Budgeting of non-commercial clinical trials: development of a budget tool by a public funding agency.

BACKGROUND: Investigator-led multicentre randomised trials are essential to generate evidence on the optimal use of medical interventions. These non-commercial trials are often hampered by underfunding, which may lead to difficulties in gathering a team with the necessary expertise, a delayed trial start, slow recruitment and even early trial discontinuation. As a new public funder of pragmatic clinical trials, the KCE Trials programme was committed to correctly pay all trial activities in order to assure timely delivery of high-quality trial results. As no appropriate trial budget tool was readily publicly available that took into account the costs for the sponsor as well as the costs for participating sites, we developed a tool to make the budgeting of a clinical trial efficient, transparent and fair across applicants. METHODS: All trial-related activities of the sponsor and sites were categorised, and cost drivers were identified. All elements were included in a spreadsheet tool allowing the sponsor team to calculate in detail the various activities of a clinical trial and to appreciate the budget impact of specific cost drivers, e.g. a delay in recruitment. Hourly fees by role were adapted from published data. Fixed amounts per activity were developed when appropriate. RESULTS: This publicly available tool has already been used for 17 trials funded since the start of the KCE Trials programme in 2016, and it continues to be used and improved. This budget tool is used together with additional risk-reducing measures such as a multistep selection process with advance payments, a recruitment feasibility check by sponsor and funder, a close monitoring of study progress and a milestone-based payment schedule with the last payment made when the manuscript is submitted. CONCLUSIONS: The budget tool helps the KCE Trials programme to answer relevant research questions in a timely way, within budget and with high quality, a necessary condition to achieve impact of this programme for patients, clinical practice and healthcare payers.

Association between surgical volume and post-operative mortality and survival after surgical resection in lung cancer in Belgium: A population-based study.

OBJECTIVES: The existence of a relationship between hospital surgical volume and outcome after lung cancer surgery remains an ongoing debate. We aimed to evaluate the association between volume and 60-day mortality, 1- and 3-year observed survival (OS) in non-small cell lung cancer (NSCLC) patients in Belgium. METHODS: Patients diagnosed with NSCLC in 2010-2011 were identified in the database of the Belgian Cancer Registry, excluding patients with multiple tumours. Regression models were applied to assess the relationship between hospital surgical volume, 60-day mortality and 1- and 3-year OS, adjusting for different patient and tumour characteristics. Surgical volume was taken into account as a continuous variable in the models. RESULTS: In 2010-2011 a total of 9,817 patients with NSCLC were diagnosed in Belgium and 2,084 of them underwent surgery. After adjusting for patient and tumour characteristics, a relationship between hospital surgical volume and patients' outcome was found. Postoperative mortality and survival improved with increasing annual surgical volume up to 10 interventions. However, no further gain in outcome has been observed above 10. While the 60-day postoperative mortality is 3.5% for hospitals with an annual volume larger than 10, the predicted mortality rate for a hospital with an annual volume of only 5 interventions is 6.5%. Similar results were observed for 1- and 3-year OS. CONCLUSION: In Belgium, a higher hospital surgical volume is associated with improved outcome in NSCLC patients after surgical resection. Minimally 10 surgical interventions per year seem to be required to achieve an optimal performance.

Use of health insurance data to identify and quantify the prevalence of main comorbidities in lung cancer patients.

BACKGROUND: Identifying comorbidities in lung cancer patients is a complex process in population-based studies and no gold standard exists. The current study aims to identify and measure the main comorbidities using administrative health insurance data, which were available on a population-based level. METHOD: A literature search was conducted to identify comorbidities in lung cancer patients and to select Anatomical Therapeutic Chemical codes to measure them. For each patient, the volume of delivered relevant drugs for each comorbidity in the year preceding the diagnosis of lung cancer was computed, based on the Defined Daily Doses reimbursed. Case definition rules were set by comparing the identification of comorbidities via health insurance data with the reporting of them in the medical files in a sample of hospitals. RESULTS: Four comorbidities were identified: chronic respiratory diseases, chronic cardiovascular diseases, diabetes mellitus and renal diseases. A very good to moderate agreement between the prevalence based on medical files versus health insurance data was obtained for diabetes mellitus (kappa = 0.83), chronic cardiovascular diseases (kappa = 0.64), chronic respiratory diseases (kappa = 0.48) but not for renal diseases (kappa = 0.22). Because only 27% of patients having renal diseases recorded in the medical files were identified using health insurance data, this comorbidity was not withheld. Among 12,839 lung cancer patients diagnosed in 2010-2011 in Belgium, 29.7% had chronic respiratory diseases, 57.5% had chronic cardiovascular diseases and 14.1% had diabetes mellitus. DISCUSSION: This study showed that it was possible to capture three major comorbidities in lung cancer patients using administrative health data, namely, diabetes mellitus, chronic cardiovascular diseases, and chronic respiratory diseases. However, the agreement was only moderate for the last one. A prerequisite for using this methodology is that administrative health data are available for all patients.

Quality of care and variability in lung cancer management across Belgian hospitals: a population-based study using routinely available data.

OBJECTIVE: To evaluate the quality of care for all patients diagnosed with lung cancer in Belgium based on a set of evidence-based quality indicators and to study the variability of care between hospitals. DESIGN, SETTING, PARTICIPANTS: A retrospective study based on linked data from the cancer registry, insurance claims and vital status for all patients diagnosed with lung cancer between 2010 and 2011. Evidence-based quality indicators were identified from a systematic literature search. A specific algorithm to attribute patients to a centre was developed, and funnel plots were used to assess variability of care between centres. INTERVENTION: None. MAIN OUTCOME MEASURE: The proportion of patients who received appropriate care as defined by the indicator. Secondary outcome included the variability of care between centres. RESULTS: Twenty indicators were measured for a total of 12 839 patients. Good results were achieved for 60-day post-surgical mortality (3.9%), histopathological confirmation of diagnosis (93%) and for the use of PET-CT before treatment with curative intent (94%). Areas to be improved include the reporting of staging information to the Belgian Cancer Registry (80%), the use of brain imaging for clinical stage III patients eligible for curative treatment (79%), and the time between diagnosis and start of first active treatment (median 20 days). High variability between centres was observed for several indicators. Twenty-three indicators were found relevant but could not be measured. CONCLUSION: This study highlights the feasibility to develop a multidisciplinary set of quality indicators using population-based data. The main advantage of this approach is that not additional registration is required, but the non-measurability of many relevant indicators is a hamper. It allows however to easily point to areas of large variability in care.

Inconsistent diagnosis of acute malnutrition by weight-for-height and mid-upper arm circumference: contributors in 16 cross-sectional surveys from South Sudan, the Philippines, Chad, and Bangladesh.

BACKGROUND: The two anthropometric indicators of acute malnutrition in children under 5 years, i.e. a Mid-Upper Arm Circumference < 125 mm (MUAC125) or a Weight-for-Height Z-score<-2 (WHZ-2), correlate poorly. We aimed at assessing the contribution of age, sex, stunting (Height-for-Age HAZ<-2), and low sitting-standing height ratio Z-score (SSRZ in the 1st tertile of the study population, called hereafter 'longer legs') to this diagnosis discrepancy. METHODS: Data from 16 cross-sectional nutritional surveys carried out by Action Against Hunger International in South Sudan, the Philippines, Chad, and Bangladesh fed multilevel, multivariate regression models, with either WHZ-2 or MUAC125 as the dependent variable and age, sex, stunting, and 'longer legs' as the independent ones. We also compared how the performance of MUAC125 and WHZ-2 to detect slim children, i.e. children with a low Weight-for-Age (WAZ<-2) but no linear growth retardation (HAZ≥-2), was modified by the contributors. RESULTS: Overall 23.1% of the 14,409 children were identified as acutely malnourished by either WHZ-2 or MUAC125, but only 28.5% of those (949/3,328) were identified by both indicators. Being stunted (+17.8%; 95 % CI: 14.8%; 22.8%), being a female (+16.5%; 95 % CI: 13.5%; 19.5%) and being younger than 24 months (+33.6%; 95 % CI: 30.4%; 36.7%) were factors strongly associated with being detected as malnourished by MUAC125 and not by WHZ-2, whereas having 'longer legs' moderately increased the diagnosis by WHZ-2 (+4.2%; 95 % CI: 0.7%; 7.6%). The sensitivity to detect slim children by MUAC125 was 31.0% (95 % CI: 26.8%; 35.2%) whereas it was 70.6% (95 % CI: 65.4%; 75.9%) for WHZ-2. The sensitivity of MUAC125 was particularly affected by age (57.4% vs. 18.1% in children aged < 24 months vs. ≥ 24 months). Specificity was high for both indicators. CONCLUSIONS: MUAC125 should not be used as a stand-alone criterion of acute malnutrition given its strong association with age, sex and stunting, and its low sensitivity to detect slim children. Having 'longer legs' moderately increases the diagnosis of acute malnutrition by WHZ-2. Prospective studies are urgently needed to elucidate the clinical and physiological outcomes of the various anthropometric indicators of malnutrition.

The Belgian Health System Performance Report 2012: snapshot of results and recommendations to policy makers.

Following the commitments of the Tallinn Charter, Belgium publishes the second report on the performance of its health system. A set of 74 measurable indicators is analysed, and results are interpreted following the five dimensions of the conceptual framework: accessibility, quality of care, efficiency, sustainability and equity. All domains of care are covered (preventive, curative, long-term and end-of-life care), as well as health status and health promotion. For all indicators, national/regional values are presented with their evolution over time. Benchmarking to results of other EU-15 countries is also systematic. The policy recommendations represent the most important output of the report.

Multidisciplinary outpatient rehabilitation following cardiac revascularization or valve surgery: patient-related factors for uptake.

BACKGROUND: There are concerns in Europe regarding the service provision and accessibility of multidisciplinary cardiac rehabilitation (MDCR) in general, and particularly in ambulatory settings. This paper analyses the utilization of outpatient MDCR and its determinants after cardiac revascularization or valve surgery in Belgium. METHODS: Claims rehabilitation data for all patients discharged in 2007 after a percutaneous cardiac intervention or cardiac surgery were available from the Belgian Common Sickness Funds Agency. Logistic regressions were performed to identify patients demographic and socioeconomic characteristics associated with the uptake of outpatient MDCR during the year following the hospital discharge. RESULTS: A total of 29,021 patients were included. During the hospitalization for the cardiac procedure, 44% were offered inpatient MDCR. After discharge, only 15.6% followed at least one session of outpatient MDCR. The chance of attending outpatient MDCR was lower for female, disabled, and older patients, as well as unemployed patients. The absence of an authorized MDCR centre in the neighbourhood of the patient's residence decreased the chance of attending outpatient MDCR, while living in a neighbourhood with a high education and income level increased this probability. CONCLUSION: These results confirm the low rates of MDCR attendance found in a previous study performed by the European Association of Cardiovascular Prevention and Rehabilitation. The study shows specific patient groups that should be targeted in priority, i.e. women, elderly, unemployed patients, disabled persons, and patients with a low socioeconomic status.

Patient socioeconomic determinants of the choice of generic versus brand name drugs in the context of a reference price system: evidence from Belgian prescription data.

The generic reference price system (RPS) can impose a financial penalty for patients using a brand name drug instead of its generic alternative. Previous studies on the impact of the RPS have not considered the potentially differential effect of using generic alternatives for individuals with a different socioeconomic background. However, patients' characteristics might determine their overall knowledge of the existence of the system and thus of the financial burden to which they may be confronted. The association between patients' characteristics and the use of generic drugs versus brand name drugs was analyzed for ten highly prescribed pharmaceutical molecules included in the Belgian generic reference price system. Prescriptions were obtained from a 10% sample of all general practitioners in 2008 (corresponding to 120,670 adult patients and 368,101 prescriptions). For each pharmaceutical molecule, logistic regression models were performed, with independent variables for patient socioeconomic background at the individual level (work status, having a guaranteed income and being entitled to increased reimbursement of co-payments) and at the level of the neighborhood (education). The percentage of generic prescriptions ranged from 24.7 to 76.4%, and the mean reference supplement in 2008 ranged from €4.3 to €37.8. For seven molecules, higher use of a generic alternative was associated with either having a guaranteed income, with receiving increased reimbursement of co-payments or with living in areas with the lowest levels of education. Globally, results provided evidence that the generic RPS in Belgium does not lead to a higher financial burden on individuals from a low socioeconomic background.

Developing and measuring a set of process and outcome indicators for breast cancer.

PURPOSE: This study aimed at developing and measuring a set of indicators to monitor the quality of breast cancer care, to make comparisons over time and to support quality improvement for all practitioners and centres involved in the care of breast cancer women. METHODS: Quality indicators were identified from a systematic literature search and the 2010 Belgian evidence-based clinical practice guideline. The selection process involved an expert panel evaluating reliability, relevance, interpretability and actionability of each indicator. The quality indicators were tested using the Belgian Cancer Registry data linked with claims data for all women registered with breast cancer in Belgium between 2001 and 2006 (n=50,039). RESULTS: The selection process led to a final set of 32 indicators. Of these, 12 were measurable using the available data, while 1 indicator was measurable using proxy information. Five-year relative survival was 98%, 87%, 68% and 29% for pStage I, II, III and cStage IV respectively. Overall 5-year survival slightly improved for pStage II, III and cStage IV between 2001 and 2004. Of the surgically treated women, 60% underwent breast conserving surgery, 85% received adjuvant systemic treatment and 86% were irradiated postoperatively. In 80% of women treated for breast cancer, at least one mammography was performed within one year after the last treatment. CONCLUSION: The present study demonstrates the feasibility to develop a multidisciplinary set of quality indicators for breast cancer. Using national cancer registry data linked to claims data, 13 indicators were measurable, showing results that largely correspond to other studies in the field.

Quality indicators for testicular cancer: a population-based study.

PURPOSE: This study aimed at developing and measuring an indicator set to monitor the quality of testicular cancer care, to make comparisons over time and to support quality improvement for all practitioners and centres involved in the care of testicular cancer patients. METHODS: Quality indicators were identified from a systematic literature search and from the 2010 Belgian evidence-based clinical practice guidelines. The selection process involved an expert panel evaluating reliability, relevance, interpretability and actionability of each indicator. The quality indicators were pilot tested using the Belgian Cancer Registry (BCR) data linked with claims data for 1307 men with testicular cancer diagnosed between 2001 and 2006. The variability between centres was displayed using funnel plots. RESULTS: Of the 12 finally selected indicators, 5 were fully and 1 was partly measurable, while 2 indicators were measurable using proxy information. Five-year relative survival was 97%, 95% and 76% for pStage I-III, respectively. Overall 5-year survival slightly improved from 91% in 2001 to 94% in 2004. Between 2004 and 2006, 14 of 97 centres performed ≥10 orchidectomies. Large variability was found between centres. The nine centres with a 5-year observed survival below the lower limit treated less than 20 patients between 2001 and 2006. CONCLUSIONS: The present study demonstrates the feasibility to develop a multidisciplinary set of quality indicators for testicular cancer. Using national cancer registry data linked to claims data, eight indicators were measurable, showing a mixed picture of the quality of care for testicular cancer patients in Belgium.

Effect of hospital volume on processes of care and 5-year survival after breast cancer: a population-based study on 25000 women.

PURPOSE: To compare processes of care and survival for breast cancer by hospital volume in Belgium, based on 11 validated process quality indicators. METHODS: Three databases were linked at the patient level: the Cancer Registry, the population and the claims databases. All women with a diagnosis of invasive breast cancer between 2004 and 2006 were selected. Hospitals were classified according to their annual volume of treated patients: <50 (very low), 50-99 (low), 100-149 (medium) and ≥ 150 patients (high). Cox and logistic regression models were used to test differences in 5-year survival and in achievement of process indicators across volume categories, adjusting for age, tumor grade and stage. RESULTS: A total of 25178 women with invasive breast cancer were treated in 111 hospitals. Half of the hospitals (N=57) treated <50 patients per year. Six of eleven process indicators showed higher rates in high-volume hospitals: multidisciplinary team meeting, cytological and/or histological assessment before surgery, use of neoadjuvant chemotherapy, breast-conserving surgery rate, adjuvant radiotherapy after breast-conserving surgery, and follow-up mammography. Higher volume was also associated with improved survival. The 5-year observed survival rates were 74.9%, 78.8%, 79.8% and 83.9% for patients treated in very-low-, low-, medium- and high-volume hospitals respectively. After case-mix adjustment, patients treated in very-low- or low-volume hospitals had a hazard ratio for death of 1.26 (95% CI 1.12, 1.42) and 1.15 (95% CI 1.01, 1.30) respectively compared with high-volume hospitals. CONCLUSION: Survival benefits reported in high-volume hospitals suggest a better application of recommended processes of care, justifying the centralization of breast cancer care in such hospitals.

Patient socioeconomic determinants for the choice of the cheapest molecule within a cluster: evidence from Belgian prescription data.

Reference pricing is a common cost-sharing mechanism, with the financial penalty for the use of costly drugs shifted from the third-party payer to the patient. Unintended distributional consequences might arise, if the weakest socioeconomic groups face a relatively higher financial burden. This study analyzed for a sample of Belgian individual prescription data for 4 clusters of commonly used drugs (proton pump inhibitors, statins and two groups of antihypertensives [drugs acting on renin-angiotensin system and dihydropyridine derivatives]) whether the probability to receive the least expensive molecule within a cluster was linked to the socioeconomic status of the patient. Logistic regression models included individual demographic, working, chronic illness and financial status and small area education data for 906,543 prescriptions from 1,280 prescribing general practitioners and specialists. For the 4 clusters, results show that patients with lower socioeconomic status consistently use slightly more the least expensive drugs than other patients. Larger effects are observed for patients residing in a nursing home for the elderly, patients entitled to increased reimbursement of co-payments, unemployed, patients treated in a primary care center financed per capita (and not fee-for-service) and patients having a chronic illness. Also, patients residing in neighborhoods with low education status use more less expensive drugs. The findings of the study suggest that although equity considerations were not explicitly taken into account in the design of the reference price system, there is no real equity problem, as the costly drugs with supplement are not prescribed more often in patients from lower socioeconomic classes.

Provider volume and short term complications after elective total hip replacement: an analysis of Belgian administrative data.

The relationship between provider volume and short term complications after an elective total hip replacement was studied on Belgian hospital discharge administrative database from 2004. The analysis included 11 856 patients. Hospitals were classified in low-volume (< or = 60/interventions per year), medium volume (61-110) or high volume (>110). Surgeons were labelled low-volume (< or = 6), medium volume (7-20) or high volume (>20). After adjustment for age, sex, principal diagnosis and comorbidity, surgeon volume was much more predictive of short term complications than centre volume. Patients treated by small volume surgeons (respectively medium volume surgeons) had a 43% higher odds of complications than patients operated by high volume surgeons (respectively 37%). Despite some limitations, Belgian administrative hospital discharge databases can be used to assess the volume outcome relationship for orthopaedic surgery. The study has emphasized the need to closely monitor individual performance, for hospitals and surgeons. Providers requiring further auditing can be effectively identified with funnel plots used routinely in quality control programs.

The protective effect of ophthalmic viscoelastic devices on endothelial cell loss during cataract surgery: a meta-analysis using mixed treatment comparisons.

BACKGROUND/AIMS: To compare ophthalmic viscoelastic devices (OVDs) in protecting the cornea from endothelial cell loss during cataract surgery. METHODS: A systematic review yielded 21 randomised controlled trials including 1769 patients. OVDs were classified according to the Arshinoff classification. Traditional pairwise meta-analyses were performed for each direct comparison. Mixed treatments comparisons (MTC) analysis was also performed to combine all direct and indirect comparisons. The outcome measure was loss in endothelial cell density 3 months after surgery. RESULTS: Direct comparison meta-analysis showed that viscoadaptives lead to a lower loss in cell density compared with very low viscosity dispersives, and compared with super viscous cohesives. The soft shell technique, a combination of viscous cohesives and medium viscosity dispersives, showed a lower loss compared with viscous cohesives, but was not compared with the other treatments. The MTC analysis shows that comparing all treatment options together, all mean differences were ≤ 100 cells/mm(2). The probability of being the best treatment option is 80% for viscoadaptives and 18% for the soft shell technique. CONCLUSION: Viscoadaptives may be superior to the other OVDs, but absolute differences in loss in endothelial cell density are <100 cells/mm(2).

Belgian methodological guidelines for pharmacoeconomic evaluations: toward standardization of drug reimbursement requests.

OBJECTIVE: To develop methodological guidelines for pharmacoeconomic evaluation (PE) submitted to the Belgian Drug Reimbursement Committee as part of a drug reimbursement request. METHODS: In 2006, preliminary pharmacoeconomic guidelines were developed by a multidisciplinary research team. Their feasibility was tested and discussed with all stakeholders. The guidelines were adapted and finalized in 2008. RESULTS: The literature review should be transparent and reproducible. PE should be performed from the perspective of the health-care payer, including the governmental payer and the patient. The target population should reflect the population identified for routine use. The comparator to be considered in the evaluation is the treatment most likely to be replaced. Cost-effectiveness and cost-utility analyses are accepted as reference case techniques, under specific conditions. A final end point-as opposed to a surrogate end point-should be used in the incremental cost-effectiveness ratio (ICER). For the calculation of quality-adjusted life-years (QALYs), a generic quality-of-life measure should be used. PE should in principle apply a lifetime horizon. Application of shorter time horizons requires appropriate justification. Uncertainty around the ICER should always be assessed. Costs and outcomes should be discounted at 3% and 1.5%, respectively. CONCLUSION: The current guidelines are the result of a constructive collaboration between the Belgian Health Care Knowledge Centre, the National Institute for Health and Disability Insurance and the pharmaceutical industry. A point of special attention is the accessibility of existing Belgian resource use data for PE. As PE should serve Belgian health-care policy, they should preferably be based on the best available data.

Trastuzumab in early stage breast cancer: a cost-effectiveness analysis for Belgium.

OBJECTIVES: Although trastuzumab is traditionally used in metastatic breast cancer treatment, studies reported on the efficacy and safety of trastuzumab in adjuvant setting for the treatment of early stage breast cancer in HER2+ tumors. We estimated the cost-effectiveness and budget impact of reimbursing trastuzumab in this indication from a payer's perspective. METHODS: We constructed a health economic model. Long-term consequences of preventing patients to progress to metastatic breast cancer and side effects such as congestive heart failure were taken into account. Uncertainty was handled applying probabilistic modeling and through probabilistic sensitivity analyses. RESULTS: In the HERA scenario, applying an arbitrary threshold of euro30000 per life-year gained, early stage breast cancer treatment with trastuzumab is cost-effective for 9 out of 15 analyzed subgroups (according to age and stage). In contrast, treatment according to the FinHer scenario is cost-effective in 14 subgroups. Furthermore, the FinHer regimen is most of the times cost saving with an average incremental cost of euro668, euro-1045, and euro-6869 for respectively stages I, II and III breast cancer patients whereas the HERA regimen is never cost saving due to the higher initial treatment costs. CONCLUSIONS: The model shows better cost-effectiveness for the 9-week initial treatment (FinHer) compared to no trastuzumab treatment than for the 1-year post-chemotherapy treatment (HERA). Both from a medical and an economic point of view, the 9-week initial treatment regimen with trastuzumab shows promising results and justifies the initiation of a large comparative trial with a 1-year regimen.

More is not better in the early care of acute myocardial infarction: a prospective cohort analysis on administrative databases.

AIMS: To assess the outcome and costs of patients with acute myocardial infarction (AMI) after initial admission to hospitals with or without catheterization facilities in Belgium. METHODS AND RESULTS: From a nationwide hospital register, we retrieved the data of 34 961 patients discharged during 1999-2001 with a principal diagnosis of AMI. They were initially admitted to hospitals without catheterization facilities (A), with diagnostic (B1) or interventional catheterization facilities (B2). Mortality has been recorded till the end of 2003 and re-admissions till the end of 2001. The mortality hazard ratio and 95% CI of 5 years mortality of A vs. B2 was 1.01 (0.97, 1.06) and of B1 vs. B2 was 1.03 (0.98, 1.09). Re-admission rates and 95% CI for cardiovascular reason per 100 patient-years were 23.5 (22.7, 24.3) for A, 23.8 (22.5, 25.1) for B1, and 22.0 (21.2, 22.9) for B2. The mean cost in hospital of a patient at low risk with a single stay was in A 4072 euro (median: 3,861; IQR: 4467-3476), in B1 5083 euro (median: 5153; IQR: 5769-4340), and in B2 7741 euro (median: 7553; IQR: 8211-7298). CONCLUSION: Services with catheterization facilities compared with services without them showed no better health outcomes, but delivered more expensive care.

Efficacy and safety of ertapenem versus piperacillin-tazobactam for the treatment of intra-abdominal infections requiring surgical intervention.

Complicated intra-abdominal infections usually mandate prompt surgical intervention supplemented by appropriate antimicrobial therapy. The aim of this study was to demonstrate that ertapenem was not inferior to piperacillin-tazobactam for the treatment of community-acquired intra-abdominal infections. A randomized open-label active-comparator clinical trial was conducted at 48 medical centers on four continents from December 2001 to February 2003. Adult patients with intra-abdominal infections requiring surgery were randomized to receive either ertapenem 1 g daily or piperacillin/tazobactam 13.5 g daily in 3-4 divided doses. The primary analysis of efficacy was the clinical response rate in clinically and microbiologically evaluable patients at the test-of-cure assessment 2 weeks after completion of therapy. All treated patients were included in the safety analysis. Patient demographics, disease characteristics, and treatment duration in both treatment groups were generally similar. The most commonly isolated pathogens at baseline were E coli (greater than 50% of cases in each group) and B fragilis ( approximately 9%). Favorable clinical response rates were 107/119 (90%) for ertapenem recipients and 107/114 (94%) for piperacillin/tazobactam recipients. The frequencies of drug-related adverse events, most commonly diarrhea and elevated serum alanine aminotransferase levels, were similar in both treatment groups. Six of 180 ertapenem recipients (3%) and two of 190 piperacillin/tazobactam recipients (1%) had serious drug-related adverse experiences. In this study, ertapenem and piperacillin/tazobactam were comparably safe and effective treatments for adult patients with complicated intra-abdominal infections.