Prediction of Drug-Related Risks Using Clinical Context Information in Longitudinal Claims Data.

OBJECTIVES: To develop and internally validate prediction models for medication-related risks arising from overuse, misuse, and underuse that utilize clinical context information and are suitable for routine risk assessment in claims data (i.e., medication-based models predicting the risk for hospital admission apparent in routine claims data or MEDI-RADAR). METHODS: Based on nationwide claims from health-insured persons in Germany between 2010 and 2012, we drew a random sample of people aged ≥65 years (N = 22,500 randomly allocated to training set, N = 7500 to validation set). Individual duration of drug supply was estimated from prescription patterns to yield time-varying drug exposure windows. Together with concurrent medical conditions (ICD-10 diagnoses), exposure to the STOPP/START (screening tool of older persons' potentially inappropriate prescriptions/screening tool to alert doctors to the right treatment) criteria was derived. These were tested as time-dependent covariates together with time-constant covariates (patient demographics, baseline comorbidities) in regularized Cox regression models. RESULTS: STOPP/START variables were iteratively refined and selected by regularization to include 2 up to 11 START variables and 8 up to 31 STOPP variables in parsimonious and liberal selections in the prediction modeling. The models discriminated well between patients with and without all-cause hospitalizations, potentially drug-induced hospitalizations, and mortality (parsimonious model c-indices with 95% confidence intervals: 0.63 [0.62-0.64], 0.67 [0.65-0.68], and 0.78 [0.76-0.80]). CONCLUSIONS: The STOPP/START criteria proved to efficiently predict medication-related risk in models possessing good performance. Timely detection of such risks by routine monitoring in claims data can support tailored interventions targeting these modifiable risk factors. Their impact on older peoples' medication safety and effectiveness can now be explored in future implementation studies.

The impact of potentially inappropriate medication on the development of health care costs and its moderation by the number of prescribed substances. Results of a retrospective matched cohort study.

BACKGROUND: In the growing population of the elderly, drug-related problems are considered an important health care safety issue. One aspect of this is the prescription of potentially inappropriate medication (PIM) which is considered to increase health care costs. OBJECTIVE: Using data from the Health Economics of Potentially Inappropriate Medication (HEPIME) study, we aimed to analyze how the number of prescribed substances moderates the association of PIM use as defined by the German PRISCUS list and health care costs applying a longitudinal perspective. METHODS: An initial number of 6,849,622 insurants aged 65+ of a large German health insurance company were included in a retrospective matched cohort study. Based on longitudinal claims data from the four separate quarters of a 12-month pre-period, 3,860,842 individuals with no exposure to PIM in 2011 were matched to 508,212 exposed individuals. Exposure effects of PIM use on health care costs and the number of prescribed substances were measured based on longitudinal claims data from the four separate quarters of the 12-month post-period. RESULTS: After successful balancing for the development of numerous matching variables during the four quarters of the pre-period, exposed individuals consumed 2.1 additional prescribed substances and had higher total health care costs of 1,237 € when compared to non-exposed individuals in the 1st quarter of the post-period. Controlling for the number of prescribed substances, the difference in total health care costs between both study groups was 401 €. The average effect of one additionally prescribed substance (other than PIM) on total health care costs was increased by an amount of 137 € for those being exposed to a PIM. In quarters 2-4 of the post-period, the differences between both study groups tended to decrease sequentially. CONCLUSIONS: PIM use has an increasing effect on the development of health care costs. This cost-increasing effect of PIM use is moderated by the number of prescribed substances.

[10-year development of spine surgery in Germany - An analysis of health insurance funds data from 2005 to 2014]. / 10-Jahres-Entwicklung operativer Eingriffe an der Wirbelsäule in Deutschland.

BACKGROUND: Analysis of the regional development of spine surgery in Germany between 2005 and 2014. MATERIAL AND METHODS: A secondary data analysis of inpatient data from the Scientific Institute of the AOK (WIdO) was carried out for the period 2005 to 2014. The number of spinal procedures was determined on the basis of 14 defined intervention groups (procedures according to OPS codes). The regional numbers of spine surgery procedures in the 402 districts in Germany and the regional age- and gender-standardised distribution are displayed as healthcare utilisation charts. RESULTS: 796,870 AOK-insured individuals received inpatient spinal surgery during the observation period. The relative increase in the 10-year period was 82%, with 51,053 interventions in 2005 and 91,971 interventions in 2014. The increase in spine surgery cases occurred mainly between 2005 and 2011. An increase in the number of operations was observed in all intervention groups except "excision of intervertebral discs and bones". It was different in different spinal procedures, with the greatest increases in "bone decompression" (280% increase). Regional differences were found in all intervention groups. In 2014, the number of interventions varied between 109 and 729 interventions per 100,000 AOK-insured individuals in the districts. CONCLUSION: The significant increases of more than 80% in 10 years cannot be explained solely by sociodemographic changes. The pronounced regional differences alone do not allow firm conclusions on the existence of regional underuse, overuse or misuse. The results, however, emphasise the need for further health services research on the quality of the medical indication and the determinants of regional variation.

Health Service Use, Costs, and Adverse Events Associated with Potentially Inappropriate Medication in Old Age in Germany: Retrospective Matched Cohort Study.

BACKGROUND: Drug-related problems are an important healthcare safety concern in the growing population of older people. Prescription of potentially inappropriate medication (PIM) is one aspect of this concern that is considered to increase the risk of adverse health outcomes. OBJECTIVE: The aim of the Health Economics of Potentially Inappropriate Medication (HEPIME) study was to analyze the association between the prescription of PIMs according to the German PRISCUS list and healthcare utilization, healthcare costs, and the occurrence of adverse events in old age. METHODS: Insurants of a large German health insurance company aged 65+ years were included in a retrospective matched cohort study. A total of 3,953,423 individuals with no exposure to PIM in 2011 were matched to 521,644 exposed individuals and compared in terms of outpatient healthcare utilization, healthcare costs, and the occurrence of adverse events in outpatient, hospital, and rehabilitation sectors during a 12-month follow-up. RESULTS: On average, individuals in the exposed group had additional 143 [95% confidence interval (CI) 140-146] daily defined doses of pharmaceuticals and 4.5 (95% CI 4.4-4.6) days in hospital. Mean annual total healthcare costs per individual in the exposed group exceeded those in the non-exposed group by €2321 (95% CI 2269-2372), resulting mainly from differences in hospitalization costs of €1718 (95% CI 1678-1759). Odds ratios for the occurrence of adverse events in the exposed group were 1.32 (95% CI 1.32-1.34) in the outpatient sector, 1.76 (95% CI 1.73-1.79) in the hospital sector, and 1.82 (95% CI 1.76-1.89) in the rehabilitation sector. CONCLUSIONS: Increased healthcare utilization and costs as well as an increased probability for adverse events in individuals exposed to PIM demonstrate the health economic relevance of PIM prescriptions. Whether avoiding PIM listed on the PRISCUS list may potentially improve the quality and efficiency of healthcare is currently unknown.

Investigating the Additive Interaction of QT-Prolonging Drugs in Older People Using Claims Data.

INTRODUCTION: Drugs that potentially prolong the QT interval carry the risk of life-threatening Torsades de pointes (TdP) ventricular arrhythmia. OBJECTIVE: The objective of this study was to investigate the potential additive risk for ventricular arrhythmia with concomitant prescriptions of QT-prolonging drugs. METHODS: Claims data for persons aged ≥65 years between 2010 and 2012 in Germany were analyzed and all cases hospitalized for ventricular arrhythmia were selected. In a case-crossover analysis, exposure with QT-prolonging drugs according to the Arizona Center for Education and Research on Therapeutics (AZCERT) classification of 'known,' 'conditional,' and 'possible' TdP risk was determined in respective event and control windows preceding hospitalization. Conditional logistic regression was applied to derive odds ratios (ORs). RESULTS: Among 6,849,622 health-insured persons, we identified 2572 patients newly hospitalized for ventricular arrhythmia. Drugs with 'known' risk were more frequently prescribed in the event window than in the control window (309 vs. 239; P < 0.001). The number of drugs with an attributed 'known' risk of TdP was significantly associated with hospitalization for ventricular arrhythmia (OR: 2.22; 95% confidence interval [1.51-3.25]; P < 0.001), while increased risk estimates were also obtained upon categorization into one and two or more drugs compared with no drugs for the combined group of drug with 'known' (1.52 [1.16-2.00]) and 'conditional' risk (2.20 [1.42-3.41]). Pairwise comparisons and trend tests based on these classification categories could not demonstrate a significantly increased risk of two or more drugs compared with one drug. CONCLUSION: Beyond suitable single-drug classifications for QT-associated risk estimation, the situation when there is co-prescription of several drugs appears to be complex and may not be extrapolated to all possible multi-drug combinations.

Predictors of non-drug psychiatric/psychotherapeutic treatment in children and adolescents with mental or behavioural disorders.

Children and adolescents with mental health problems need effective and safe therapies to support their emotional and social development and to avoid functional impairment and progress of social deficits. Though psychotropic drugs seem to be the preferential treatment, psychotherapy and psychosocial interventions are essential in mental health care. For Germany, current data on the utilization of psychotherapy and psychosocial interventions in children with mental health problems is lacking. To analyse why certain children and adolescents with mental or behavioural disorders do and others do not receive non-drug treatment, we assessed predictors associated with specific non-drug psychiatric/psychotherapeutic treatment including psychosocial interventions, psychotherapy and other non-drug treatments. The study is based on data of two large German health insurance funds, AOK and TK, comprising 30 % of the German child and adolescent population. Predictors of non-drug psychiatric/psychotherapeutic treatment were analysed for 23,795 cases and two controls for every case of the same age and sex in children aged 0-17 years following a new diagnosis of mental or behavioural disorder in 2010. Predictors were divided according to Andersen's behavioural model into predisposing, need and enabling factors. The most prominent and significant predictors positively associated with non-drug psychiatric/psychotherapeutic treatment were the residential region as predisposing factor; specific, both ex- and internalizing, mental and behavioural disorders, psychiatric co-morbidity and psychotropic drug use as need factors; and low area deprivation and high accessibility to outpatient physicians and inpatient institutions with non-drug psychiatric/psychotherapeutic department as enabling factors. In conclusion, the present study suggests that the residential region as proxy for supply of therapist and socioeconomic situation is an influencing factor for the use of psychotherapy. The analysis sheds further light on predisposing, need and enabling factors as predictors of non-drug psychotherapeutic/psychiatric treatment in children and adolescents with mental or behavioural health disorders in Germany. More research is needed to further understand the factors promoting the gap between the need and utilization of mental health care.

Comparative evaluation of methods approximating drug prescription durations in claims data: modeling, simulation, and application to real data.

PURPOSE: The purpose of this study was to compare the predictive accuracy of different methods suggested for approximation of drug prescription durations in claims data. METHODS: We expanded a well-established modeling and simulation framework to compare approximated drug prescription durations with 'true' (i.e., simulated) durations. Real claims data of persons aged ≥65 years insured by the German nationwide 'Statutory Health Insurance Fund' AOK between 2010 and 2012 provided empiric input parameters that were completed with missing information on actual dosing patterns from an observational cohort. The distinct approximation methods were based on crude measures (one tablet a day), population-averaged measures (defined daily doses), or individually-derived measures (longitudinal coverage approximation of the applied dose, COV). As a proof-of-principle, we assessed the methods' performance to predict the well-characterized bleeding risks of anticoagulant, antiplatelet, and/or non-steroidal anti-inflammatory drugs. RESULTS: When applied to modeling and simulation data sets, the closest, least biased, and thus most accurate approximation was observed using the COV approximation. In a real-data example, rather similar results to an external reference were obtained for all methods. However, some of the differences between methods were meaningful, and the most reasonable and consistent results were obtained with the COV approach. CONCLUSION: Based on theoretically most accurate approximations and practically reasonable estimates, the individual COV approach was preferable over the population-averaged defined daily dose technique, although the latter might be justified in certain situations. Advantages of the COV approach are expected to be even bigger for drug therapies with particularly large dosing heterogeneity. Copyright © 2016 John Wiley & Sons, Ltd.

Psychopharmacological Prescriptions in Children and Adolescents in Germany.

BACKGROUND: In view of the well-known increase in prescriptions of stimulants for children and adolescents over the last 20 years, it is important to study trends in the prevalence and incidence of the use of other psychotropic drugs by this age group as well, to enable an early response to potential problems in the current care situation. METHODS: We used nationwide data from German statutory health insurance funds (Allgemeine Ortskrankenkasse [AOK], all insurees; Techniker Kranken - kasse [TK], a 50% randomized sample) concerning all insurees aged 0-17 years (5.0 million people in 2012) to study trends in the prevalence and incidence of psychotropic medication use as well as initially prescribing medical specialties over the period 2004-2012, both for the overall group of psychotropic drugs and for selected subgroups of drugs. RESULTS: From 2004 to 2012, the prevalence of psychotropic drug prescriptions (not including herbal and homeopathic substances) for children and adolescents rose from 19.6 to 27.1 per 1000 individuals. Marked rises were seen for stimulants (10.5 to 19.1 per 1000) and antipsychotic drugs (2.3 to 3.1 per 1000), while the prevalence of antidepressant prescriptions remained constant at about 2 per 1000. The rates of new prescriptions from 2006 to 2012 were generally constant or decreasing; for the overall group of (non-herbal, nonhomeopathic) psychotropic drugs, the rate of new prescriptions fell from 9.9 to 8.7 per 1000. There was a trend toward the issuance of new prescriptions by medical specialists, rather than by family physicians and pediatricians. CONCLUSION: The observed increased prevalence of psychotropic drug use among children and adolescents appears to be due not to an increased rate of initial prescriptions for these drugs, but rather to a rise in the number of patients who, once having received such drugs, were given further prescriptions for them in the years that followed.

Cost-components of lung cancer care within the first three years after initial diagnosis in context of different treatment regimens.

OBJECTIVES: Although lung cancer is of high epidemiological relevance in Germany, evidence on its economic implications is scarce. Sound understanding of current care structures and associated expenditures is required to comprehensively judge the additional benefit of novel interventions in lung cancer care. Adopting a payer perspective, our study aims to analyze expenditures for individuals with incident lung cancer. MATERIAL AND METHODS: Patients with an initial diagnosis of lung cancer (ICD-10 code C34) in 2009 were searched in a large, nationwide base of health insurance claims data and grouped according to initial treatment (Surgery, Chemotherapy/Radiotherapy, No specific treatment). All-cause SHI and lung cancer-related spending was assessed for a patient-individual three-year time frame after initial diagnosis. Expenditures per case and expenditures per year survived were calculated via Generalized Linear Gamma Models adjusted for age, gender, living region, baseline metastases, multiple tumors and initial treatment regimen using time under observation as a weighting factor. RESULTS: 17,478 individuals were identified. Lung cancer-related expenditures peaked within the first six months after initial diagnosis. Following, they declined subsequently and so did their share in all-cause SHI spending. Lung cancer-related expenditures per case were estimated at €20,400 (53% of all-cause expenditures) with a huge variance according to initial treatment regimen [ SURGERY: €20,400, Chemotherapy/Radiotherapy: €26,300, No specific treatment: €4200]. Cost per year survived amounted to €15,500 (55% of all cause expenditures) [ SURGERY: €11,600, Chemotherapy/Radiotherapy: €20,200, No specific treatment: €7600]. CONCLUSION: Analyses of lung cancer-related expenditures need to take into account treatment strategies and survival. Our study is representative for a large share of the population and provides detailed, patient-level information on costs of care and their compilation. Results render estimates available for the cost of lung cancer e.g. for budget impact analyses, cost-effectiveness analyses of screening and prevention schemes, or prognostic models of life-time expenditures per lung cancer case.