FDA Guidance on Assessment of Patient-Reported Outcomes in Cancer Trials: A Breath of Fresh Air or a Storm in a Teacup?

Abstract

In June of this year, the US Food and Drug Administration (FDA) released a draft guidance to fill a much-needed gap related to formulating a strategy for the use of patientreported outcomes (PROs) in cancer trials [1]. Based on recognition of the diverse use of PRO measures employed in cancer trials, this draft guidance, which focuses on anticancer products, is an evolution of the PRO guidance released in 2009 [2]. It also further builds upon a previous FDA guidance that acknowledges the importance of PROs in cancer studies [3]. It is important to note that this latest draft guidance is not meant to be a road map to PRO labeling. Quite the opposite, in fact. Rather than offering a set of “FDA-approved” approaches to PRO assessment that guarantees labeling based on PRO-based endpoints, the latest guidance recommends core concepts to be assessed in cancer studies and underlines the merits of study-specific strategies. Moreover, and perhaps most importantly, the guidance signals reviewers’ increased flexibility to entertain PRO instruments and approaches that best fit a study’s need when considering the benefits and risks of new cancer therapies and highlights that the one-size-fits-all approach often historically used is not appropriate. Sponsors should no longer rely on inefficient strategies and fossilized instruments. Instead, the FDA’s emphasis on the importance of using appropriate instruments and efficient assessment schedules opens new opportunities for sponsors to design trials that better reflect patient experience. The 2021 draft guidance incorporates advice that the FDA has previously offered in separate discussions [4, 5]. For this reason, readers versed in the PRO guidance of 2009 will recognize a few familiar threads. Consistent with the 2009 PRO guidance, there is a call for PRO-based endpoints to be well defined, valid, and reliable [1, 6]. This is particularly important to emphasize because most PRO instruments used in cancer studies were developed prior to the 2009 PRO guidance and before the emergence of novel anticancer therapies. Recognizing this need, the agency offers flexibility for sponsors to demonstrate the appropriateness of legacy instruments, or appropriate components of legacy instruments, within the context of use based on prior experience or evidence from the literature. Additionally, two primary aspects of formulating PRO strategies stand out as new contributions to this guidance. These address the types of assessments that FDA reviewers will consider and the timing of PRO data collection. One of the major contributions of this latest guidance is the FDA’s increased willingness to consider a la carte items or domains from established PRO item libraries (e.g., European Organisation for Research and Treatment of Cancer, PRO-Common Terminology Criteria for Adverse Events). This is a refreshing and much-needed acknowledgement from the agency that may resolve limitations arising from the use of legacy instruments, many of which contain items and/or concepts that may not be relevant to the condition or treatment and which, consequently, present an unnecessary burden on patients [4]. Patient burden is clearly at the forefront of the FDA’s consideration: while admitting that there is no “magic number,” the FDA suggests that PRO assessments should not take more than 10 min of the patient’s time per visit [7], and they should measure what is relevant and important to the patient. In concert with a reduction in the number of items administered to patients is the recommendation that PRO assessments be designed strategically to maximize the relevance of data while minimizing patient burden. The emphasis on frequent assessments of PROs during the early part of the study (while most patients are enrolled) with flexibility to stagger the assessment of different concepts at relevant assessment points is a pragmatic solution. This approach can lessen study and patient burden and meet the needs of multiple stakeholders without compromising scientific rigor. * Ari Gnanasakthy [email protected]