Quantifying the likely harms and benefits of novel, disruptive therapeutics such as genome editing will always involve considerable uncertainty. Within the permissible spectrum of CRISPR-mediated activities, rigorous regulatory approaches for risk and benefit assessment will be essential. This is not to assert that all regulatory insufficiencies require probing evaluations of their specific applicability and adequacy in respect of genome editing. Jurisdictions may legitimately set different thresholds for an acceptable risk–benefit ratio. Nonetheless, several features of any assessment process should be universally required. In particular, regulatory processes must be grounded in adequate scientific expertise, but take into account social as well as technical aspects of risk.
We argue that it will be challenging for clinicians or regulatory agencies to navigate the risks and benefits of translating genome editing into the clinic by relying on expert judgement alone, and that broader consultation is required. Trials of CRISPR-mediated somatic cell therapies present an opportunity to engage a wider range of stakeholders, especially patients and patient groups, in determining the acceptable thresholds for risk and benefit. Ideally, this means not only considering what magnitude of risk is acceptable, but discussing which outcomes are taken into consideration, and what counts as harm or benefit, and to whom .
Regulators have traditionally shown reluctance to engage widely in the course of their risk–benefit assessments. National regulators of medical products, for example, often operate in conditions of secrecy, with the European Medicines Agency, the Japanese Pharmaceuticals and Medical Devices Agency, and the Australian Therapeutic Good Administration typically only publishing information about product reviews and the evidence on which they rest after they have made made their decision. By contrast, US Food and Drug Administration Advisory Committee meetings are open to public participation.
Human research ethics committees, which take responsibility for approving and monitoring clinical trials in most countries, present a greater opportunity for broad engagement. They are generally required to have a diverse membership base, including members who are not trained in science. Nonetheless, medical and scientific members have consistently been assessed as having a greater influence on committee decision-making than others, even where community-wide ethical issues are present . And astonishingly, some research ethics codes (e.g., the US Common Rule ) expressly prohibit considering the potential long-term social implications of a research project.
Some programmes, such as the European Patients’ Academy on Therapeutic Innovation and the US Professional Patient Advocate Institute provide training and support to enable patients to engage as advocates in the drug discovery process. But it remains unclear whether there will be longer-term institutional support for more direct involvement of patients and their representatives . Incorporating improved public and stakeholder engagement mechanisms will assist in future-proofing regulation. More work needs to be done to develop appropriate mechanisms for open and inclusive multi-stakeholder dialogue.