The determination of how 'serious' a condition is has direct and important implications for policy and clinical translation of existing and emerging genomic technologies. It can affect prevention strategies, treatment decisions (eg, type, duration, intensity), as well as the evaluation of clinical outcomes. It can also influence expectations regarding range of functionality and disability.
Currently, many laws, regulations, and policies include a 'serious' threshold to justify the appropriate use of genomic technologies, such as preimplantation genetic testing (PGT) or human germline genome editing, to a certain subset of serious conditions. Yet, 'serious' remains undefined, and there is a lack of guidance regarding how the threshold ought to be applied or whether it should be defined at all. Hence, it falls to clinicians and regulators to interpret what ought to be considered a 'serious' condition.
If 'serious' is to be used as a threshold or filter for access to emerging genomic technologies (including reproductive choices, human genome editing, cell and gene therapies, or clinical decision-making), it is essential to develop a common understanding of what it means. When reflecting on what factors a common understanding may encompass, it becomes apparent that a tension exists between clinical (individual) versus policy (population) decision-making. Unpacking the notion of a 'serious' condition is part of our current research. Early in 2021, we held a virtual workshop, sponsored by the Stem Cell Network, including a variety of key stakeholders and end-users, with the goal of contextualising what constitutes a 'serious' genetic condition. Some preliminary outputs are presented below with the complete results to follow.
Individual decision-making is at the heart of clinical care. Decisions are made through an exchange between clinicians and their patients regarding treatment options tailored to their specific situation. In this scenario, the patient is considered the most important player. They know what a 'serious' condition means to them and can determine this threshold for themselves. Imposing a definition of 'serious' on patients could be seen as restricting their autonomy and freedom to decide.
Indeed, clinical experience demonstrates that 'serious' is a subjective notion, as it appears to be a moving target across different contexts and time, and best understood along a continuum (eg, degree of severity). Objectively qualifying a condition as not 'serious' would be difficult and dismissive of the patient's lived experience. Examples of factors that influence patients' interpretation or understanding of 'serious' include, ethnocultural and spiritual-religious factors, which shape concepts such as health and disease. Proponents of keeping 'serious' vague and undefined argue that the absence of a definition is a positive thing and ought to be seen constructively. By avoiding or resisting a legislative definition, the determination is left to the professional determination of clinicians and personal choices of patients. It leaves room for subjective and flexible interpretations of 'serious' that are adaptable to the patient's reality.
While such a discretionary approach may be appropriate in a clinical context, where decisions are being made at the level of the individual, this level of deference to patient preferences and perspectives would be inappropriate and create challenges for decision-making at the population level. When considering the policy context, it becomes important to have certain thresholds and parameters in place to ensure a coherent and equitable application of laws and policies.
When we reflect on policy decisions that affect populations, such as funding or equitable access to treatments or social support, the discretionary approach promoted in a clinical context no longer works. Policy decisions affecting populations require operational definitions to ensure a consistent and coherent application; otherwise, 'serious' is arbitrary and confusing.
Still, recommendations and decisions as to whether or not something is considered 'serious' are being made in the absence of a framework or a common understanding of what it means. Variability and divergence in the interpretation of a 'serious' condition have been demonstrated among clinicians and medical geneticists. This leads to disparity between policy expert recommendations that seek to frame or interpret 'serious'. This lack of an operational definition or guidance regarding how the notion of 'serious' should be framed is particularly problematic in the policy context where equity and procedural justice require clearly defined terms, or at the very least, terms that have operational clarity.
Moreover, the few laws, regulations, and policies that do attempt to provide some clarity, typically acknowledge the complex and contextual nature of 'serious', and admit it is not a purely medical determination or one that requires a list. They recognise the need to consider a multitude of contextual factors, including the patient's perceptions and lived experience. While consideration of lived experience is essential, policymakers require further overall guidance and tools to facilitate decisions between different choices and possible scenarios. Therefore, if there is any hope of a coherent and consistent application of the notion, a shared understanding of the relevant factors is essential.
To address these tensions in both a clinical and policy context, we propose that a framework of relevant factors to consider in the determination of 'serious' could be helpful and provide a common understanding. To further unpack the notion of 'serious', and work towards an eventual framework, it is essential to engage with the stakeholders most likely to be impacted. 'Serious' is a minimum threshold term, an entry point into a discussion that requires further contextualisation. Patients and their families can make individual decisions, but system-level decisions need more consensual perspectives. Therefore, any eventual framework will need to be attentive to these contexts and adaptable to different situations. This can then be used to frame conversations with patients and discussions among regulators and legislators, and ultimately facilitate decision-making.