study of CIM model [16] caught the attention of the Danish Regions Organisation and The Danish Organization of General Practitioners. The collective agreement accepted in 2022 for general practice introduced on a trial basis a fee-for-service covering an extended overview consultation for people with complex multimorbidity[32]. The CIM2 pilot study is expected to improve and strengthen the CIM2 model, and the results will be used to inform further interventions.

Note [page 22]: Methods - Qualitative Evaluation

Thank you for your feedback regarding the focus of our qualitative evaluation. Based on your suggestion, we have decided to concentrate the qualitative analysis on gathering experiences from participants who have directly engaged with the CIM2 model. This approach is aimed at deeply understanding how the model functions in a real-world setting and assessing its practical viability. Therefore, we will not include participants from the standard care group in this part of the study, as their input would not contribute to our primary objective of evaluating the model's direct impacts. This method ensures that our qualitative data is highly relevant and focused on the intervention's effects.

Here is the revised qualitative evaluation that incorporates your recommendations:

The qualitative evaluation employs two primary methods – semi-structed interviews and focus group interviews. Semi-structured interviews will be conducted with general practitioners and nurses from the seven intervention practices and with patients with a cross-sectorial course of treatment. Focus group interviews interview will be conducted with health professionals representing all three sectors. The interviews are designed to capture comprehensive insight into the interviewees’ experiences with CIM2, their assessment of the potential and challenges of using the model, and their potential input for improving the model. The semi-structured interviews are guided by interview guides.

For the healthcare professionals, the following experiences/topics are queried: Recruitment of patients, the content and relevance of the extended consultation, medical benefits of the extended overview consultation, their perception of patient benefits, referral to municipal rehabilitation and/or to hospital, individual treatment plan, cross-sectoral education of healthcare professionals, and suggestions for improvements.

For the patients, the following topics are queried: Everyday life and networks, experience of the overview consultation including communication and patient-centeredness, individual treatment plan, experiences with cross-sectorial course of treatment and suggestions for improvement.

The focus group interview guide will address the following topics: The cross-sectorial teaching program for healthcare professionals, integration of care via CIM2, information sharing, referral to rehabilitation and the content of community rehabilitation programs.

All interviews will be recorded, transcribed, and analyzed using Nvivo software.

Note [page 22]: Outcomes.

This has now been incorporated in the revised introduction in the above comment.

Note [page 25]: Discussion

Thank you for your feedback. We appreciate the opportunity to revise our discussion to better align with the focus. We have added the following paragraph to the discussion:

The study’s primary outcome measure is the patients’ experience of quality of care, assessed using the PACIC, with secondary outcomes including health-related quality of life and treatment burden. By evaluating patient-reported outcomes and conducting qualitative assessment through interviews with patients and healthcare professionals, the study aims to assess the effectiveness of the CIM2 model in improving care for patients with complicated multimorbidity.

Note [page 27]: Source of potential bias

Please clarify this sentence: Patients recruited by their GP be more likely to participate when asked by a familiar healthcare professional whom they trust.

I am sure you are aware of this but your sentence is misleading and needs to be clarifie

PLoS One. doi: 10.1371/journal.pone.0310697.r005

Decision Letter 2

Kathleen Finlayson

6 Sep 2024

A patient-centred care model for patients with complicated multimorbidity: Protocol for a cluster randomised trial in general practice, municipalities, and hospitals

PONE-D-23-28616R2

Dear Dr. Lundstrøm,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Kathleen Finlayson

Academic Editor

PLOS ONE

Additional Editor Comments:

Thank you for the revised article addressing the reviewers' feedback. There are just a few areas where inconsistency needs amending, where you have addressed feedback in one spot however not in others. Specifically,

- the aim in your abstract should include your primary outcome, i.e., effectiveness of xxx on ?outcome. The objective on p.4 does not match this aim, as 'treatment' is not your primary outcome, this should be patients' experience of quality care

- should economic outcomes be included in your secondary outcomes?

- in the sources of bias section, consider the reviewer's comments about the conflict of interest involved in relying on the patients' GPs to recruit, there is an ethical issue

- double check the grammar throughout, e.g. the pilot RCT WILL involve ....; DRGs should be Diagnosis (not diagnose as in abstract) etc.

PLoS One. doi: 10.1371/journal.pone.0310697.r006

Acceptance letter

Kathleen Finlayson

15 Sep 2024

PONE-D-23-28616R2

PLOS ONE

Dear Dr. Lundstrøm,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

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PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Checklist. SPIRIT 2013 checklist: Recommended items to address in a clinical trial protocol and related documents*.

(DOC)

pone.0310697.s001.doc^{(128KB, doc)}

S1 Protocol

(PDF)

pone.0310697.s002.pdf^{(636.8KB, pdf)}

Data Availability Statement

[pone.0310697.ref001] 1.Bahler C, Huber CA, Brungger B, Reich O. Multimorbidity, health care utilization and costs in an elderly community-dwelling population: a claims data based observational study.(Report). BMC Health Serv Res. 2015;15: 23. doi: 10.1186/s12913-015-0698-2 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref002] 2.Souza DLB, Oliveras-Fabregas A, Minobes-Molina E, de Camargo Cancela M, Galbany-Estragués P, Jerez-Roig J. Trends of multimorbidity in 15 European countries: a population-based study in community-dwelling adults aged 50 and over. BMC Public Health. 2021;21: 76–76. doi: 10.1186/s12889-020-10084-x [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref003] 3.Smith SM, Wallace E, O’Dowd T, Fortin M. Interventions for improving outcomes in patients with multimorbidity in primary care and community settings. Cochrane Database Syst Rev. 2021;1: CD006560–CD006560. doi: 10.1002/14651858.CD006560.pub4 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref004] 4.Tran PB, Kazibwe J, Nikolaidis GF, Linnosmaa I, Rijken M, van Olmen J. Costs of multimorbidity: a systematic review and meta-analyses. BMC Med. 2022;20: 1–234. doi: 10.1186/s12916-022-02427-9 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref005] 5.van Den Akker M, Buntinx F, Knottnerus JA. Comorbidity or multimorbidity: what’s in a name? A review of literature. Eur J Gen Pract. 1996;2: 65–70. doi: 10.3109/13814789609162146 [DOI] [Google Scholar]

[pone.0310697.ref006] 6.Willadsen TG, Bebe A, Køster-Rasmussen R, Jarbøl DE, Guassora AD, Waldorff FB, et al. The role of diseases, risk factors and symptoms in the definition of multimorbidity—a systematic review. Scand J Prim Health Care. 2016;34: 112–121. doi: 10.3109/02813432.2016.1153242 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref007] 7.Blaakilde AL, Eiriksson S, Hansen B, Olesen L, Wingstrand A. Sundhedsprofil 2017 for Region Sjælland og kommuner– »Hvordan har du det?« [Health profile 2017 for Region Zealand and municipalities—“How are you?”]. Region Sjælland: Produktion, Forskning og Inniovation; 2018. [Google Scholar]

[pone.0310697.ref008] 8.Nanna Borup Johansen Maja Bülow Lykke, Maj Bekker-Jeppesen Lone Prip Buhelt, Karen Allesøe Anne Helms Andreasen, et al. Sundhedsprofil for Region Hovedstaden og kommuner 2017 –Kronisk sygdom [Health profile for the Capital Region and municipalities 2017 –Chronic disease]. Center for Klinisk Forskning og Forebyggelse, Bispebjerg og Frederiksberg Hospital, Region Hovedstaden; 2018. [Google Scholar]

[pone.0310697.ref009] 9.Willadsen T, Siersma V, Nicolaisdóttir D, Køster-Rasmussen R, Jarbøl D, Reventlow S, et al. Multimorbidity and mortality: A 15-year longitudinal registry-based nationwide Danish population study. J Comorbidity. 2018;8. doi: 10.1177/2235042X18804063 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref010] 10.Rijken M, Valderas JM, Heins M, Schellevis F, Korevaar J. Identifying high-need patients with multimorbidity from their illness perceptions and personal resources to manage their health and care: A longitudinal study. BMC Fam Pract. 2020;21: 75–75. doi: 10.1186/s12875-020-01148-3 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref011] 11.Heins M, Korevaar J, Schellevis F, Rijken M. Identifying multimorbid patients with high care needs—A study based on electronic medical record data. Eur J Gen Pract. 2020;26: 189–195. doi: 10.1080/13814788.2020.1854719 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref012] 12.Fortin M, Lapointe L, Hudon C, Vanasse A, Ntetu A, Maltais D. Multimorbidity and quality of life in primary care: a systematic review. Health Qual Life Outcomes. 2004;2: 51. doi: 10.1186/1477-7525-2-51 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref013] 13.Makovski TT, Schmitz S, Zeegers MP, Stranges S, van Den Akker M. Multimorbidity and quality of life: Systematic literature review and meta-analysis. Ageing Res Rev. 2019;53: 100903–100903. doi: 10.1016/j.arr.2019.04.005 [DOI] [PubMed] [Google Scholar]

[pone.0310697.ref014] 14.Eriksen CU, Kamstrup–Larsen N, Birke H, Helding SAL, Ghith N, Andersen JS, et al. Models of care for improving health-related quality of life, mental health, or mortality in persons with multimorbidity: A systematic review of randomized controlled trials. J Multimorb Comorbidity. 2022;12. doi: 10.1177/26335565221134017 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref015] 15.Schiøtz ML, Stockmarr A, Høst D, Glümer C, Frølich A. Social disparities in the prevalence of multimorbidity–A register-based population study. BMC Public Health. 2017;17. doi: 10.1186/s12889-017-4314-8 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref016] 16.Birke H, Jacobsen R, Jønsson AB, Guassora ADK, Walther M, Saxild T, et al. A complex intervention for multimorbidity in primary care: A feasibility study. J Comorbidity. 2020;10. doi: 10.1177/2235042X20935312 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref017] 17.Brilleman SL, Salisbury C. Comparing measures of multimorbidity to predict outcomes in primary care: a cross sectional study. Fam Pract. 2012;30: 172–178. doi: 10.1093/fampra/cms060 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref018] 18.Mads Aage Toft Kristensen, Tina Drud Due, Bibi Hølge-Hazelton, Ann Dorrit Guassora, Frans Boch Waldorff “More constricting than inspiring”—GPs find chronic care programmes of limited clinical utility. A qualitative study. 2018. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref019] 19.Wolff JL. Prevalence, expenditures, and complications of multiple chronic conditions in the elderly.(Archives of Internal Medicine). JAMA J Am Med Assoc. 2003;289: 824. [DOI] [PubMed] [Google Scholar]

[pone.0310697.ref020] 20.World Health Assembly 69. Framework on integrated, people-centred health services: report by the Secretariat. 2016. [cited 30 Jun 2021]. Available: https://apps.who.int/iris/handle/10665/252698. [Google Scholar]

[pone.0310697.ref021] 21.Smith SM, Wallace E, O’Dowd T, Fortin M. Interventions for improving outcomes in patients with multimorbidity in primary care and community settings. Cochrane Database Syst Rev. 2016;3: CD006560–CD006560. doi: 10.1002/14651858.CD006560.pub3 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref022] 22.Smith SM, Soubhi H, Fortin M, Hudon C, O’dowd T. Managing patients with multimorbidity: systematic review of interventions in primary care and community settings. BMJ. 2012;345: e5205. doi: 10.1136/bmj.e5205 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref023] 23.Wagner EH. Chronic disease management: what will it take to improve care for chronic illness? Eff Clin Pract. 1998; 2–4. [PubMed] [Google Scholar]

[pone.0310697.ref024] 24.Bodenheimer T, Wagner EH, Grumbach K. Improving Primary Care for Patients With Chronic Illness: The Chronic Care Model, Part 2. JAMA J Am Med Assoc. 2002;288: 1909–1914. doi: 10.1001/jama.288.15.1909 [DOI] [PubMed] [Google Scholar]

[pone.0310697.ref025] 25.Leijten FRM, Struckmann V, van Ginneken E, Czypionka T, Kraus M, Reiss M, et al. The SELFIE framework for integrated care for multi-morbidity: Development and description. Health Policy. 2018;122: 12–22. doi: 10.1016/j.healthpol.2017.06.002 [DOI] [PubMed] [Google Scholar]

[pone.0310697.ref026] 26.Frølich A, Ghith N, Schiøtz M, Jacobsen R, Stockmarr A. Multimorbidity, healthcare utilization and socioeconomic status: A register-based study in Denmark. Kwon YD, editor. PLOS ONE. 2019;14: e0214183. doi: 10.1371/journal.pone.0214183 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref027] 27.Schiøtz ML, Høst D, Christensen MB, Domínguez H, Hamid Y, Almind M, et al. Quality of care for people with multimorbidity–a case series. BMC Health Serv Res. 2017;17. doi: 10.1186/s12913-017-2724-z [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref028] 28.Rozing M P Jønsson A, Koster-Rasmussen R, Due T D, Brodersen J, Bissenbakker K H. The SOFIA pilot trial—a cluster-randomized trial of coordinated, co-produced care to reduce mortality and improve quality of life in people with severe mental illness in the general practice setting. Pilot Feasibility Stud. 2021; 1–158. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref029] 29.Webmaster. Overblikskonsultation. Københavns Universitet; 16 Apr 2018. [cited 9 Mar 2023]. Available: https://overblikskonsultation.ku.dk/. [Google Scholar]

[pone.0310697.ref030] 30.Skivington K, Matthews L, Simpson SA, Craig P, Baird J, Blazeby JM, et al. A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. BMJ Online. 2021;374: n2061–n2061. doi: 10.1136/bmj.n2061 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref031] 31.Craig P, Dieppe P, Macintyre S, Michie S, Nazareth I, Petticrew M. Developing and evaluating complex interventions: the new Medical Research Council guidance. BMJ. 2008;337: a1655–983. doi: 10.1136/bmj.a1655 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref032] 32.OK22 | læger.dk. [cited 10 Mar 2022]. Available: https://www.laeger.dk/PLO/OK22.

[pone.0310697.ref033] 33.Glasgow E, Wagner H, Schaefer D, Mahoney J, Reid M, Greene M. Development and Validation of the Patient Assessment of Chronic Illness Care (PACIC). Med Care. 2005;43: 436–444. doi: 10.1097/01.mlr.0000160375.47920.8c [DOI] [PubMed] [Google Scholar]

[pone.0310697.ref034] 34.Maindal HT, Sokolowski I, Vedsted P. Adaptation, data quality and confirmatory factor analysis of the Danish version of the PACIC questionnaire. Eur J Public Health. 2012;22: 31–36. doi: 10.1093/eurpub/ckq188 [DOI] [PubMed] [Google Scholar]

[pone.0310697.ref035] 35.Salisbury C, Man M-S, Bower P, Guthrie B, Chaplin K, Gaunt DM, et al. Management of multimorbidity using a patient-centred care model: a pragmatic cluster-randomised trial of the 3D approach. The Lancet. 2018;392: 41–50. doi: 10.1016/S0140-6736(18)31308-4 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref036] 36.Szecsenyi J, Rosemann T, Joos S, Peters-Klimm F, Miksch A. German diabetes disease management programs are appropriate for restructuring care according to the chronic care model: an evaluation with the patient assessment of chronic illness care instrument. Diabetes Care. 2008;31: 1150–1154. doi: 10.2337/dc07-2104 [DOI] [PubMed] [Google Scholar]

[pone.0310697.ref037] 37.Bell ML, Kenward MG, Fairclough DL, Horton NJ. Differential dropout and bias in randomised controlled trials: when it matters and when it may not. BMJ Online. 2013;346: e8668–e8668. doi: 10.1136/bmj.e8668 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref038] 38.Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42: 377–381. doi: 10.1016/j.jbi.2008.08.010 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref039] 39.overbliksstatus-og-rsstatus.pdf. [cited 30 Jun 2021]. Available: https://vejledninger.dsam.dk/media/files/21/overbliksstatus-og-rsstatus.pdf.

[pone.0310697.ref040] 40.Freund KS, Guassora AD, Hegelund T, Hvas L, Lous J. Resources in vulnerable young adults: self-assessments during preventive consultation with their general practitioner in Denmark. Health Promot Int. 2020;35: 1180–1189. doi: 10.1093/heapro/daz114 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref041] 41.Williams J. The Declaration of Helsinki and public health. Bull World Health Organ. 2008;86: 650–651. doi: 10.2471/blt.08.050955 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref042] 42.Herdman M, Gudex C, Lloyd A, Janssen B, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20: 1727–1736. doi: 10.1007/s11136-011-9903-x [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref043] 43.Duncan P, Murphy M, Mei-See M, Chaplin K, Gaunt D, Salisbury C. Development and validation of the Multimorbidity Treatment Burden Questionnaire (MTBQ). BMJ Open. 2018;8: e019413. doi: 10.1136/bmjopen-2017-019413 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref044] 44.Bang H, Zhao H. Median-Based Incremental Cost-Effectiveness Ratio (ICER). J Stat Theory Pract. 2012;6: 428–442. doi: 10.1080/15598608.2012.695571 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref045] 45.DRG-takster 2019—Sundhedsdatastyrelsen. [cited 27 Feb 2020]. Available: https://sundhedsdatastyrelsen.dk/da/afregning-og-finansiering/takster-drg/takster-2019.

[pone.0310697.ref046] 46.Schünemann HJ, Guyatt GH. Commentary—Goodbye M(C)ID! Hello MID, Where Do You Come From? Health Serv Res. 2005;40: 593–597. doi: 10.1111/j.1475-6773.2005.00374.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref047] 47.Drummond MF. Methods for the economic evaluation of health care programmes. 2. ed., reprint. Oxford: University Press; 1997. [Google Scholar]

[pone.0310697.ref048] 48.Fenwick E O’Brien BJ, Briggs A. Cost-effectiveness acceptability curves–facts, fallacies and frequently asked questions. Health Econ. 2004;13: 405–415. doi: 10.1002/hec.903 [DOI] [PubMed] [Google Scholar]

[pone.0310697.ref049] 49.Lochmiller C. Conducting Thematic Analysis with Qualitative Data. Qual Rep. 2021;26: 2029–2044. doi: 10.46743/2160-3715/2021.5008 [DOI] [Google Scholar]

[pone.0310697.ref050] 50.Prior A, Vestergaard CH, Ribe AR, Sandbæk A, Bro F, Vedsted P, et al. Chronic care services and variation between Danish general practices: a nationwide cohort study. Br J Gen Pract. 2021; BJGP.2021.0419-. doi: 10.3399/BJGP.2021.0419 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref051] 51.Pedersen AF, Nørøxe KB, Vedsted P. Influence of patient multimorbidity on GP burnout: a survey and register-based study in Danish general practice. Br J Gen Pract. 2020;70: e95–e101. doi: 10.3399/bjgp20X707837 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref052] 52.Almirall J, Fortin M. The coexistence of terms to describe the presence of multiple concurrent diseases. J Comorbidity. 2013;3: 4–9. doi: 10.15256/joc.2013.3.22 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0310697.ref053] 53.Islam MM, Valderas JM, Yen L, Dawda P, Jowsey T, McRae IS. Multimorbidity and Comorbidity of Chronic Diseases among the Senior Australians: Prevalence and Patterns. Laks J, editor. PLoS ONE. 2014;9: e83783. doi: 10.1371/journal.pone.0083783 [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

A patient-centred care model for patients with complicated multimorbidity: Protocol for a pilot cluster randomised trial in general practice, municipalities, and hospitals

Sanne Lykke Lundstrøm

Nina Kamstrup-Larsen

Barbara Ann Barrett

Louise Marie Bidstrup Jørgensen

Solvej Skriver Hansen

John Sahl Andersen

Bolette Friderichsen

Anders Stockmarr

Anne Frølich

Roles

Abstract

Introduction

Methods

Trial registration

Introduction

Objective

Methods

Study design

Fig 1. Time schedule of enrolment, interventions, and assessments on participant outcome inspired by the SPIRIT 2013 reporting guidelines.

Study setting

Sample size

Randomization and blinding

Eligibility criteria

Control general practices

Intervention general practices

Fig 2. An overview of the patient-centred care model for patients with complicated multimorbidity (CIM2).

Ethics

Outcomes

Qualitative evaluation

Monitoring

Data management

Analyses

Discussion

Limitations

Source of potential bias

Dissemination

Conclusion

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Kathleen Finlayson

Roles

Author response to Decision Letter 0

Decision Letter 1

Kathleen Finlayson

Roles

Author response to Decision Letter 1

Decision Letter 2

Kathleen Finlayson

Roles

Acceptance letter

Kathleen Finlayson

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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