[Secondary data for budget impact analyses]. / Sekundärdaten für Budget Impact Analysen.

AIM: Budget impact analyses are performed to estimate the possible influence of a new health-care technology on the available budget. Scenarios should be if at all possible, evidence-based assumptions on the proportion of treated patients, the current and future mix as well as the direct costs of treatment. For the example of the atypical antipsychotic paliperidone, it is demonstrated that secondary data from routine health-care are well suited for this purpose. METHODS: By means of the IMS database Disease Analyzer, which consists of the electronic records of a nation-wide representative panel of German physicians (family doctors/general practitioners and neurologists/pschiatrists), various subgroups of schizophrenia patients were identified and the composition and costs of antipsychotic therapy determined in a retrospective longitudinal or, respectively, cross-sectional analysis. RESULTS: The demographic data were obtained via the patient records from the offices of 895 general practitioners/family doctors and 102 neurologists/psychiatrists. The number of ill and treated patients with schizophrenia (N=7 927) was determined from the diagnoses and prescriptions. By means of the prescription data (substance and form of administration) the treatment mix was defined. Total costs (2.7 million Euro in 2008) for the antipsychotic therapy were evaluated by links in the databank between individual prescription and the exact monthly pricelists of the pharmacy. CONCLUSIONS: With the example of a budget impact analysis for the atypical antipsychotic paliperidone ER it was shown that the specific secondary data of the IMS Disease Analyzers are suitable to set up an evidence-based, comprehensive model.

Validity and representativeness of the "Disease Analyzer" patient database for use in pharmacoepidemiological and pharmacoeconomic studies.

OBJECTIVES: Patient and health care databases are available in many countries. These are often based on routinely collected diagnosis and prescription data. Various research questions, such as those related to pharmacoepidemiological health services or drug supply, can be evaluated on the basis of these databases. In Germany, the Disease Analyzer patient database is the largest database of its kind. Using various validity criteria, the representativeness of this database is examined with respect to variables relevant to pharmacoepidemiological and pharmacoeconomic studies. METHODS: The Disease Analyzer patient database contains data on diagnoses, prescriptions, risk factors (such as smoking and obesity), and laboratory values for approximately 10 million patients from Germany, the UK, France, and Austria. The database also contains data from various groups of specialist physicians as well as from general practitioners and specialists for internal medicine. Data from physicians' practices in Germany form the basis of this investigation. To check the validity and representativeness of the data, the distributions of several variables are analyzed. These variables refer partly to the physicians' practices participating in the study and partly to the patients in these practices. The factors observed include prescriptions for generic drugs, the distribution of diagnostic groups among participating physicians' practices, the distribution of patients according to health insurance fund, the most frequent products, the distribution of package sizes prescribed, and the age structure of patients with various incident cancer diagnoses. These factors were compared with available reference statistics. RESULTS: The sampling methods for the selection of physicians' practices appear to be appropriate. Prescription statistics for several drugs were very similar to available data from the pharmaceutical prescriptions report (Arzneimittelverordnungsreport). The age structures for given diagnoses in Disease Analyzer also agreed well with those from corresponding disease registries. Additional comparisons were also in good agreement with data from available sources. CONCLUSION: The analyses carried out in comparison with reference statistics find no indication of lack of representativeness or validity of the Disease Analyzer database. In principle, the database appears suitable for pharmacoepidemiological and pharmacoeconomic studies. Development and maintenance of large pharmacoepidemiological databases is needed for modern health services. Such databases allow assessment of health care quality and rare adverse drug effects.

Longitudinal change in HbA1c in patients with type 2 diabetes: comparison of short-acting, biphasic and basal insulin.

OBJECTIVE: To evaluate the annual change in HbA1c values among patients with type 2 diabetes in primary care practices comparing different insulin regimens. RESEARCH DESIGN AND METHODS: Longitudinal data from 666 nationwide general and internal medicine practices in Germany (Disease Analyser, IMS HEALTH) from 7/2004 to 6/2006 were analysed, including 348 patients (mean age+/-SD: 61+/-11 years) with continuous short-acting (regular insulin or analogues), 1 906 with biphasic (72+/-9 years), 439 with basal-bolus (68+/-10 years), and 1 719 with basal insulin therapy (65+/-10 years). The mean of the individual relative changes in HbA1c (level in 2006 divided by level in 2005) were compared between insulin groups, adjusting for age, sex, BMI, diabetes duration, oral antidiabetics, comorbidity, health insurance, visits, hospitalisations, and practice type using general linear models. RESULTS: There was only a small difference in baseline HbA1c values (range 7.3-7.5%) between the four insulin groups (p=0.008). Substantial group differences were observed for age, diabetes duration, and additional prescriptions of oral antidiabetics (p<0.0001). After adjusting for potential confounders, the relative annual increase in HbA1c was highest for biphasic insulin (1.021; 95%CI 1.016-1.025), followed by basal-bolus therapy (1.017; 1.012-1.022), and basal insulin (monotherapy) (1.012; 1.002-1.021). No significant change in HbA1c was found for short-acting insulin (1.006; 0.996-1.016). CONCLUSIONS: Although many options for insulin therapy are now available, a progression of glycemia still occurs in the majority of insulin-treated type 2 diabetic patients in primary care.

Cost comparison analysis: pentaerythrithyl tetranitrate (PETN) and isosorbide dinitrate (ISDN) prescribed to diabetic patients in primary care practices in Germany.

INTRODUCTION: Both pentaerythrithyltetranitrate (Pentalong, PETN) and isosorbide dinitrate (ISDN) are commonly used in the therapy of ischemic heart disease (IHD). However, little is known about the therapeutic patterns in diabetic patients and no comparative data are available regarding the prescription costs of these two substances. Thus, the aim of this investigation was to compare the costs for PETN and ISDN therapy in diabetic patients in primary care. MATERIAL AND METHODS: All continuously treated patients aged > or = 40 years with diabetes (anti-diabetic agents) and IHD or angina pectoris (ICD codes) and newly started on PETN or ISDN therapy (index date) in the period 2000-2005 were selected from a database containing data from 400 practices throughout Germany (Disease Analyzer, IMS Health). Prescriptions costs for PETN and ISDN, as well as costs for cardiovascular comedication, were determined for the period 183 days before and after the index date, and that changes in costs after the index date were calculated. Differences in costs between the two groups were evaluated using multivariate regression, adjusting for age, sex and comorbidity. Patients in Eastern (n = 137, age 71 +/- 10 years, 55% male) and Western Germany (n = 212, age 73 +/- 9 years, 50% male) were analyzed separately since there is a longer history of PETN use in Eastern Germany. RESULTS: Significantly more patients were treated with PETN in Eastern Germany (61 vs. 11%, p < 0.05). The patient groups treated with PETN and ISDN differed with respect to sex and comorbidity. PETN therapy was more expensive than ISDN therapy in both German regions (adjusted cost differences were 10 and 17 Euro). However, when comedication was taken into account, a smaller cost increase after the index date was observed in the PETN group than in the ISDN group (non-significant cost savings of 43 and 52 Euro after adjustment for Western and Eastern Germany, respectively). CONCLUSION: PETN therapy tends to produce a saving in costs compared to ISDN therapy in diabetic patients when costs for comedication are taken into account and after adjustment for age and comorbidity. The prescription patterns in Eastern and Western Germany and the patient characteristics of those receiving PETN and ISDN differed, indicating differences in patients selection and prescribing by physicians in the two regions.

Isopropanolic black cohosh extract and recurrence-free survival after breast cancer.

OBJECTIVE: To investigate the influence of an isopropanolic Cimicifuga racemosa extract (iCR) on recurrence-free survival after breast cancer, including estrogen-dependent tumors. METHODS: This pharmacoepidemiologic observational retrospective cohort study examined breast cancer patients treated at general, gynecological and internal facilities linked to a medical database in Germany. The main endpoint was disease-free survival following a diagnosis of breast cancer. The impact of treatment with iCR following diagnosis was analyzed by Cox-proportional hazards models, controlling for age and other confounders. RESULTS: Of 18,861 patients, a total of 1,102 had received an iCR therapy. The mean overall observation time was 3.6 years. Results showed that iCR was not associated with an increase in the risk of recurrence but associated with prolonged disease-free survival. After 2 years following initial diagnosis, 14% of the control group had developed a recurrence, while the iCR group reached this proportion after 6.5 years. The primary Cox regression model controlling for age, tamoxifen use and other confounders demonstrated a protractive effect of iCR on the rate of recurrence (hazard ratio 0.83, 95% confidence interval 0.69 0.99). This effect remained consistent throughout all variations of the statistical model, including subgroup analyses. TNM status was unknown but did not bias the iCR treatment decision as investigated separately. Hence, it was assumed to be equally distributed between treatment groups. Correlation analyses showed good internal and external validity of the database. CONCLUSION: An increase in the risk of breast cancer recurrence for women having had iCR treatment, compared to women not treated with iCR is unlikely.

Off-label use of proton pump inhibitors and P-blockers in general practices: an analysis using the Disease Analyzer--mediplus patient database.

OBJECTIVE: The off-label use of medicines is a widespread phenomenon in medical practice but discussion on the legality of using drugs outside their licensed indications is still ongoing. Prescription recommendations and prescribing habits can differ greatly. We have used a database tool to analyze replies to a batch of questions which included the question "Is the off-label use of medications common?". The analysis was carried out using the Disease Analyzer--mediplus patient database, which is a database tool registered in Germany. It enabled the anonymous access to a representative panel of physicians and patients. More than 1,500 medical practices representing approximately 2.5 million patients were analyzed in a cross-sectional or longitudinal manner. The Disease Analyzer--mediplus database is unique in that it has direct links to individual diagnoses and the corresponding therapy. RESULTS: The findings demonstrated that proton pump inhibitors (PPI), which are licensed for the treatment of gastric ulcer and gastric reflux, are also used off-label in gastritis. The off-label use varies from 30 - 40% of prescriptions. The data indicate that the prescribing behavior has been influenced by the ending of the patent protection on omeprazole. A second instance which has been identified involves the beta-blocker carvedilol, which is licensed for the treatment of heart failure (24% of the total number of patients receiving the drug) but it was found that other beta-blockers are used off-label in this indication at a rate of more than 10% of prescriptions. CONCLUSION: The off-label use of drugs is high, especially in gastritis and heart failure. The investigation has also confirmed that the Disease Analyzer--mediplus database provides quantitative and qualitative analyses combining all relevant information concerning physicians, patients, diagnoses and therapy and that this information can be used to evaluate prescribing habits and trends with regard to the off-label use of drugs.

Doctors' prescription behaviour regarding dosage recommendations for preparations of kava extracts.

BACKGROUND: There are many publications on the use of kava extracts as a treatment alternative to tricyclic antidepressants and benzodiazepines, but little has been done to investigate the potential adverse effects that may be associated with prolonged or high-dose usage. OBJECTIVES: To investigate the extent to which physicians comply with the recommended daily dose (RDD) of an antidepressant such as kava and the consequences of this behaviour with regard to the safety and efficacy of frequently prescribed kava extracts (Trade names: Antares, Laitan and Kavasporal forte). METHOD: The analysis was carried out using the patient database MediPlus, which provides anonymous access to a representative and valid panel of physicians and patients in Germany. RESULTS: Prescriptions for Antares showed that the RDD of 1 tablet per day was exceeded in 58.2% of the cases, while those for Laitan showed that the RDD of 1 capsule per day was significantly exceeded in 75.6% of the cases; a one-off prescription was issued in 66% of the cases. As a result, the required effect diminished very quickly. Prescriptions for Kavasporal forte showed that the daily dosage of 2 capsules per day complied with the recommendations in only 49.1% of the cases; in 38.8% of the cases, the dosage dropped below the respective recommendation. As a consequence, the lower-dosed Kavasporal forte was prescribed for longer periods than the higher-dosed Antares and Laitan. CONCLUSIONS: In the case of a low-dosage recommendation, we saw a trend to over-dose in prescribing behaviour, which increases the risk of undesirable adverse reactions. On the other hand, we saw a trend to under-dose in the case of a higher dosage recommendation. This fact may explain the unexpected inefficacy of the therapy. These trends affected the duration of therapy, whereby a dosage lower than the RDD was prescribed for a longer period than a dosage higher than the RDD.

Lipid-lowering therapy: do hospitals influence the prescribing behavior of general practitioners?

OBJECTIVE: This investigation addresses the question whether physicians in hospitals influence the prescribing behavior of general practitioners regarding patients who are discharged following hospitalization. Case studies for patients on lipid-lowering therapy were used as an example. METHODS: All analyses described were carried out with mediplus, a longitudinal patient database with anonymous access to a representative and valid panel of physicians and patients in Germany. A total of more than 1,000 medical practices with over 6 million patients and over 100 million prescriptions can be analyzed using a cross- and/or longitudinal section of the database. The longest time period per patient exceeds 12 years commencing in 1989 and there are monthly updates. This allows not only cross-tabulation analysis but also time-dependent longitudinal analysis. RESULTS: The results of the study demonstrated that hospitals significantly influence the prescribing behavior of general practitioners. The sum of lipids lowering drugs prescribed in hospitals after admission increased by approximately 45% compared to the initial situation in practices. Physicians in hospitals play a significant role in causing a shift in treatment patterns of practice-based physicians with a reduction in use traditional fibrates in favor of cholesterin synthesizing enzyme inhibitors. CONCLUSION: The results of this investigation showed a significant increase in lipid-lowering therapy with a shift from fibrates to the more innovative CSE-inhibitors in the treatment pattern of patients following hospitalization. This study also demonstrates that the patient database used provides a useful insight into the extent of hospital physician influence on prescribing behavior of general practitioners and that this behavior can be quantified.

Treatment behavior of doctors regarding Helicobacter pylori infections.

OBJECTIVE: Since the detection of the gastric acid resistant bacterium Helicobacter pylori in the year 1982 there has been a fundamental change regarding the therapy of ulcers. According to expert opinion these infections should be treated and eradicated, whereby the so-called triple-therapies are considered to be the most effective ones. Whether such recommendations to eradicate Helicobacter pylori can be put to use in daily practice is an important question that is frequently asked. METHODS: All analyses described in the study here were done using mediplus, a longitudinal patient database with anonymous access to a representative and valid panel of physicians and patients within Germany. A total of more than 1,000 medical practices and over 75 million prescriptions can be analyzed in a cross- and/or longitudinal section. The longest time period per patient is more than 10 years starting in 1989 with monthly updates. RESULTS: With regard to existing recommendations, doctors overestimate their own compliance with the recommendations because only a fraction of traceable Helicobacter pylori infections are actually eradicated. Within the period of observation the therapy behavior has changed significantly in favor of the triple-therapies, but there are relevant differences between practitioners and internal specialists. DISCUSSION: Only a fraction of traceable Helicobacter pylori infections are adequately treated by doctors. The results show a very alarming situation due to the gap between "state of the art" and what is being achieved and carried out in daily practice. The potential for possible cost reductions and saving on resources is probably high. CONCLUSION: The results lead to the conclusion that in the treatment of Helicobacter pylori infections there is a potential for cost saving which is unused from the pharmacoeconomical point of view.

Use of the mediplus patient database in healthcare research.

OBJECTIVE: Public health systems require fast and precise analyses of physicians' day-to-day diagnoses and therapy behavior regarding qualitative, safety or economical aspects. A partnership between physicians in practices and a database organization (IMS Health, Frankfurt, Germany) which has been in existence for more than 10 years has developed a procedure for documenting various types of studies with regard to diagnosis and therapy behavior. This endeavor has facilitated scientific progress by providing precise analytical information and guidelines. METHODS: The database used has the name mediplus. It is a longitudinal patient database with anonymous access to a representative and valid panel of physicians and patients in Germany. A total of more than 1,000 medical practices and over 75 million prescriptions have been documented in a cross and/or longitudinal section. The longest time period per patient is more than 10 years starting in 1989, with monthly updates. RESULTS: Analyses have been obtained detailing prescription behavior of doctors regarding diabetes therapy and enable recommendations to be made regarding the therapy of migraine and the eradication of Helicobacter pylori infections. Information is also retrievable on drug safety studies in general and the extent to which hospitals influence the prescription behavior of doctors treating patients after discharge. DISCUSSION: The mediplus patient database combines all decision relevant information on physicians, patients, diagnoses and course of therapies and thus makes possible the investigation of the courses of diseases and therapy patterns. The monthly update enables trends to be identified at an early stage. The mediplus database is an ideal instrument for the enforcement of quantitative and qualitative analyses of patient histories because it directly links the individual diagnoses with the corresponding therapies. The database is currently undergoing extension with additional specialist groups such as pediatricians, neurologists, orthopedists, urologists, ENT specialists, surgeons and pulmonologists.

Compliance with prescription recommendations by physicians in practices.

OBJECTIVES: Few investigations are available on the primary supply of patients in Germany. But they play a key role due to their relevance in health politics and economics. An analysis has been carried out to determine the extent to which physicians in practices adhere to the recommendations in the package inserts and to determine the consequences of this behavior regarding the safety and efficacy of prescribed drugs. METHOD: The analysis was carried out with the IMS HEALTH mediplus patient database, which is a database providing anonymous access to a representative panel of physicians and patients in Germany. More than 1,000 medical practices including more than 5 million patients and over 75 million prescriptions can be analyzed in a cross and/or longitudinal section. The evaluation time period per patient currently exceeds 10 years with monthly updates. RESULTS: Kava-Kava drug prescriptions indicate that the recommended daily dose was significantly overstepped in 78% of the cases. The recommended daily dose complied in only 41% of the cases whereas in 3 9% of the cases, the drug was underdosed. DISCUSSION: These results may give an explanation why Kava-Kava prescriptions are associated with a high incidence of adverse drug reactions. On the other hand, lack of efficacy in many patients was mainly due to the fact that the drug was underdosed.

Migraine consultation patterns in primary care. Results from the PCAOM study 1994-96.

In order to establish a basis for the planning of improved medical care of migraine in Germany, we report on the proportion of migraine patients under primary care and the continuity of consultations for migraine as determined by age, gender, and history of migraine and nonmigraine practice contact (Primary Care of Migraine, PCAOM Study). A primary-care-physician-based migraineurs' sample of 16,573 women and 4,636 men (MediPlus, IMS Health) was placed in relation to cases expected according to International Headache Society criteria in the base population, and was followed for up to 3 years for repeat consultations. Overall, no more than 51% and 37%, respectively, of female and male statutory health-insured migraine headache sufferers had a migraine diagnosis mentioned at least once a year in primary care. At younger ages, substantially less advantage was taken of available primary healthcare for migraine; 79% of the women and 74% of the men were estimated to present again to the same primary-care physician within 3 years because of migraine, the corresponding figures for patients with no history of migraine in the practice concerned being 41% and 31%, respectively. Following first migraine contacts, time to recontact and quarterly recontact prevalences for migraine did not differ, whether on the basis of an established nonmigraine primary care relationship or a first encounter with a medical practice. Trust evidenced by an existing nonmigraine doctor-patient relationship apparently did not carry over to migraine. Results indicate that one of the greatest challenges in relation to the care of migraine patients in Germany is to establish and maintain solid doctor-patient relationships.