Validation and clinical application of the hereditary hemorrhagic telangiectasia-specific quality of life scale

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is the second most common inherited bleeding disorder worldwide and results in substantial medical and psychosocial morbidity due to recurrent, often severe epistaxis, chronic gastrointestinal bleeding, hematologic support-dependent iron deficiency anemia, and serious bleeding and nonbleeding complications of visceral arteriovenous malformations. With disease-modifying therapeutics entering clinical trials, disease-specific health-related quality of life (HRQoL) instruments capable of longitudinal assessment of HHT-specific manifestations are essential. OBJECTIVES: To externally validate and define the features relevant to clinical application of the HHT-specific Quality of Life scale. METHODS: The HHT-specific Quality of Life (HHT-QoL) scale was developed as an easily administered, 4-item instrument assessing physical, social, personal, and work impacts due to HHT longitudinally. Utilizing comprehensive, longitudinal data from pomalidomide for the treatment of HHT, the largest HHT randomized clinical trial to date, we evaluated internal consistency and external validity of the HHT-QoL and defined essential characteristics for clinical application. RESULTS: The HHT-QoL demonstrated good internal consistency and external validity, including directionally and clinically consistent correlations with the Epistaxis Severity Score, bleeding duration as assessed by epistaxis diary, and multiple well-validated generic HRQoL instruments measuring emotional distress, social roles and activities, and fatigue. Development of an HHT HRQoL severity classification utilizing HHT-QoL total scores was successful (0 as no limitation, 1-3 as mild, 4-7 as moderate, and 8-16 points as severe limitation), and the minimal clinically important difference was calculated to be 1.1 points (best rounded to 1 point as the scores are integers) utilizing anchor-based and distribution-based methods. CONCLUSION: This study successfully externally validates the HHT-QoL. The HHT-QoL is a validated disease-specific HRQoL instrument with defined severity classification and minimal clinically important difference, making it ideal for use in clinical trials of bleeding in HHT.