What is clearance worth? Patients' stated risk tolerance for psoriasis treatments.

PURPOSE: The purpose of this study was to provide quantitative evidence of patients' tolerance for therapeutic risks associated with psoriasis treatments that could offer psoriasis improvements beyond the PASI 75 benchmark. MATERIALS AND METHODS: We used a discrete-choice experiment in which respondents chose between competing psoriasis treatments characterized by benefits (i.e. reduced plaque severity, reduced plaque area), risks (i.e. 10-year risk of tuberculosis, 10-year risk of death from infection), and treatment regimen. We analyzed choice data using random-parameters logit models for psoriasis affecting the body, face, or hands. RESULTS: Of 927 eligible members of the National Psoriasis Foundation who completed the survey, 28% were unwilling to accept any greater risk of treatment-related infection mortality. Among the remaining 72%, respondents were willing to accept higher risks of infection-related mortality associated with treatment to completely remove plaques covering only 1% of the body, compared to reducing lesions from 10 to 1% of the affected area. This finding was more pronounced for lesions on the face. CONCLUSIONS: Most patients placed greater value on eliminating even very small plaques compared to avoiding treatment-related risks. The perceived importance of complete versus near-complete clearance was stronger than previously documented.

Recommendations for benefit-risk assessment methodologies and visual representations.

PURPOSE: The purpose of this study is to draw on the practical experience from the PROTECT BR case studies and make recommendations regarding the application of a number of methodologies and visual representations for benefit-risk assessment. METHODS: Eight case studies based on the benefit-risk balance of real medicines were used to test various methodologies that had been identified from the literature as having potential applications in benefit-risk assessment. Recommendations were drawn up based on the results of the case studies. RESULTS: A general pathway through the case studies was evident, with various classes of methodologies having roles to play at different stages. Descriptive and quantitative frameworks were widely used throughout to structure problems, with other methods such as metrics, estimation techniques and elicitation techniques providing ways to incorporate technical or numerical data from various sources. Similarly, tree diagrams and effects tables were universally adopted, with other visualisations available to suit specific methodologies or tasks as required. Every assessment was found to follow five broad stages: (i) Planning, (ii) Evidence gathering and data preparation, (iii) Analysis, (iv) Exploration and (v) Conclusion and dissemination. CONCLUSIONS: Adopting formal, structured approaches to benefit-risk assessment was feasible in real-world problems and facilitated clear, transparent decision-making. Prior to this work, no extensive practical application and appraisal of methodologies had been conducted using real-world case examples, leaving users with limited knowledge of their usefulness in the real world. The practical guidance provided here takes us one step closer to a harmonised approach to benefit-risk assessment from multiple perspectives.

Implementing Benefit-Risk Assessment for the Periodic Benefit-Risk Evaluation Report.

BACKGROUND: In 2012, the International Conference on Harmonisation (ICH) E2C (R1) guideline for periodic safety update reporting (PSUR) for medicines was revised. Several new concepts that expanded the scope of the report were added, including a new section focused on benefits and an additional section focused on integrated benefit-risk (B-R) assessment. These changes are reflected in the new title of the report, namely, the Periodic Benefit-Risk Evaluation Report (PBRER). Recently, structured frameworks have been developed by the pharmaceutical industry and regulatory agencies to facilitate B-R analysis for medicines. METHODS: This manuscript provides suggestions for incorporating the elements of a structured B-R assessment into the PBRER and also includes practical approaches for implementing the ICH guidelines for the B-R analysis section. RESULTS: The main components of a B-R assessment for the PBRER include decision context; key benefits and key risks; strengths, limitations, and uncertainties of the evidence; risk management; and the overall B-R conclusions. CONCLUSIONS: A structured, systematic approach to defining a medicine's B-R profile will help ensure compliance with this ICH objective for the PBRER.

Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study.

OBJECTIVE: The objective of this study was to assess the risk of acute pancreatitis in patients with type 2 diabetes compared with that in patients without diabetes. We also examined the risk of biliary disease (defined as occurrence of cholelithiasis, acute cholecystitis, or cholecystectomy), which is a major cause of pancreatitis. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using a large, geographically diverse U.S. health care claims database. Eligible patients (>or=18 years) were enrolled for at least 12 continuous months (1999-2005), with no incident events of pancreatitis or biliary disease during that 1 year baseline period. ICD-9 codes and prescription data were used to identify patients with type 2 diabetes; ICD-9 codes were also used to identify cases of pancreatitis and biliary disease. Overall, 337,067 patients with type 2 diabetes were matched on age and sex with 337,067 patients without diabetes. Incidence rates of disease and 95% CI were calculated per 100,000 person-years of exposure. RESULTS: The type 2 diabetic cohort had a 2.83-fold (95% CI 2.61-3.06) greater risk of pancreatitis and 1.91-fold (1.84-1.99) greater risk of biliary disease compared with the nondiabetic cohort. Relative to patients of corresponding age without diabetes, younger type 2 diabetic patients had the highest risk of pancreatitis (<45 years: incidence rate ratio [IRR] 5.26 [95% CI 4.31-6.42]; >or=45 years: 2.44 [2.23-2.66]). CONCLUSIONS: These data suggest that patients with type 2 diabetes may have an increased risk of acute pancreatitis and biliary disease.

A multiattribute model for evaluating the benefit-risk profiles of treatment alternatives.

The assessment of the benefits and risks associated with a medicine's use requires careful consideration of a wealth of information of varying format and quality, ranging from efficacy and safety data derived from randomized clinical trials to statistical results from health outcomes studies to spontaneously reported adverse events. Contrary to the expectations of patients, physicians, and regulators, the literature offers little guidance as to how to strike an appropriate balance between benefit and risk. Although a qualitative listing of a medicine's benefits and risks is useful, much could be gained from a systematic and transparent process to evaluate a medicine's pre- and postmarketing performance. The authors propose a representational model based on multicriteria decision analysis that can incorporate both evaluative judgments from different perspectives (e.g., physician, patient) and quantitative data to inform tradeoffs between multiple benefit and multiple risk elements in a logically consistent and transparent manner. The model is designed to highlight the relative merits and deficits of treatment alternatives in well-defined and specific contexts. It is intended to serve as a common platform to facilitate focused benefit-risk tradeoff discussions between scientists, physicians, regulatory authorities, and pharmaceutical companies, and to assist in the communication of clear and consistent messages regarding those tradeoffs.