Behind the Breakthroughs: What Every Caregiver Should Know About Clinical Trial Design

For families facing rare diseases, clinical trials often represent more than just a research protocol—they represent hope. But what actually goes into designing those trials? A research team has to make high-stakes decisions that will directly affect whether a child qualifies, what dose they receive, or how often a family must travel.

On March 12 at the Empowering Patients: A Cell and Gene Therapies Summit, a panel of leading clinician researchers unpacked the “Complexity of Study Design in Cell and Gene Therapy” where they shared honest, practical insights about the decisions that shape trial access, burden, and outcomes for patients and caregivers alike. The session was moderated by Sharon King a caregiver and patient advocate leader at Aldevron and Taylor’s Tale, the panel featured Dr. Heather Lau (Yale University), Dr. Amy Waldman (Children’s Hospital of Philadelphia), and Dr. Raymond Wang (Children’s Hospital Orange County).

Managing hope – The panel opened with a discussion on managing the gap between patient hope and clinical reality. As Dr. Lau explained, early-phase trials are grounded in safety and discovery—not guaranteed treatment. Setting realistic expectations through informed consent is essential, especially in phase 1 trials, where both risks and potential benefits are largely unknown. Panelists emphasized the importance of honest, compassionate conversations with families from the very beginning. 

Informed consent is a process, not a form – A recurring theme throughout the session was informed consent and framed as more than just a form—it's a process. Dr. Waldman highlighted the hours-long conversations needed to thoroughly explain trial protocols, possible side effects, and even the limits of what can be disclosed during the study. In a pediatric settings, where parents make decisions for their children, the process becomes even more nuanced and emotionally charged. 

Need for family-centered trials to reduce burden – The panel also tackled the ethical and logistical challenges of trial participation, including the burden of travel. Dr. Wang and Dr. Waldman both called for greater flexibility and financial support from sponsors to ensure equitable access, including considerations for caregiver needs, sibling support, and indirect costs that often go unaddressed. Caregivers must also contend with the increased burden of frequent site visits and follow-up during early dosing phases. As Dr. Lau put it, “We need to think about the whole family” when designing trials that are both scientifically sound and ethically responsible. Long-term safety monitoring, potentially extending 15–25 years, poses additional burdens that must be transparently communicated from the start. Importantly, patient advocacy groups were named as powerful allies in negotiating these supports and shaping trial designs that are family-centered. 

Alternatives to placebo-control – A particularly thought-provoking part of the discussion focused on study design alternatives to placebo-controlled trials. For many rare diseases with fast progression and irreversible damage—especially in neurological conditions—traditional control groups can pose ethical dilemmas. While a placebo-control is widely accepted as the research gold-standard, Dr. Lau advocated for the use of external controls and natural history data. She stressed that innovative and adaptive trial designs are not only possible but necessary in the rare disease space. 

Eligibility criteria can result in painful exclusions – Dr. Waldman clarified that these decisions are made at the sponsor level, not by individual sites. Sponsors are ultimately looking to design a trial that can show safety and efficacy in the fewest amount of participants possible to expose the least amount of people to potential risks and unknowns. While criteria aim to detect measurable changes within a short timeframe, they often mean that families must confront painful exclusions due to age or disease progression. It’s a balance between scientific rigor and inclusivity that continues to evolve. 

Participants can’t control if they’ll receive a low or high dose – The panel highlighted how dose escalation in gene therapy trials—where treatments are often “one and done”—can have significant implications for caregivers and participants. Early enrollees may receive lower doses with uncertain efficacy, while later participants might access more optimal dosing after safety reviews are complete. This rolling enrollment creates emotional and logistical strain for families navigating tight windows of eligibility, travel requirements, and the fear of missing the best opportunity for benefit. As Dr. Waldman noted, the order in which a family is enrolled (early vs. late phase) is often out of the families’ control, and transparency is essential to managing those expectations. 

In the end, one message rang clear: patient voices matter—not only during trial participation but at every stage of design and planning. “We are not separate,” King concluded. “We need advocacy, science, and community to move together.” 

Save the date for more impactful sessions!  
Empowering Patients 2026: A Cell and Gene Therapies Summit | Happening March 11 + 12