LAUSR

Background Many treatments developed for rare diseases will have an Orphan Medicinal Product (OMP) designation, indicating that they are likely to deliver benefit in an area of high unmet need. Their approval may be based on a small or uncontrolled trial, as randomised controlled trials (RCTs) of sufficient size are often difficult to conduct, or repeat, as a result of the rarity of the condition, sparsity of patients, or for ethical reasons. Furthermore, many products are given a conditional marketing authorisation, requiring additional evidence to be collected after product launch. This is even more challenging with the advent of advanced therapeutic medicinal products, which use novel scientific approaches like gene or somatic cell therapy. Issue Given the high unmet need associated with these products, there is pressure for Health Technology Assessment (HTA)/reimbursement bodies to enable rapid access to effective treatments. However, there is often only limited evidence available for assessment. Methods TRUST4RD proposes an approach to identify uncertainties of most concern for decision-makers by developing an iterative and informed dialogue amongst stakeholders (including manufacturers, clinicians, patients, regulatory- and HTA agencies and payers), so that potential approaches to resolution can be discussed. As evidence is generated, uncertainties are reviewed and prioritised, and evidence-generation plans revised or clarified accordingly. The aim is to develop – both pre- and post HTA submission – a better understanding of evidence requirements versus evidence-generation trade-offs as an evidence base grows and the potential value of a product becomes clearer. Conclusion TRUST4RD presents guidance on defining uncertainties and evidence gaps in the assessment of value and value for money of specialised treatments for rare diseases. It also provides guidance on the potential of Real World Evidence (RWE) to help address such uncertainties, including the typology of evidence uncertainties, the importance of different uncertainties and the data sources available to address them before and after HTA submission. In making use of the guidance, authorisation and reimbursement discussions on such treatments can be embedded in an evidence-rich context, thereby ensuring value to all parties, particularly to patients.