Patient Reported Outcomes in Metastatic Breast Cancer Studies: Evaluating the Impact of the FDA Guidance for Industry

Introduction: Over the last two decades, a number of new therapies have demonstrated improved overall survival in metastatic breast cancer (MBC) [10]. Despite these advances, MBC remains incurable with a median survival of less than three years [7, 10, 11, 15]. Prolonging survival and maintaining quality of life (QoL) continue to be the central goals of therapy. Unlike the early stages of breast cancer, the management of MBC is less clearly defined, with no specific treatment recognized as the standard of care [15]. Several studies have sought to determine an optimal regimen for the management of MBC with aims to prolong survival, however relatively few adequately powered studies have directly addressed QoL [8].

Patient reported outcomes (PROs) are instruments used to elicit the patient experience thereby gaining insight into a particular health state and aiding in the assessment of QoL [5]. As the prevalence of PROs grew, the FDA released in December 2009 an industry guidance on the implementation of PROs in clinical trials for the development of medical products and to support labeling claims [1]. This study was undertaken with aims to evaluate the impact of the FDA guidance on the use of PROs as standard endpoints in randomized phase two or three clinical trials assessing therapeutic options in MBC.

Methods: Clinicaltrials.gov’s advanced search tool was used to capture registered interventional phase two or three clinical trials in adult patients with MBC conducted in the United States that began recruitment between January 1, 2002 and December 31, 2017. Trials with QoL or PROs listed as primary or secondary endpoints on Clinicaltrials.gov were subsequently identified. Segmented regression analysis of the interrupted time series data [18] was used to estimate dynamic changes pre and post adoption of the FDA guidance.

Results: A total of 677 studies were identified, 72 of which used PROs. Prior to adoption of the FDA guidance, there is a nonsignificant trend towards increasing PRO use at a rate of 0.4% per year (p > 0.05). At the time of adoption, there is a one-time nonsignificant increase of 0.6% in PRO use (p > 0.05). After adoption, there is a nonsignificant trend towards decreasing PRO use at a rate of 0.3% per year (p > 0.05).

Discussion: Our study results demonstrated that despite the FDA guidance, there has been little change in the use of PROs as endpoints in MBC studies. This missed opportunity to elicit the patient experience inherently limits evidence often used to counsel patients and support their decision-making framework as they focus on their priorities in selecting treatment options.