A benefit-risk analysis of pegvaliase for the treatment of phenylketonuria: A study of patients' preferences.

BACKGROUND: Phenylketonuria (PKU) leads to an accumulation of phenylalanine (Phe) in the blood and subsequent neurologic, cognitive, psychiatric, and behavioral dysfunction. Many patients report social isolation and decreased quality of life. Pegvaliase is an enzyme substitution therapy that reduces blood Phe levels in patients with PKU and is associated with a risk of hypersensitivity reactions. OBJECTIVE: To define the minimum acceptable benefit (MAB) of pegvaliase, i.e., the minimum probability of achieving a blood Phe level <360 µmol/L, which patients require to tolerate the risks of hypersensitivity associated with pegvaliase. METHODS: Adult, pegvaliase-naïve patients with blood Phe levels >600 µmol/L participated in a patient-preference web survey using two surveys: adapted swing-weighting and thresholding. Participants were asked to make ordinal choices between varying clinical benefit and severity levels for hypersensitivity. Disease effects and treatment satisfaction were also assessed. RESULTS: Among 45 participants, the mean (standard deviation) self-reported blood Phe level was 976.9 (429.9) µmol/L; only 28.8% reported satisfaction with their current treatment. Most (84.4%) indicated difficulty in following a PKU diet; 60% reported that the PKU diet was burdensome, and 58% reported feeling socially isolated. Most (≥69%) reported their MAB to be less than the expected clinical benefit provided by pegvaliase; the mean MAB was 22.7% and 34.4% in the swing-weighting and thresholding surveys, respectively. CONCLUSION: Most participants felt the burden of PKU on their daily lives, were dissatisfied with current treatments, and were willing to accept the risks of hypersensitivity reactions to achieve recommended blood Phe levels with pegvaliase treatment.

An integrated process and management tools for ranking multiple emerging threats to animal health.

The UK's Department for Environment, Food and Rural Affairs supports the use of systematic tools for the prioritisation of known and well defined animal diseases to facilitate long and medium term planning of surveillance and disease control activities. The recognition that emerging events were not covered by the existing disease-specific approaches led to the establishment of the Veterinary Risk Group (VRG), constituted of government officials, and supporting structures such as the Risk Management Cycle and the Emerging Threat Highlight Report (ETHiR), to facilitate the identification, reporting and assessment of emerging threats to UK's animal health. Since its inception in November 2009 to the end of February 2011, the VRG reviewed 111 threats and vulnerabilities (T&V) reported through ETHiR. In July 2010 a decision support system (DSS) based on multi-criteria-decision-analysis (MCDA) improved ETHiR to allow the systematic prioritisation of emerging T&V. The DSS allows the regular ranking of emerging T&V by calculating a set of measurement indices related to the actual impact, possible impact on public perception and level of available capabilities associated with every T&V. The systematic characterisation of the processes leading to the assessment of T&V by the VRG has led to a consistent, auditable and transparent approach to the identification and assessment of emerging risks. The regular use of MCDA to manage a portfolio of emerging risks represents a different and novel application of MCDA in a health related context.