Lessons Learnt From PICO Exercise Developed by the Joint Clinical Assessment Subgroup for Etranacogene Dezaparvovec
Author(s)
Izabela Jochymek, PharmD, Aleksandra Matjaszek, MSc, Aleksandra Caban, PharmD.
Clever-Access, Cracow, Poland.
Clever-Access, Cracow, Poland.
OBJECTIVES: Since January 2025, Joint Clinical Assessment (JCA) has been mandatory for oncology drugs and advanced medicinal products. JCA scope, defined by population, intervention, comparator, and outcome (PICO) framework, should reflect clinical practice in Member States. In spring 2024, the JCA subgroup conducted six PICO exercises to refine and test the draft scoping process. The aim of this researach was to critically analyse JCA-published PICO exercise on etranacogene dezaparvovec, a haemophilia B gene therapy, and to conclude on potential challenges for health technology developers (HTDs).
METHODS: Critical analysis of JCA-published PICO exercise.
RESULTS: PICOs 1-5 focused on the full label population, while PICOs 6 and 7 targeted sub-populations, based on FIX prophylaxis use. Additionally, for PICOs 1-4, further stratification by disease severity, antibody presence, and annualized bleeding rate was requested. All PICOs shared the same intervention, but differed in comparators, distinguished by the type of FIX product and treatment approach. One PICO comparator included on-demand treatment, while current guidelines clearly prioritize prophylaxis in haemophilia care. Some comparators were not clearly defined - for example, whether FIX products referred to prophylaxis, on-demand treatment, or both. Also, the term 'individualised treatment' was unclear. Outcome scopes varied across PICOs, with PICOs 1-3 being similar in this regard, PICO 5 notably distinct, and PICOs 4 and 6-7 falling between these groups. The review revealed that although etranacogene dezaparvovec PICO exercise included 7 PICOs, population subgroups increased required comparisons to over 20.
CONCLUSIONS: The published etranacogene dezaparvovec PICO exercise included 7 PICOs, with the number increasing to over 20 comparisons when considering requested stratification. This represents a huge workload for HTDs and creates challenges for novel drug market entries. Furthermore, PICOs should be anticipated early to conduct systematic literature reviews and indirect treatment comparisons effectively, as evidence submission is expected within 100 days after the scoping process finalization.
METHODS: Critical analysis of JCA-published PICO exercise.
RESULTS: PICOs 1-5 focused on the full label population, while PICOs 6 and 7 targeted sub-populations, based on FIX prophylaxis use. Additionally, for PICOs 1-4, further stratification by disease severity, antibody presence, and annualized bleeding rate was requested. All PICOs shared the same intervention, but differed in comparators, distinguished by the type of FIX product and treatment approach. One PICO comparator included on-demand treatment, while current guidelines clearly prioritize prophylaxis in haemophilia care. Some comparators were not clearly defined - for example, whether FIX products referred to prophylaxis, on-demand treatment, or both. Also, the term 'individualised treatment' was unclear. Outcome scopes varied across PICOs, with PICOs 1-3 being similar in this regard, PICO 5 notably distinct, and PICOs 4 and 6-7 falling between these groups. The review revealed that although etranacogene dezaparvovec PICO exercise included 7 PICOs, population subgroups increased required comparisons to over 20.
CONCLUSIONS: The published etranacogene dezaparvovec PICO exercise included 7 PICOs, with the number increasing to over 20 comparisons when considering requested stratification. This represents a huge workload for HTDs and creates challenges for novel drug market entries. Furthermore, PICOs should be anticipated early to conduct systematic literature reviews and indirect treatment comparisons effectively, as evidence submission is expected within 100 days after the scoping process finalization.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA218
Topic
Health Policy & Regulatory, Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes, Value Frameworks & Dossier Format
Disease
Genetic, Regenerative & Curative Therapies, Rare & Orphan Diseases