Comment from Keaka Stokes

I am a patient living with a rare autoimmune disease, and a mother of four children. I appreciate the FDA's efforts to create a pathway for individualized therapies; however, I have several concerns. 1. TREATMENT DISPARITIES ACROSS DEMOGRAPHICS The guidance does not adequately address how individuals across racial, ethnic, socioeconomic, and geographic lines will be able to access these individualized therapies equally. Clinical trial populations for rare disease therapies have historically underrepresented minority patients. If the evidence base supporting approval is drawn from a narrow demographic, the resulting therapies may be less effective or carry uncharacterized risks for underrepresented patients. Also, patients facing socioeconomic barriers, including those lacking full coverage insurance, rural communities impacted by transportation issues, and those lacking resources to navigate complex medical systems, may be effectively excluded from accessing these therapies even after approval. The guidance should require sponsors to include diversity plans in their development programs and address anticipated barriers to access in their marketing applications. 2. LONG-TERM FOLLOW-UP The guidance acknowledges that long-term follow-up may be required for gene-editing products and that post-marketing requirements (PMRs) may be issued. However, the language used feels loose and permissive; "may require," "FDA intends to monitor", rather than mandatory. As a patient, I am deeply concerned about what happens after approval when commercial incentives shift, and sponsors deprioritize follow-up data collection. The FDA has the legal authority to issue binding, enforceable PMRs. I urge the FDA to dutifully exercise that authority clearly by requiring that PMRs for individualized therapies, particularly those involving genome editing, be issued at the time of approval. Deferring this determination creates a loophole that has historically allowed sponsors to delay or avoid post-marketing obligations with little consequence. I urge the FDA to establish clear, enforceable timelines for post-marketing safety and efficacy reporting, with real consequences for non-compliance. The rare disease community has seen examples where post-approval commitments go unfulfilled for years. Patients who receive permanent, irreversible therapies such as genome edits need a firm commitment that their long-term outcomes will be tracked and acted upon. 3. HEALTH LITERACY AND MEANINGFUL INFORMED CONSENT The current guidance does not adequately account for the reality that most patients and caregivers lack sufficient health literacy to fully comprehend what they are consenting to, especially for something as permanent and irreversible as a genome edit. Signing a consent form is not the same as truly understanding one. I urge the FDA to require sponsors to conduct a validated health literacy assessment at the time of informed consent, using tools such as the REALM or the Newest Vital Sign. Also require sponsors to meaningfully tailor all consent materials, explanations, and discussions to each subject's assessed literacy level. For irreversible interventions like genome editing, comprehension, not just signature, should be the standard. Understanding matters even more because the patient population pursuing individualized therapies skews toward children. In some cases, it may be a parent or guardian who bears the full weight of this decision. I speak from personal experience: as a mother of four, the pressure and burden of deciding whether to pursue an individualized therapy for my child would cause immense stress and profoundly impact my mental health. Having a well-rounded, accessible understanding of what the therapy involves, its risks, its permanence, and its unknowns would not only help me make a truly informed decision but also allow me to explain it honestly and clearly to my child and our family. Comprehension and understanding are basic requirements for ethical consent. Low health literacy also disproportionately affects the same communities that are already underrepresented in clinical trials, further compounding the disparities raised above. Addressing health literacy at the consent stage is therefore both an equity and a patient-safety issue. 4. CONCLUSION I support the FDA's recognition that patients with rare, debilitating diseases can’t wait for traditional trial timelines. But speed must not come at the cost of equity, accountability, or genuine understanding. I ask that the final guidance include enforceable diversity requirements in clinical development, mandatory long-term follow-up with PMRs issued at the time of approval, and real consequences for non-compliance, and strengthened informed consent standards, including health literacy assessments, that reflect both the complexity of these therapies and the very human and long-term burden placed on patients and families navigating them.