A Systematic Review of Patient‐Reported Outcomes in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis

Abstract

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with decreased health-related quality of life and debilitating symptoms. These experiences can be defined as patient-reported outcome (PRO) concepts and measured using PRO instruments. We identified all PRO concepts and instruments used in the PBC and PSC literature. This systematic review identified PBC and/or PSC studies from January 1, 1990, to May 6, 2019, that measured at least one PRO concept. Study population, design, PRO concept, PRO instrument, and validation data for PRO instruments were investigated. We provided descriptive statistics of PRO concepts and instruments used, stratified by population type. Use of PRO concepts and instruments were assessed over time. The search yielded 318 articles (69% in PBC, 18% in PSC, 13% in both, and 24% in drug trials). Forty-nine unique PRO concepts were identified. The five most common PRO concepts included pruritus (25%), fatigue (19%), broad health-related quality of life (16%), gastrointestinal adverse events (6%), and physical adverse events (6%). Only 60% of PRO concepts were measured with a PRO instrument, most of which were nonvalidated visual analogue or numeric rating scales. Only three of 83 PRO instruments were developed with feedback from the target populations (one for PBC, one for PSC, and one for both), and only six documented any psychometric testing in the target populations. Use of PRO instruments increased over time from 30% in the 1990s to 67% by 2019. Conclusion: The overwhelming majority of PRO instruments used in PBC/PSC were nonspecific and lacked patient validation or empirical justification. Significant opportunities exist to use qualitative methods to better understand patient experiences, and translate this knowledge into meaningful, patient-driven study outcomes. (Hepatology Communications 2020;4:1502-1515). P rimary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases associated with significant morbidity, including decreased quality of life, (1-6) pruritus, (7-9) and fatigue, (10-14) among other symptoms. The primary outcomes of most clinical trials include disease endpoints or surrogates (e.g., alkaline phosphatase), rather than patient-reported outcomes (PROs), which capture how patients feel or function. PROs reflect a patient's health status, as it comes directly from the patient, without interpretation by anyone else including the clinician. (15) Patient experiences and perceptions are best evaluated using validated PRO instruments that were developed with Abbreviations: FDA, Food and Drug Administration; HRQOL, health-related quality of life; NOS, not otherwise specified; PBC, primary biliary cholangitis; PRO, patient-reported outcome; PSC, primary sclerosing cholangitis.

EASL Clinical Practice Guidelines on sclerosing cholangitis

“…188,[454][455][456] Symptoms are among the top concerns of people with PSC; according to a recent systematic review, the 5 most common symptoms in PSC are pruritus, fatigue, abdominal pain, diarrhoea and nausea/vomiting. 457 In particular, pruritus is associated with reduced social and physical functioning as well as general and mental health, and depression is significantly worse in patients with severe pruritus. 458 The mental component scores appear to be influenced by lifestyle modifications secondary to liver disease, social interactions and loneliness, and were worse in patients with more severe itching, shorter IBD duration and depression.…”

“…The use of patient-reported outcome measures (PROMS) in routine clinical practice may help to guide the implementation of a more patient-centred approach to care in PSC. 457,459 By using PROMS in the clinical setting, we expect to i) improve communication between patients and clinicians, ii) enhance patient engagement in his/her care and improve adherence to treatment, iii) improve monitoring and reporting of symptoms and iv) aid patient recall of issues to be discussed during the clinic appointment. 459 Although it is expected that the use of PROMS in clinical settings will be very beneficial, well-validated, disease-specific instruments are scarce in PSC.…”

Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives

“…Each assessment tool should be validated not to compromise the quality of research. In a systematic review by Kim et al [ 22 ], the authors found that, between 1990 and 2019, patient reported outcomes in PBC had been mostly assessed with unlabelled, nonspecific versions of numeric ratings or Likert scales and that fatigue has been measured with over ten different instruments although ideally, the use of questionnaires should be standardised to allow comparison.…”

The Role of B Cells and B Cell Therapies in Immune-Mediated Liver Diseases

“…Recent data from the UK-AIH national cohort study indicate quality of life is significantly impaired in AIH patients, as is particularly associated with steroid use (177). A recently published systematic review of patient reported outcomes in studies of PBC and PSC concluded that although the use of patient reported outcomes has increased over time, many are nonspecific and unvalidated (178). This underscores the importance in developing and evaluating relevant patient reported outcomes in clinical trials of novel therapeutics alongside clinical efficacy signals.…”