Considerations for Health Economic Modeling in Phenylketonuria (PKU): Insights From a Modified Delphi Panel
Author(s)
Rongrong Zhang, MSc1, Anupam Chakrapani, MD2, Takashi Hamazaki, MD3, Melissa Lah, MD4, Ania C Muntau, MD5, Danielle J Ruebel, RDN4, Suresh Vijay, MD6, Roberto T Zori, MD7, Francois Feillet, MD8, Nicola Longo, MD9, Hope Northrup, MD10, Suzanne Hollander, MD11, Thomas OConnell, BA, MA12, Jonathan J. Woolley, MSc12, Ioannis Tomazos, MBA, PhD13;
1PTC Therapeutics Sweden AB, Askim, Sweden, 2Great Ormond Street Hospital for Children, London, United Kingdom, 3Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan, 4Indiana University School of Medicine, Indianapolis, IN, USA, 5University Medical Center Hamburg-Eppendorf, University Children’s Hospital, Germany, 6Birmingham Children's Hospital, Birmingham, United Kingdom, 7University of Florida, Pediatric Genetics and Metabolism, Gainesville, FL, USA, 8Children's Hospital of Nancy, Department of Pediatrics, Nancy, France, 9University of California Los Angeles, Division of Clinical Genetics, Los Angeles, CA, USA, 10The University of Texas Health Science Center at Houston, Houston, TX, USA, 11Children’s Hospital Boston, Boston, MA, USA, 12Medicus Economics, Boston, MA, USA, 13PTC Therapeutics, Warren, NJ, USA
1PTC Therapeutics Sweden AB, Askim, Sweden, 2Great Ormond Street Hospital for Children, London, United Kingdom, 3Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan, 4Indiana University School of Medicine, Indianapolis, IN, USA, 5University Medical Center Hamburg-Eppendorf, University Children’s Hospital, Germany, 6Birmingham Children's Hospital, Birmingham, United Kingdom, 7University of Florida, Pediatric Genetics and Metabolism, Gainesville, FL, USA, 8Children's Hospital of Nancy, Department of Pediatrics, Nancy, France, 9University of California Los Angeles, Division of Clinical Genetics, Los Angeles, CA, USA, 10The University of Texas Health Science Center at Houston, Houston, TX, USA, 11Children’s Hospital Boston, Boston, MA, USA, 12Medicus Economics, Boston, MA, USA, 13PTC Therapeutics, Warren, NJ, USA
Presentation Documents
OBJECTIVES: In PKU, elevated blood phenylalanine (Phe) levels lead to a wide range of neurocognitive and neurobehavioral outcomes. Cost-effectiveness analyses (CEAs) of PKU treatments can be challenging due to the lack of consensus on a clinically-accurate CEA model structure. This study aimed to identify areas of consensus among PKU medical experts regarding key clinical components for inclusion in a model.
METHODS: A modified Delphi panel approach was employed using two rounds of questions. Eleven PKU medical experts were recruited, representing various clinical perspectives. Round 1 included 14 questions on clinical outcomes, diet, Phe-level classification, and treatment discontinuation. Participants rated their level of agreement using a 5-point Likert scale. After Round 1, participants received a summary of anonymized responses and shared comments. Round 2 refined questions that did not reach consensus (defined as ≥70% agreement) in Round 1.
RESULTS: Consensus was reached on 8/14 questions in Round 1, including topics on duration of time required for stable blood Phe measurement, safety concerns at Phe 0-29 µmol/L, association between sustained uncontrolled Phe levels and intellectual disability or other health outcomes, variation in unmet need across patient subgroups, and long-term continuation of pharmacotherapy. In Round 2, consensus was reached on 6/10 questions, including on age ranges when Phe levels are typically maintained, safety of Phe 30-120 µmol/L with sufficient protein intake, mechanisms underlying the association between PKU and chronic comorbidities, possibility of dietary-Phe tolerance challenges at Phe 240-299 µmol/L, and possibility of resuming pegvaliase after discontinuation. Lack of consensus on other questions highlighted areas where CEA could address uncertainty via sensitivity analyses.
CONCLUSIONS: Findings from this study could inform future CEAs in PKU by establishing expert consensus on outcomes to include, as well as clinically-accurate modeling of such outcomes. These insights address the limitations in previous CEAs of PKU treatments.
METHODS: A modified Delphi panel approach was employed using two rounds of questions. Eleven PKU medical experts were recruited, representing various clinical perspectives. Round 1 included 14 questions on clinical outcomes, diet, Phe-level classification, and treatment discontinuation. Participants rated their level of agreement using a 5-point Likert scale. After Round 1, participants received a summary of anonymized responses and shared comments. Round 2 refined questions that did not reach consensus (defined as ≥70% agreement) in Round 1.
RESULTS: Consensus was reached on 8/14 questions in Round 1, including topics on duration of time required for stable blood Phe measurement, safety concerns at Phe 0-29 µmol/L, association between sustained uncontrolled Phe levels and intellectual disability or other health outcomes, variation in unmet need across patient subgroups, and long-term continuation of pharmacotherapy. In Round 2, consensus was reached on 6/10 questions, including on age ranges when Phe levels are typically maintained, safety of Phe 30-120 µmol/L with sufficient protein intake, mechanisms underlying the association between PKU and chronic comorbidities, possibility of dietary-Phe tolerance challenges at Phe 240-299 µmol/L, and possibility of resuming pegvaliase after discontinuation. Lack of consensus on other questions highlighted areas where CEA could address uncertainty via sensitivity analyses.
CONCLUSIONS: Findings from this study could inform future CEAs in PKU by establishing expert consensus on outcomes to include, as well as clinically-accurate modeling of such outcomes. These insights address the limitations in previous CEAs of PKU treatments.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
EE509
Topic
Economic Evaluation
Disease
SDC: Rare & Orphan Diseases