cardiovascular-agents and Sleep-Initiation-and-Maintenance-Disorders

Patient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process.. Concept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items.. During concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders.. Development of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program.

Topics: Aged; Aged, 80 and over; Cardiac Myosins; Cardiovascular Agents; Clinical Trials as Topic; Dizziness; Dyspnea; Edema; Fatigue; Female; Focus Groups; Heart Failure; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Qualitative Research; Quality of Life; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration; Urea

A patient with a history of cerebrovascular disease, hypertension, and previous gastrectomy developed metabolic alkalosis and myoclonus. His medications included the anti-hypertensive agents nicardipine hydrochloride, delapril, prazosin; dihydroergotoxin and ticlopidine for cerebral infarction; estazolam for insomnia; azuren-L-glutamine compound and S-M powder. In addition, he had taken 12 grams per day of Ohta's Isan antacid, which contained 625 mg sodium bicarbonate per 1.3 g of antacid powder over a 6-month period. This antacid is commonly used in Japan. This is the first report of a case of metabolic alkalosis and myoclonus secondary to ingestion of a commercially available antacid in Japan.

Topics: Aged; Alkalosis; Antacids; Cardiovascular Agents; Cerebral Infarction; Dyspepsia; Gastrectomy; Humans; Hypertension; Hypnotics and Sedatives; Hypokalemia; Male; Myoclonus; Sleep Initiation and Maintenance Disorders; Sodium Bicarbonate

Topics: Barbiturates; Biomedical Research; Cardiovascular Agents; Ergot Alkaloids; Scopolamine; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders