Lieven Annemans

Interpreting Indirect Treatment Comparisons and Network Meta-Analysis for Health-Care Decision Making: Report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: Part 1

Evidence-based health-care decision making requires comparisons of all relevant competing interventions. In the absence of randomized, controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best choice(s) of treatment. Mixed treatment comparisons, a special case of network meta-analysis, combine direct and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than a traditional meta-analysis. This report from the ISPOR Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on the interpretation of indirect treatment comparisons and network meta-analysis to assist policymakers and health-care professionals in using its findings for decision making. We start with an overview of how networks of randomized, controlled trials allow multiple treatment comparisons of competing interventions. Next, an introduction to the synthesis of the available evidence with a focus on terminology, assumptions, validity, and statistical methods is provided, followed by advice on critically reviewing and interpreting an indirect treatment comparison or network meta-analysis to inform decision making. We finish with a discussion of what to do if there are no direct or indirect treatment comparisons of randomized, controlled trials possible and a health-care decision still needs to be made.

Gout in the UK and Germany: Prevalence, comorbidities and management in general practice 2000-2005

Objective: To investigate and compare the prevalence, comorbidities and management of gout in practice in the UK and Germany. Methods: A retrospective analysis of patients with gout, identified through the records of 2.5 million patients in UK general practices and 2.4 million patients attending GPs or internists in Germany, using the IMS Disease Analyzer. Results: The prevalence of gout was 1.4% in the UK and Germany. Obesity was the most common comorbidity in the UK (27.7%), but in Germany the most common comorbidity was diabetes (25.9%). The prevalence of comorbidities tended to increase with serum uric acid (sUA) levels. There was a positive correlation between sUA level and the frequency of gout flares. Compared with those in whom sUA was <360 μmol/l (<6 mg/dl), odds ratios for a gout flare were 1.33 and 1.37 at sUA 360–420 μmol/l (6–7 mg/dl), and 2.15 and 2.48 at sUA >530 μmol/l ( >9 mg/dl) in the UK and Germany, respectively (p<0.01). Conclusions: The prevalence of gout in practice in the UK and Germany in the years 2000–5 was 1.4%, consistent with previous UK data for 1990–9. Chronic comorbidities were common among patients with gout and included conditions associated with an increased risk for cardiovascular disease, such as obesity, diabetes and hypertension. The importance of regular monitoring of sUA in order to tailor gout treatment was highlighted by data from this study showing that patients with sUA levels ⩾360 μmol/l (⩾6 mg/dl) had an increased risk of gout flares.

Systematic review: Effects, design choices, and context of pay-for-performance in health care

BackgroundPay-for-performance (P4P) is one of the primary tools used to support healthcare delivery reform. Substantial heterogeneity exists in the development and implementation of P4P in health care and its effects. This paper summarizes evidence, obtained from studies published between January 1990 and July 2009, concerning P4P effects, as well as evidence on the impact of design choices and contextual mediators on these effects. Effect domains include clinical effectiveness, access and equity, coordination and continuity, patient-centeredness, and cost-effectiveness.MethodsThe systematic review made use of electronic database searching, reference screening, forward citation tracking and expert consultation. The following databases were searched: Cochrane Library, EconLit, Embase, Medline, PsychINFO, and Web of Science. Studies that evaluate P4P effects in primary care or acute hospital care medicine were included. Papers concerning other target groups or settings, having no empirical evaluation design or not complying with the P4P definition were excluded. According to study design nine validated quality appraisal tools and reporting statements were applied. Data were extracted and summarized into evidence tables independently by two reviewers.ResultsOne hundred twenty-eight evaluation studies provide a large body of evidence -to be interpreted with caution- concerning the effects of P4P on clinical effectiveness and equity of care. However, less evidence on the impact on coordination, continuity, patient-centeredness and cost-effectiveness was found. P4P effects can be judged to be encouraging or disappointing, depending on the primary mission of the P4P program: supporting minimal quality standards and/or boosting quality improvement. Moreover, the effects of P4P interventions varied according to design choices and characteristics of the context in which it was introduced.Future P4P programs should (1) select and define P4P targets on the basis of baseline room for improvement, (2) make use of process and (intermediary) outcome indicators as target measures, (3) involve stakeholders and communicate information about the programs thoroughly and directly, (4) implement a uniform P4P design across payers, (5) focus on both quality improvement and achievement, and (6) distribute incentives to the individual and/or team level.ConclusionsP4P programs result in the full spectrum of possible effects for specific targets, from absent or negligible to strongly beneficial. Based on the evidence the review has provided further indications on how effect findings are likely to relate to P4P design choices and context. The provided best practice hypotheses should be tested in future research.

Clinical and Economic Outcomes in Critically Ill Patients with Nosocomial Catheter-Related Bloodstream Infections

BACKGROUND Central venous catheters are universally used during the treatment of critically ill patients. Their use, however, is associated with a substantial infection risk, potentially leading to increased mortality and costs. We evaluate clinical and economic outcomes associated with nosocomial central venous catheter-related bloodstream infection (CR-BSI) in intensive care unit (ICU) patients. METHODS A retrospective (1992-2002), pairwise-matched (ratio of case patients to control subjects, 1:2 or 1:1), risk-adjusted cohort study was performed at a 54-bed general ICU at a university hospital. ICU patients with microbiologically documented CR-BSI (n = 176) were matched with control subjects (n = 315) on the basis of disease severity, diagnostic category, and length of ICU stay (equivalent or longer) before the onset of CR-BSI in the index case patient. Clinical outcome was principally evaluated by in-hospital mortality. Economic outcome was evaluated on the basis of duration of mechanical ventilation, length of ICU and hospital stays, and total hospital costs, as derived from the patients hospital invoices. RESULTS The attributable mortality rate for CR-BSI was estimated to be 1.8% (95% confidence interval, -6.4% to 10.0%); in-hospital mortality rates for patients with CR-BSI and matched control subjects were 27.8% and 26.0%, respectively. CR-BSI was associated with significant excesses in duration of mechanical ventilation, duration of ICU and hospital stays, and a significant increase in total hospital cost. Linear regression analysis with adjustment for duration of hospitalization and clinical covariates, revealed that CR-BSI is independently associated with higher costs. CONCLUSIONS In ICU patients, CR-BSI does not result in increased mortality. It is, however, associated with a significant economic burden, emphasizing the importance of continuous efforts in prevention.

Effectiveness of pharmacist intervention for asthma control improvement

Education on optimal medication use is an essential strategy to improve asthma control. The current authors investigated whether pharmacist interventions, focused on appropriate use of asthma medication and tailor-made to the patients current asthma control, would improve asthma control in adult patients. A 6-month randomised, controlled, parallel-group trial was conducted in 66 community pharmacies in Belgium. Patients were randomly assigned to receive usual pharmacist care (n = 94) or a pre-defined pharmacist intervention (n = 107). This intervention mainly focused on improving inhalation technique and medication adherence. Primary outcome was the level of asthma control, as assessed by the Asthma Control Test® (ACT). Mean ACT scores did not change from baseline for both study groups. However, a pre-defined subgroup analysis of patients having insufficiently controlled asthma at baseline showed that the intervention had significantly increased the ACT score after 6 months compared with usual care. The intervention also reduced, for the complete study group, reliever medication use and the frequency of night-time awakenings due to asthma. Inhalation technique and adherence to controller medication were significantly better in the intervention group. In conclusion, pragmatic community pharmacy-based programmes can significantly improve therapeutic outcomes in adult asthma patients.

Incidence, medical resource utilisation and costs of hyperuricemia and tumour lysis syndrome in patients with acute leukaemia and non-Hodgkin's lymphoma in four European countries

Hyperuricemia (HU) and tumour lysis syndrome (TLS) are complications of acute leukaemia and non-Hodgkin lymphoma (NHL) leading to increased morbidity and mortality. The objective of this study was to define incidence and calculate health care cost associated with HU and TLS. 788 acute leukaemia and NHL patients from Belgium, The Netherlands, Spain and UK were screened retrospectively for HU and TLS. Resource use related to HU and TLS was recorded and costs were calculated applying local unit costs. Results showed that HU occurred in 18.9% of patients, and 27.8% of them fulfilled TLS criteria. The cost of HU without TLS was €672 (SE 181), the cost of TLS €7,342 (SE 1,412). TLS requiring dialysis incurred an average cost of €17,706. In conclusion, it is noted that the observed incidence rates were lower than earlier reports. In addition, some risk factors for HU and TLS (e.g. paediatric patients versus adults) were not associated with increased rates of HU or TLS as a consequence of higher rates of prevention. TLS cases incurred 11 times higher costs than HU cases in which TLS was absent. The main cost drivers in TLS are interventions requiring intensive care.

Health economic consequences related to the diagnosis of Fibromyalgia syndrome

OBJECTIVE To evaluate the use and costs of medical resources before and after a diagnosis of fibromyalgia syndrome (FMS) in a large primary care population in the UK. METHODS We applied an existing data set for medical resource use among patients with a coded diagnosis of FMS. The observed quantities of 157 types of medical resource use before and after the diagnosis of FMS were multiplied by unit costs in order to calculate the cost of care (general practitioner [GP] visits, drugs, referrals, and diagnostics) within the National Health Service, excluding hospital costs. Costs before diagnosis were used in a trend analysis to predict later costs, assuming the diagnosis had never been made, and these predicted costs were compared with the observed costs after diagnosis. RESULTS Following a diagnosis of FMS, a decrease in costs as compared with the predicted trend was observed. In the 4 years after diagnosis, the average difference between the predicted and observed cost was pound66.21 per 6 months per patient. This suggests that making the diagnosis leads to savings and a decrease in resource use. The main effect was observed for tests and imaging ( pound24.02 per 6 months), followed by pharmaceuticals ( pound22.27), referrals ( pound15.56), and GP visits ( pound4.36). CONCLUSION Failure to diagnose a true case of FMS has its own costs, largely in excess GP visits, investigations, and prescriptions.

Societal and patient burden of fibromyalgia syndrome.

AbstractFibromyalgia syndrome (FMS) is an under-diagnosed disorder of unknown aetiology, characterized by chronic widespread muscular pain, often accompanied by somatic and psychological symptoms. Several studies have described the impact of FMS on patients’ functionality, disability and quality of life. Other studies have reported on the burden to patients, healthcare payers and society. This review brings the existing evidence together and concludes that the patient burden of fibromyalgia is very high in comparison with many other conditions. The burden to healthcare payers and society is important as well, and can be mostly explained by factors not directly related to the treatment of FMS. Data suggest that the cost before diagnosis may even be higher than the cost after diagnosis. It is very likely that the combination of symptoms not only complicates the recognition and treatment of FMS, but also magnifies the burden of FMS.Despite the complex and controversial construct of this syndrome, the results in terms of patient, healthcare payer and societal burden are quite consistent.

Challenges in the Development and Reimbursement of Personalized Medicine—Payer and Manufacturer Perspectives and Implications for Health Economics and Outcomes Research: A Report of the ISPOR Personalized Medicine Special Interest Group

BACKGROUND Personalized medicine technologies can improve individual health by delivering the right dose of the right drug to the right patient at the right time but create challenges in deciding which technologies offer sufficient value to justify widespread diffusion. Personalized medicine technologies, however, do not neatly fit into existing health technology assessment and reimbursement processes. OBJECTIVES In this article, the Personalized Medicine Special Interest Group of the International Society for Pharmacoeconomics and Outcomes Research evaluated key development and reimbursement considerations from the payer and manufacturer perspectives. METHODS Five key areas in which health economics and outcomes research best practices could be developed to improve value assessment, reimbursement, and patient access decisions for personalized medicine have been identified. RESULTS These areas are as follows: 1 research prioritization and early value assessment, 2 best practices for clinical evidence development, 3 best practices for health economic assessment, 4 addressing health technology assessment challenges, and 5 new incentive and reimbursement approaches for personalized medicine. CONCLUSIONS Key gaps in health economics and outcomes research best practices, decision standards, and value assessment processes are also discussed, along with next steps for evolving health economics and outcomes research practices in personalized medicine.

Daily cost of antimicrobial therapy in patients with Intensive Care Unit-acquired, laboratory-confirmed bloodstream infection

This study analysed daily antimicrobial costs of Intensive Care Unit (ICU)-acquired, laboratory-confirmed bloodstream infection (BSI) per patient admitted to the ICU of a university hospital, based on prospectively collected data over a 4-year period (2003-2006). Costs were calculated based on the price of the agent(s) initiated on the first day of appropriate treatment and according to: (i) focus of infection; (ii) pathogen; and (iii) antimicrobial agent. The study included 310 adult patients who developed 446 BSI episodes. Mean overall daily antimicrobial cost was euro114.25. Daily antimicrobial cost was most expensive for BSIs with unknown focus (euro137.70), followed by catheter-related (euro122.73), pulmonary (euro112.80), abdominal (euro98.00), wound (euro89.21), urinary (euro87.85) and other inciting focuses (euro81.59). Coagulase-negative staphylococci were the most prevalent pathogens isolated. Treatment of BSIs caused by Candida spp. was the most costly. The daily antimicrobial costs per infected patient with multidrug-resistant BSI was ca. 50% higher compared with those without (euro165.09 vs. euro82.67; P<0.001). Among the total of 852 prescriptions, beta-lactam antibiotics accounted for approximately one-third of the overall daily cost of antimicrobial agents. The antibiotic cost associated with ICU-acquired, laboratory-confirmed BSI is significant and should be reduced by implementing infection control measures and preventive strategies.