CDER Finds Broad Variations Among PROs in Multiple Myeloma Trials
Despite the FDA’s efforts to make patient reported outcome (PRO) collection and analysis more consistent in clinical research, a recent agency review has found wide variation in how PROs are approached in multiple myeloma trials.
Looking at 17 pivotal trials that contained submitted PRO data and were conducted to support multiple myeloma indications between 2007 and 2020, researchers with the agency’s Center for Drug Evaluation and Research (CDER) and Oncology Center of Excellence saw variation in a number of PRO-related areas.
After reviewing trial protocols, statistical analysis plans and clinical study reports, the researchers found “substantial heterogeneity” in how PROs were collected, measured, defined and analyzed.
For example, the researchers found that these trials varied in the types of PRO questionnaires they used, according to the study, which was published in the Blood Cancer Journal.
The trials also varied in the number of PRO questionnaires they employed. Specifically, seven of the trials (41 percent) used two surveys, five trials (29 percent) used three, two trials (12 percent) used four, and three trials (18 percent) used just a single survey.
PRO measure compliance, similarly, saw variation across the trials in how it was described. While a majority of the 17 trials (14) defined compliance as “completing enough items to calculate the score in any domain [or some variant],” two trials defined it as completing half of the questions, while a single trial defined it as full questionnaire completion.
In addition, the researchers observed substantially different methods used across the trials to deal with missing data and to conduct statistical analyses.
“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 researchers advised.
To begin making PRO approaches more consistent, at least in multiple myeloma trials, sponsors should begin referring to the core PRO outcome guidance published by the FDA for oncology trials. The guidance is intended to help industry become more consistent in PRO collection and analysis and was published in June (CenterWatch Weekly, June 14).
The researchers also advised sponsors that synchronization of PRO research questions “with the [ICH E9 R1] estimand framework, clear description of statistical methods and justification for thresholds will lead to more meaningful PRO results that can be shared with patients and healthcare providers.”
Read the full study here: https://go.nature.com/2X3pX9h.