An Iterative Survey of Phenylketonuria (PKU) Medical Experts to Inform Health Economic Modeling Methods

Speaker(s)

Zhang R1, Chakrapani A2, Hamazaki T3, Lah M4, Muntau AC5, Ruebel DJ4, Vijay S6, Zori RT7, Feillet F8, OConnell T9, Woolley JJ9, Crowell M9, Teng Y9, Tomazos I10
1PTC Therapeutics Sweden AB, Stockholm, AB, Sweden, 2Great Ormond Street Hospital, London, UK, 3Osaka Metropolitan University Graduate School of Medicine, Osaka, 545-8585, Japan, 4Indiana University School of Medicine, Indianapolis, IN, USA, 5University Children’s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 6Birmingham Children's Hospital, Birmingham, UK, 7University of Florida, Gainesville, FL, USA, 8Children's Hospital of Nancy, Nancy, France, 9Medicus Economics, Boston, MA, USA, 10PTC Therapeutics Inc, Warren, NJ, USA

Presentation Documents

OBJECTIVES: In PKU, elevated blood phenylalanine (Phe) leads to a wide range of clinical outcomes, including neurocognitive and neurobehavioral impairments. Various approaches for cost-effectiveness analysis (CEA) have historically been used in health technology assessments (HTAs) of PKU treatments, reflecting lack of consensus for a clinically accurate CEA model structure.

METHODS: An iterative survey process was used to identify: (1) clinical outcomes of greatest importance to model in CEA for PKU; and (2) how to model outcomes of greatest importance. First, a targeted evidence review of PKU clinical/economic literature and HTA evaluations was conducted. Second, qualitative discussions were conducted with N=8 international, multidisciplinary (pediatrics, metabolic, dietetics, genetics) PKU medical experts. Third, distinct clinical outcomes in PKU were identified from the previous steps, and experts rated the importance of these outcomes for CEA (i.e., degree to which they affect: prognosis for other PKU outcomes/comorbidities, patient/family/caregiver quality of life, patient healthcare resource use/costs, other direct [e.g., medical foods, paid caregiving] or indirect [e.g., employment outcomes, informal caregiving] costs). For clinical outcomes identified as important for CEA, additional survey rounds will explore areas of agreement/disagreement on how to model the outcomes, in an expanded expert panel.

RESULTS: Seventeen clinical outcomes in PKU were identified across the following categories: physiological/neurologic (5), psychiatric (3), psychological/behavioral (3), dietary/pharmacotherapeutic (3), maternal PKU (3). The N=8 experts rated the importance of modeling clinical outcomes in CEA on a 1-5 (limited-high) scale. Five outcomes had a median rating of 5: blood Phe concentration, intellectual disability (severe reduction in intelligence quotient), tolerance of natural Phe/protein, child's physiological health (in maternal PKU), and executive function deficit disorders. The 17 outcomes were considered comprehensive, with physical disabilities and adults’ social engagement/autonomy noted as additional relevant outcomes.

CONCLUSIONS: This study identified clinical outcomes important to model in CEA of PKU, which may inform clinically relevant approaches for HTA.

Code

EE316

Topic

Clinical Outcomes, Economic Evaluation, Health Technology Assessment, Study Approaches

Topic Subcategory

Cost-comparison, Effectiveness, Utility, Benefit Analysis, Decision & Deliberative Processes, Decision Modeling & Simulation, Relating Intermediate to Long-term Outcomes

Disease

Diabetes/Endocrine/Metabolic Disorders (including obesity), Drugs, Rare & Orphan Diseases