Nina Galipeau

Patient-Reported Outcomes in Metastatic Breast Cancer: A Review of Industry-Sponsored Clinical Trials

Introduction Patient-reported outcome (PRO) measures serve to capture vital patient information not otherwise obtained by primary study endpoints. This paper examines how PROs are utilized as endpoints in industry-sponsored metastatic breast cancer clinical trials. Methods A search was conducted in the clinicaltrials.gov web site for trials involving common treatments for metastatic breast cancer. Thirty-eight clinical trials were identified which included a PRO endpoint in the study, and data were extracted and summarized. Results Overall, 17 unique PRO questionnaires and 14 concepts of measurement were identified as secondary or exploratory endpoints. The Functional Assessment of Cancer Therapy—Breast was the most frequently utilized questionnaire, commonly implemented to assess quality of life. The EORTC QLQ-C30 was also frequently used to measure quality of life or pain. Conclusion This review shares insights into the role of PROs in trials for metastatic breast cancer from which treatment developers and other stakeholders can enhance successful implementation of the patient voice into future trials.

Informing a priori Sample Size Estimation in Qualitative Concept Elicitation Interview Studies for Clinical Outcome Assessment (COA) Instrument Development

OBJECTIVE Evidence-based recommendations for the a priori estimation of sample size are needed for qualitative concept elicitation (CE) interview studies in clinical outcome assessment (COA) instrument development. Saturation is described as the point at which no new data is expected to emerge from the conduct of additional qualitative interviews. STUDY DESIGN A retrospective evaluation of 26 CE interview studies conducted with patients between 2006 and 2013 was completed to assess the point at which saturation of concept was achieved in each study. METHODS For each of the 26 interview studies, saturation of symptom concepts was assessed by dividing the sample into quartiles and then comparing the number of responses elicited from the first 25% of participants to the next 25% of participants, from the first 50% of participants to the next 25% of participants, and then from the first 75% of participants to the last 25% of participants. The number of interviews required to achieve saturation was documented for each study and then summarized across studies. RESULTS Findings indicate that 84% of symptom concepts emerged by the 10th interview, 92% emerged by the 15th interview, 97% emerged by the 20th interview, and 99% by the 25th interview. CONCLUSIONS Results provide practical guidance for estimating the number of interviews that may be needed to achieve saturation in a qualitative CE interview study for COA instrument development; address an important gap in qualitative research for the development of COAs in the context of medical product development; and offer useful information for study design and implementation.

The use of patient-reported outcomes in advanced breast cancer clinical trials: a review of the published literature

Abstract Objective: As a means to measure quantifiable signs, symptoms, and impacts of a disease or its treatment, patient-reported outcome (PRO) instruments can be applied to numerous settings, including use in drug development to support labeling claims. This research summarizes the use of PROs in trials for 16 commonly used regulatory approved treatments for advanced or metastatic breast cancer. Methods: For each treatment (n = 16), a literature search was conducted in MEDLINE, Embase, and PsycINFO. The primary criterion for selection was the report of studies that used PROs to evaluate treatment benefit and/or toxicity in advanced or metastatic breast cancer. From this, a sub-set of articles for each treatment were selected for full-text review where PRO-related information was extracted and summarized. Results: The searches yielded 1727 publications. Following abstract review, 1702 were excluded because they failed to meet criteria, or were duplicates or less relevant for PRO information reported. Thus, 25 articles were reviewed in detail for this evaluation. Eleven PRO instruments were identified from these publications. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core (EORTC QLQ-C30) was utilized the most frequently (n = 13, 52.0%). Most publications reported PROs positioned as secondary endpoints (n = 20, 80.0%); described some of the statistical analyses applied to PRO data (n = 21, 84.0%); and specified PRO results (n = 23, 92.0%). Conclusions: While several of the publications provided some information on how PROs were utilized, many did not describe details for PRO administration, scoring, analyses, and results interpretation. While it is encouraging that PROs are often used in clinical trials for patients with metastatic breast cancer, they are not commonly used to support endpoints that establish the basis for label claims. Because they yield direct insight into the patient experience of a condition, PROs may be used to provide a more comprehensive perspective of the benefits and risks from treatment.

Patient-reported outcomes in advanced breast cancer: inside the label and approval documents

ABSTRACT Patient-reported outcome (PRO) measures are used in clinical research and practice for the assessment of disease-related symptoms and impacts as well as treatment-related side effects, from the patient perspective. However, a systematic examination of the role of PROs in metastatic breast cancer treatment approvals is lacking. A review of FDA labels and historical drug approval documents for metastatic breast cancer treatments was conducted to determine how PROs had been used or pursued to support labeling claims. In the historical drug approval documents, PROs were often being implemented by sponsors, and regulatory reviewers noted several issues limiting their suitability to support label claims. The findings suggest there is much room for improvement in how sponsors develop, implement, and report PRO measurement strategies as part of drug approval.