The PBC Ireland patient registry: study protocol for a national platform on primary biliary cholangitis

Abstract

Background:

Primary Biliary Cholangitis (PBC) is a chronic, progressive liver disease. This paper outlines how a PBC patient registry was developed to address the gaps in evidence, care and policy affecting PBC patients in Ireland.

Objectives:

The PBC patient registry is designed to collect patient-reported data regarding medical history, pruritus, fatigue and quality of life of PBC patients living in Ireland. This data can be used to identify care and treatment gaps and ensure that the PBC patient voice is included in new treatment decisions and healthcare policy. This real-world data will support further scientific and clinical research, drive patient-led advocacy efforts and facilitate collaboration with the liver disease communities globally.

Design:

A patient-led, observational, registry-based study of PBC patients in Ireland.

Methods and analysis:

Participants must have a PBC diagnosis and be 18 years of age or older. PROMs (patient-reported outcome measures) were administered through a secure web-based system. After providing electronic informed consent, participants completed online data collection forms. These included demographic information, medical history, standard of care and validated PROMs for fatigue, pruritus and quality of life. This was followed by an anonymous survey to collect usability and comprehensiveness metadata.

Ethics:

The protocol was approved by TIER IRB Services, protocol ID: 5250715 (July 18th, 2025), which determined the study to be exempt as an observational, minimal-risk, non-interventional research activity involving anonymised patient-reported data.

Discussion:

At the time of publication, 52 participants were registered in the patient registry, of which 40 completed all data collection forms. The results of the post-completion survey suggest high satisfaction across the domains of usability, comprehension, relevance, privacy/confidentiality and overall experience. The PBC patient registry shows that web-based PROMs can be used to collect real-world evidence from patients. Participants reported that the system was easy to use and comprehensive, confirming the usability and effectiveness of this approach. It also provides a starting point to identify healthcare and treatment gaps and facilitates the inclusion of PBC patients’ voices in national and international health policy decisions that affect them.

Trial Registration:

Not applicable.

Plain language summary

The PBC Ireland registry: a patient-led study to collect real-world information on primary biliary cholangitis patients in Ireland

Primary biliary cholangitis (PBC) is a rare, autoimmune liver disease whereby the body attacks the bile ducts in the liver. It mostly affects women and its symptoms can seriously impact daily life. At present, there is little national data about how PBC affects people in Ireland.

The PBC Ireland Registry is the first national project created and led by patients to collect information directly from people living with PBC. Adults with a confirmed diagnosis can join by giving their consent and completing online forms. These forms ask about medical history, symptoms such as tiredness and itching, treatments, and quality of life.

The aim of this study is to give patients a stronger voice in research and healthcare decisions that affect them. The data collected can help improve care, highlight treatment gaps, and support advocacy for better policies.

This project shows that a patient group can successfully build a secure, ethical, and scientifically valuable registry. It can connect Ireland’s PBC community with international researchers and advocacy groups, helping to improve PBC patient care.

Introduction

Primary Biliary Cholangitis (PBC) is a rare, chronic, progressive disease whereby the immune system destroys the bile ducts in the liver. In Ireland, there is little data available on people living with PBC, which is hindering research, treatment availability and policy development. In response to this lack of research data, this paper outlines how the PBC patient registry was developed to address the gaps in evidence, care and policy affecting PBC patients in Ireland. ¹

Although rare diseases affect millions of people worldwide, each disease affects only a small number of people. The diagnosis is often slow, treatment options are limited, the disease is poorly researched, and the patient’s voice is frequently absent from discussions. In this context, patient-led patient registries are emerging as powerful tools for generating real-world patient data, highlighting unmet needs and ensuring that there is “nothing about patients without patients.” ² Furthermore, it’s important to acknowledge that estimates of prevalence and incidence for rare diseases are often unreliable, ³ so PBC could have a higher prevalence compared with some other rare diseases.

Rare diseases in the EU

A disease is defined as rare in the EU if it affects fewer than 5 in 10,000 people. ⁴ Between 27 million and 36 million people in the EU live with a rare disease, and there are between 6000 and 8000 different types of rare diseases. ⁵ With rare disease research being so underfunded, ⁶ the needs of rare disease patients are typically ignored ⁷ when compared to other common diseases.

Patient-led rare disease groups usually work at the country level, often reflecting the need to navigate local healthcare systems. However, engagement at the EU level provides opportunities to collaborate, influence policy and contribute to shared research initiatives. Organisations such as the European Reference Network (ERN) ⁸ aim to address rare, low-prevalence and complex diseases, but participation is restricted to clinicians. The European Patient Advocacy Group (“ePAG”) within the ERN provides an opportunity for patient-led advocacy groups to bridge this gap and ensure that patients’ voices help shape the network’s priorities. Insights from this patient-led registry can guide the activities and priorities of the ePAG network for PBC and other liver diseases.

Primary biliary cholangitis

PBC is a rare, chronic autoimmune liver disease characterised by the gradual destruction of the small bile ducts in the liver. ⁹ This liver damage can lead to scarring, fibrosis and even cirrhosis. Current treatments focus on slowing disease progression. PBC has no cure, and the precise cause is unknown. Genetic factors may also predispose a person to disease, with environmental factors triggering an autoimmune response.^10,11 The primary symptoms of PBC are fatigue and pruritus (itching), and the disease is also associated with numerous comorbidities, including Sjögren’s syndrome, thyroid disease, rheumatoid arthritis and systemic lupus erythematosus, among others. ¹² These symptoms can severely affect patients’ quality of life.

The reported prevalence of PBC varies significantly, but a recent pooled global estimate revealed a prevalence rate of 18.1 cases per 100,000 people and an incidence rate of 1.8 per 100,000 new cases annually. ¹³ Compared with males, PBC disproportionately affects females at a ratio of approximately 9:1. There are no figures available for Ireland, but approximate estimates using these pooled estimates would suggest a prevalence of 959 and an incidence of 95 annually (Figure 1), although the actual figures may be higher.

Figure 1.

Estimated prevalence and incidence of PBC in the Republic of Ireland.

Current and new PBC treatments

The first-line approved treatment for PBC is Ursodeoxycholic acid (UDCA), also known as Ursodiol (or URSO). However, a significant proportion of patients have an incomplete biochemical response to URSO and are sometimes referred to as “non-responders.” Despite the use of URSO at the recommended dosage of 13–15 mg/kg/day, ¹⁴ the liver function tests of these patients remain elevated. Obeticholic acid (OCA) was used as a second-line treatment for PBC, but the European Medicines Agency (EMA) revoked its marketing authorisation ¹⁵ in 2024. There are off-label second-line treatments, such as fibrates (e.g., bezafibrate or fenofibrate), ¹⁶ but these are not licenced for treating PBC, and their use is at the discretion of the treating clinician.

The development of new treatments for PBC has several challenges, including the slow progressive nature of the disease, ethical and practical difficulties with a placebo arm (untreated and worsening conditions), and difficulties in capturing effects on quality of life.^17–19 In this context, real-world evidence gathered from patient registries is an important tool for evaluating new emerging treatments.

In 2024, the EMA approved two new drugs as second-line treatments for PBC, Elafibranor ²⁰ and Seladelpar. ²¹ In Ireland, at the time of this writing, their availability to patients in Ireland is pending approval by the Health Service Executive (HSE), Ireland’s public healthcare system and the National Centre for Pharmacoeconomics (NCPE), which conducts Health Technology Assessments (HTAs) of pharmaceutical products. The outcomes of these assessments will determine whether the treatments are reimbursed under Ireland’s drug payment scheme, which caps monthly household expenditure on approved medicines at €80. But the HTA processes can often fail to accommodate the complexities of rare disease and can result in approved medicines being unavailable to rare disease patients. ²² The patient registry can play a role in this process by providing real-world data on treatment gaps, quality-of-life concerns and unmet needs. This sort of evidence might prove pivotal in strengthening the case to support HTA approvals and accelerate access to new treatments.

Treatment guidelines for PBC

There are multiple guidelines available from professional liver-related organisations that offer a systematic and evidence-based approach to the treatment of PBC. These include those from the European Association for the Study of the Liver (EASL), ²³ the American Association for the Study of Liver Diseases (AASLD), ²⁴ the British Society of Gastroenterology/UK-PBC ²⁵ and the Asian Pacific Association for the Study of the Liver (APASL). ²⁶ However, as some of these guidelines are now five or more years old, they have not kept pace with new developments. In the UK, there is evidence that these guidelines are not consistently followed by clinicians, leading to inconsistencies in treatment and care. ²⁷ It is reasonable to conclude that the same situation applies in Ireland. The PBC patient registry can be used to identify where clinical practice diverges from these guidelines and provide real-world data to support better care.

Patient consultation

Patients often do not know what questions to ask during consultations regarding important aspects of their care. Suggested questions are available, ²⁸ but patients may not be aware of them, and failing to ask the right questions might adversely affect their outcomes. This underscores the importance of gathering data on patients’ treatment experiences and the role patient-led organisations have in disseminating pertinent information and news.

Patient registry

A patient registry can be defined as a system for collecting uniform data (patient-reported or clinical) via observational study methods on individuals who have a specific medical condition or disease to assess and measure defined disease outcomes. ²⁹ Registries can be used to gather patient-reported outcome data to track the natural history of a disease and collect disease data not typically collected in a clinical setting (e.g., quality of life). Without this registry, there is no ‘patient voice’, and identifying gaps in care would be difficult. Therefore, it bridges the void between clinical trials and everyday patient experience, offering insights into how PBC affects patients in their daily lives.

The purpose of the PBC patient registry is to collect real-world data. Insights from this can influence research, policy development and regulatory activities (Figure 2). However, there are potential barriers to the use of patient registry data, ³⁰ including heterogeneity in the data collected and uncertainties about data quality and quality management. We address these concerns by transparently outlining the registry’s quality safeguards, including data collection methods, governance structures and quality assurance activities, thereby providing confidence in the reliability of the data collected. This strengthens the integrity of the registry data as a source of real-world PBC patient experiences.

Figure 2.

PBC patient registry data flow.

Sample size constraint

Due to Ireland’s small population of 5.3 million ³¹ and the fact that PBC is considered a rare disease, the PBC patient registry will inevitably only enrol a relatively modest number of patients. Despite this, it is expected that the patient registry can generate valuable scientific insights and yield significant conclusions about PBC in Ireland,^32,33 which can help to provide valuable data to inform clinical decision-making, support regulatory submissions and enable patient-centred research. When clinical trial data are limited, real-world patient data become even more important because they can fill gaps in knowledge about a disease.^34,35 This data can empower patient-led advocacy groups to influence policy through real-world data ³⁶ and build credibility and influence with clinicians, pharmaceutical companies and rare disease organisations. ³⁷

Objectives

By systematically gathering relevant, high-quality patient-reported data, this registry can highlight the current knowledge and care gaps in Ireland (Figure 3) while also strengthening the case for access to new treatments and improved adherence to up-to-date guidelines.

Figure 3.

Purpose of the PBC Patient Registry.

Collecting real-world data on PBC in Ireland

This registry is building the first national profile of PBC patients in Ireland, capturing real-world data on the medical history, pruritus, fatigue, quality of life and standards of care. Unlike in a clinical trial or a clinical setting, the registry reflects what it is like to live with PBC from the patients’ perspective, offering insights that go beyond the clinical data.

Understand unmet needs and treatment gaps

Real-world data from the registry can help detect inadequacies in a patient’s treatment. These gaps may include delays in diagnosis or treatment, inadequate symptom management, or inconsistencies in care. Analysing these data can guide the development of better support, healthcare services and disease treatments.

Enabling research and advocacy

Patient registries can provide valuable data resources for approved researchers, enabling both scientific research and policy-focused advocacy. Potential applications include the following:

• Producing peer-reviewed publications, for example, research papers on treatment patterns, quality of life, or disease burden in Ireland.

• Identifying gaps in care, for example, highlighting patients with an inadequate UDCA response who are not receiving appropriate second-line therapy.

• Supporting policy change, for example, advocating for the patient to ensure that new PBC treatments are added to Ireland’s drug payment scheme.

• Inform clinical guidelines, for example, identifying low adherence to PBC treatment guidelines and prompting improvements to PBC care protocols.

• Facilitating research collaboration, for example, enabling joint studies and publications with Irish and international academic researchers, and pharmaceutical companies.

• Empowering the patient voice, for example, presenting registry findings at national and international conferences, policy briefings and patient forums.

Improved access to new and emerging therapies

The patient’s voice is typically sought in situations such as when clinical trials are initiated, when pharmaceutical companies launch new treatments, or when Ireland’s HSE/NCPE decides on whether a new treatment should be made available on the HSE’s drug payment scheme. In such cases, the patients’ input can be pivotal in determining whether a new treatment is made available or not. The real-world patient data can demonstrate a need for these therapies, strengthening the need for faster approval, such as an early drug access programme for promising therapies.

Methods and analysis

Recruitment methods

Recruitment efforts focused mainly on online PBC community groups, including the PBCers Organisation, the PBC Foundation on HealthUnlocked and PBC Ireland’s private Facebook group. This may result in an underrepresentation of patients with no online presence. To mitigate this, paper-based versions of the consents and data collection forms were also made available. No Irish clinical sites were involved, and no printed recruitment materials were produced.

Recruitment occurs through established PBC community channels, and requests to participate are screened to confirm eligibility. Where necessary, we follow up with the participant to clarify eligibility and location. Participants are required to self-report their diagnosis of primary biliary cholangitis. They complete data collection instruments to capture their diagnostic and treatment history, including PBC-specific questions. The participant’s responses are reviewed so that any incoherent responses can be identified during data monitoring. Access to the registry is not publicly advertised.

Enrolment inclusion/exclusion criteria

Study participants must be 18 years of age or older with a confirmed diagnosis of PBC. The goal is to recruit 50 participants within 6 months of launch and 100 within 12 months. The patient registry is an ongoing endeavour in which data are collected at yearly intervals. There is no upper limit on participant numbers, although this is obviously constrained by the small number of PBC patients in Ireland. There are no restrictions for sex, pregnancy status, or race or ethnic origin. Patients younger than 18 years of age were excluded.

Data collection forms and Patient-Reported Outcome Measures (PROMs)

Data collection is conducted through a secure, GDPR-compliant, web-based patient portal. Participants must create their own user account using their email address and a secure password. After registration, they provide electronic informed consent, followed by GDPR consent. The participant then proceeds to the data collection forms, which include the following:

Demographics

This records the participant’s date of birth, biological sex, ethnicity, county (if in Ireland) and country.

Medical history

This form captures the patient’s medical history, such as:

• PBC diagnosis and disease history, including year of diagnosis and detailed symptom history

• Family history of autoimmune and liver diseases

• Autoimmune conditions diagnosed in addition to PBC

• Self-reported disease severity and investigations, including:

• ○ Liver biopsy (year and reported findings)

• ○ Bone density (DEXA) scans and outcomes

• Major clinical outcomes, including history and timing of liver transplantation

• PBC treatment history, including:

• ○ Approved second-line therapies

• ○ Off-label and supportive medications

• ○ Treatment-related side effects

• Cancer history

• Lifestyle and health factors, including smoking status, alcohol consumption, weight status, exercise patterns and diet

• Additional health conditions or relevant comments

The purpose of the medical history form is to create a picture of the participants’ health and lifestyle, enabling identification of patterns, risk factors and treatment responses.

Standard of care

The standard of care form captures people’s real-life experiences of being diagnosed, treated and monitored by their clinician. It collects information on:

• Initial care and referral by the patient’s family clinician (GP)

• Hepatologist/gastroenterologist visit

• Monitoring and follow-up

• Areas where care could be improved

• Medications and side effects

• Further information and support

• Financial burden

• Stigma

• Overall experience and suggestions

The goal is to highlight what is working and what could be improved. This information can be used to push for better care and support for PBC patients in Ireland.

The registry incorporates several PROMs (validated instruments) for measuring aspects of living with PBC that matter most to the patient. This design allows us to compare generic PROMs against disease-specific instruments. For instance, the PROMIS Fatigue – Short Form 7a can be compared against the Fatigue Impact Scale (FIS – 8 Item and MFIS - 21 Item) and Quality of Life (PBC-10 and PBC-40) instruments to assess their applicability to the PBC population. ³⁸

Chronic Liver Disease Questionnaire (CLDQ-PBC)

The CLDQ-PBC is a validated PBC-specific PROM used to assess a patient’s overall health-related quality of life (HRQoL). ³⁹ It contains 35 questions and covers the domains of fatigue, emotional function, abdominal symptoms, systemic symptoms, itch and cognitive function. A higher score indicates that a person has a better quality of life.

Fatigue Impact Scale (FIS – 8 items)

The FIS-8 measures the impact that fatigue has on a person’s daily life. ⁴⁰ A higher score indicates that fatigue has a greater impact.

Fatigue Impact Scale Modified (MFIS – 21 Item)

The MFIS-21 measures the effect that fatigue has on patients’ physical, cognitive and psychosocial functions. ⁴¹ A higher score indicates greater impact of fatigue.

PROMIS Fatigue – Short Form 7a

The PROMIS Fatigue – Short Form 7a (available from https://www.healthmeasures.net) measures the effect of fatigue over the previous week. ⁴² A higher score indicates greater impact of fatigue.

Pruritus Scale (5-D)

The 5-D Pruritus Scale questionnaire measures the severity and impact of itching over the previous 2 weeks. The questions cover five dimensions: duration, degree, direction, disability and distribution. ⁴³ A higher score indicates greater severity of pruritus.

Pruritus Severity Scale (12 items)

The Pruritus Severity Scale (12-item) assesses itch severity, frequency, duration and impact on daily life. ⁴⁴ A higher score indicates a more severe degree of pruritus.

Quality of Life (PBC-10)

The QoL PBC-10 is a quality-of-life questionnaire specifically designed for people with primary biliary cholangitis. ⁴⁵ A higher score indicates that the patient has a greater symptom burden and a lower quality of life.

Quality of Life (PBC-40)

The PBC-40 is a quality-of-life questionnaire for people with PBC. ⁴⁶ It contains 40 questions that cover six dimensions: fatigue, emotional function, social function, cognitive function, general symptoms and pruritus. A higher score indicates that the patient experiences greater symptom burden and a lower quality of life.

Longitudinal follow-up

The participants will be requested to complete forms approximately 12 months after they have completed their initial forms. The medical history follow-up form will capture any changes since the baseline. This will enable tracking of disease status, treatment changes, identification of emerging issues and any new concerns of interest to the PBC community. PROMs for fatigue, pruritus and quality of life are also re-administered.

We used multiple overlapping PROM instruments to assess fatigue, pruritus and quality of life (Figure 4) for several reasons. First, this can provide a perspective from multiple approaches. Some are broad, while others explore specific topics more deeply. It also allows patients’ responses to be cross-checked, which can improve accuracy compared with the use of a single instrument. Finally, having multiple overlapping instruments increased our ability to compare our data on a like-with-like basis with a wider range of other PBC research studies.

Figure 4.

PBC patient registry data collection.

Post data collection evaluation (Metadata Survey)

A sample of 26 participants who completed all the data collection forms were invited to complete a short anonymous Evaluation Questionnaire (Appendix B). This survey included Likert-scale statements to collect metadata on instrument usability, comprehension, relevance, privacy/confidentiality and overall satisfaction. Additional free-text questions captured feedback on missing topics, suggestions to better reflect living with PBC, and areas that could be removed or shortened.

Data analysis plan

Data analysis will include descriptive statistics, PROM scoring, internal consistency and construct validity. Descriptive statistics will include mean and standard deviation, median, counts and percentages. PROM scoring will calculate total and domain scores in accordance with each instrument’s scoring instructions. Internal consistency reliability will be measured using Cronbach’s alpha, which will indicate how well each validated instrument performs in an Irish patient-led registry. Because multiple overlapping instruments are used for measuring fatigue, pruritus and quality of life, convergent validity will be explored using Pearson or Spearman correlation coefficients to measure the degree of association across instruments. For instance, patients reporting high fatigue on one scale should also score high on the other fatigue scales. Furthermore, we acknowledge that the participants in the registry may not fully represent the wider PBC patient population in Ireland. The results will be reported as reflecting the participants in the registry, and not all PBC patients in Ireland.

IT and data management

IT server infrastructure

The PBC patient registry has been implemented using the CLIRINX clinical research management system. ⁴⁷ The server infrastructure is installed on secure servers in an Amazon AWS Data Centre (Figure 5) located in Ireland and provides multiple layers of operational and physical security to help ensure the integrity and safety of research data. The infrastructure consists of an application load balance (ALB) to direct incoming application traffic, a web server (Amazon EC2 instance running RHEL Linux), a MySQL database server (Amazon RDS), a mounted file system (Amazon EFS) and a data backup/restore service (AWS Backup). These services are accessible only by the system administrator via a virtual private network (VPN). The web server has no public IP address and can only be accessed via the application load balancer. The management ports are all locked down and accessible only via the VPN. Amazon AWS complies with a multitude of IT standards, laws and regulations, ⁴⁸ which include ISO27001, SOC 1/2/3, HIPAA, HITRUST and various privacy standards, including the GDPR.

Figure 5.

IT server infrastructure on the Amazon AWS cloud.

Encryption

All communications between the web server (EC2) and the user’s internet browser are encrypted via SSL. This means that all the data is encrypted while in-transit. All the data in the database and files on the file server are encrypted at rest.

Research data extracts

No protected health (PHI) information or personally identifiable information (PII) will be included in the data extracts supplied to approved researchers. If multiple files are provided, a “de-identified” patient identifier (DPID) is generated via randomised text so that a patient’s data can be linked across the files in this dataset only. This DPID has no meaning or significance outside of each data extraction.

Clinical Research ID

The Clinical Research ID (CRID) is a unique patient identifier used in rare disease clinical research to enable researchers to link de-identified datasets across disparate research study protocols. ⁴⁹ A CRID identifier is optional and participants in the study may create one for themselves. This identifier enables safe, ethical and patient-driven data connectivity across research, helping to eliminate data silos and promote collaboration.

Post data collection evaluation results

26 participants were invited to complete the post registry evaluation survey, of which 21 (80%) completed it (see Figure 6). In terms of overall satisfaction with the registry experience (question O2), four (19%) participants were satisfied, and seventeen (81%) were very satisfied (median 5, mean 4.8, SD 0.4).

Figure 6.

Results of metadata survey.

Usability

Nineteen participants (90%) used a smartphone, one (5%) used a computer and one (5%) used both to complete the instruments (U1). Sixteen (76%) strongly agreed that the instructions were clear and PROMs easy to use (U2), four (19%) agreed and 1 (5%) was neutral (median 5, mean 4.71, SD 0.56). Sixteen (76%) strongly agreed that the questions were easy to answer on their device (U3), three (14%) agreed and 2 (10%) were neutral (median 5, mean 4.67, SD 0.66). Sixteen (76%) strongly agreed that the overall length of the PROMs was reasonable (U4), three (14%) agreed and 2 (10%) were neutral (median 5, mean 4.67, SD 0.66). In terms of time taken to complete all the PROMs (U6), twelve (57%) completed the forms within 0–20 min, six (29%) completed them within 21–40 min and three (14%) completed them within 41–60 min.

Comprehension

Seventeen (81%) strongly agreed that the PROMs wording avoided confusing medical jargon or explained it well (C1), three (14%) agreed and one (5%) was neutral (median 5, mean 4.76, SD 0.54). Sixteen (76%) strongly agreed that the recall periods were clear (C2), four (19%) agreed and one (5%) was neutral (median 5, mean 4.67, SD 0.66). Seventeen (81%) strongly agreed that it was easy to understand what each question meant (C3), three (14%) agreed and one (5%) was neutral (median 5, mean 4.76, SD 0.54).

Relevance and privacy

Fifteen (71%) strongly agreed that the questions covered the important areas of living with PBC (R1) and six (29%) agreed (median 5, mean 4.71, SD 0.46). Seventeen (81%) strongly agreed that the privacy/GDPR information was clear (P1) and four (19%) agreed (median 5, mean 4.81, SD 0.4). Sixteen (76%) strongly agreed that they felt comfortable with how their data are handled (P2) and five (24%) agreed (median 5, mean 4.76, SD 0.44).

Ethics

PBC Ireland is a patient-led support and advocacy organisation for individuals affected by PBC in Ireland. The group provides information, support and advocacy to improve awareness, care and access to emerging therapies. PBC Ireland is responsible for the design, governance and implementation of the PBC Ireland patient registry. Ethics oversight is provided by TIER IRB Services, protocol ID: 5250715 (July 18th, 2025), which determined the study to be exempt as an observational, minimal-risk, non-interventional research activity involving anonymised patient-reported data.

All the data are stored securely on a GDPR-compliant platform hosted in Ireland. Identifiable information (e.g., name, email) is stored separately from survey responses. All data handling, storage and processing follow GDPR requirements to protect participant privacy and ensure the lawful, ethical use of health information. No identifiable data are shared with third parties. The data provided for approved research are fully anonymised and governed by strict data use agreements with IRB oversight. Decisions regarding how data are analysed and shared will be made within the registry’s governance framework, to ensure scientific integrity and ethical oversight.

All study participants must read and agree to the registry’s explicit informed consent and GDPR consent. The consent is captured in a digital signature, recording what was consented, and when and where consent was given, ensuring integrity, non-repudiation and confidentiality.

Discussion

The value of patient registries

Patient-led groups play a pivotal role in deciding what data are important to the registry. Pruritus, fatigue and quality of life are likely the most important issues for PBC patients, and this guided us in choosing the most appropriate validated PROMs to use. This is also important because it allows the registry to collect valuable data on what it is like to live with PBC, which are not always collected in a clinical setting. This registry can help highlight the unmet needs of PBC patients, inform priorities for patient care and strengthen the voice of PBC patients locally and internationally in the areas of research, policy development and new treatment availability.

Gaps in real-world data

There is a lack of real-world data on PBC patients in Ireland, and a national study of the lived experiences of PBC patients has never been conducted. This lived experience includes response to treatments and symptoms commonly associated with PBC, such as fatigue and pruritus, and the impact these symptoms have on quality of life. Without such data, it is impossible to identify areas where improvements can be made or where gaps in care exist. This lack of data means that Irish patients are underrepresented in global PBC datasets. A patient registry is the first step in filling these gaps and allows us to make our case for the availability of new treatments, better treatments and advocate for policy changes.

Potential research use

The registry provides PBC Ireland with a valuable resource for a broad range of research opportunities and collaborations. This is the first step in establishing a natural history of PBC, where we track the patient’s disease progression and monitor symptoms over time. The registry establishes the credibility that patient-led groups seek to collaborate with research organisations, pharmaceutical companies, and other rare disease organisations locally and internationally, thereby contributing to global PBC initiatives.

Registry evaluation results

Twenty-one participants completed the post-registry evaluation survey. The results suggest a high satisfaction level across the domains of usability, comprehension, relevance, privacy/confidentiality and overall experience. The PROMs selected for this patient registry were acceptable to patients, and we have shown that these can be completed effectively via a web-based platform. Collecting this type of metadata on user experience strengthens the validity of the findings that will result from the registry data. This can also serve as a model for other PBC patient registries and possibly other rare disease registries. A limitation of the evaluation is the small sample size, which reflects the inherent challenges of research in rare diseases. Nonetheless, the evaluation results demonstrate a consistent level of satisfaction across all domains.

Registry strengths

The PBC patient registry is designed for PBC patients and operates under independent IRB ethics oversight while satisfying GDPR compliance. It is implemented on a highly secure server and network infrastructure. The registry uses validated data collection PROMs (Appendix A) for fatigue, pruritus and quality of life. Because informed consent and data collection are performed online, PBC patients anywhere in Ireland can access the registry. It can also become a perpetual resource because patients are followed up with annually. The system can be adapted to accommodate changing needs and support new patient registries, clinical trial readiness studies and natural history studies, even across different diseases. It encourages involvement from the PBC community and has helped foster trust, given that this registry is their voice. It is aligned with international standards for rare disease registries, enabling greater data sharing and collaboration.

Registry limitations and challenges

The main limitation of the patient registry is the inevitable low number of PBC patients who will enrol in the registry. With Ireland’s small population size and the rarity of PBC, the registry will be limited to a relatively small number of participants. Therefore, analysis may be restricted to descriptive statistics to summarise various aspects of the results and will not fully represent the wider PBC patient population in Ireland. Despite this, the registry can generate valuable scientific insights. The data are patient-reported, so patients may not recall all aspects of their PBC experience from memory, unlike data retrieved from clinical charts. Enrolment is focused on online communities, so it may not reflect all PBC patients, and some degree of digital exclusion may be experienced because of limited access to digital devices or a lack of confidence using these technologies. Finally, some questions or forms may have been skipped or incomplete, even after multiple follow-up attempts to contact these patients.

Long-term vision for the registry

The long-term goal of the PBC patient registry is to become a trusted resource supporting PBC research, care and policy. It can be a comprehensive and high-quality dataset that contains real-world data on people living with PBC in Ireland. This not only advances knowledge about PBC but also informs decisions that affect PBC patients and influences policy. It can foster opportunities to collaborate with clinicians, pharmaceutical companies, researchers and patient-led groups both locally and internationally. Longitudinal data collection will also start to provide insights into disease progression, thus creating a sustainable, trusted resource for the PBC community. Indeed, the registry platform could also evolve to support additional PBC and other liver-related research initiatives.

Peer-reviewed publication pipeline

The registry data has the potential to create a pipeline for follow-on peer-reviewed publications. Analysis of baseline data can describe characteristics of PBC patients in Ireland and support publications on fatigue, pruritus and quality of life. These areas are often neglected in the clinical literature. When longitudinal data is collected, papers on the natural history of disease progression can be produced. Medical history and standard of care data can facilitate publications that target health policy, using real-world evidence to influence policy and improve care. Collectively, these publications will ensure the PBC patients’ voice is represented in research, policy and decisions that affect their care.

Lessons learned

The enthusiastic participation of PBC patients at the launch of the registry demonstrates the PBC community’s willingness to participate and contribute to PBC research. Clear, plain, informative messages on PBC-related websites and in our private online community have built trust and encouraged participation. For the initial group of participants, the form completion rates were high. The private online community members benefited from the regular updates on the registry progress, as well as updates on important new developments, such as status changes in drug availability, new research publications and other PBC-related news. However, a limitation of the registry is that the patients’ past blood test results are not collected in the registry, owing to the complexity of data de-identification and a lack of resources. This would have provided a fuller picture of the patient’s baseline disease status.

Conclusion

The PBC patient community in Ireland has built a patient registry to ensure that their voice is heard and that no decisions about PBC patients are made without the involvement of PBC patients. The registry has independent IRB ethics oversight, uses a GDPR-compliant IT platform and uses electronic consents and data collection forms to capture patient-reported real-world data. These instruments include demographics, standard of care, medical history and validated PROMs for pruritus, fatigue and quality of life. Although the registry is still in its early stages, it is proving to be very feasible.

As participant numbers grow and the registry accumulates more longitudinal data, the emerging dataset can become a vital resource for the PBC community. This resource will facilitate collaborations with other PBC organisations worldwide and ensure the voices of PBC patients in Ireland are part of local and global conversations about this rare disease.

The post evaluation has demonstrated that validated PROMs can be administered via a web-based platform with a high level of patient-reported satisfaction, across the domains usability, comprehension, relevance and privacy. These results suggest confidence in the registry’s findings and provide a model for other disease registries.

The long-term goal is to establish a continually growing dataset that can support and accelerate further research and inform policy decisions that affect PBC patients.