From rationing to rationality: an n-of-one trial service for off-label medicines for rare (neuromuscular) diseases

Excerpt

In the Netherlands, off-label prescription of medicines is tolerated as a suboptimal but inevitable practice. However, patients with rare diseases are disadvantaged in claiming reimbursement for off-label or off-license drugs (here summarised as ‘off-label’). It is difficult to meet the burden of evidence-based proof on efficacy of such medicines. Consensus-based guidelines, a second-best but accepted form of evidence, are also often lacking. Both industry and academia are challenged to perform classical randomized, controlled trials for rare diseases. Moreover, reimbursement rules discourage doctors from prescribing medicines off-label, even to small groups of patients. Thus there is an impasse to creating evidence. Conditionally reimbursed, controlled n-of-one (single-patient) trials with internal randomisation (e.g. AB-BA-BA) could generate evidence on efficacy for rare, chronic conditions where the aim of treatment is symptom control. Practical and scientific support might be provided by a dedicated trial service. …