ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drugs Outcomes Research and Policies
This article is part of the Research TopicAdvancing Health Technology Assessment and Patient-Reported Outcomes: Innovations and Implications for Health Economics and Outcomes ResearchView all 10 articles
A Hierarchical and Configurational Analysis of Health Technology Assessment Outcomes for Cell and Gene Therapies
Provisionally accepted
Ziyad S Almalki1
Renad M. Alshammari2Nadia A. Dahduli2
Mouaddh Abdulmalik Nagi3*Syeda Juweria2Moayad M. Alhamdani1Yazan M. Alzahrani1
Saja Almazrou4
Nehad Jaser Ahmed1
Abdullah Khaloofah Alahmari1Areej A. Alshlowi2- 1Prince Sattam bin Abdulaziz University College of Pharmacy, Al Kharj, Saudi Arabia
- 2Almaarefa University College of Pharmacy, Riyadh, Saudi Arabia
- 3Aljanad University for Science and Technology, Taizz, Yemen
- 4King Saud University, Riyadh, Saudi Arabia
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Background: Cell and gene therapies (CGTs) challenge traditional Health Technology Assessment (HTA), creating a fragmented global access landscape. This study identifies the determinants of CGT reimbursement outcomes by quantifying the influence of key variables and identifying the configurations leading to a positive recommendation. Methods: A dual-methodology approach was employed. We constructed a comprehensive dataset of all HTA decisions for CGTs across seven major jurisdictions between January 2017 and July 2025. Hierarchical Linear Modeling (HLM) was used to identify independent predictors of HTA outcomes, and Fuzzy-Set Qualitative Comparative Analysis (fsQCA) was used to identify sufficient pathways to success. Novel composite indicators were developed to measure system-level adaptability and the influence of patient advocacy groups (PAGs). Results: The HLM analysis, accounting for data clustering (Intraclass Correlation Coefficients (ICCs): 42% country-level, 24% agency-level variance), confirmed that strong clinical efficacy (Coef. = 0.40), high unmet need, and disease rarity were significant positive predictors. High therapy cost was a powerful negative predictor (Coef. = -0.29 per $1M USD). Crucially, high System Adaptability (Coef. = 0.35) and strong PAG Influence (Coef. = 0.28) emerged as major positive determinants. The fsQCA revealed three distinct pathways to a positive recommendation with high consistency: a "Transformative Value" path (consistency: 0.93), a "Strategic Mitigation" path (consistency: 0.90), and an "Economic Dominance" path (consistency: 0.94). The overall QCA solution explained a majority of positive outcomes (solution coverage: 0.68). Conclusions: HTA success for CGTs is not determined by isolated attributes but by the strategic alignment of therapy-level evidence, agency-level processes, and country-level context. The influence of organized patient advocacy and the structural flexibility of HTA systems are critical, previously under-quantified components of this alignment.
Keywords: cell and gene therapies, decision-making, Health Technology Assessment, reimbursement, value
Received: 30 Aug 2025; Accepted: 19 Nov 2025.
Copyright: © 2025 Almalki, Alshammari, Dahduli, Nagi, Juweria, Alhamdani, Alzahrani, Almazrou, Ahmed, Alahmari and Alshlowi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mouaddh Abdulmalik Nagi, muadhalmashwali@yahoo.com
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