Existing economic evaluations might undervalue the potential of cutting-edge cell and gene therapies for rare diseases, which can influence HTA frameworks, access, and pricing choices. In this insight article we review the benefits of gene therapy valuation beyond QALYs, and examine their quantification and impact on economic modeling. Drawing from our thematic analysis of 3 presentations, this insight article will explore the importance of value assessment methods, the incorporation of novel elements, and addressing challenges in the field. The 3 presentations were by Omar Dabbous, Additional Benefits of Value for Gene Therapies; Mike Drummond, Gene Therapy Measuring Value Beyond QALYS; and Sean Sullivan, Economic Evaluation of Gene Therapy: Where do we go from here?

Introduction

The purpose of the thematic analysis applied below is to synthesize the key concepts and implications from various presentations on gene therapy valuation and health technology assessment (HTA) processes. By organizing the information into overarching themes, this analysis highlights common threads and contrasting viewpoints, ultimately facilitating a coherent and easily understandable synthesis. The identified themes include value assessment methods, incorporating novel elements, and challenges and future directions in the evaluation of gene therapies. This approach not only offers a comprehensive understanding of the current state of the field but also enables stakeholders, such as pharmaceutical, medical technology, and biotechnology companies, to better navigate the complexities of HTA processes, develop innovative therapies, and address unmet medical needs.

Theme 1: Value Assessment Methods

This theme explores the different approaches used by healthcare technology assessment (HTA) bodies to evaluate the value of gene therapies, including the cost per quality approach, added clinical value approach, and the value flower framework, highlighting the need for transparency and consistency.

Key Concepts:

• Cost per quality approach: Evaluating treatments based on incremental cost per quality-adjusted life year (QALY) gained.
• Added clinical value approach: Assessing the added clinical value of a treatment based on clinical data, which is then used in price negotiations.
• Value flower: A framework identifying various elements of value that could be considered in HTA, such as adherence improving factors, equity, and option value.
• Quality shortfall: Quantifying the severity of a patient’s condition based on the difference between their potential maximum QALYs and the QALYs they can expect with their current treatment.

Implications:

• Companies should be aware of different HTA approaches and develop therapies accordingly.
• There is a need for more transparent and consistent approaches to quantifying elements of value.
• Addressing unmet needs and potential health improvements could give companies a competitive advantage.

Theme 2: Incorporating Novel Elements in Gene Therapy Valuation

This theme examines the integration of novel elements such as disease severity, equity, insurance value, hope, and option value into the evaluation of gene therapies, emphasizing the importance of quantifying and incorporating these factors into cost-effectiveness models.

Key Concepts:

• Disease severity: The degree to which a disease impacts a person’s health and well-being, affecting the value assigned to treatments.
• Equity: Fair distribution of health outcomes and resources across different income groups and disease severity levels.
• Insurance value: The value derived from health insurance in terms of physical risk protection and financial risk protection.
• Hope: The preference for treatments with a greater distribution of possible benefits, even if the average outcome is the same as other treatments.
• Option value: The value a treatment provides by creating a bridge to another therapy option, which can affect cost-effectiveness estimates.

Implications:

• Companies should research ways to quantify and incorporate novel elements into cost-effectiveness models.
• Collaborate with researchers and HTA bodies to ensure a comprehensive understanding of gene therapy value.
• Address equity concerns by considering the distribution of health outcomes and resources for various income groups and disease severity levels.
• Evaluate the insurance value and option value of new therapies and incorporate this information into product development and pricing strategies.

Theme 3: Challenges and Future Directions

This theme addresses the challenges and inconsistencies in applying value modifiers and additional benefits across HTA bodies, the need for further research to quantify novel elements, and the importance of collaboration among companies, researchers, and HTA bodies to improve gene therapy evaluation and understanding.

Key Concepts:

• Inconsistent application of value modifiers and consideration of additional benefits across HTA bodies.
• The need for further research and development of methods to quantify novel elements of value.
• Collaboration between companies, researchers, and HTA bodies to improve the evaluation and understanding of gene therapies.

Implications:

• Companies should be aware of the varying application of value modifiers and additional benefits in HTA assessments, affecting the valuation of their products.
• Continue researching and developing ways to quantify and incorporate novel elements into cost-effectiveness models.
• Engage in collaborative efforts with researchers and HTA bodies to ensure a more comprehensive understanding of the value of gene therapies and address challenges in their evaluation.

Three Background Presentations on Gene Therapy Valuation

Omar Dabbous: Additional Benefits of Value for Gene Therapies

Summary:

The presentation discusses the valuation of gene therapy in healthcare technology assessment (HTA) processes, focusing on the cost per quality approach and added clinical value approach. The speaker emphasizes that the cost per quality approach is the minority approach to HTA worldwide, and many other HTA bodies work on an assessment of added value, which is then used in price negotiations. The presentation also touches upon the consideration of additional benefits, rare diseases, and the use of modifiers in HTA assessments.

Key Concepts:

• Cost per quality approach: A method used by some HTA agencies to calculate the incremental cost per quality-adjusted life year (QALY) gained.
• Added clinical value approach: An alternative method used by HTA bodies, which focuses on assessing the added value of a therapy based on clinical data.
• Rare diseases: Conditions with a low prevalence, often with unmet medical needs, for which gene therapies may provide significant benefits.
• Modifiers: Factors that HTA bodies may consider to adjust the cost per quality estimate or added value assessment, taking into account additional elements of value.

Implications for pharmaceutical, medical technology, and biotechnology companies:

• While some HTA bodies consider additional elements of value beyond QALYs, these considerations are largely qualitative and made through deliberative decision-making processes.
• There is scope for further quantification of these additional elements of value, which could potentially impact the assessment and valuation of gene therapies.
• Companies developing gene therapies should be aware of the different approaches used by HTA bodies and understand how their products might be assessed based on added clinical value and cost per quality.
• A focus on developing gene therapies for rare diseases with significant unmet medical needs may lead to a more favorable assessment by HTA bodies.

Mike Drummond: Gene Therapies, Measuring Value Beyond QALYS

Summary:

The speaker discussed the valuation of gene therapies in healthcare technology assessment (HTA) processes worldwide. They compared the cost per quality approach and the added clinical value approach, exploring how these methods take different elements of value into consideration. They also highlighted how certain aspects of gene therapy are considered by HTA bodies, such as their potential for meeting unmet needs and generating substantial health improvements. However, the speaker noted that the application of value modifiers is inconsistent and that there is room for further quantification of these elements.

Key Concepts:

• Cost per quality approach: A method used by some HTA agencies to evaluate treatments based on their incremental cost per quality-adjusted life year (QALY) gained.
• Added clinical value approach: A method used by other HTA agencies to evaluate treatments based on the added clinical value they provide, which is then used in price negotiations.
• Value flower: A framework that identifies various elements of value that could be considered in HTA, such as adherence improving factors, equity, and option value.
• Quality shortfall: A concept used by NICE (UK) to quantify the severity of a patient’s condition, based on the difference between their potential maximum QALYs and the QALYs they can expect with their current treatment.

Implications for pharmaceutical, medical technology, and biotechnology companies:

• As HTA bodies consider various elements of value in their assessments, companies should consider these factors when developing new therapies, particularly for rare diseases and gene therapies.
• There may be a need to develop more transparent and consistent approaches to quantifying elements of value, which could lead to better decision-making processes in HTA.
• Companies should be aware that the application of value modifiers and the consideration of additional benefits can vary across different HTA bodies, affecting the valuation of their products.
• Exploring and addressing unmet needs and potential health improvements through innovative therapies could help companies gain a competitive advantage in the market.

Sean Sullivan, Economic Evaluation of Gene Therapy: Where do we go from here?

Summary

The presentation covered the exploration of novel elements, or “petals,” in evaluating gene therapies, emphasizing that current methods might not fully capture their value. It discussed the importance of incorporating disease severity into value assessments, as this can help prioritize high-severity treatments that may be undervalued in existing models. The presenter also highlighted the need for a more explicit incorporation of equity considerations into cost-effectiveness evaluations and acknowledged that further research is required in this area. The presentation touched on the significance of insurance value, both physical and financial risk protection, but noted that integrating it into cost-effectiveness frameworks remains a challenge. Additionally, the speaker addressed the concept of hope, valued by risk-loving patients, and option value, which refers to a treatment providing a bridge to another therapy option, stressing that quantifying and incorporating these concepts into cost-effectiveness models is still a work in progress.

Key Concepts:

• Value flower: A conceptual framework that identifies various elements, or “petals,” that could be considered in evaluating the value of gene therapies.
• Disease severity: The degree to which a disease impacts a person’s health and well-being, which may affect the value assigned to different treatments.
• Equity: The fair distribution of health outcomes and resources across different income groups and disease severity levels.
• Insurance value: The value derived from health insurance in terms of physical risk protection (valuing treatments for diseases one does not currently have) and financial risk protection (protection against catastrophic income loss due to illness).
• Hope: The preference some patients have for treatments with a greater distribution of possible benefits, even if the average outcome is the same as other treatments.
• Option value: The value a treatment provides by creating a bridge to another therapy option, which can affect cost-effectiveness estimates.

Implications for Pharmaceutical, Medical Technology, and Biotechnology Companies:

• Continue researching and developing ways to quantify and incorporate novel elements into cost-effectiveness models for gene therapies.
• Collaborate with researchers and health technology assessment bodies to ensure a more comprehensive understanding of the value of gene therapies.
• Address equity concerns by considering the distribution of health outcomes and resources for various income groups and disease severity levels in the development and pricing of new therapies.
• Consider the insurance value of new therapies in the context of physical risk protection and financial risk protection when developing and pricing products.
• Acknowledge and address the value of hope in treatment decisions and cost-effectiveness evaluations.
• Evaluate the option value of new therapies, considering their potential to provide a bridge to additional treatment options, and incorporate this information into product development and pricing strategies.