Researchers have developed a novel patient‑reported outcome instrument to assess the symptoms of paroxysmal nocturnal hemoglobinuria (PNH), called the PNH‑Symptom Questionnaire (PNH-SQ). Their report was published in the Journal of Patient-Reported Outcomes.

PNH is a rare, acquired, life-threatening disease characterized by hemolytic anemia, thrombosis, and impaired bone marrow function that is caused by chronic dysregulation of the complement system.

The investigators aimed to gain a better understanding of the patient experience with PNH symptoms and to develop a content-valid questionnaire capable of capturing the presence, severity, and day-to-day fluctuations in PNH-specific symptoms for use in clinical trials.

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They developed a draft of the PNH-SQ and a patient-centered conceptual model of PNH symptoms based on a literature review and consultation with a PNH expert. The draft PNH-SQ was then refined based on hybrid interviews, with concept elicitation and cognitive debriefing, with patients with PNH. Patient interview data and feedback were used to finalize the PNH-SQ and conceptual model.

The study included 15 participants with PNH (53% female), with a mean age of patients of 42.8 years (standard deviation [SD], 10.4). The majority (93%) of patients were White. The average time since diagnosis was 13.4 years (SD, 10.3). Participants self-reported the disease as very mild/mild in 67%, moderate in 13%, and severe/very severe in 20% of cases. At the time of the study, 7 patients were receiving treatment for PNH.

During the interviews, patients mentioned 27 signs or symptoms of PNH, and 93% of participants reported experiencing ≥1 PNH symptom. All PNH symptoms reached concept saturation. The concept elicitation component of the interviews confirmed that the PNH-SQ captured the most common PNH symptoms, including fatigue (87%), abdominal pain (60%), and difficulty swallowing (47%). The cognitive debriefing component of the interviews confirmed that participants understood the items of the PNH-SQ (90-100%) and considered the symptoms relevant (>50->90%), the recall period appropriate (>80-100%), and the response options suitable (>80-100%).

The finalized PNH-SQ, which included changes based on participant feedback, can be used to assess the presence and severity of 10 symptoms of PNH (abdominal pain, chest discomfort, difficulty sleeping, difficulty swallowing, difficulty thinking clearly, fatigue, headache, muscle weakness, pain in the legs or back, and shortness of breath) over 24 hours.

The main limitations of the study were a small sample size, a lack of ethnic and racial diversity among participants, and a lack of clinical confirmation of PNH diagnosis (only possible for 4 patients).

“In conclusion, the PNH-SQ is a new, content-valid [patient‑reported outcome] measure suitable for assessing daily symptoms experienced by patients with PNH in a clinical trial context,” the authors wrote, “because the PNH-SQ was developed for daily administration, it can capture daily variations in symptoms of PNH patients, providing a more granular assessment of symptom changes among patients enrolled in clinical trials.”

Disclosure: This research was sponsored by Regeneron. Please see the original reference for a full list of disclosures.


Daly RP, Jalbert JJ, Keith S, Symonds T, Shammo J. A novel patient-reported outcome instrument assessing the symptoms of paroxysmal nocturnal hemoglobinuria, the PNH-SQ. J Patient Rep Outcomes. 2021;5(1):102. doi:10.1186/s41687-021-00376-0