Ethical and Legal Aspects of Adaptive Decision Making (D3.08)

Executive Summary

Medicines Adaptive Pathways to Patients (MAPPs) can be viewed as an engagement framework with which stakeholders collectively – through coordinated and repeated dialogue – prospectively plan and use various existing tools and procedures for medicines development, marketing authorization (MA), reimbursement, on-market use, and post marketing monitoring, in a lifecycle approach1. Thus MAPPs seeks to foster access to beneficial treatments addressing an unmet medical need at the earliest appropriate time in the product life-span in a sustainable fashion.

MAPPs is not a new designation, but will operate within the existing legal and regulatory framework, making better use of existing tools, processes and authorisation routes.  MAPPs products will have a MA with a minimal data package that allows authorisation, in small populations and with the need for long term data collection, similar to the situation today, for example, with conditional marketing authorization (CMA) or orphan products.

This work stream did not identify any general legal blocks to the MAPPS process, fundamentally because such products are deemed to have reached the required regulatory standard for market authorisation (MA) (albeit within a small clinical indication). Thus it is considered that there is greater chance that the benefit: risk assessment at MA approval will change with time, as more information on the product accumulates. Concerns from medicine developers and HCP were raised that liability claims or legal challenge from patients may increase as a result, although it was acknowledged that liability claims could occur under these scenarios currently.

We found little evidence that prescribers knew the legal status of medicines they were prescribing – whether conditional or full (standard) MA. An educational opportunity exists to inform prescribers, so that they in turn can explain to patients the novel nature of a MAPPs product, the degree of (un)certainty, and how it will be managed.  Prescribers also need to maintain an up-to-date knowledge to avoid the accusation by a patient that they have not been informed of a potential risk or change in risk which had, nonetheless, been identified to prescribers in approved regulatory materials.

Likewise no new ethical issues have been identified per se that are specific to MAPPs, but a number of existing ethical challenges that are present today – with small or restrictive populations based on disease or geography, and an emerging post-authorisation evidence base (e.g. CMAs, orphan products, etc) – were considered potentially more likely to occur, or have a greater impact to one or more stakeholders. Examples include: the need for ongoing data collection and the patient and HCP burden this entails, the degree and format of information available to patients in order to make an informed decision, implicit or explicit patient consent to treatment, the societal need for ongoing data collection to reduce uncertainty set against the patients right to opt out of data collection without jeopardizing access, and issues around enacting and maintaining equity of access across healthcare systems in different Member States (MS).

None of these legal or ethical uncertainties are considered to be a block per se on progress towards a better use of adaptive design and adaptive licensing. However, these uncertainties require more careful and prospective consideration, taking into account the divergences that may occur on matters which are national MS competencies rather than those that are governed at centralised EU level, and the ethical and legal frameworks that govern those differences – for which further research is needed.