Analyses reveal wide variation in PRO measures in cancer trials

Regulatory NewsRegulatory News | 07 September 2021 |  By 

The passage of 21st Century Cures Act in 2015 helped to bolster the inclusion of patient experience data and specifically patient reported outcome (PRO) measures in clinical trials. But even with an increased emphasis on patient reported data, analyses of registrational trials for cancer therapies have shown wide variation in how PRO measures are included and analyzed.

A recent analysis of registrational trials for multiple myeloma treatments submitted to the US Food and Drug Administration (FDA) between January 2007 and January 2020 showed “substantial heterogeneity” in PRO collection methods, definitions of the patient population being analyzed, completion of the measures, and what constitutes a clinically meaningful change. The analysis, published in Blood Cancer Journal, found that 40 PRO instruments were used across the 17 clinical trials analyzed. The timing of the PRO assessments “were heterogeneous and usually sparse,” wrote Laura L. Fernandes, of the FDA Center for Drug Evaluation and Research (CDER), and colleagues at the agency.

Trial sponsors had different ways of handling missing patient data and employed a range of statistical methods, the FDA research team found. “These differences in PRO analyses within the same disease and therapeutic setting may hinder the ability to effectively capture and interpret patient experience in [multiple myeloma] clinical trials, which are valuable information for patients and clinicians.”

The analysis showed that the registrational trials also had varying definitions of baseline. For instance, seven trials defined baseline as “Cycle 1, Day 1,” while two trials defined baseline as being “on or prior to Cycle 1, Day 1,” and eight trials defined baseline as being the “screening phase/before randomization.” The trials also used different definitions to show completion of PRO instruments. While one trial defined this as completing all the questions, two trials defined it as completing half of the questions, and 14 trials defined it as “completing enough items to calculate the score in any domain.” The researchers reported that trial sponsors also varied on whether they included the intent-to-treat population in their analysis or a safety population.

In another analysis, published in the journal Value in Health, a different team of FDA researchers examined the use of PROs after treatment discontinuation across four solid tumor cancer types: prostate cancer, breast cancer, pancreatic cancer, and hepatocellular carcinoma. They found variation in PRO measure completion rates and in the duration of follow-up when examining registrational cancer trials for therapies approved by the FDA between January 2010 and January 2019.

Bellinda L. King-Kallimanis, PhD, of the FDA Oncology Center of Excellence, and colleagues, reviewed 54 trials and found that PRO data were collected for at least one follow-up assessment in 46% of the trials. The schedules for follow-up varied with a first assessment occurring anywhere between 30 days and 6 months after the end of treatment. Mean completion rates for PROs at the first follow up also varied based on the type of cancer, with completion rates of more than 70% for breast cancer trials and nearly 55% for prostate cancer. PRO completion rates at the first follow up assessment were not available for hepatocellular or pancreatic cancer trials.

The researchers concluded that the follow up phase of PRO assessments has “not been given the same attention as on-treatment assessments.”

These analyses come as the FDA moves to standardize the approach to the collection and analysis of PROs in cancer trials. In June 2021, the agency issued draft guidance to industry outlining a set of “core” PRO measures that can be used in cancer clinical trials. The core set includes disease-related symptoms, symptomatic adverse events, overall side effect impact, physical function, and role function.

“Selection of outcomes outside of the core PRO set should be carefully considered to minimize patient burden and improve the quality of data collected by focusing on the most meaningful and measurable outcomes,” agency officials wrote in the draft guidance for industry. (RELATED: FDA releases draft guidance on assessment of PROs for cancer trials, Regulatory Focus 09 June 2021).
Blood Cancer Journal article
Value in Health article


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you