Care management intervention to strengthen self-care of multimorbid patients with type 2 diabetes in a German primary care network: A randomized controlled trial

Purpose This study aimed to assess the effectiveness of a care management intervention in improving self-management behavior in multimorbid patients with type 2 diabetes; care was delivered by medical assistants in the context of a primary care network (PCN) in Germany. Methods This study is an 18-month, multi-center, two-armed, open-label, patient-randomized parallel-group superiority trial (ISRCTN 83908315). The intervention group received the care management intervention in addition to the usual care. The control group received usual care only. The primary outcome was the change in self-care behavior at month 9 compared to baseline. The self-care behavior was measured with the German version of the Summary of Diabetes Self-Care Activities Measure (SDSCA-G). A multilevel regression analysis was applied. Results We assigned 495 patients to intervention (n = 252) and control (n = 243). At baseline, the mean age was 68 ±11 years, 47.8% of the patients were female and the mean HbA1c was 7.1±1.2%. The primary analysis showed no statistically significant effect, but a positive trend was observed (p = 0.206; 95%-CI = -0.084; 0.384). The descriptive analysis revealed a significantly increased sum score of the SDSCA-G in the intervention group over time (P = 0.012) but not in the control group (p = 0.1973). Conclusion The sum score for self-care behavior markedly improved in the intervention group over time. However, the results of our primary analysis showed no statistically significant effect. Possible reasons are the high baseline performance in our sample and the low intervention fidelity. The implementation of this care management intervention in PCNs has the potential to improve self-care behavior of multimorbid patients with type 2 diabetes.


Introduction
The increasing prevalence of multiple, co-occurring chronic conditions places a burden for contemporary health systems (1, 2). Multi-morbidity is associated with worse health outcomes, more complex clinical management, and increased health care costs (3). Several suggestions are available to take up the challenge by re-organizing the delivery of chronic illness care (4,5). Based on these concepts, care management interventions have been developed and evaluated focusing on patients with multiple chronic conditions (6). Care management refers to 'a set of activities designed to assist patients and their support systems in managing medical conditions and related psychosocial problems more effectively, with the aim of improving patients' health status and reducing the need for medical services' (7). These interventions share four core elements (8) In the context of type II diabetes, the concept of "self-care" (a synonym for self-management) plays an increasingly important role in preventing complications and coping with consequences of the condition (9). Relevant interrelated self-care dimensions for patients with type II diabetes include adaptations to diet, exercise, self-monitoring of blood glucose (SMBG), foot care, medication adherence and smoking (10). Diabetes typically occurs with or has other chronic diseases as consequences. Discordant comorbidities, such as depression (11), constitute an additional challenge for patients with diabetes to effectively conduct self-care activities.
Evidence suggests that, at least in the short run, self-care behaviors can be modified through selfmanagement interventions (12). However, it is important that interventions aimed at supporting patients to cope with diabetes and potentially co-occurring conditions are person-centered (not disease-centered), comprehensive, embedded in the process of primary care within the health care system and take into account and mobilize community resources (13), especially in the context of socially disadvantaged populations (14). Isolated interventions, that use didactic teaching alone (14) or rely on technological, computer-based approaches alone (15) have been shown to be less (14) or not effective to improve cognitive, behavioral or emotional outcomes (15).
Although structured disease management programs (DMP) are embedded in routine primary care for patients with type II diabetes in Germany (16), their 'disease-centered' design does not sufficiently take into account the challenge of comorbidity. For care management programs, however, positive effects on quality of care and patients' quality of life has been reported (7). But still, the effect of care management interventions on healthcare utilization and costs remains heterogeneous (7). This finding is reinforced by a recent systematic review of complex interventions designed to improve outcomes in patients with multi-morbidity (including comorbidity) in primary care and community settings (17). The Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29. 10.2013 2 review concludes that there is limited evidence on the care of patients with multi-morbidity, despite the prevalence of multi-morbidity and its impact on patients and healthcare systems. Included studies provided mixed results; partially due to the heterogeneity of included study populations as far as their chronic conditions are concerned. Research gaps were identified with respect to a paucity of economic analyses, the neglect of the impact of socioeconomic deprivation on multi-morbidity, and a small number of interventions with a clear definition of the 'multi-morbid' study population (17).
There are also specific research gaps related to care management among diabetes patients. Most interventions designed to improve the management of this population in primary care, outpatient or community settings have used biomedical surrogate parameters as primary outcome, and few have assessed the effects on patient reported outcomes (PROs) (13), such as self-care behavior, selfefficacy, attitudes, health service utilization, quality of life and/or psychological indicators (18). There are also few trials that report 'patient-important' outcomes related to death, morbidity (including hypoglycemic events) and quality of life. In a systematic review of 1057 ongoing and registered trials (in 2007), only 18% of trials reported such 'patient-important' outcomes (19).
The following features of interventions have been reported as promising to improve diabetes relevant outcomes (HbA1c, weight/BMI, lipids, blood pressure, health care utilization, physical activity), particularly among socially disadvantaged populations with diabetes (14): cultural tailoring, individualized assessment and reassessment, use of treatment algorithms by health care providers, focus on behavior-related tasks, use of feedback about patients' control of disease or performance, and high intensity interventions (> 10 contact times) delivered over a long duration (≥ 6 months).
Care management interventions in the German healthcare system have been evaluated with promising results for patients with osteoarthritis (20), depression (21), systolic heart failure (22), and index diseases such as diabetes mellitus, chronic obstructive lung disease, and chronic heart failure (6).
However, further studies are necessary to explore the full potential of care management interventions to improve outpatient diabetes care in the context of multi-morbidity in Germany. Care management is particularly challenging to deliver for small primary care practices (PCPs). Practice-net based approaches might be a solution in this context, because they allow providing intensified care for patients from several practices, thus reducing the workload for smaller PCPs. These approaches in turn entail challenges regarding the flow of information between care managers, PCPs and other sectors in the delivery of relevant health care services according to individual need.
Based on an existing pilot project, we have developed a complex primary care practice-net (PCPnet) based, health-care-assistant (HCA) led, IT-supported care management intervention with integrated telephone-monitoring to improve diabetes care for patients with type II diabetes mellitus and multiple comorbidities. This study protocol documents the evaluation methods to be deployed during the 'evaluation stage' (23) of the complex intervention.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 3

Study objectives
The primary objective of this study is to assess the efficacy of a PCPnet-based, HCA-led, IT-supported   care management intervention with integrated telephone-monitoring for the improvement of self-care   behavior among patients with type II diabetes mellitus and two or more comorbidities (see Chapter 8 and Figure 1 for a detailed description of the intervention).

Primary objective:
To determine, if there is a difference in the degree of change in diabetes related self-care behavior after 9 months (T1) of intensified care management (as add-on to usual care) compared to baseline (T0) between the intervention group (PTC) and the control group (TAU), which receives usual care only.

Secondary objectives
To assess: 1. if potential differences between both groups (PTC vs. TAU) in change of diabetes related selfcare behavior compared to baseline (T0) can be sustained over an 18 months period (T2) with reduced intensity of care management and enhanced by self-monitoring of bloodglucose (whereas 'reduced intensity' refers to longer time-lags between telephonemonitoring contacts (Figure 1)). 7. if the care management intervention is equitable in the distribution of potential health gains (self-care behavior, HbA1c% and HRQL) at T1. 8. differences between the intervention-and the control-group related to service utilization, direct and indirect costs of health care provision as well as the financial burden of informal care provided by patients' relatives at the end of observation time. 9. the cost-effectiveness of the primary endpoint (change in self-care behavior) and the secondary endpoint (HRQL) at end of observation time (if the intervention is efficacious).

Primary outcome
The intervention primarily aims at improving "self-care" as a multi-dimensional construct consisting of the five dimensions diet, exercise, self-monitoring of blood glucose (SMBG), foot care, and smoking behavior. This primary outcome is a patient reported outcome (PRO) and will be operationalized by the German version of the revised "Summary of diabetes self-care activities measure" (10) (SDSCA). The English version of the revised SDSCA is a widely used, appropriate (24) valid and reliable tool with moderate test-retest-reliability (10) for capturing self-care behavior.
The German version (SDSCA-G) is based on a structured forward/backward translation of the original English instrument. The SDSCA-G will be deployed as part of paper-based questionnaire (see Appendix: Patientenfragebogen zur Erfassung der Selbstsorge) and consists of 11 items.
Scoring of items 1-10 (excluding smoking) uses days per week on a scale of 0-7 in which patients performed respective self-care tasks (24). For each group of items (e.g. diet) a mean number of days are calculated. The SDSCA scale is used as a continuous measure to determine if there are improvements compared to baseline at subsequent time points. As a result of strong ceiling effects, the 'medication' item is not included in the most recent recommended version [16].
No cut-off point has been determined to discriminate between adherence and non-adherence (24) and no minimal clinically relevant change in SDSCA 'scores' has yet been formulated (25). This means that, in order to determine a minimal clinically relevant change for this study, the research team needs to draw upon (i) published data on the degree of change in SDSCA values reported in interventions designed to improve self-management, and (ii) estimates about 'realistic' changes that the intervention can bring about.
The primary outcome used to assess the efficacy of the intervention is the difference in mean change in SDSCA-G 'score' of items 1-10 (excluding smoking) per patient compared to baseline (T0) after 9 months of intervention (T1) between both groups (PTC vs. TAU) determined on the basis of patients' self-reports.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 5

Secondary outcomes
In light of the secondary objectives, the secondary outcomes of this study refer to: 1. The mean change in SDSCA-G 'score' of items 1-10 (excluding smoking) for each group (PTC vs. TAU) compared to baseline (T0) after 18 months of intervention (T2), to assess sustainability of effects with reduced intensity of care management and enhanced by self-monitoring of bloodglucose 2. The mean change in each of the five dimension of self-care captured by the SDSCA-G instrument compared to baseline (T0) for each group (PTC vs. TAU) at T1/T2 of intervention to assess the influence of the intervention on specific self-care behaviors 3. The mean change in physician-reported glycosylated hemoglobin A1 (HbA1c %) at T1/T2 compared to baseline among the subgroup of patients with a baseline value of HbA1c > 7.5 %.
A 10 % improvement from the baseline value (25) after 9 months/18 months will be regarded as clinically relevant change.
4. The cumulative incidence of physician-reported (severe) symptomatic hypoglycemia at T1/T2 among those patients at risk of this event during the respective observation period.
'Symptomatic hypoglycemia' refers to hypoglycemia with blood glucose < 60 mg/dl, and 'severe symptomatic hypoglycemia' as those events of hypoglycemia, which necessitated external support. Patients are regarded 'at risk' of (severe) symptomatic hypoglycemia for the subsequent time period if they receive oral anti-diabetic medication and/or insulin therapy at T0 or T1.
5. The mean change in patient-reported HRQL, captured by the EuroQol instrument EQ-5D, at T1/T2 compared to baseline. EQ-5D is a 5-item, simple preference-based index measure which has frequently been applied in the measurement of HRQL in type 2 diabetes (including the United Kingdom Prospective Diabetes Study). The overall EQ-Index score (on a scale of 0 to 1) can be incorporated into Quality Adjusted Life-Years (QALY) for cost-utility analysis. A difference of 0.03 on overall EQ-Index score after 9 months/18 months will be considered to be clinically relevant (25).
6. The mean change in patient-reported self-efficacy, captured using the SES6-G instrument, a short and validated instrument with 6-items (26).
7. The equity-efficacy ratio calculated as the ratio between the change (compared to T0 at T1) in SDSCA-G 'score' of items 1-10 (excluding smoking), HbA1c% and EQ-Index among the lowest vs.
highest socioeconomic group (including education, occupation, income and subjective social status) in both arms of the trial (PTC vs. TAU). This includes subgroup analyses for migrant populations.
8. Further secondary outcomes will be captured by the Client Socio-demographic and Service Receipt Inventory (CSSRI) (27,28) and the financial family burden questionnaire. Both instruments have been adapted to the special needs of patients with type II diabetes and were Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 6 pretested before general application. CSSRI provides data on service utilization and refers to costs of health care provision and financial burden of informal care. Direct and indirect costs will be measured and analyzed from a societal perspective.
For an overview of all instruments used in this study to capture primary and secondary outcomes see Table 1. Physician reported secondary outcomes (HbA1c, events of hypoglycemia) are reported via a chart-review (for details see Chapter 10: Data collection).

General Aspects
The study is designed as a prospective, multicenter, two-armed, open-label, individual-level randomized controlled superiority trial (RCT). Since the main elements of the intervention are delivered by an NCM (for details see Chapter 8: Intervention/Study Implementation), it is feasible to have both intervention and control group based in each study center (i.e. in each PCP).
Eligible participants will be randomly selected from the overall patient population of 30 study centers (PCPs) and asked for their consent to take part in the study. Participating patients will be reported pseudonymized to the study central office (Dept. for General Practice and Health Services Research, AMV) and centrally randomized on an individual level by a clinical monitor, who acts as sole randomization authority. This person -not involved in care of the trial patients or analysis of data -will be responsible for allocation to control (treatment as usual, TAU) vs. intervention group (pathway to change, PTC) according to a pre-defined randomization schedule (for details see Chapter 7: Randomization). As illustrated in Figure 1, the intervention is additional to usual care. Blinding of either patients or practice teams is not possible due to the character of the intervention. The baseline (T0) assessment of primary and secondary outcomes will be conducted prior to allocation of patients, and after allocation at 9 months (primary endpoint: T1), and 18 months (follow-up: T2) ( Figure 1).
Both intervention and control group receive usual care. Usual care consists of diabetes care in the scope of the DMP Diabetes. Care for high-prevalence chronic comorbidities such as chronic obstructive lung disease (COLD), heart failure (HF) and coronary heart disease (CHD) are also organized in the scope of DMPs on a voluntary basis in the statutory health insurance system (16). Care for other diseases (chronic or acute) is managed by PCP physicians individually based on personal experience, guidelines and/or patients' preferences.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 7 Patients allocated to the PTC-group will be subject to the 18-month care management intervention as add-on to usual care. This complex care management intervention consists of three main elements ( Figure 1): (i) assessments by a net-case manager (NCM) including home visits, (ii) regular telephone-monitoring contacts and (iii) digital structured blood glucose monitoring (introduced after T1).
Within the first week after entry to the study, the NCM visits patients in the PTC group at home to conduct a standardized assessment of medical and non-medical problems (see Appendix: In the second week, the patient visits his/her primary care physician in order to agree upon goals related to the identified problems. The goals will be documented and serve as the basis for the telephone-monitoring. A total of 24 telephone-monitoring sessions will occur according to the schedule presented in Figure 1 (every two weeks for a period of 6 months, once a month throughout the rest of the intervention period for patients in the PCT-group). The objective of the telephone-monitoring is to detect acute clinical needs and to provide support related to self-care goals and health care related issues. Follow-up home visits (FUPHV) will occur 6 months (FUPHV-1) and 12 months (FUPHV-2) after entry to the study for patients in the PTC-group (see Appendix: Studienhilfsmittel Formular "Folgekontakt Assessment"). Additionally, after 11 months, digital structured blood sugar testing is used for symptom-monitoring in a 3-months-interval (3 in total). The blood sugar profiles serve as the basis for the coaching of patients by the NCMs in the scope of the telephone-monitoring. NCMs support patients in the PTC-group to locate and access additional services within the health system or the broader community according to patients' individual preferences and needs.
A preceding, unpublished scoping review (29) conducted by the investigators identified relevant determinants of diabetes self-care to be considered as potential confounders in the context of this RCT.
These include general demographical aspects (sex, age, marital status/domestic partnerships), the individual social status (education, income, occupation), cultural factors potentially related to the migration status, type of comorbidity (e.g. discordant ones such as depression (11,30) and/or arthrosis), type of diabetes therapy (insulin vs. oral medication), perceived quality of health care, alcohol abuse and emotional distress. The potential confounders will be captured at T0-T2 as PROs. We further account for the type of medical therapy (insulin vs. oral medication/no medication) during the randomization process through stratified randomization (see Chapter 7: Randomization). For a full list of instruments and variables used in this study see Table 1 and Table 2.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 8 Study findings will be reported according to the CONSORT 2010 checklist with extensions for PROs in RCTs (31).  Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 9

(Therapeutic) Effects
The above-mentioned elements ( Figure 1) are hypothesized to be the 'active ingredients' (23) of the complex intervention. They are hypothesized to exert their effect in the following way: NCM-led needs assessment including home visits: Individualized assessment (including repeated reassessment) of medical and non-medical needs by non-physician health workers has been reported as important element in attempts to improve diabetes related outcomes such as HbA1c, weight/BMI, lipids, blood pressure, health care utilization, physical activity (14). Further elements leading to improved outcomes are the use of decision algorithms by health care providers and a focus on behavior-related tasks (14), both of which are incorporated in the IT-supported assessment tool deployed in this intervention. The focus on both medical and nonmedical needs ensures that the intervention is person-centered (not disease centered) and thus coherent with the evidence on how to improve diabetes care (13). The assessment of patients' needs in their own environment is a reach-out element which ensures that needs are assessed comprehensively, taking into account the social environment of the patients. The assessment is embedded in the process of primary care within the health care system and mobilizes community resources in order to meet patients' identified medical and non-medical needs. This approach aims to reduce barriers for patients in using support systems and medical/non-medical services based in their local communities, in order to improve management of the disease. There is evidence that the combination of these features is effective in improving diabetes care (13).
However, due to the paucity of research into the effects of care management interventions on PROs in general, the positive effects on the primary and secondary outcomes used in this study can only be hypothesized.
NCM-led structured telephone monitoring: The NCMs will deliver to each patient in the PTC-group a minimum of 24 structured, telephone monitoring contacts throughout the 18-month period ( Figure 1). Evidence suggests that such high intensity interventions (>10 contact times) delivered over a long duration (≥6 months) are necessary in order to improve and sustain any change in self-care behavior, especially in "hard to reach" populations (14). Application of this element in care management interventions has been shown to be effective in early diagnosis and treatment of acute complications and problems, thereby reducing avoidable hospitalizations among chronically ill patients in the German health care context (6). The monitoring is also used as feedback instrument related to patients' control of disease or performance, which is also important to reinforce positive behavior change.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 10 Digital structured self-monitoring of blood glucose: Digital structured self-monitoring of blood glucose (SMBG) will be deployed for the PTC-group after T1 in a 3-month interval using Roche Diagnostics' Accu Chek® Smart Pix Device and ACCU-Chek® 360˚.
The results are used to monitor trends in glycemic control and progress towards improved self-care behavior, and will be used as feedback tool towards patients in terms of bio-feedback.
SMBG is an essential self-care element among patients with insulin treated type 2 diabetes. However, for non-insulin treated diabetic patients a synthesis of the existing evidence published by the German Institute for Quality and Efficiency in Health Care (IQWIG) concludes that there is no evidence that SMBG improves diabetes related outcomes (40). However, as noted by the IQWIG report, these conclusions need to be interpreted in light of scarce data, especially in terms of potential effects on the incidence of severe hypoglycemia in non-insulin treated patient populations (40). A recent systematic review by the Cochrane Collaboration including 12 RCTs (duration range: 6-12 months) concluded that "[..] when diabetes duration is over one year, the overall effect of self-monitoring of blood glucose on glycemic control in patients with type 2 diabetes who are not using insulin is small up to six months after initiation and subsides after 12 months. Furthermore, based on a best-evidence synthesis, there is no evidence that SMBG affects patient satisfaction, general wellbeing or general health-related quality of life. More research is needed to explore the psychological impact of SMBG and its impact on diabetes specific quality of life and well-being, as well as the impact of SMBG on hypoglycemia and diabetic complications." (41) The use of self-monitoring for non-insulin treated people has been controversial because estimates of benefit in reducing levels of HbA1c vary between systematic reviews (42). Meta-analysis using individual patient data did also not provide convincing evidence to support the routine use of selfmonitoring of blood glucose in people with non-insulin treated type 2 diabetes (42). Thus, better evidence that self-monitoring can provide feedback on treatment and behavior are needed (42).
The 'scarce-data-argument' and the potential effects on the incidence of severe hypoglycemia are the main rationale for including this element in the intervention for non-insulin treated patients with type 2 diabetes after T1 in order to add to the existing evidence base in the scope of a secondary, descriptive analysis. In the course of the study, both groups (PTC vs. TAU) undergo clinical assessments at T0-T2 and fill out questionnaires related to their self-care behavior. The clinical assessments mainly contain chartreviews by PCP physicians, routine measurement of weight, blood pressure and history taking

Risks and (unintended) effects
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 11 regarding new diagnoses and/or medications. Unintended effects mainly refer to time issues and potentially cost issues linked to these additional doctor visits. However, given that the intervention takes place over a period of 18 months, the additional visits appear to be justifiable in terms of both time and costs. Filling out the questionnaires related to patients' self-care behavior can trigger positive as well as negative consequences: On the one hand, it is possible that patients become increasingly aware of their daily behavior in the context of their diabetes, and use this awareness as a resource to adapt the behavior accordingly. On the other hand, it is also possible that patients' awareness about individual weaknesses related to self-care issues results in desperation and blaming of ones 'self'. This is an inherent danger in the concept of 'self-care' which gains particular relevance in light of the combination of patients' self-reports on self-care behavior with the financial family burden (FFB) questionnaire. Since the FFB attempts to capture the burden of costs of informal care provided by a designated family member of the patient, feelings of guilt and blaming of ones 'self' about the consequences of the disease could be perpetuated.
To hamper the outlined potential unintended effects, all PCP physicians will be informed about the possibility of these potential effects (in the information leaflet for physicians). In order to qualify as study center, PCP physicians must give their written consent to offer extra-consultations to all participating patients in case they want to discuss or report any unintended effects. Furthermore, participating patients are encouraged to contact the principal investigator at any time throughout the course of the study to discuss potential risks and find solutions to potential problems.

Risks and (unintended) effects of participation in the study for patients in the intervention group (PTC)
In addition to the above, patients in the intervention group are exposed to a complex intervention effects of SMBG among patients with type II diabetes who do not use insulin (40). In light of scarce data, a report of the Institute for Quality and Efficiency in Health Care (IQWIG) concludes that -for this group of patients -no clinically relevant side effects have been reported as far as HRQL is concerned, and no statistically significant difference as far as patient satisfaction or 'other unintended effects' are concerned (40). However, qualitative studies often report unease, uncomfort or pain related to SMBG.
NCMs will be trained to enquire about these side effects and discuss appropriate strategies with the PCP physician, should a patient feel considerably impaired by this element of the intervention. In this context, the patient decides whether or not he/she feels 'considerably impaired'. To hamper the outlined potential unintended effects, all PCP physicians will be informed about the possibility of these potential effects (in the information leaflet for physicians). Additionally, all patients will be informed about the contents of the FFB questionnaire, so that they can decide whether or not they hand on the questionnaire to their 'caring' family member. In order to qualify as study center, PCP physicians must give their written consent to offer extra-consultations to all participating patients in case they want to discuss or report any unintended effects in this context. Unintended effects will be captured by the physician by means of a pre-determined reporting form if reported by a patient (see Appendix: Studienhilfsmittel "Meldebogen Unerwünschte Ereignisse"). Furthermore, participating patients are encouraged to contact the principal investigator at any time throughout the course of the study to discuss potential risks and find solutions to potential problems linked to the FFB questionnaire.

Study design
The study is designed as a prospective

Inclusion criteria for patients
To be eligible for participation in the study, patients have to be: Additionally, written informed consent is a prerequisite for participation in the study.

Inclusion criteria for a patient's caregiving family member
One of the secondary research objectives is to assess costs of informal care in both groups (PTC vs TAU). This will be collected by the FFB questionnaire (see Appendix: Angehörigenfragebogen), which addresses the family member who 'cares most' for the respective patient with type II diabetes. A caregiving family member is defined as  The family member who (from the patients' perspective) spends the largest amount of time with informal care (e.g. spouse, partner, father, mother, son, daughter, others)  and lives in the same household.
It is important to note that it is up to the individual patient to identify, from their social relationships, the family member 'who cares most'. As such, this construct explicitly considers patients' views and does not apply to an external definition. Only one family member per patient will be recruited. It is important to note that the patient decides whether or not to pass on the questionnaire along with the informed consent and information material to his/her selected informal caregiver.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 14 6. Exclusion criteria 6.1 Exclusion criteria for primary care practices (PCPs) and patients' caregiving family members PCPs and patients' caregiving family members who do not fulfill the inclusion criteria will be excluded.

Exclusion criteria for patients
Patients who do not fulfill the inclusion criteria will be excluded. Additional exclusion criteria are patients with: Type of medical treatment has been identified as the strongest predictor of diabetes self-care in the preceding (unpublished) scoping review, and is thus captured by a physician reported questionnaire to serve as validated stratification criteria. We will hence perform stratified block randomization with variable block lengths to ensure study groups of approximately equal size. The block sizes will not be disclosed, to ensure concealment. Instead, this specific information will be provided in a separate document with restricted access only to the randomization authority. The randomization procedure is closely linked to the data collection procedure (see Chapter 10) in so far as that it is performed centrally using the ICW Care Manager as platform.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 15 All eligible patients participating in the study will be registered in the software during a three-month wash-in phase, along with the physician-reported information about eligibility criteria (see Chapters 5 & 6) and type of medical therapy. The ICW Care Manager contains virtual folders for the two groups (PTC vs. TAU) within participating primary care practices.
The randomization authority (a designated person not involved in care of the trial patients and analysis of data) will access the database of registered patients in a weekly interval to monitor the recruitment process. Recruited and registered patients who fulfill the inclusion criteria will be centrally randomized (stratified by type of medical therapy and PCP) to PTC vs. TAU using a computerized random number generator to create randomization lists for each stratum. The allocation will be documented separately in an Excel file with restricted access except for the randomization authority.
Patients' allocation to either intervention or control group will remain concealed until data collection related to primary and secondary outcomes at baseline (T0) has been completed. After baseline data collection has been completed, PCPs will be informed about the allocation of "their" patients (identified through their unique study-ID) with an official letter from the intervention coordinating center (GGM), who in turn receives the information from the study coordinating center (AMV).

Intervention/Study implementation
The intervention is a complex case management intervention (23)  The complex intervention is delivered as add-on to usual care and consists of 3 main elements:

Assessment
At the beginning, patients in the PTC-group receive an IT-based assessment (see Appendix: Studienhilfsmittel Formulare "Erstkontakt Assessment"/"Folgekontakt Assessment") of medical and non-medical needs and resources using a structured protocol by a PCP-net based HCA who functions as net-case manager (NCM).
The NCM is authorized to the ICW Care Manager with a unique password and username. At the beginning, the NCM has only access to pseudonymized data of those recruited patients in the intervention arm, which are based at the PCPs for which she is in charge. The NCM contacts the PCPs in order to de-pseudonymize 'her' patients and to deliver the assessment. The results of the initial assessment will be reported to a dialogue assistant based at the PCP, who in turn reports to the caring PCP in charge of the patient. The assessment results serve as the basis to set common goals between patient and PCP based on individual need.
Assessment results will be digitally stored by the software on a secured server (see Chapter 15) to inform the NCM during follow-up (FUP) home visits and during the telephone-monitoring. FUP home visits will occur 6 months (FUP1) and 12 months (FUP2) after entry to the study for patients in the PTCgroup (Figure 1).
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 17

Symptom and Needs Monitoring
NCMs will deliver a regular telephone-monitoring using a structured monitoring list (see Appendix X).
Content and frequency of the monitoring are fixed, but additional items may be determined by the PCP and the NCM. The NCM will deliver (at least) a total of 24 telephone-monitoring sessions according to a fixed schedule (2-weekly for a period of 6 months, monthly for the rest of the intervention period for patients in the PCT-group (Figure 1). N=1 NCM is a native Turkish-speaker specialized in the provision of diabetes education. This NCM will be responsible to deliver the care management intervention to patients with a Turkish background in case of language barriers or cultural preferences. We thereby aim to address the special needs of this social group, which constitutes about 22% of the population (on December 30, 2012) in the city where the majority of study centers (PCPs) will be based (i.e. Mannheim, Germany). Potential language barriers to data collection will be accounted for by means of a Turkish version of the patient questionnaire.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 18 Prior to the beginning of the intervention, all NCMs will be trained according to a team-based training curriculum. The curriculum was developed based on experiences from the preceding pilot study (GEDIMA) and inputs from representatives of local patient self-help groups. Completion of a 32 hours team-based training course is mandatory for participating HCAs to function as NCM.

Control
In the control group (TAU), practice teams will continue to provide standard care in the context of the PC-centered care contract. This involves gate keeping for enrolled patients as well as regular training in evidence-based guidelines through structured pharmacotherapy feedback in peer review groups [39].
As population-based disease management programs (DMPs) for diabetes and other selected chronic diseases are part of routine care in Germany, patients may voluntarily participate in these disease specific care programs. German DMPs consist of regular follow up visits up to every three months. They include clinical examination, laboratory tests (e.g. HbA1c tests), patient education, and referral to specialists (opthalmologists, cardiologists, nephrologists, neurologists) on a regular basis and according to acute needs (16). However, essential elements of care management interventions like individualized assessment, care planning including non-medical aspects, home visits, and frequent (symptom) monitoring are not routinely part of DMPs (6).
Fidelity to the study protocol and variability between sites and care management teams The intervention seeks to ensure fidelity to the study protocol as far as adherence to the elements of the intervention and the timeline (see Figure 1) are concerned. The IT-supported delivery of the intervention allows assessing fidelity to the main intervention elements for all participants in the intervention group. However, the intervention is explicitly designed to allow adaptations to local contexts, individual needs, preferences and cultural backgrounds as far as the consequences of structured assessment and telephone monitoring are concerned. Adaptations to local contexts and individual preferences (e.g. differential use in community resources and services) will be documented in the ICW Care Manager by the NCM during her routine contacts. 9. Recruitment of study centers, patients and patients' caregiving family members 9.1 Study centers The multicenter RCT will be conducted in 30 PCPs. PCPs who formerly participated in a pilot study (GEDIMA) of the GGM will be invited by an official letter from the study central office to participate in the study and need to give their written consent for participation.

Patients
From the study central office (via the intervention coordination center GGM), the 30 PCPs receive a list with inclusion and exclusion criteria for patients (see above) along with a screening list with random numbers. PCPs are asked to create a list of all potentially eligible patients registered in their practice software based on the inclusion and exclusion criteria.
In a next step, PCPs select 40 patients from the list according to the sequence indicated by the random numbers. Randomly selected patients will be contacted and asked for participation in the study by the PCP physician. Patients not willing to participate will be asked to give a reason for their decision (on a voluntary basis). The number of patients screened, asked, asked and not included as well as the reasons for inclusion, exclusion or non-participation will be documented by the PCP physician and reported to the study central office.
The procedure will be repeated until a total of 20 patients per PCP are recruited.
Patients willing to participate will be informed by the PCP physician about aims, content, privacy issues and risks related to the study. Patients giving their consent to participate in the study will undergo clinical examination and will receive the patient questionnaires (see Appendix) which capture the PROs.

Patients' 'caring' family member
Patients giving their consent to participate in the study will be asked to hand over (on a voluntary basis) an information leaflet, an informed consent form and a questionnaire in a closed-envelope to their family member who 'cares most' for them. The participation of the 'chosen' family member is completely voluntarily, and independent from the participation of the patient who 'chooses' the family member (for details see Chapter 10: Data collection). Data collected from the patients' family member will be pseudonymized in a way that allows linking the informal care burden with the disease severity of respective patients.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" The intervention coordinating center of the "Genossenschaft Gesundheitsprojekt Mannheim e.V." (GGM) will carry joint responsibility for administration, validation and data entry.
Patients will be asked by the recruiting physician to fill in a pseudonymized paper-based questionnaire and hand them back to the recruiting physician in a closed envelope. This questionnaire (see Appendix: Patientenfragebogen) captures the patient reported outcomes (PROs) analyzed in this study.
PCPs will document additional data from patients' chart in a pseudonymized paper-based questionnaire (including inclusion/exclusion criteria, diagnoses, medication, and hospitalization/hypoglycemia prior to recruitment) and assess the clinical status of the patient (e.g. blood pressure, blood glucose, latest HbA1c value). The pseudonymized physician questionnaire will not contain any data that allows identification of patients' identity. The patient questionnaire and physician reported chart-review will be performed at baseline (T0), 9 months (T1), and 18 months (T2) follow-up.
In addition, patients will be asked to hand over the FFB questionnaire (in a closed envelope along with additional background information) to their relative who 'cares most' for them regarding their diabetes, in order to capture the cost of informal care for the health economic evaluation. This questionnaire will be pseudonymized in a way that allows a linkage to the study ID of respective patients.
The collected data is directed to the study central office (AMV) via the following channels: 1. Physician reported chart-review and patient questionnaires will be sent by the PCPs in paper-based 2. The paper-based patient questionnaires containing the chart reviews and PROs will be stored at the GGM office and picked up by an employee of the study central office (AMV) in regular intervals.
3. The FFB questionnaire designed for patients' relatives will be sent directly to the AMV by patients' relatives using enclosed, postpaid envelopes. The written consent forms for patients' relatives will be sent to the GGM.
Patient questionnaires and FFB questionnaires will be scanned and digitally stored on a secured server of the AMV.

Monitoring
The following risk adapted strategy will be deployed to ensure adherence to the study protocol as far as data collection and legal/ethical aspects are concerned. Authorized employees of the study central office (AMV) will conduct practice visits at 10% of PCPs randomly selected from the pool of participating PCPs during the first 3 months of the intervention. The monitoring will include: (i) an inspection of informed consents and patients existence of all patients recruited by the PCP, (ii) a review of patient charts of 10% of patients recruited by these PCP's in order to check conformity among documented items (see Appendix: Arztfragebogen für Ersterhebung) and source data.
A detailed monitoring manual will be developed by the study central office prior to the beginning of the intervention. Depending on the results of these visits, further quality assurance measures will be defined by the study central office (AMV) and the intervention coordinating center (GGM).

Statistics
A detailed description of the statistical methods of this study will be provided in a Statistical Analysis Plan (SAP). Data analysis will be done blinded to treatment arm allocation (i.e. the treatments will be identified as 1 and 2 until analysis is complete). The primary analysis will be based on the 9-month follow-up data (T1).
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 23

Populations for analysis
The Intention-to-treat (ITT) population will consist of all randomized patients. Following the ITT principle, patients will be analyzed in the treatment arms to which they were originally randomized, regardless of whether they refused or discontinued treatment, or whether other protocol deviations are known.
The Per-protocol (PP) population will consist of those ITT patients with no major protocol violations. The criteria for the exclusion of patients from the PP population will be determined by the study team at the latest before database lock.

Statistical hypotheses, methods and analyses
The primary objective of this study is to determine the effectiveness of a complex intervention compared to usual care. The primary efficacy endpoint is the change in SDSCA-G score from baseline (T0) to 9 months after baseline (T1), i.e. the difference SDSCA-G T1-T0. The study objective will be statistically formulated as a test of the null hypothesis H0: μ1 = μ2 (the mean difference SDSCA-G T1-T0 is equal in the two groups) against the alternative hypothesis H1: μ1 ≠ μ2 (the mean differences SDSCA-G T1-T0 are different in the two groups). The null hypothesis will be tested at the two-sided significance level of α=0.05.
The primary efficacy analysis will use a multilevel regression approach with patients at level one and NCMs at level two. The primary model will include treatment group as fixed factor, NCMs as random factor with the baseline value of SDSCA-G and type of medical treatment as covariates. The results will be presented as the mean between-group difference in SDSCA-G T1-T0 with the corresponding 95% confidence interval. The associated Cohen's effect size d will be calculated. To support the primary analysis, all potentially relevant baseline characteristics will be added as covariates to the model in sensitivity analyses. A further sensitivity analysis of the primary endpoint will include an unadjusted two-sample t-test on change in SDSCA-G from baseline to 9 months after baseline. Results from these sensitivity analyses will serve to explain and interpret the results of the primary analysis.
The primary analysis will be performed adhering to the intention-to-treat principle. An additional sensitivity analysis will be conducted on a per-protocol analysis set.
The statistical analyses of the secondary endpoints numbered 1-6 (see pages 4-5) will use the same multilevel approach as the primary analysis. According to the scaling of the considered endpoint, a linear or logistic two-level regression model will be fitted. The results will be presented in an analogous manner to the primary analysis. All statistical tests will be two-sided at the significance level of α=0.05.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 24 The equity-efficacy ratio (45) (and respective 95 % confidence intervals) will be calculated as the ratio of effects at T1 on health outcomes (change in SDSCA score; HbA1c%; HRQL) between the highest and the lowest socioeconomic group (related education/income/subjective social status) for both groups (PTC vs. TAU) compared to T0. Additional consideration of social group sizes will be ensured by calculating the concentration index (PTC vs TAU) and plotting concentration curves at T0 and T1 respectively.
Subgroup analysis for nominal social groups will be performed by means of interaction terms for migration status (Turkish migrants, non-Turkish migrants, participants without migration background) to be included in the regression equations for respective health outcomes (change in SDSCA score; HbA1c%; HRQL) at T. If the tests of subgroup interaction effects are significant below the 0.05 level, further analysis will be performed to check whether their effects are independent (46).
Statistical analyses related to secondary outcomes 8 and 9 (see pages 4-5) focus on the incremental cost effectiveness ratio (ICER) (47,48). The ICER relates cost differential to outcome differential between intervention and control groups. Bootstrap methods model statistical uncertainty and the netbenefit approach is applied (49,50). Maximum willingness to pay thresholds and cost-acceptability curves (51, 52) will be determined. Sensitivity analyses will provide information on robustness of assumptions.
Because no adjustments for multiple endpoints are planned, findings (especially those related to secondary outcomes and subgroup analyses(46)) will be interpreted with caution in view of the number of statistical tests undertaken. Only the result of the primary efficacy analysis will be interpreted in a confirmatory manner. Confirmatory subgroup analyses are not planned. No interim analysis with regard to efficacy will be done.
In case of missing data, multiple imputation will be used to complete the data set for analysis. A complete-case analysis will be performed to assess the influence of missing data and the value of adopting multiple imputation methods.

Process evaluation
Data collected during NCM-led assessments and delivery of the intervention will be exported by from the ICW Care Manager in pseudonymized format to perform a process evaluation. This will include data related to: participation in DMPs, hospitalizations, use of social services, existence of patient advance directives, clinical parameters (blood pressure, body weight, height, blood sugar, use of podiatrists, use of psychotherapy, participation in diabetes education, results of clinical assessments and actions taken. Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 25

Sample size calculation
Sample size was calculated based on the expected difference between the two treatment groups in mean change in the SDSCA-G score from baseline (T0) compared to 9 months after baseline (T1). Based on data from published studies, which used the revised SDSCA as outcome measure (53-55) we estimated a mean change of 0.5 days (standard deviation 2.0) in the overall SDSCA-G "score" (calculated as the sum of days of items 1 -10 divided by 10) per patient in 9 months as minimal clinically relevant change.
Based on these estimates, a total of 506 patients (253 per arm) would be required to detect an effect size (Cohen's d) of 0.25 between-groups (PTC vs. TAU) (50% relative increase in self-care) with a power of 80 % applying a two-sided t-test for two independent samples at a significance level of 5%.
Assuming a drop-out rate of 15% over the period of 9 months, the overall required sample size amounts to a total of 582 participants (291 per arm).

Concomitant therapy
All participants undergo usual care according to individual needs, which means that the intervention is supplementary to and not replacing usual care.

Safety laboratory
Not applicable.

General
Reasons for general termination of the study are: new insights and findings of other studies, which make the conduct of this study dispensable.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 26

Ethics and legal aspects
The study is being conducted in accordance with medical professional codex and the Helsinki Declaration (2008). The study is also in accordance with German Federal Data Security Law (BDSG). All professionals participating in the study oblige to adhere to the abovementioned declarations and laws.
Participation for PCPs, patients and/or their relatives is voluntary. Consents can be withdrawn at any time without any consequences for patients' (usual) care. All patients will be informed about aims, content, duration and process of the trial, particularly as far as risks and unintended consequences are concerned, through written information brochures and through face-to-face communication with their PCP physician.
Data will be collected and analyzed in pseudonymized form for patients, relatives, physicians, and NCMs. Data obtained from DAs will be anonymized.
Pseudonymization will occur as follows: PCPs will be numbered 1-30, the key remains in the intervention coordinating center (GGM). Patients recruited in each PCP will obtain a pseudonym consisting of a combination of the PCP number and a running number (e.g. 3-15 for patient number 15 in PCP number 3). The key remains in the recruiting PCP. Relatives obtain a pseudonym consisting of the letter "R" plus the patient pseudonym (e.g. R-3-15 for the relative of patient number 15 in PCP number 3). No key will be generated for patient's relatives. NCMs will be numbered 1-11. The key remains in the intervention coordinating center (GGM). Access to all keys is restricted for anyone except for the keyholders.
Special emphasis in the information brochure will be paid to the following privacy issue: During the data entry of physician chart-reviews into the ICW Care Manager at T1/T2, the authorized employee of GGM will have access to electronic patient records data, including full names, dates of birth, and assessment results of the preceding time-period since T0 for all patients in the intervention arm. This means that pseudonymization will not be ensured during data entry at T1 and T2.
For the data analysis, however, all data will be exported by the authorized data manager at the study central office (AMV) fully pseudonymized.
This privacy issue will be handled as follows: (i) through the written informed consent, in which we explicitly mention that patients' identity may be disclosed during data entry at T1/T2, and (ii) through a written declaration of confidentiality which must be signed by the authorized employee of GGM in order to qualify for the data entry.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 27 Patients' relatives will be informed about aims, content, duration and process of the trial, particularly as far as risks and unintended consequences are concerned, through written information brochures.
Written informed consent will be obtained from patients' relatives.
Further privacy issues are related to the hardware-and software-infrastructure, that is deployed in this study in the scope of the ICW Care Manager. The software will be deployed on a secured server of the Center for Information-and Medical Technologies (Zentrum für Informations-und Medizintechnologie, ZIM).
The system-architecture for this project draws upon two virtual servers: an application-server and a database-server (including a test-system). A general proxy server precedes these servers to ensure security of data stored on the database-server. Access to the application-server via internet will be necessary for the NCM to conduct the intervention, and physician reported data entered at T0-T2 by the GGM employee will also be transferred via internet. Both external communication (proxy-server with the internet) and internal communication (proxy-server with the application server) will be encrypted (HTTPS).
Access control to the application is guaranteed via person/entity authorization using a username and password combination that is transmitted over a secure channel (TLS). ICW Care Manager implements TLS 1.1 encryption to guard against unauthorized access to protected health information that is being transmitted over an electronic communications network. Passwords are salted with a 128-bit salt and hashed using a cryptographically strong mechanism. Password complexity is enforced by the application according to the password complexity configured by the customer.
Access control in the application is ensure via user administration, which allows definition of roles and permission to restrict functionality (read, write, create, update, delete) on an GUI level and to restrict access to data objects. Patient level security is guaranteed via restriction of visibility of patients and all patient related data to a user or a group of users (e.g. to guarantee that NCMs only have access to digital records of 'their' patients in the intervention am, but not to those of other NCMs or to the control group).
Audit control includes a GUI based audit feature, which allows a user with the relevant permissions (e.g. the authorized clinical monitor) to query an audit log that contains entries of all relevant accesses on the system with specification of accessing user, date, time, type, scope and accessed data object.
Furthermore, through technical, file based logging the application itself logs technical information to disk based log files that may contain relevant information such as system startup, shutdown timestamps and import processes.
The study protocol will be submitted to the ethics committee of the Medical Faculty of the University of Heidelberg prior to the start of the study. Neither patients nor their relatives will be recruited before obtaining the committee's approval.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 28 As mandated by the International Committee of Medical Journal Editors (ICMJE), the trial will be registered in a clinical trial registry after obtaining ethical approval.
Dept. for General Practice and Health Services Research-University Hospital Heidelberg " A multi-center, individual-level randomized, 18-month, parallel-group superiority trial to compare the efficacy of a complex primary care practice network-based care management intervention versus usual care in the improvement of self-care behavior among patients with type II diabetes and multiple comorbidities (GEDIMAplus)" Version 1.0 -29.10.2013 29