The underlying study (Trial registration: ISRCTN, ISRCTN58150046) is a prospective observational trial with fourteen PCNs and RGs that reflect standard care in two German federal states (Bavaria and North Rhine-Westphalia). The ARena-study was approved by the ethics committee of the Medical Faculty of the University of Heidelberg (reference number: S-353/2017). The study was planned with an intervention period of 24 months, and with two parts of evaluation: (a) an outcome evaluation based on claims-data and (b) a process evaluation based on surveys.
Fourteen PCNs situated in two German federal states (Bavaria and North Rhine-Westphalia) were recruited to participate in the ARena study. For administrative reasons, the focus was on their patients insured by AOK health insurance and registered within a specific healthcare delivery program (defined by German law § 140a SGB V a.F. and § 140a Abs. 1. S. 2 Alt. 1 SGB V n.F). At baseline, approximately 40 000 patients with AOK health insurance were registered in 196 participating primary care practices in these 14 networks. Medical specialties included were general practice, otolaryngologist, pediatricians, urology and gynecology. The patient population for the three intervention arms comprised patients who sought primary care for one of the following reasons: acute non-complicated infections (upper respiratory tract infections (URTI), bronchitis, sinusitis, tonsillitis and otitis media). Thus, study populations differed per indexed consultation reason regarding number of cases, age of patients and insurance status. The diagnoses were based on physician-recorded ICD codes in administrative data provided for quarterly reimbursement periods. Each physician-recorded ICD code for the defined index diagnoses represents a case, where each patient can produce multiple cases. A patients’ case is recorded for each ICD code within each quarter. Written informed patient consent was prerequisite for participation in the study in North Rhine-Westphalia.
The primary outcome is the proportion of patients who were treated with systemic or local antibiotics of all patients with acute non-complicated infections consulting primary care practices. More precise, patients suffering from acute bronchitis (18–75 years), sinusitis (> 18 years), otitis media (> 2 years), acute URTI (> 1 year), or tonsillitis (> 1 year) are considered in the primary outcome. Specifically excluded are diagnoses for streptococcal tonsilitis and other pathogen-caused acute forms of tonsillitis that warrant antibiotic therapy. (Additional file 1, Supplementary Table 1 details included diagnoses and related ICD codes, Supplementary Table 2 provides a list of the excluded diagnoses.)
The following secondary outcomes were examined:
Proportion of patients with acute non-complicated infections receiving a quinolone prescription when consulting primary care practices (patients suffering from acute bronchitis (18–75 years), sinusitis (> 18 years), otitis media (> 2 years), URTI (> 1 year), or tonsillitis (> 1 year)).
Proportion of patients with acute URTI (> 1 year) receiving a prescription for recommended antibiotics (amoxicillin).
Proportion of patients with acute bronchitis (18–75 years) receiving a prescription for recommended antibiotics (amoxicillin, tetracycline, macrolides).
Proportion of patients with sinusitis (> 18 years) receiving a prescription for recommended antibiotics (amoxicillin, cefuroxime).
Proportion of patients with tonsillitis (> 1 year) receiving a prescription for recommended antibiotics (penicillin, erythromycin).
Proportion of patients with otitis media (> 2 years) receiving a prescription for recommended antibiotics (amoxicillin, erythromycin, cefuroxime).
Consumption of broad-spectrum antibiotics in DDD% (on practice level)
(penicillin and beta-lactamase inhibitors, cephalosporines of 2nd, 3rd and 4th generation, macrolides (excluding Erythromycin) and gyrase inhibitors (fluoroquinolones).
Categorization of recommended antibiotics is based on existing evidence-based clinical guidelines developed by the German College of General Practitioners and Family Physicians (DEGAM)  and the Association of the Scientific Medical Societies in Germany (AWMF) . (See Additional file 1, Supplementary Table 3 for currently recommended and alternative antibiotics.)
Regarding patients, the following sociodemographic, disease, and treatment characteristics in the claims data provided by AOK were included: age, sex, Charlson comorbidity index (CCI) (predicts 1-year survival in patients based on sum of relevant comorbidities [13, 14]), employment status, nationality (missing values aggregated to ‘other’), insurance status (main member, family, retiree), participation in a disease management program (DMP) (type 1 diabetes, type 2 diabetes, coronary heart disease, breast cancer, bronchial asthma, COPD, cardiac insufficiency), classified degree of necessary nursing care , and season. Regarding primary care practices, type of location (urban, urbanized, countryside), type of practice (single or group) and medical specialty group are documented.
The baseline data of practices participating in ARena were analyzed regarding the four quarters prior to the ARena intervention (Q3 2016 – Q2 2017) with a focus on prescription rates of antibiotics for acute non-complicated self-limiting infections and the comparison between characteristics of PCNs including their member physicians and RGs that reflect usual care. In addition, patients’ sociodemographic and disease-specific characteristics in either of these groups are summarized. Infections considered are tonsillitis, sinusitis, otitis media, bronchitis, and URTI. Also focused are the use of guideline-recommended indication-appropriate antibiotics and the group of quinolones.
The primary and all secondary outcomes, as well as all documented data (patient characteristics, disease characteristics, treatment data, and practice characteristics), were first analyzed descriptively. For continuous variables, mean and standard deviation, median, 25%/75%-quantiles [Q1-Q3], min and max are provided, for categorical variables absolute and relative frequencies are given. Note that the description of patients and disease characteristics, as well as treatment data and practice characteristics differ between endpoints, because the considered patients are defined for each endpoint by the respective disease and prescription of antibiotics. Therefore, the descriptive analysis is done for each outcome individually. For the subgroups gender, DMP and the CCI, the primary and all secondary outcomes are contrasted using descriptive methods based on patients in PCNs and RGs.
A logistic mixed effects regression model was used to identify factors influencing the primary outcome. The model considers the nested structure of the data with patients nested in practices, which means practice is included as random effect in the logistic mixed effects model. As fixed effects, medical specialty group (Fachgruppe – FGR), urbanization, age group, sex, and the CCI as indication of health status are considered. Secondary outcomes are analyzed using mixed logistic (1.-6.) or beta regression models (7.). Adjustment is done as described for the primary outcome model. Since this is an explorative study, all p-values do not have confirmatory value.