Quality assurance in non-interventional studies

Nowadays, drug research and surveillance after authorisation becomes more and more important for several reasons. Non-interventional studies (NIS) investigate various aspects of drug use including efficacy and safety under real life conditions. Such kind of health services research should be on a high scientific, methodological and organisational level. Therefore accompanying measures to improve or to keep the quality are highly recommended. The aim of quality management is: first to avoid bias of results by using an appropriate study design and an adequate data analysis, second to assure authenticity, completeness and validity of the data and third to identify and resolve deficiencies at an early stage. Basic principles are laid down in corresponding guidelines and recommendations of authorities, institutes and societies. Various guidelines for good epidemiological practice (GEP) were published by the U.S. Food and Drug Administration (FDA) and international and regional societies for epidemiology. In addition in Germany the Federal Institute for Drugs and Medical Devices (BfArM) together with the Paul Ehrlich Institute (PEI) and the German Association of Research-Based Pharmaceutical Companies (VFA) have published respectively recommendations dealing with quality aspects of non-interventional observational studies. Key points are the advanced publishing of information about the project, developing of a study plan/protocol containing the scientific objectives, a sample size justification and a description of the planned analyses and the publishing of a summary of the results timely after completion of the study. The quality of the data can be improved by using standardized case report forms (CRF) and the CRF should be reviewed and tested before start of study by some participants. A source data verification (SDV) should be performed in randomly selected centres – in between 2% and 5% of the centres depending on the number of participating centres. Before start of statistical analysis a statistical analysis plan (SAP) should be created. The use of standardized tables and figures is highly recommended. The basis of the report writing should be the STROBE-statement “Strengthening the Reporting of Observational studies in Epidemiology Initiative” containing a checklist of 22 points to be covered in the report. The development of own standard operating procedures (SOP) describing the processes during planning, conduct and evaluation of a non-interventional study as well as the quality management and the regular training of all involved people is also highly recommended. All accompanying measures to improve or to keep the quality of the NIS should not violate the concept of non-intervention

Epidemiology and treatment of adult patients with atopic dermatitis Analysis of longitudinal data of the statutory health insurance scheme

Background The goal was to report incidence, prevalence, and treatment patterns in adult atopic dermatitis (AD) patients in the German statutory health insurance system. Patient and methods Anonymized claims data were evaluated at patient level for 3.3 million persons insured by six different statutory health insurance companies (SHI). Patients for whom the ICD-10 diagnosis code L20 (AD) was applied at least twice were analyzed and data on prescription patterns for AD were reported for the years 2011-2015. Results AD prevalence in adults was 1.6-1.9% in 2012-2015. Annual incidence was 0.28%. In Q3/Q4 2015, 44.2% of the adult population with AD diagnosis by a dermatologist received prescriptions for AD medications: 1.6% low-potency topical glucocorticoids (without previous prescription of systemic drugs), 46.9% moderate or high-potency topical glucocorticoids or topical calcineurin inhibitors, 23.9% current systemic therapy (systemic glucocorticoids, ciclosporin, methotrexate, azathioprine, mycophenolate mofetil) and 27.6% systemic therapy in the past. Conclusions The AD prevalence estimate was in the range of previous reports (1.35-4%) that used different methodologies. Based on treatment proxy, it appeared that almost more than half of AD patients treated with prescription ready-to-use drugs had a severe form of AD which required treatment with systemic drugs

Treatment satisfaction and quality-of-life between type 2 diabetes patients initiating long- vs. intermediate-acting basal insulin therapy in combination with oral hypoglycemic agents – a randomized, prospective, crossover, open clinical trial

Background: Pharmacological and clinical differences between insulin glargine and NPH insulin may translate into differences in patient reported outcomes, but existing data are equivocal. Methods: In this 48-week, open-label, randomized, multi center, crossover phase IV trial, insulin naïve type 2 diabetes patients with blood glucose not at target on oral hypoglycemic agents had basal insulin added to their treatment regimen. A total of 343 patients were randomized to either receive insulin glargine (n = 176; sequence A) or neutral protamine Hagedorn (NPH) insulin (n = 167; sequence B) in period 1 (weeks 1–24) and vice versa in period 2 (weeks 25–48). The primary objective was to assess patient reported outcomes using a composite Diabetes Related Quality of Life (DRQoL) score based on an unweighted Insulin Treatment Experience Questionnaire (ITEQ) score, a Problem Areas in Diabetes (PAID) questionnaire score, and the mental health score in the Short Form (SF)-12® Health Survey, analyzed by analysis of covariance (ANCOVA). Results: Patients (mean age 62.3 ± 9.0; 39.5 % female) had a mean diabetes duration of 9.6 ± 5.9 years, a mean baseline HbA1c of 8.15 ± 0.72 %, and a mean fasting blood glucose (FBG) level of 9.37 ± 2.19 mmol/L. A total of 229 patients were available for primary endpoint evaluation (modified intention to treat population). Combining all data from both periods for each insulin treatment, on a 0–100 scale, the mean DRQoL score was 69.6 (±9.04) with insulin glargine and 70.0 (±9.40) with NPH insulin. Neither an effect of treatment with insulin glargine vs NPH insulin (p = 0.31) nor a period effect (p = 0.96), nor a sequence effect (p = 0.76) was observed using ANCOVA. Conclusions: The results show that in a patient population with sub-optimal glycemic control at baseline, and a low target achievement rate together with a low rate of hypoglycemia, differences in the patient reported outcomes evaluated in this study were negligible between insulin glargine and NPH insulin. Trial registration: Clinicaltrials.gov identifier: NCT0094136