Surveillance and care for confirmed and suspected patients with COVID-19 in general practice (CovidCare): study protocol for an observational trial

Background A SARS-CoV-2 infection can lead from asymptomatic through to critical disease in a dynamic and unpredictable course within a few days. The challenge in outpatient monitoring the highly contagious COVID-19 disease during the ongoing pandemic is to filter severe courses followed by admission to hospital with the aim of preventing an overburdening of clinics. However, little is known of the effect of risk factors on the course of the infection of outpatient patients. To support general practices in managing high risk patients, we designed a COVID-19 surveillance and care tool (CovidCare). It includes an initial assessment of yet known risk factors and symptoms and a continuous telephone monitoring of signs and symptoms. This study aims to investigate the effects of different risk factors on the course of the COVID-19 disease, utilisation of different health care services and to gain insights into the utilisation of CovidCare in general practices. Methods We will conduct a multi-centered prospective, longitudinal non-controlled observational trial of COVID-19 patients in general practices. Overall, 700 GPs who participate in general-practice centered care by the AOK Baden-Württemberg (large German sickness fund) are eligible and will be invited for study participation, including adult, outpatient COVID-19 patients (or urgent suspicion and ≥ 50 years) with at least one additional known risk factor, who participate in general-practice centered care. The primary outcome is hospitalisation due to COVID-19. Secondary outcomes are diagnosis of pneumonia, utilisation of palliative care, mortality rate, anxiety and identification of predictive risk factors. Quantitative data analysis will focus on valid descriptive figures and mixed regression models. The accompanying process evaluation is based on interviews and questionnaires from general practice staff and patients. The analysis of the process evaluation is descriptive and explorative. Discussion The use of the COVID-19 surveillance and care tool is expected to encourage the provision of structured quality of care during the ongoing pandemic. This trial will provide an understanding of the COVID-19-disease and the effect of several risk factors on the course of the disease and health care utilisation. The results can be used for a better management of the COVID-19 pandemic and its consequences. Trial registration German Clinical Trials Register DRKS00022054.

P377 Inadequate response with advanced therapies in real-world patients with Ulcerative Colitis – Results of a German claims database study

Background Therapeutic management of Ulcerative Colitis (UC) is challenging, and clinicians are often obliged to attempt a variety of therapies in sequence until an adequate clinical response is achieved. However, real-world data regarding response rates in UC treatment are rare, particularly for later lines of therapy. Thus, this study aimed to investigate the incidence of inadequate response to advanced therapies in patients with UC. Methods This retrospective study was based on claims data from a regional German sickness fund covering the period from 01/2014-06/2019. Patients were included if they had at least two outpatient diagnoses in two different quarters or one inpatient diagnosis of UC (ICD-10: K51) and started a newly introduced advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) in 01/2015-06/2019. Patients were followed from treatment initiation (index date) until the end of the study period or loss to follow-up (median = 23.4 months). Proxies of inadequate response included: discontinuation (a supply gap of >60 days), switch, escalation (as dose increase exceeding 1.5 times the recommended maintenance dose), augmentation with 5-ASA, corticosteroid (CS) dependency (two CS prescriptions were observed starting more than 14 weeks after the index date), UC-related hospitalization, or UC-related surgery. CS dependency and treatment escalation were only assessed in the maintenance phase. Inadequate response in the analyzed sample was evaluated by means of Kaplan-Meier survival analysis. Results Among 574 UC patients (median age: 39 years; female: 53.5%), in whom an advanced therapy was initiated, 458 (79.8%) received an anti-TNF therapy, 113 (19.7%) vedolizumab and 3 (0.5%) tofacitinib. According to the available baseline period, 72 (12.4%) patients were identified as biologic-experienced. Most patients received CS (86.4%) and/or 5-aminosalicylic acids (81.7%) in the 12-month pre-index period. The median time to inadequate response to the initiated advanced therapy was 4.8 months (IQR: 2.6-11.9; Figure 1) with an inadequate response over 12 months in 75% (Figure 2). There was no significant difference in median time to inadequate response between biologic-naïve and biologic-experienced patients (4.9 vs. 4.7 months; p-value = 0.285). During the observable follow-up period, 172 (61%) patients switched from their index agent to another advanced therapy. Conclusion From the real-world settings in Germany, we found an inadequate response in UC-patients starting an advanced therapy in 75% of patients over 12 months. There is a need for more effective therapies among these patients.

P662 A retrospective claims analysis on the prevalence and incidence of ulcerative colitis in Germany and the frequency of advanced therapy use

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease that requires continuous medical treatment. Current epidemiological data about UC in Germany are lacking, and in particular, it is unknown how many patients are treated with advanced therapies. This study aimed to investigate the prevalence and incidence of UC in Germany and describe the frequency of advanced therapy use in this population. Methods We used claims data from a regional German sickness fund (AOK PLUS). Continuously insured persons from 01/01/2015 until 31/12/2019 or death with at least 2 outpatient diagnoses documented by a specialist in 2 quarters within 12 months or one inpatient diagnosis (ICD-10: K51.-) were defined to be UC prevalent. Patients were defined to be incident in 2019 if the respective selection criteria could be observed in 2019, but no UC diagnosis was documented in the previous 4 years. Age- and gender-standardized point prevalence was calculated on 01/01/2019, cumulative incidence was evaluated for the year 2019. Standardization was based on the age/gender distribution within the entire population of the German statutory insurance (KM-6 statistic), which covers about 90% of the whole German population. Main characteristics and comorbidity status were assessed at the index date based on diagnoses documented in the 12-month pre-index period (index: 01/01/2019 or date of incident diagnosis in 2019). The proportion of prevalent patients receiving advanced therapies (infliximab, adalimumab, golimumab, vedolizumab, tofacitinib) was evaluated in 2019, considering both out- and inpatient treatments. Results The standardized incidence in 2019 was 0.36 cases/1,000 persons. Incident patients were, on average, 59.7 years old (SD: 21.6; 95% CI: 58.2–61.1), and 56.1% were females. The mean Charlson Comorbidity Index (CCI) was 2.7 (SD: 3.1; 95% CI: 2.5–2.9). The standardized prevalence at 01/01/2019 was 5.29 cases/1,000 persons. In 2019, 12,736 prevalent patients were observed (12,510.8 person-years), with 56.2% of the patients being female. The mean age was 60.6 years (SD: 18.8; 95% CI: 60.2–60.9), and the mean CCI was 2.3 (SD: 2.8; 95% CI: 2.2–2.3). 827 patients (6.5%) were treated with advanced therapy in 2019. These patients were considerably younger (44.9 (95% CI: 43.9–46.0) versus 61.7 years (95% CI: 61.3–62.0)) and less comorbid (CCI: 1.2 (95% CI: 1.0–1.3) vs. 2.4 (95% CI: 2.3–2.4)) than patients who have not been treated with an advanced therapy. Conclusion Our analysis showed a considerable UC incidence and a high disease burden in Germany, with a prevalence surpassing 0.5%. Advanced therapies were prescribed only in a minority of UC patients, who were generally younger and less comorbid.

P404 Healthcare utilization and expenditures for patients with Ulcerative Colitis on advanced therapies in Germany

Background Ulcerative Colitis (UC) is a chronic inflammatory condition, which significantly impacts patients’ health-related quality of life and burdens healthcare budgets. Our objective was to provide an overview of the healthcare resource use (HCRU) for the treatment of moderate to severe UC in Germany. Methods A retrospective analysis was conducted using claims data from a German sickness fund (AOK PLUS). Patients were included if they had ≥2 outpatient diagnoses in different quarters and/or one inpatient UC diagnosis (ICD-10: K51), were aged ≥18 years and initiated an advanced therapy (anti-TNFs, vedolizumab, tofacitinib) between 01/01/2015-30/06/2019. HCRU associated with UC treatment was assessed in terms of outpatient visits, work-related sick leave days, and UC caused hospitalizations. Direct UC-related costs (inpatient, outpatient and medication costs based on pharmacy sales price at prescription date) were calculated from the perspective of the German statutory health insurance. All patients were followed from the start of treatment until the end of the study period, or loss to follow-up. In case of treatment discontinuation or change of index therapy, patient follow-up was censored 90 days after the last prescription of index therapy. UC-related HCRU and cost were reported per observable patient-year (PY) and stratified according to prior use of advanced therapies (naïve vs. experienced). Results 574 patients were included (adalimumab: 230, infliximab: 172, golimumab: 56, vedolizumab: 113, tofacitinib: 3). Mean age was 41.9 years; 53.5% were female. On average, 2.5 outpatient visits per PY were billed by general practitioners and 1.4 by gastroenterologists. 27.0% of patients had at least one UC-related hospitalization (mean length of stay: 11.2 days). The mean number of documented UC-related sick leave days amounted to 13.1 per PY. HCRU was similar in therapy-naïve vs. experienced patients (Table 1). Inpatient costs for any cause amounted on average to €4,522/PY, with UC accounting for €3,190/PY (70.5%). Total UC costs amounted to €34.068/PY (Table 2). Expenses for prescribed UC-related drugs amounted to €28,885/PY (95.6% of total drug costs), and outpatient treatment to €511/PY with only €123/PY for Gastroenterologists’ visits (0.4% of total UC-costs/PY). In addition, indirect cost resulting from sick leave due to UC were estimated at €2,979/PY. Conclusion Our study indicates a high economic burden in UC patients who initiated treatment with advanced therapies. UC-related medication was identified as the main cost driver. Furthermore, a substantial proportion of UC patients required hospitalization in the first 12 months after starting new advanced therapy.

Surveillance and Care for Confirmed and Suspected Patients with COVID-19 in General Practice (CovidCare): Study Protocol for an Observational Trial

BackgroundA SARS-CoV-2 infection can lead from asymptomatic through to critical disease in a dynamic and unpredictable course within a few days. The challenge in outpatient monitoring the highly contagious COVID-19 disease during the ongoing pandemic is to filter severe courses followed by admission to hospital with the aim of preventing an overburdening of clinics. However, little is known of the effect of risk factors on the course of the infection of outpatient patients. To support general practices in managing high risk patients, we designed a COVID-19 surveillance and care tool (CovidCare). It includes an initial assessment of yet known risk factors and symptoms and a continuous telephone monitoring of signs and symptoms. This study aims to investigate the effects of different risk factors on the course of the COVID-19 disease, utilisation of different health care services and to gain insights into the utilisation of CovidCare in general practices. MethodsWe will conduct a multi-centered prospective, longitudinal non-controlled observational trial of COVID-19 patients in general practices. Overall, 700 GPs who participate in general-practice centered care by the AOK Baden-Württemberg (large German sickness fund) are eligible and will be invited for study participation, including adult, outpatient COVID-19 patients (or urgent suspicion and ≥ 50 years) with at least one additional known risk factor, who participate in general-practice centered care. The primary outcome is hospitalisation due to COVID-19. Secondary outcomes are diagnosis of pneumonia, utilisation of palliative care, mortality rate, anxiety and identification of predictive risk factors. Quantitative data analysis will focus on valid descriptive figures and mixed regression models. The accompanying process evaluation is based on interviews and questionnaires from general practice staff and patients. The analysis of the process evaluation is descriptive and explorative. DiscussionThe use of the COVID-19 surveillance and care tool is expected to encourage the provision of structured quality of care during the ongoing pandemic. This trial will provide an understanding of the COVID-19-disease and the effect of several risk factors on the course of the disease and health care utilisation. The results can be used for a better management of the COVID-19 pandemic and its consequences. Trial registration: German Clinical Trials Register DRKS00022054; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022054

Influence of COVID-19 confinement measures on appendectomies in Germany—a claims data analysis of 9797 patients

Purpose COVID-19 pandemic had multiple influences on the social, industrial, and medical situation in all affected countries. Measures of obligatory medical confinement were suspensions of scheduled non-emergent surgical procedures and outpatients’ clinics as well as overall access restrictions to hospitals and medical practices. The aim of this retrospective study was to assess if the obligatory confinement (lockdown) had an effect on the number of appendectomies (during and after the period of lockdown). Methods This retrospective study was based on anonymized nationwide administrative claims data of the German Local General Sickness Fund (AOK). Patients admitted for diseases of the appendix (ICD-10: K35-K38) or abdominal and pelvic pain (ICD-10: R10) who underwent an appendectomy (OPS: 5-470) were included. The study period included 6 weeks of German lockdown (16 March–26 April 2020) as well as 6 weeks before (03 February–15 March 2020) and after (27 April–07 June 2020). These periods were compared to the respective one in 2018 and 2019. Results The overall number of appendectomies was significantly reduced during the lockdown time in 2020 compared to that in 2018 and 2019. This decrease affects only appendectomies due to acute simple (ICD-10: K35.30, K35.8) and non-acute appendicitis (ICD-10: K36-K38, R10). Numbers for appendectomies in acute complex appendicitis remained unchanged. Female patients and in the age group 1–18 years showed the strongest decrease in number of cases. Conclusion The lockdown in Germany resulted in a decreased number of appendectomies. This affected mainly appendectomies in simple acute and non-acute appendicitis, but not complicated acute appendicitis. The study gives no evidence that the confinement measures resulted in a deterioration of medical care for appendicitis.

Influence of COVID-19 confinement measures on appendectomies in Germany - administrative claims data analysis of 9,797 patients

Purpose: COVID 19 pandemic had multiple influences on the social, industrial and medical situation in all affected countries. Measures of obligatory medical confinement were suspensions of scheduled non-emergent surgical procedures and outpatients clinics as well as overall access restrictions to hospitals and medical practices. The aim of this retrospective study was to assess if the obligatory confinement (lockdown) had an effect on the number of appendectomies (during and after the period of lockdown). Methods: This retrospective study was based on anonymized nationwide administrative claims data of the German Local General Sickness Fund (AOK). Patients admitted for disease of the appendix (ICD-10: K35-K38) or abdominal and pelvic pain (ICD-10: R10) who undergone an appendectomy (OPS: 5-470) were included. The study period included six weeks of German lockdown (16.03.-26.04.2020) as well as six weeks before (03.02.-15.03.2020) and after (27.04.-07.06.2020). These periods were compared to the respective in 2019. Results: Overall number of appendectomies was significantly reduced during the lockdown time in 2020 compared to 2019. This decrease affects only appendectomies due to acute simple and non-acute appendicitis. Numbers for appendectomies in acute complex appendicitis remained unchanged. Female patients and in the age group 1-18 years showed the strongest decrease in number of cases. Conclusion: The lockdown in Germany resulted in a decreased number of appendectomies. This affected mainly appendectomies in simple acute and non-acute appendicitis, but not complicated acute appendicitis. The study gives no evidence, that the confinement measures resulted in a deterioration of medical care for appendicitis.

A Comparison of Matching and Weighting Methods for Causal Inference Based on Routine Health Insurance Data, or: What to do If an RCT is Impossible

Due to a multitude of reasons Randomized Control Trials on the basis of so-called “routine data” provided by insurance companies cannot be conducted. Therefore the estimation of “causal effects” for any kind of treatment is hampered since systematic bias due to specific selection processes must be suspected. The basic problem of counterfactual, which is to evaluate the difference between two potential outcomes for the same unit, is discussed. The focus lies on the comparison of the performance of different approaches to control for systematic differences between treatment and control group. These strategies are all based on propensity scores, namely matching or pruning, IPTW (inverse probability treatment weighting) and entropy balancing. Methods to evaluate these strategies are presented. A logit model is employed with 87 predictors to estimate the propensity score or to estimate the entropy balancing weights. All analyses are restricted to estimate the ATT (Average Treatment Effect for the Treated) Exemplary data come from a prospective controlled intervention-study with two measurement occasions. Data contain 35 857 chronically ill insurants with diabetes, congestive heart failure, arteriosclerosis, coronary heart disease or hypertension of one German sickness fund. The intervention group was offered an individual telephone coaching to improve health behavior and slow down disease progression while the control group received treatment as usual. Randomization took place before the insurants’ consent to participate was obtained so assumptions of an RCT are violated. A weighted mixture model (difference-in-difference) as the causal model of interest is employed to estimate treatment effects in terms of costs distinguishing the categories outpatient costs, medication costs, and total costs. It is shown that entropy balancing performs best with respect to balancing treatment and control group at baseline for the first three moments of all 87 predictors. This will result in least biased estimates of the treatment effect.