Patient Global Impression of Benefit-Risk (PGI-BR): Incorporating Patients' Views of Clinical Benefit-Risk into Assessment of New Medicines.

INTRODUCTION: There is a need to understand how patients assess perceived benefits and risks of treatments. OBJECTIVES: The study aimed to (i) elucidate how patients evaluate treatment experiences and (ii) develop a brief patient-reported outcome (PRO) instrument for use across disease areas for perceived benefit-risk evaluation of a new medicine in a clinical trial setting. METHODS: Concepts relating to patient-perceived benefit-risk were identified from literature reviews and qualitative concept elicitation interviews with patients across a variety of primary medical conditions. Draft instrument items were developed from identified concepts and evaluated for clarity, relevance and appropriateness of response options in cognitive interviews. Items were iteratively revised to address patient feedback. RESULTS: Qualitative interviews were conducted with 47 patients (primary condition: 20 oncological, 12 respiratory, 10 metabolic, 5 cardiovascular), of whom 32 contributed to concept elicitation and 42 to cognitive debriefing. Elicited concepts could be grouped into four medication-related categories: effectiveness of treatment, burden of side effects, convenience of use and overall acceptance/satisfaction. Cost, trial experience and altruism were additional concept categories unrelated to medication. The final instrument contained one item each on the medication's effectiveness, side effects and convenience, and an overall item capturing patient benefit-risk assessment. An upfront question was included to separate out non-medication aspects of patients' experiences. CONCLUSION: We developed a brief PRO instrument, the Patient Global Impression of Benefit-Risk (PGI-BR), which can be applied across disease areas to assess patient views of benefit-risk of a new medicine in the clinical trial setting.

Development of a Conceptual Model of Chronic Lymphocytic Leukemia to Better Understand the Patient Experience.

BACKGROUND AND OBJECTIVE: Understanding the patient experience is important for identifying the unmet need in chronic lymphocytic leukemia. The current study aimed to develop a comprehensive chronic lymphocytic leukemia conceptual model. METHODS: The conceptual model was based on literature searches, review of chronic lymphocytic leukemia patient blogs/forums, and interviews with five expert clinicians, with 20 patients who received at most one treatment (first line) for their chronic lymphocytic leukemia, and with 20 patients with relapsed or refractory chronic lymphocytic leukemia. De-identified interviews were transcribed, coded, and evaluated using qualitative data analysis software. RESULTS: Thirty-five prevalent chronic lymphocytic leukemia-related symptom and impact concepts were identified from literature searches, patient blogs/forums, and clinician interviews. Patient interviews confirmed the identified concepts and revealed five additional concepts. Fatigue-related sub-components were identified from how patients described their fatigue, covering symptoms (tiredness/need for sleep, lack of energy, weakness, cognitive fatigue), and impacts (decreased ability to maintain their social, familial, or professional role, decreased physical functioning, frustration). Three versions of the conceptual model were created: an overall model with all concepts; a model highlighting the most prominent concepts in first line; and a model highlighting the most prominent concepts in relapsed or refractory disease. Prominent concepts in both first line and relapsed or refractory disease were fatigue-related symptoms and impacts, muscle/joint aches, night sweats, bruising, fever, recurrent infections/illness, insomnia, decreased cognitive/emotional functioning, anxiety/worry, stress, depression, financial difficulty, and fear of death. Dyspnea and cough were prominent in first line only, and enlarged lymph nodes, headaches, pain/discomfort, weight loss, nausea/vomiting, and infusion reactions were prominent in relapsed or refractory disease only. CONCLUSIONS: The results show that fatigue is a dominant issue affecting patients with chronic lymphocytic leukemia. The three versions of the conceptual model can help researchers to understand patients' unmet needs and guide the patient-reported outcome strategy for clinical trials.