FDA releases draft guidance on assessment of PROs for cancer trials

Regulatory NewsRegulatory News | 09 June 2021 |  By 

The US Food and Drug Administration (FDA) has released a draft guidance that recommends how sponsors can collect “meaningful” patient-reported outcome (PRO) measurements to assess results from cancer clinical trials.
The draft guidance focuses on a set of “core” PRO measures that can be used to gather data on patients’ symptoms, symptomatic adverse events and physical function and is specific to registration trials for anti-cancer treatments intended to demonstrate an effect on survival, tumor response or delay in the progression of a malignancy. The guidance also discusses trial design and labeling considerations when core PROs are used.
FDA also clarifies that “demonstration of a clinically meaningful improvement in patient-reported symptoms of functional impacts alone (i.e., in the absence of evidence of anti-tumor activity) would be more applicable to supportive care drugs and is outside the scope of this guidance.” For situations where a PRO endpoint will be used as the primary evidence of effectiveness, FDA points sponsors to its 2009 PRO guidance.
Richard Pazdur, director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research announced  on 9 June that the guidance “is intended to improve the quality and consistency of data in order to inform patients with cancer about the symptoms and impacts they may experience during treatment with a cancer therapy." 
He further noted that “achieving sufficient consistency and quality of these data in cancer drug applications submitted to the FDA has been a challenge.” 
The guidance emerges from a series of public workshops and publications on the most appropriate PROs to measure and how frequently to assess these measures. (RELATED: FDA Officials look to tackle PRO bias in cancer trials, Regulatory Focus 21 January 2019; Project Patient Voice a focus of ASCO-FDA workshop, Regulatory Focus 17 July 2020).
Manufacturers should select PRO instruments that are “well-defined” and “reliable” for results to “meaningfully contribute” in evaluating a therapy’s benefits and risks.
The FDA recommends collecting and separately analyzing PROs on disease-related symptoms, adverse events, side effects, physical function, and role function.
For example, for disease-related symptoms, the guidance suggests the use of disease symptom scales, such as use of Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ). The guidance states that, “In contexts where disease symptoms are heterogeneous in type and incidence, symptoms that patients have reported as being important across advanced cancer settings, such as pain, anorexia, and fatigue, can be measured either individually or within a symptom score with other important disease-related symptoms.”
For assessing adverse events, FDA recommends using the National Cancer Institute’s PRO version of the common terminology criteria for adverse events (PRO-CTCAE).
The guidance adds that the frequency of the assessment should be higher within the first few treatment cycles and may be less frequent in later cycles.
Some general principles to determine whether the PRO instrument is fit-for-purpose include the following: the instrument is appropriate for its intended use in terms of the study design, and patient population, the PRO instrument validly and reliably measures concepts that are clinically relevant and important to patients, and the PRO data can be communicated in a way that is accurate, interpretable and are not misleading.
The deadline for submitting comments is 10 August.
Draft Guidance
Editor's Note: The article was updated on 10 June to distinguish between what the PROs are intended to measure and the scope of the trials addressed by the guidance.


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