Patients’ Perspective in Development & Access of Gene Therapies

Gene therapies offer new opportunities for the treatment of orphan diseases and chronic diseases, for which limited, or no effective treatment options are available. However, the novelty and complexity associated with gene therapies and other advanced therapy medicinal products raised new social, ethical, health, and economic issues, which require the input of patients, careers, and the public (Aiyegbusi et al., 2020; EMA, 2018; Goula et al., 2020).

Awareness, understanding, and acceptance of gene therapies vary among patients with different demographic, clinical, and cultural profiles. Patients may express uncertainty about the long and short-term benefits of new treatments, confusion about the goals of research and clinical care, and unrealistic expectations about the timescale availability of new treatments (Aiyegbusi et al., 2020; Carvalho, et al., 2021).

Patients’ engagement is a collaborative approach that aims at understanding patients’ experiences and perspectives and supporting the development of a robust research strategy and enhancing the relevance of the results.  

The role of patients’ perspective analysis

Patient-Reported Outcomes (PRO) are “…report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else” (FDA, 2009). PROs are used to understand the impact of disease and its treatment on a patient’s day-to-day life and include assessment of physical, emotional, and social wellbeing, report of symptoms, and treatment satisfaction from the perspective of the patient. In the regulatory space, guidelines were developed to outline rules and best practice to help researchers and sponsor in the selection, modification, administration, and report of PROs.  

The selection of PRO measures to support labeling claims is driven by a strong, evidence-based rationale. The development of ‘conceptual model’, ‘endpoint model’, and ‘conceptual framework’ supports researchers and sponsors measure what matters to patients (Donatti et al., 2008).

Conceptual model of the disease and endpoint model to support labeling claims

Factors that characterize a disease or condition are represented with a Conceptual Model, which is defined as “…a diagram of proposed causal linkages among a set of concepts believed to be related to a particular public health problem” (Earp & Ennet, 1991). The model can be utilized to explore the disease area, represent the relevant concepts and their interactions, and support the identification of treatment targets and endpoint selection.

PRO-related concepts can be simple (e.g., covering only one concept or factor, such as pain intensity) or complex (e.g., representing multiple interrelated concepts, such as quality of life) (Rothman et al., 2007). A comprehensive scientific review/conceptual model of the disease and the target product profile (TPP), as well as feedback from elicitation activities with clinicians and patients, are used to develop an Endpoint model, which is a diagram representing the relationships among endpoints (e.g., primary, key secondary, exploratory) and the measures that can be used to assess the identified PRO and non-PRO concepts in a clinical trial (Donatti et al., 2008; FDA, 2009; Wild et al., 2007).

Selection of PRO measures and the conceptual framework

The selection of PRO measures, or the modification of existing instruments, is guided by an accurate evaluation of the properties of each tool to ensure the collection of robust and meaningful data. Qualitative interviews, such as concept elicitation and cognitive debriefing, and quantitative methods based on classic test theory and item response theory are typically used to assess the content validity and the psychometric properties of the PRO measures. The overall approach described by FDA guidelines is based on reviews of the scientific literature and input from clinical experts, patients, and caregivers/family members.

Contribution PRO strategy plan to your research design

Patients’ and caregivers’ misconceptions and uncertainty around risks and benefits of gene therapies, long and short-term consequences, treatment burden, and the logistic requirements of trial participation, such as the need for travel or hospital stay, are thought to influence patient’s acceptance of treatment, their recruitment and retention in clinical trials (Aiyegbusi et al., 2020: Carvalho et al., 2021).

The engagement of patients and caregivers contributes to the quality of the research activities (Brett et al., 2012 Cook et al., 2018; Crocker et al., 2018). Patients’ feedback systematically gathered and used to inform the study design will promote the evidence-based approach and provide several advantages, including:

• Enhanced relevance of information gathered by selecting endpoints and measures that are meaningful and important to patients
• Maximized patients’ understanding of the treatment risks and benefits by ensuring the development of user-friendly and culturally appropriate information
• Improved recruitment and retention rates by addressing patients’ concerns and misconceptions
• Implementation of appropriate data collection strategies by accounting for patients’ needs and preference
• Implementation of study results informed by patients’ needs and expectations