Benefits & Risks of PFIC Clinical Trials

Key takeaways

Patients and parents shared how to weigh risk when considering novel therapies based on their experience.

• Reversibility of clinical intervention strongly shapes risk appraisal

Multiple parent participants reported lower willingness to accept risk of their child trying a treatment with effects that cannot be undone. One adolescent patient recalled whether the pruritus was severe enough to justify transplant — and decided it wasn’t:

“The big concern was: is my itch that bad to where I get a liver transplant? I decided it wasn’t, in retrospect, compared to the cons of transplant—being immunocompromised, in the hospital a lot. My biggest concerns were (related to) irreversibility… If I try different medications, I can stop taking them. You can’t just get your old liver back.”

Reflecting their decision-making process for transplant, multiple parents reported lower willingness to participate in clinical trials when a trial treatment induces a permanent change to the health conditions of their children. Three parents took this further, stating they would not consider a new trial therapy carrying any risk of fatality unless no other options remained. One parent and one clinician independently recommended listing the degree of reversibility (transient vs. permanent effect) as the first item in clinical trial consent forms, given its weight in patients’ risk appraisal.

• Clinical status and quality of life shift willingness to accept risk

Reversibility was not the only factor shaping patient risk tolerance. Several parents reported that their willingness to accept risk is dynamic and depends on their child’s clinical status — reporting far less willingness to take on risk when their child is stable. One parent illustrated this in the context of future gene therapy:

“Because she’s doing quite well, I don’t think we’d try gene therapy until it’s in like “Phase 4” trial. But if she got dramatically sick and it was a choice between transplant and gene therapy…my risk analysis would probably change.”

Quality of life also emerged as a factor in risk appraisal. Among parent participants who had pursued liver transplant, some reported that severely diminished quality of life from pruritus — rather than end-stage liver disease — was what ultimately drove their decision to pursue transplant, despite its irreversibility. One parent said:

“In my child’s case, (the reason we chose to transplant was) a horrible itch— it won’t kill you, but it produces an appalling quality of life for the patient and family. It was a tough decision, but it seemed simple at the time in the thick of itch.”