Guidance on communication and informed consent with patients and their families for experimental individualized...

With advanced tools and techniques, it is now possible to genetically diagnose an increasing number of individuals with rare diseases for which no disease-modifying treatment exists. For a subset of affected individuals, it is possible to develop individualized interventions to modulate and/or correct the underlying genetic defect. Communicating to such individuals and their guardians about the potential risks and benefits of such experimental therapies poses special challenges. In addition to typical procedures used for consenting subjects of clinical trials or off-label therapy, individualized therapy protocols involve a complex interplay between biological plausibility, preclinical data, risks, uncertainties, and ethical considerations of equipoise, especially since individualized treatments are usually developed for serious conditions. While no formal guidance exists, this perspective was drafted from the shared experience of clinicians and developers involved in treating affected individuals with individualized antisense oligonucleotides (ASOs) to provide preliminary guidance on communication and consent. As additional experience and expertise accrue over time, we anticipate that these principles will evolve with subsequent modifications to this document.