Roadmap Part 2 — Future Directions for PFIC CER

Considerations for Developing CER Questions in PFIC

Variability in Care Common in Rare Diseases

  • Initial participant discussions in project IMPACT underscored the need to start by identifying systemic barriers to reduce care variability in PFIC. 
  • Understanding these barriers is a crucial first step toward understanding how patient-centered CER specifically can address these challenges and lead to better care outcomes for the PFIC community.

Addressing Variability in Care for PFIC

Participants identified specific barriers and associated solutions to reducing variability in care for PFIC:

Problem
Cost and accessibility of treatments and surgeries
Solution
Patient treatment and self-advocacy education
Problem
Lack of standard care practices for PFIC
Solution
Develop consensus treatment plans
Problem
Lack of designated “centers of excellence”
Solution
Establish PFIC centers of excellence
Problem
Variability in provider knowledge of PFIC subtypes
Solution
Facilitate provider education on the different PFIC diseases and respective treatment choices
Problem
Lack of communication between providers at different centers
Solution
Develop realistic treatment guidance for under-resourced care centers
Problem
Clinicians not involving patients as partners in care decisions
Solution
Develop guidance for patient-centered care decision-making
Problem
Lack of comprehensive evidence regarding patient-centered treatment outcomes
Solution
Patient-centered comparative effectiveness research

Variability in Care Across PFIC Subtypes

  • PFIC is a group of similar yet unique rare genetic diseases.
  • Treatment choices vary considerably across the different diagnoses and stages of disease (e.g., PFIC1/FIC 1 vs. PFIC 2/BSEP, pre- vs. post-transplant).
  • Treatment variability is therefore one of the challenges that needs to be addressed when evaluating which treatments and outcomes would be most relevant to investigate in a patient-centered CER study. 

Implications for PFIC CER

Given the instances of variability in care mentioned above, participants  identified the following considerations for designing PFIC CER studies, and specifically, for evaluating which treatments and outcomes to investigate.

Is there specific variability in PFIC care approaches that we can investigate with CER?

Variability in care can be due to the uniqueness of each PFIC patient but can also be due to lack of sufficient systematic knowledge related to treatment success. Treatment variability can therefore help to reveal which treatments would be insightful to compare. IMPACT participants discussed how PFIC patients’ care has varied between centers, including differences in nutritional interventions and the combination of treatments used to manage itch.

Which treatments are feasible to compare?

Not all treatments are feasible to compare. For example, IMPACT members would like to know which of the two available IBAT inhibitors, maralixibat and odevixibat, work better to treat itch. However, clinical trials conducted separately for the two medications have shown very similar effects and effect sizes, and it would be very challenging if not practically impossible to recruit enough study participants to detect reliable differences between the two treatments.

Can the outcomes be measured reliably?

 To identify treatment outcomes that are important to patients and their families we designed the IMPACT Treatment Experience App (TEA), which is a web app hosted on PFIC Network’s website. The TEA showed that itch, sleep, and different aspects of quality-of-life rank among the most important treatment-related outcomes in PFIC. These outcomes can be measured reliably by using validated questionnaires such as the PROMIS scales used in the PFIC Network Patient Registry. In addition, both the TEA data and the focus group discussions revealed the importance of growth, malnutrition, and diarrhea. These outcomes can be reliably captured with established clinical measures.

Can the outcomes be measured in a reasonable timeframe?

When designing a study, it’s important to check if outcomes can be measured within a reasonable timeframe that fits the study’s goals, budget, and participant availability. For example, changes in itch levels or growth can be assessed in a reasonable timeframe whereas native liver survival (while being a crucial clinical outcome), can take years to measure.

How many PFIC patients and families are affected by these treatments and outcomes?

Which treatments and outcomes are meaningful to investigate can vary depending on diagnosis and transplant status. As a community, we must decide whether to prioritize studies that focus on specific PFIC subtypes or whether to address treatments and outcomes that are relevant across all subtypes and stages of the disease. For example, interventions such as nutrition support and itch medications, along with the respective outcomes revealed by the TEA and focus group discussions can be relevant across different subtype diagnoses.

For a practical worksheet and tools to support developing CER questions on PFIC, download the Researcher Companion (see p.5).

Future Directions for PFIC CER

PFIC Patient-Centered CER Priorities

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