Illustrating Emerging Good Practices for Quantitative Benefit-Risk Assessment: A Hypothetical Case Study of Systemic Biologic Treatments for Plaque Psoriasis.

OBJECTIVES: Quantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct, and reporting of qBRA. This report presents a hypothetical case study illustrating how to apply the Task Force's recommendations toward a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval. The qBRA evaluated 2 dosing regimens of brodalumab (210 mg or 140 mg twice weekly) compared with weight-based dosing of ustekinumab and placebo. METHODS: We followed the 5 steps recommended by the Task Force. Attributes included treatment response (≥75% improvement in Psoriasis Area and Severity Index), suicidal ideation and behavior, and infections. Performance data were drawn from pivotal clinical trials of brodalumab. The qBRA used multicriteria decision analysis and preference weights from a hypothetical discrete choice experiment. Sensitivity analyses examined the robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, consideration of a subgroup (nail psoriasis), and the maintenance phase of treatment (52 weeks instead of 12). RESULTS: Results from this hypothetical qBRA suggest that brodalumab 210 mg had a more favorable benefit-risk profile compared with ustekinumab and placebo. Ranking of brodalumab compared with ustekinumab was dependent on brodalumab's dose. Sensitivity analyses demonstrated robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, as well as choice of attributes and length of follow-up. CONCLUSION: This case study demonstrates how to implement the ISPOR Task Force's good practice recommendations on qBRA.

Quantitative Benefit-Risk Assessment in Medical Product Decision Making: A Good Practices Report of an ISPOR Task Force.

Benefit-risk assessment is commonly conducted by drug and medical device developers and regulators, to evaluate and communicate issues around benefit-risk balance of medical products. Quantitative benefit-risk assessment (qBRA) is a set of techniques that incorporate explicit outcome weighting within a formal analysis to evaluate the benefit-risk balance. This report describes emerging good practices for the 5 main steps of developing qBRAs based on the multicriteria decision analysis process. First, research question formulation needs to identify the needs of decision makers and requirements for preference data and specify the role of external experts. Second, the formal analysis model should be developed by selecting benefit and safety endpoints while eliminating double counting and considering attribute value dependence. Third, preference elicitation method needs to be chosen, attributes framed appropriately within the elicitation instrument, and quality of the data should be evaluated. Fourth, analysis may need to normalize the preference weights, base-case and sensitivity analyses should be conducted, and the effect of preference heterogeneity analyzed. Finally, results should be communicated efficiently to decision makers and other stakeholders. In addition to detailed recommendations, we provide a checklist for reporting qBRAs developed through a Delphi process conducted with 34 experts.

Selecting the optimum plot size for a California design-based stream and wetland mapping program.

Accurate estimates of the extent and distribution of wetlands and streams are the foundation of wetland monitoring, management, restoration, and regulatory programs. Traditionally, these estimates have relied on comprehensive mapping. However, this approach is prohibitively resource-intensive over large areas, making it both impractical and statistically unreliable. Probabilistic (design-based) approaches to evaluating status and trends provide a more cost-effective alternative because, compared with comprehensive mapping, overall extent is inferred from mapping a statistically representative, randomly selected subset of the target area. In this type of design, the size of sample plots has a significant impact on program costs and on statistical precision and accuracy; however, no consensus exists on the appropriate plot size for remote monitoring of stream and wetland extent. This study utilized simulated sampling to assess the performance of four plot sizes (1, 4, 9, and 16 km(2)) for three geographic regions of California. Simulation results showed smaller plot sizes (1 and 4 km(2)) were most efficient for achieving desired levels of statistical accuracy and precision. However, larger plot sizes were more likely to contain rare and spatially limited wetland subtypes. Balancing these considerations led to selection of 4 km(2) for the California status and trends program.

The persistence of fluoroquinolone-resistant Campylobacter in poultry production.

BACKGROUND: The use of antibiotics in food animal production has been associated with antibiotic-resistant infections in humans. In 2005, the Food and Drug Administration (FDA) banned fluoroquinolone use in U.S. poultry production in order to reduce the prevalence of fluoroquinolone-resistant Campylobacter. Little is known about the potential efficacy of this policy. OBJECTIVES: Our primary objective was to follow temporal changes in the prevalence of fluoroquinolone-resistant Campylobacter among poultry products from two conventional producers who announced their cessation of fluoroquinolone use in 2002 (3 years before the FDA's ban). Our secondary objective was to compare, over time, the prevalence of fluoroquinolone-resistant Campylobacter in conventional poultry products to those from producers who claim to use no antibiotics. METHODS: We collected poultry samples from two conventional producers and three antibiotic-free producers over the course of 20 weeks in 2004 (n = 198) and 15 weeks in 2006 (n = 210). We compared the rates of fluoroquinolone resistance among Campylobacter isolates from the different producers. RESULTS: We found no significant change in the proportion of fluoroquinolone-resistant Campylobacter isolates from the two conventional producers over the study period. In addition, Campylobacter strains from the two conventional producers were significantly more likely to be fluoroquinolone resistant than those from the antibiotic-free producers. CONCLUSIONS: The results from this study indicate that fluoroquinolone-resistant Campylobacter may be persistent contaminants of poultry products even after on-farm fluoroquinolone use has ceased. The FDA's ban on fluoroquinolones in poultry production may be insufficient to reduce resistant Campylobacter in poultry products.

Elevated risk of carrying gentamicin-resistant Escherichia coli among U.S. poultry workers.

BACKGROUND: Antimicrobial use in food-animal production is an issue of growing concern. The application of antimicrobials for therapy, prophylaxis, and growth promotion in broiler chicken production has been associated with the emergence and dissemination of antimicrobial-resistant enteric bacteria. Although human exposure to antimicrobial-resistant bacteria through food has been examined extensively, little attention has been paid to occupational and environmental pathways of exposure. OBJECTIVE: Our objective was to measure the relative risk for colonization with antimicrobial-resistant Escherichia coli among poultry workers compared with community referents. METHODS: We collected stool samples and health surveys from 16 poultry workers and 33 community referents in the Delmarva region of Maryland and Virginia. E. coli was cultured from stool samples, and susceptibility to ampicillin, ciprofloxacin, ceftriaxone, gentamicin, nitrofurantoin, and tetracycline was determined for each E. coli isolate. We estimated the relative risk for carrying antimicrobial-resistant E. coli among poultry workers compared with community referents. RESULTS: Poultry workers had 32 times the odds of carrying gentamicin-resistant E. coli compared with community referents. The poultry workers were also at significantly increased risk of carrying multidrug-resistant E. coli. CONCLUSIONS: Occupational exposure to antimicrobial-resistant E. coli from live-animal contact in the broiler chicken industry may be an important route of entry for antimicrobial-resistant E. coli into the community.

Prevalence of potentially neuropathic Campylobacter jejuni strains on commercial broiler chicken products.

Campylobacteriosis is the most common antecedent infection leading to the development of inflammatory neuropathies including Guillain Barré syndrome (GBS) and Miller Fisher syndrome (MFS), with alterations in surface proteins and genetic polymorphisms conferring increased risk. Poultry is the most common source of C. jejuni infection in industrialized countries, including the US. There are no data on the prevalence on consumer poultry products of various strains of C. jejuni, including those hypothesized to be associated with neuropathy. To study this, C. jejuni was isolated from fresh broiler chicken products purchased from grocery stores in the Baltimore area. LOS subtypes and specific genetic polymorphisms were determined by PCR and DNA sequencing. The observed relative proportions of LOS subtypes and genetic polymorphisms in the cstII gene (encoding bacterial sialyltransferases involved in LOS synthesis in C. jejuni) were characterized and compared to those reported in published studies of patients with GBS, MFS and uncomplicated enteritis. Commercial poultry products carry a relatively high prevalence of C. jejuni strains that have been associated with neuropathic sequelae. The relative proportions of LOS classes in poultry isolates were similar to those reported in isolates from human enteritis cases, and in some instances also similar to isolates from patients diagnosed with neuropathic disease. In terms of cstII polymorphisms, there were also similarities between isolates from poultry and those from patients with GBS and MFS.