Intraindividual Comparisons to Determine Comparative Effectiveness: Their Relevance for G-BA's Health Technology Assessments.

OBJECTIVES: Health technology assessments (HTA) rely on head-to-head comparisons. We searched for intraindividual comparisons (IIC) qualifying as head-to-head design to develop comparative evidence. METHODS: Gemeinsamer Bundesausschuss (G-BA) appraisals between January 2011 and April 2020 were reviewed for inclusion of IIC. Identified IIC were grouped according to disease characteristics into nonprogressive, progressive, irregular, or symmetrical conditions. Evaluation of IIC by Institut für Qualität und Wirschaftlichkeit im Gesundheitswesen (IQWIG) and acceptance of IIC by G-BA were determined, and criteria for the usage and quality of IIC were developed. RESULTS: A total of 483 appraisals finalized between January 2011 and April 2020 were reviewed. Eleven appraisals included IIC: nonacog beta (hemophilia B), turoctocog alpha (hemophilia A), emicizumab (2 appraisals: hemophilia A), pasireotide (unresectable pituitary tumor), lomitapid (homozygous familial hypercholesterolemia), glycerol phenylbutyrate (2 appraisals: urea cycle disorders), asfotase alfa (hypophosphatasia), lumacaftor (cystic fibrosis), and larotrectinib (NTRK+ solid tumors). All those appraisals related to rare genetic conditions with hemophilia and its bleeding rate are considered mainly a nonprogressive condition. All the other diseases show progressive disease characteristics. None of the identified IIC has been accepted by G-BA. Inconsistencies of before/after study design, lack of clarity on treatments prior to the switch, and different time intervals were among the most commonly cited methodological concerns. CONCLUSIONS: IICs provide a rare opportunity to determine comparative effectiveness in distinct clinical settings that are not suitable or difficult to randomize into parallel groups. While manufacturers and researchers should aim for highest methodological standards when running an IIC, HTA bodies should accept IIC in distinct settings when determining relative effectiveness.

Type I Diabetes is the Main Cost Driver in Autoimmune Polyendocrinopathy.

CONTEXT: Autoimmune polyendocrinopathy (AP), a chronic complex orphan disease, encompasses at least two autoimmune-induced endocrine diseases. OBJECTIVE: To estimate for the first time total, indirect and direct costs for patients with AP, as well as cost drivers. DESIGN: Cross-sectional cost of illness study. SETTING: Academic tertiary referral center for AP. PATIENTS: 146 consecutive, unselected AP patients. INTERVENTION: Interviews pertaining to patients' socioeconomic situation covered a recall period of 12 months. Both the human capital (HCA) and the friction cost approaches (FCAs) were applied as estimation methods. MAIN OUTCOME MEASURES: Direct and indirect annual costs, and sick leave and medication costs. RESULTS: AP markedly impacts healthcare expenses. Mean overall costs of AP in Germany ranged from €5 971 090 to €29 848 187 per year (HCA). Mean indirect costs ranged from €3 388 284 to €16 937 298 per year (HCA) while mean direct costs ranged from €2 582 247 to €12 908 095/year. Mean direct costs per year were €1851 in AP patients with type 1 diabetes (T1D, 76%) and €671 without T1D, which amounts to additional direct costs of €1209 for T1D when adjusting for concomitant autoimmune disease (95% CI = €1026-1393, P < 0.0001). Sick leave cost estimates for AP patients with T1D exceeded those without T1D by 70% (FCA) and 43% (HCA), respectively. In multiple regression analyses, T1D predicted total and direct costs, medication costs and costs for diabetic devices (all P < 0.001). Overall, AP patients with T1D were 54% (FCA) more expensive than those without T1D. CONCLUSIONS: Public health socioeconomic relevance of AP was demonstrated, with T1D as main cost driver.

Pregnancy Related Health Care Needs in Refugees-A Current Three Center Experience in Europe.

Background: Immigration into Europe has reached an all-time high. Provision of coordinated healthcare, especially to refugee women that are at increased risk for adverse pregnancy outcomes, is a challenge for receiving health care systems. Methods: We assessed pregnancy rates and associated primary healthcare needs in three refugee cohorts in Northern Germany during the current crisis. Results: Out of n = 2911 refugees, 18.0% were women of reproductive age, and 9.1% of these were pregnant. Pregnancy was associated with a significant, 3.7-fold increase in primary health care utilization. Language barrier and cultural customs impeded healthcare to some refugee pregnant women. The most common complaints were demand for pregnancy checkup without specific symptoms (48.6%), followed by abdominal pain or urinary tract infections (in 11.4% of cases each). In 4.2% of pregnancies, severe complications such as syphilis or suicide attempts occurred. Discussion: We present data on pregnancy rates and pregnancy associated medical need in three current refugee cohorts upon arrival in Germany. Healthcare providers should be particularly aware of the requirements of pregnant migrants and should adapt primary caretaking strategies accordingly.

Measles, Rubella and Varicella IgG Seroprevalence in a Large Refugee Cohort in Germany in 2015: A Cross-Sectional Study.

INTRODUCTION: The current extent of migration to the European continent is associated with exceptional humanitarian challenges. In 2015, Western Europe faced an enormous immigration of refugees with largely unknown protection status against communicable diseases. To adapt vaccination strategies, we aimed at assessing seroprevalences against three of the most relevant vaccine preventable diseases (VPD) in a large representative cohort. METHODS: IgG seroprevalences for rubella, varicella (n = 554) and measles (n = 552) were analyzed in inhabitants of a Northern German refugee camp in the summer of 2015. RESULTS: Of the refugees, 77.9% were male (mean age 27.4 years for male and 26.8 years for female migrants). Most refugees came from the Eastern Mediterranean region (83.4%), followed by immigrants from Eastern Europe (7.4%), Africa (4.6%), or other regions (4.5%). The vast majority of migrants were protected against the three VPD: overall IgG seropositivity was 88.5% for measles, 77.9% for rubella and 95.9% for varicella. However, seroprevalences showed age- and origin-dependent differences. Varicella immunity, for example, was lowest in the youngest age group of both genders (10.1% of male/4.5% of female seronegative refugees <18 years vs. 100% seropositivity in men and women >49 years of age), and Sudanese migrants displayed particularly low rates of protection against varicella. CONCLUSION: In accordance with previous studies, our analyses show an overall satisfactory seropositivity against measles, rubella, and varicella in refugees entering Europe during the current exodus. However, this rate is not sufficient for preventing transmission. For example, the rate of 12.9-17.9% female refugees at reproductive age unprotected against measles and the low protection levels against varicella in minors observed in our cohort emphasizes the need for stringent vaccination strategies in refugees coming to Europe during the current crisis.

Cost-effectiveness simulation model of biologic strategies for treating to target rheumatoid arthritis in Germany.

OBJECTIVES: The treatment of active rheumatoid arthritis (RA) usually requires different therapeutic options used sequentially in case of an insufficient response (IR) to previous agents. Since there is a lack of clinical trials comparing biologic treatment sequences, simulation models might add to the understanding of optimal treatment sequences and their cost-effectiveness. The objective of this study was to assess the cost-effectiveness of different biologic treatment strategies in patients with an IR to anti-TNF agents, based on levels of disease activity from the German public payer's perspective. METHODS: A cost-effectiveness sequential model was developed in accordance with local RA treatment strategies, using DAS28 scores as dichotomous effectiveness endpoints: achieving remission/no remission (RS/no RS) or a state of low disease activity (LDAS/no LDAS). Costs were estimated using resource utilisation data obtained from a large observational German cohort. Advanced simulations were conducted to assess the cost-effectiveness over 2 years of four sequential biologic strategies composed of up to 3 biologic agents, namely anti-TNF agents, abatacept or rituximab, in patients with moderate-to-severe active RA and an IR to at least one anti-TNF agent. RESULTS: Over two years, the biological sequence including abatacept after an IR to one anti-TNF agent appeared the most effective and cost-effective versus (vs.) use after two anti-TNF agents (€633 vs. €1,067/day in LDAS and €1,222 vs. €3,592/day in remission), and vs a similar sequence using rituximab (€633 vs. €728/day in LDAS and €1,222 vs. €1,812/day in remission). The sequence using a 3rd anti-TNF agent was less effective and cost-effective than the same sequence using abatacept (€2,000 vs. €1,067/day in LDAS and €6,623 vs. €3,592/day in remission). All differences were statistically significant (p<0.01). CONCLUSIONS: The results suggest that in patients with an IR to at least one anti-TNF agent, biologic sequences including abatacept appear more efficacious and cost-effective than similar sequences including rituximab or only cycled anti-TNF agents.

Public health relevance of Graves' orbitopathy.

CONTEXT: Disfiguring proptosis and functional impairment in patients with Graves' orbitopathy (GO) may lead to impaired earning capacity and to considerable indirect/direct costs. OBJECTIVE: The aim of the study was to investigate the public health relevance of GO. DESIGN AND SETTING: This cross-sectional study was performed between 2005 and 2009 at a multidisciplinary university orbital center. PATIENTS: A total of 310 unselected patients with GO of various degrees of severity and activity participated in the study. INTERVENTIONS: We conducted an observational study. MAIN OUTCOME MEASURES: We measured work disability and sick leave as well as the resulting indirect/direct costs of GO-specific therapies. RESULTS: Of 215 employed patients, 47 (21.9%) were temporarily work disabled, and 12 (5.6%) were permanently work disabled. Five (2.3%) had lost their jobs, and nine (4.2%) had retired early. The mean duration of sick leave was 22.3 d/yr. Compared with the German average of 11.6 d/yr, 32 (15%) patients had taken longer sick leaves. The duration of sick leave correlated with the disease severity (P = 0.015), and work disability correlated with diplopia (P < 0.001). Multivariable analysis identified diplopia as the principal predictor for work disability (odds ratio, 1.7; P < 0.001). The average costs due to sick leave and work disability ranged between 3,301€ (4,153$) and 6,683€ (8,407$) per patient per year. Direct costs were 388 ± 56€ (488 ± 70$) per patient per year and per year were higher in sight-threatening GO (1,185 ± 2,569€; 1,491 ± 3,232$) than in moderate-to-severe (373 ± 896€; 469 ± 1,127$; P = 0.013) or in mild GO (332 ± 857€; 418 ± 1,078$; P = 0.016). Total indirect costs ranged between 3,318€ (4,174$) (friction cost method) and 6,738€ (8,476$) (human capital approach). Work impairment as well as direct and indirect costs of GO significantly correlated with the scores of the internationally standardized and specific GO quality-of-life questionnaire. CONCLUSIONS: Productivity loss and a prolonged therapy for GO incur great indirect and direct costs.

Interest of modelling in rheumatoid arthritis.

Such as prospective studies can provide evidence-based information for clinicians and regulatory agencies, modelling studies provide useful information when experimental studies are to complex, too long, or too expensive to carry out. If modelling has been widely used in pharmacokinetics, it is in the field of pharmacoeconomics that numerous models have been published in recent years, including models relevant to the management of rheumatoid arthritis (RA). The most common modelling techniques published in RA are decision trees and Markov models which are used to perform cost-effectiveness and cost-utility analyses using real or simulated populations. This paper reviews the main types of modelling techniques used in pharmacoeconomic studies with the aim of clarifying their interest and limitations for the clinicians. Generating such evidence is highly relevant to assisting clinical recommendations and reimbursement decisions towards enabling the optimal management of RA and reducing its overall clinical and economic burden, for the benefits of patients and health systems.

Cost-effectiveness of TNF-α inhibition in active ankylosing spondylitis: a systematic appraisal of the literature.

Ankylosing spondylitis (AS) is the most frequent prototype of spondyloarthritides. Substantial direct costs and productivity losses often arise in young patients. Currently, tumor necrosis factor (TNF) inhibitors are the only approved therapy escalation when usual care (physiotherapy and NSAIDs) proves to be insufficient. Owing to their high medication costs, TNF inhibitors are a target of cost-effectiveness analyses. There is consistent evidence regarding the use of TNF inhibitors according to recommendations in patients with active AS finding TNF inhibitors to be cost effective from a societal perspective. However, there are relevant uncertainties (discontinuation rate and progression rate) in the long-term estimates of the cost-effectiveness analyses analyzed. Whether TNF inhibitors are cost effective from an insurance perspective in the long run will have to be addressed by models based on observational data.

Cost of illness in rheumatoid arthritis in Germany in 1997-98 and 2002: cost drivers and cost savings.

OBJECTIVE: Comparison of overall RA-related costs and of relative contribution of single-cost domains before and after the introduction of TNF-blocking agents in Germany. METHODS: Two cohorts of RA outpatients (ACR '87 criteria) with long-standing disease are assessed in terms of disease-related costs and cost composition (n = 106 patients in 1997-98 and n = 180 patients in 2002 with similar patient characteristics). Full-cost analyses are performed including direct disease-related costs (medical and non-medical) and productivity costs as collected by patient questionnaires. Absolute costs (€/patient/year) are compared and the impact of single-cost domains on overall costing in RA is estimated (relative proportions of cost components within samples). RESULTS: Overall costs are comparable (1997-98: €4280; 2002: €3830; not significant). Differences can be observed in medication (1997-98: €550; 2002: €1580; P < 0.001) and hospitalization costs (1997-98: €1240; 2002: €500; P < 0.001). Productivity costs are significantly lower (€1480 vs €850; P < 0.05) in 2002. The impact of medication costs is outstanding in the 2002 sample (42 vs 12%), the proportion of hospitalization costs is substantially lower (29 vs 13%). Costs for DMARDs in 2002 are mostly driven by TNF blockers (37%). The number of DMARDs per patient is higher in 2002 as are costs for osteoporosis medication and gastroprotective treatment. CONCLUSION: Although overall costs before and after the introduction of TNF blockers are comparable, the decrease in hospitalization and productivity costs is promising in terms of future long-term cost savings. The development of these aspects and of the increasing medication costs will have to be evaluated with longer time frames.

Cost-effectiveness analysis of rituximab treatment in patients in Germany with rheumatoid arthritis after etanercept-failure.

OBJECTIVE: The present health economic analysis investigated the cost-effectiveness-ratios of either (1) rituximab or (2) an alternative TNF-alpha-inhibiting agent as second line biological treatment in patients with active rheumatoid arthritis (RA) and an inadequate response to etanercept therapy. METHODS: Incremental cost per quality-adjusted life-year (QALY) gained by rituximab treatment of RA is compared to TNF-inhibitor change (standard sequence) in a Markov-model (perspective: health care payer, full life-time approach). Direct cost components taken into account were treatment costs (medication-, administration- and monitoring costs) and resource utilisation (outpatient costs, inpatient costs). Indirect costs were estimated separately by the assessment of impaired work capacity due to RA (2008 Euro currency, discount rate 3.5%). Utility measures for the different treatment options were obtained from the ACR-response rates of published pivotal clinical trials. RESULTS: Direct costs amount to euro 178,373 (standard sequence) and euro 192,295 (rituximab sequence), respectively, rendering incremental direct costs of euro 13,922. Incremental utilities yield 0.57 QALYs and the incremental cost-effectiveness-ratio (ICER) of rituximab compared to the standard sequence amounts to euro 24,517. Inclusion of indirect costs leads to less incremental costs and a lower ICER of euro 15,565/QALY. Thus, ICERs stay beneath the accepted threshold of euro 50,000/QALY. CONCLUSION: Rituximab appears to be a cost-effective treatment alternative compared to the switch between TNF-inhibitors as second line biological treatment in patients with active RA having failed etanercept.

Sustained effects of comprehensive inpatient rehabilitative treatment and sleeping neck support in patients with chronic cervicobrachialgia: a prospective and randomized clinical trial.

The objective of this study was to investigate the long-term efficacy of inpatient rehabilitation using sleeping neck support in patients suffering from chronic cervicobrachialgia. A prospective, randomized clinical trial with a 12-month follow-up was done. A total of 149 patients suffering from chronic cervicobrachialgia received a 4-week inpatient rehabilitation programme. The patients were randomly divided into two groups. The patients in one group were given a special neck pillow to use during and after the rehabilitative treatment (n=76); the patients in the other group were not given the pillow (n=73). Two weeks before, during, and after (3, 6, 9, and 12 months) the 4-week treatment period, the patients completed a questionnaire dealing with the intensity of their cervicobrachial complaints (pain intensity, muscular tension, paraesthesia, and sleep disorders caused by pain or paraesthesia). During the inpatient treatment period, no significant differences were detected between the groups; however, 1-12 months after discharge, the group with sleeping neck support showed a significantly (P<0.05) smaller increase in the intensity of cervical spine pain. Sleep disturbances caused by pain were also reduced significantly (P<0.001 after 3 months, respectively, P<0.05 after 12 months). Inpatient rehabilitative treatment has sustained effects in patients suffering from chronic cervicobrachialgia, particularly when a sleeping neck support is added.

Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival.

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m(2)), doxorubicin (50 mg/m(2)), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics, toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4+/-1.5 courses per patient). Mean maximum tumor size was 75 (+/-43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size 30 months, R(2)=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications were managed conservatively. The mortality within 6 weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were combined successfully in the palliative TACE treatment of advanced HCC resulting in high rates of tumor response and survival at limited toxicity. Favourable tumor response was associated with tumor extent and vascularization. TACE using DSM and Lipiodol can be considered a suitable palliative measure in patients who might not tolerate long acting embolizing agents.

Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma.

AIM: To evaluate the treatment effect of percutaneous ethanol injection (PEI) for patients with advanced, non-resectable HCC compared with combination of transarterial chemoembolisation (TACE) and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. METHODS: All patients who received PEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent: combination of TACE and repeated single-session PEI, repeated single-session PEI alone, repeated TACE alone, or best supportive care. Prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis, presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase (CHE), as well as Child-Pugh stage, alpha-fetoprotein (AFP), fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses. RESULTS: The 1- and 3-year survival of all patients was 73% and 47%. In the subgroup analyses, the combination of TACE and PEI (1) was associated with a longer survival (1-, 3-, 5-year survival: 90%, 52%, and 43%) compared to PEI treatment alone (2) (1-, 3-, 5-year survival: 65%, 50%, and 37%). Secondary PEI after initial stratification to TACE (3) yielded comparable results (1-, 3-, 5-year survival: 91%, 40%, and 30%) while PEI after stratification to best supportive care (4) was associated with decreased survival (1-, 3-, 5-year survival: 50%, 23%, 12%). Apart from the chosen treatment modalities, predictors for better survival were tumor number (n < 5), tumor size (< 5 cm), no ascites before PEI, and stable serum cholinesterase after PEI (P < 0.05). The mortality within 2 wk after PEI was 2.8% (n = 3). There were 24 (8.9%) major complications after PEI including segmental liver infarction, focal liver necrosis, and liver abscess. All complications could be managed non-surgically. CONCLUSION: Repeated single-session PEI is effective in patients with advanced HCC at an acceptable and manageable complication rate. Patients stratified to a combination of TACE and PEI can expect longer survival than those stratified to repeated PEI alone. Furthermore, patients with large or multiple tumors in good clinical status may also profit from a combination of TACE and reconsideration for secondary PEI.

Preoperative volume calculation of the hepatic venous draining areas with multi-detector row CT in adult living donor liver transplantation: Impact on surgical procedure.

OBJECTIVE: The purpose was to assess the volumes of the different hepatic territories and especially the drainage of the right paramedian sector in adult living donor liver transplantation (ALDLT). METHODS: CT was performed in 40 potential donors of whom 28 underwent partial living donation. Data sets of all potential donors were postprocessed using dedicated software for segmentation, volumetric analysis and visualization of liver territories. During an initial period, volumes and shapes of liver parts were calculated based on the individual portal venous perfusion areas. After partial hepatic congestion occurring in three grafts, drainage territories with special regard to MHV tributaries from the right paramedian sector, and the IRHV were calculated additionally. Results were visualized three-dimensionally and compared to the intraoperative findings. RESULTS: Calculated graft volumes based on hepatic venous drainage and graft weights correlated significantly (r = 0.86, P < 0.001). Mean virtual graft volume was 930 ml and drained as follows: RHV: 680 ml, IRHV: 170 ml (n = 11); segment 5 MHV tributaries: 100 ml (n = 16); segment 8 MHV tributaries: 110 ml (n = 20). When present, the mean aberrant venous drainage fraction of the right liver lobe was 28%. CONCLUSION: The evaluated protocol allowed a reliable calculation of the hepatic venous draining areas and led to a change in the hepatic venous reconstruction strategy at our institution.

Prediction of costs-of-illness in patients with low back pain undergoing orthopedic outpatient rehabilitation.

The objectives of this study were (1) to assess societal costs-of-illness and their changes in the year prior to and after outpatient rehabilitation (OPR) in initially gainfully employed persons with low back pain and (2) to identify predictors (cost drivers) for high overall costs in the year after the intervention. The health economical analysis is part of a prospective clinical trial investigating patients participating in orthopedic OPR. In all gainfully employed patients (n=244) resource consumption and productivity losses were assessed prior to OPR and 12 months afterwards. Overall annual medical costs per person were estimated. Parameters associated with high overall costs in the 12 months after OPR were predicted by multivariate logistic regression analysis. All sociodemographic, motivational, clinical, psychological, therapeutic and vocational variables were included as possible predictors. Costs due to sick leave periods represent the major component (83%/58%) of overall costs in both periods. The comparison of costs 12 months before and after OPR reveals a significant reduction from 8050 to 3200 per person, primarily caused by decreasing sick leave costs and the reduction of costs related to inpatient treatment. The prediction analysis reveals that patients with limited functional abilities, with problems due to strenuous labour, with low expectations in terms of possible improvement after OPR, with a high pain score or with limited satisfaction with working colleagues have a significantly higher risk for costs exceeding 2200 after OPR. The identified cost drivers can be used to develop multimodal therapeutic measures, which should be employed during the OPR intervention in order to prevent future costs.

[Costs of ambulatory care for RA patients in Germany]. / Arztkontaktpreise bei der ambulanten Versorgung der chronischen Polyarthritis in Deutschland.

BACKGROUND: In 2000, the Regional Cooperative Center for Rheumatic Conditions in Hannover, Germany, initiated a project to introduce and evaluate a case-based clinical quality management system to enhance the quality of care for patients with rheumatoid arthritis. Building on that, it was possible to combine all resource uses, as paid by the sickness funds, including those in ambulatory care. METHODS: The purpose of this study was to reach average "per-visit prices" for single physician visits, not only for rheumatologists, but also for other specialists as well as generalists. Those visits all had to be connected to the rheumatic condition of the patients. All ambulatory care visits for 1 year (2001) were evaluated. RESULTS: Due to the high number of physician visits of the 338 patients with clinically assured rheumatoid arthritis included in the study (rheumatologist visits 4,488, generalist visits 3,901), statistically significant subgroups could be built. The average costs per visit associated with rheumatoid arthritis are: rheumatologist euro 22.71; generalist euro 8.02; as well as other specialties ranging from euro 5.81 to euro 19.48. The low price for generalists care is due to the selection of the cohort, as all patients are under constant specialist care. The prices were further broken down to certain subgroups of care. CONCLUSION: The prices are calculated under the premises that no budgetary constraints apply to ambulatory care. This is not the reality in Germany. Hence, looking at the average frequency of rheumatologist visits in this cohort (13.2/year), the conclusion has to be that not all rheumatologic ambulatory care is being covered by the reimbursement system within the Statutory Health Insurance in Germany.

Indirect cost assessment in patients with rheumatoid arthritis (RA): comparison of data from the health economic patient questionnaire HEQ-RA and insurance claims data.

OBJECTIVE: To render information on the accuracy of patient-reported indirect cost data compared with payer-derived data of the real indirect costs on a patient-by-patient basis concerning disease-related productivity losses in rheumatoid arthritis (RA). METHODS: The assessment of indirect cost data was part of a clinical, multicenter, randomized RA trial. A total of 234 patients of working age with a diagnosis of RA (according to 1987 American College of Rheumatology criteria) were recruited. Demographics of the cohort were mean age 53 years, mean disease duration 8 years, 76% were women, and all had membership in the regional statutory health insurance plan. Every 3 months corresponding indirect cost data were derived for the cohort from a health economic questionnaire for cost assessment in patients with RA and the payer's database over a period of 18 months. Comparative statistical analyses were performed between patient-reported and insurance claims data. RESULTS: The mean annual productivity losses due to sick leave amounted to 14 and 17 days per patient (questionnaire versus payer data), and productivity losses due to work disability amounted to 3 days (both); monetary valuation renders overall costs of 1,240 and 1,590, respectively. The difference of 17% in overall productivity losses is not significant. Comparison of productivity losses reveals a strong correlation of r = 0.83 in those due to sick leave and of kappa = 0.84 in those due to work disability between questionnaire and payer data. CONCLUSION: The comparison of questionnaire and payer data shows that RA patients report their productivity losses adequately. Indirect cost assessment should therefore be included in further RA trials and observational studies.

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver.

AIM: In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver. METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m(2)) and additional transarterial chemoembolization procedures (50 mg/m(2) cisplatin, 50 mg/m(2) doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity. RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO III/IV) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo. CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.