INtegration of care for reaching targetS In Diabetic patiEnts: Design of the INSIDE Study

In many health systems, integrated care is seen as a possible solution to the growing demand for improved quality of life and health outcomes of multimorbid and long-term care patients. During the last decade, different models and approaches to integrated care have been widely applied and documented across a variety of settings. However, there is no unifying definition or common conceptual understanding of integrated care. Probably the best definition of “integrated care” is the following:

“Integrated health services delivery is defined as an approach to strengthen people-centred health systems through the promotion of the comprehensive delivery of quality services across the life-course, designed according to the multidimensional needs of the population and the individual and delivered by a coordinated multidisciplinary team of providers working across settings and levels of care. It should be effectively managed to ensure optimal outcomes and the appropriate use of resources based on the best available evidence, with feedback loops to continuously improve performance and to tackle upstream causes of ill health and to promote well-being through intersectoral and multisectoral actions” [1].

In most cases, primary care in the Italian Health National Service has complex structures (PCCS or UCCP = Unità Complesse di Cure Primarie = Complex Primary Care Units): these are groups of GPs (and sometimes family pediatricians) that work together in the same center in an integrated way with nurses, administrative staff, social workers and medical specialists. PCCS/UCCPs are similar to the Community Health Centers in other parts of the world. However, in the actual organization of the Italian NHS, difficulties in communication and collaboration frequently exist between primary and secondary care settings. According to the Italian Ministry of Health and several academic institutions, it seems that:

The best integrated care systems seem to be those that might implement the chronic care models theorized in the JAMA articles by Bodenheimer and Wagner [8, 9]. Recently, the European Society of Cardiology in collaboration with the European Association for the Study of Diabetes published their guidelines for the treatment of people with diabetes, prediabetes and ASCVD (atherosclerotic cardiovascular diseases) and summarized the benefit of a “centred care model” in a box [10] (see Table 1, reproduced from the ESC EASD Guidelines 2019).

Type 2 diabetes is perhaps the chronic disease that best fits the requested needs for clinical research on the efficacy of the chronic care model. Several research groups have tried to compare integrated systems versus “usual care” by testing the results on intermediate outcomes, such as HbA1c or blood pressure values. In the USA, Panattoni and collaborators [11] found a significant reduction in HbA1c at 6 months and a clinically negligible effect on systolic and diastolic blood pressure values. Another interesting experience was made in Boston [12], where a group of elderly people with diabetes was placed in a treatment system that used a pathology register that allowed centralization of all clinical information on a computerized folder and designed a treatment path according to the guidelines. In the groups of patients following this protocol, all the examined parameters (HbA1c, systolic and diastolic pressure, lipids) related to primary outcomes improved significantly. A thorough review, with data coming from different countries, was published on diabetes care about a year ago, and the authors’ conclusions are clearly in favor of the chronic care model [13]. However, the outcomes evaluated in the published papers are usually of an intermediate type, and the focus of most of the studies is parameters of metabolic control (HbA1c) and arterial pressure; sometimes, patient satisfaction has also been evaluated. Moreover, these and other published data are nevertheless limited to numerically reduced groups of patients and cannot be translated to large territorial realities, such as those of a national health service. Moreover, almost all the papers published in this field concern quite heterogeneous populations of people with diabetes, without distinction between high or low risk of macrovascular complications. For these reasons, the present study was designed to evaluate a large nationwide sample of subjects with type 2 diabetes, without known cardiovascular disease but at high risk because of the presence of any additional risk factors.

The aim was to assess whether an integrated care organization involving three different levels of care is able to produce better adherence and achievement of the guideline targets in a population of people with type 2 diabetes without established cardiovascular disease, but at high risk (≥ 20% at 10 years according to the CUORE.ISS risk cards) [14] compared with the current standards of care provided by the Italian National Health Service.

The three Scientific Societies (AMD Associazione Medici Diabetologi—Italian College of Diabetologists, ANMCO Associazione Nazionale Cardiologi Ospedalieri—National Association of Hospital Cardiologists, SIMG Società Italiana di Medicina Generale—Italian College of General Practice) promoting the study produced a list of centers disseminated throughout the country with adequate proportionality between the regions. These centers have to guarantee high levels of clinical practice, have experience in clinical research and have documented collaborative capacity with other specialties. In addition to physicians, each primary care unit is staffed with at least one nurse; each diabetes service includes at least three professionals (nurse, dietician, podologist); each cardiology service includes at least two nurses.

From these lists, 30 centers for each of the three specialties are then further selected, with territorial proximity and previous collaborative experience among them, which represent, in their respective locations, the groups of experimenting centers or proband groups (IC, integrated care). The primary care units will have to be characterized by the association of professionals, with a minimum number of ten. The AMD and ANMCO centers will preferably be those that have already collaboratively carried out other joint studies [15, 16]. The number of centers was chosen in order to perform the study in all the Italian regions. In each center, the recording of all the clinical data of the patients belonging to the institution on electronic sheets must be in place, and such data must be exportable on a specific protected web CRF. The primary care units will have to determine from their computer records beforehand the percentage at which their type 2 diabetic patients, presenting the inclusion criteria for the study, reach the targets set by the guidelines (Italian Standards of Diabetes Mellitus Care AMD SID) [17] based on the data available during the previous year. Using their databases, physicians from the 30 selected SIMG centers will extract 100 patients (for each center) with type 2 diabetes and HbA1c ranging between 6.5 and 8.5%, with at least one other major cardiovascular risk factor (arterial hypertension, defined as BP > 135/80 mmHg or in antihypertensive treatment, LDL > 70 mg/dl or treatment, tobacco smoke, first degree familiarity for CHD, central obesity according to the WHO criteria), but without history, signs or symptoms of previous or ongoing cardiovascular disease, > 45 years old. Of the 30 selected centers, 15, chosen randomly by a computer-generated randomization list, will continue the treatment of the 100 patients identified according to their “usual care,” driven by Good Clinical Practice and current guidelines (control group or “UC”), collecting all available clinical and instrumental data and transferring them to the CRF. The remaining 15 centers, after receiving informed consent, will involve their 100 patients in a specific integrated pathway (see Appendix 1), which entails the mandatory operational integration and exchange of information with the identified diabetes specialists and cardiologists. The integrated care path for the proband group (“IC”) patients is based on the application of the recommendations of the guidelines aimed at achieving the proposed targets for the main risk factors [LDL < 70 mg/dl; SBP < 130 mmHg; HbA1c ≤ 7% (52 mmol/mol)].

This is the first trial aiming to evaluate the efficacy, safety and economic impact of a large system of integrated care for diabetic subjects inside a National Health System. The system is based on a strong relationship among three different health specialists (GPs, cardiologists and diabetologists) and their professional team. If the primary outcome is reached, it will probably be the final evidence that this kind of model is better than the current one.

The performance of this trial presents several risks: for instance, the patient education sessions are intensive for GPs and cardiologists, who already have heavy workloads in daily routine practice. Therefore, the therapeutic education will probably only be done in diabetes centers. In this respect, the work of the nurses, dieticians, podologists and social workers will be crucial. Another problem is the use of several different laboratories for the examination measurements, with no centralization of the samples. However, our choice was determined by the large extension of the participating territories, the need to design a large-scale, pragmatic trial and the very high costs of a centralized system. However, all laboratories have to be certified with a quality system that guarantees the reliability of the results.

The trial will be funded autonomously by the scientific societies, and this fact guarantees the total independence of the researchers.