Objectives

Thresholds for the minimally important difference (MID) or responder definition (RD) in health-related quality-of-life (HRQoL) scores are required to interpret the impact of an intervention or change in the trajectory of the condition which is meaningful to patients. This study aimed to establish MID and RD for the European Organisation for Research and Treatment of Cancer Quality of Life Multiple Myeloma questionnaire (EORTC QLQ-MY20).

Methods

A novel mixed-methods approach was applied by utilizing both existing clinical trial data and prospective patient interviews. Anchor-based, distribution-based, and qualitative-based estimates of meaningful change were triangulated to form recommended RDs for each scale of the EORTC QLQ-MY20. Anchor-based MIDs were summarized using weighted correlation.

Results

Recommended MIDs were as follows: Disease Symptoms (DS 10 points), Side Effects of Treatment (SE 10 points), Body Image (BI 13 points), and Future Perspective (FP 9 points). Recommended RDs were as follows: DS (16 improvement; 11 worsening), SE (6 improvement; 9 worsening), BI (33 improvement; 33 worsening), and FP (11 improvement; 11 worsening).

Conclusions

The study generated estimates of the MID and RD for each scale of the EORTC QLQ-MY20. Published estimates will enable investigators and clinicians to adopt these as standard for interpretation and for hypothesis testing. Consequently, analyses from trials of different interventions can be more comparable.

Background

Hereditary Angioedema (HAE), a rare genetic disease, manifests as intermittent, painful attacks of angioedema. Attacks vary in frequency and severity and include skin, abdominal and life-threatening laryngeal swellings. This study aimed to develop a patient reported outcome (PRO) tool for the assessment of HAE attacks, including their management and impact on patients' lives, for use in clinical studies, or by physicians in general practice.

Methods

The results of open-ended face to face concept elicitation interviews with HAE patients in Argentina (n = 10) and the US (n = 33) were used to develop the first draft questionnaire of the HAE patient reported outcomes questionnaire (HAE PRO). Subsequently, in-depth cognitive debriefing interviews were performed with HAE patients in the UK (n = 10), Brazil (n = 10), Germany (n = 11) and France (n = 12). Following input from eight multinational clinical experts further cognitive interviews were conducted in the US (n = 12) and Germany (n = 12). Patients who experienced abdominal, cutaneous or laryngeal attacks of varying severity levels were included in all rounds of interviews. Across the rounds of interviews patients discussed their HAE attack symptoms, impacts and treatments. Cognitive debriefing interviews explored patient understanding and relevance of questionnaire items. All interviews were conducted face to face following a pre-defined semi-structured interview guide in the patient's native language.

Results

Patients reported a variety of HAE symptoms, attack triggers, warning signs, attack impacts and treatment options which were used to develop the HAE PRO. The HAE PRO was revised and refined following input from patients and clinical experts. The final 18-item HAE PRO provides an assessment of the HAE attack experience including symptoms, impacts, treatment requirements, healthcare resource use and loss of productivity caused by HAE attacks.

Conclusions

Patient and expert input has contributed to the development of a content valid questionnaire that assesses concepts important to HAE patients globally. HAE patients across cultures consider the HAE PRO a relevant and appropriate assessment of HAE attacks and treatment.