How to Incorporate Patient-Reported Outcomes in Clinical Trials

Gaurav Goyal, MD, a hematologist oncologist at UAB Medicine, spoke to Blood Cancers Today about strategies for incorporating patient-reported outcomes (PROs) into clinical trials, as presented at the International Ultmann Chicago Lymphoma Symposium (IUCLS).

Dr. Goyal highlighted the importance of patient-centric research and guidelines that researchers can utilize when including PROs in clinical trials.

Can you please describe your presentation at IUCLS?

I discussed strategies for including PROs in clinical trials. We reviewed the definitions of PROs, what they measure, and why it’s important to have effective and efficient PRO measures in cancer clinical trials and beyond. Then, I identified appropriate strategies recommended by consensus guidelines.

PROs have been increasingly used in trials, but systematic analyses have shown that the way they’re reported is lacking in the checklist items that are recommended to be included. For example, the reporting standards and the protocol were found to be inadequate, and approximately a third of the checklist items were met in protocol. Some of the missing items included a rationale and objectives for why PROs were included. Only about 20% to 25% of checklist items were met in publications, such as missing hypotheses and the validity and reliability of the measure used.

The other problematic piece was that many trials include PROs but do not report them. Or, there is a huge lag between the first publication and subsequent PRO publications. Approximately 40% were not published in a study at the last follow-up of 6 and a half years, and 40% were missing in the primary publication. Several were published 5 to 8 years after the first publication.

Finally, the other problem is that most of those PRO publications only reported on better or improved PROs with treatment, or stable PROs. There was a publication bias for that. That is why it is essential to include PROs systematically. The FDA itself has made it clear that there is heterogeneity in PRO assessment strategies, which lessens the regulatory utility of PRO data from cancer trials. This was in the “Core Patient-Reported Outcomes in Cancer Clinical Trials Guidance for Industry” document by the FDA in 2024.

In terms of strategies, part of the issue is identifying the PRO measure being used. There are many PRO measures announced monthly, making it hard to know which one to choose. There are many ways to divide them based on whether they are focusing on one disease such as cancer, if they are disease agnostic (meaning they’re universal), if they are global (like measuring global health-related quality of life), or if they are specific to one domain like physical function, fatigue, and pain.

It’s important to know what you’re using and for what measure. For example, if you look at health-related quality of life [HRQOL], a global HRQOL is composed of many domains such as physical function, social well-being, mental well-being, cognition, symptoms from the disease, or side effects from the drug. This can include many items that may have nothing to do with the drug or the intervention being studied.

In our studies of histiocytosis, we have found that mental health improves regardless of whether patients are on treatment or not, especially for indolent diseases. Therefore, a single HRQOL assessment may not be sufficient. It’s a good screening tool, but it may not be sufficient for us to figure out whether the drug is helping because there are other factors that go into HRQOL. It may be more beneficial to focus on individual domains when you’re especially studying an intervention.

Why is it important to include PROs in clinical trials?

The landmark studies published over a decade ago showed that patients tended to live longer when patient-reported symptom monitoring was included compared with usual care. It was also found that patients whose PROs were being measured had better overall health-related quality of life.

This becomes even more pertinent when the trials currently do not have overall survival as the primary endpoint. A lot of the time, the primary endpoint is progression-free or event-free survival, which are surrogate endpoints. It’s important to include PROs, as they give a patient’s voice a chance to be heard in the trial results themselves. It’s patient-centric research.

It’s often thought that the length of the PRO measure may add additional participant burden, but studies have shown that may not be the case, and participants may prefer longer surveys if they capture the things that matter to them and if they can inform their care. It is important to let them know when they’re participating, why we are collecting the PRO measures, and who will have access.

How can researchers best capture and utilize PROs in clinical trials?

Training all the study staff about the importance of PRO measures is important. Sometimes, study staff think that the survey will pose a burden, but participants may be fully willing and capable.

I want to highlight the publications that discuss some of these aspects in detail. Depending on your phase in the study design or data analysis, you could look at these guidelines to help.

The key guideline is the SPIRIT-PRO [Standard Protocol Items: Recommendations for Interventional Trials Patient-Reported Outcomes] extension, which outlines what should be included in PROs in the protocol of clinical trials. The other is the “international standards for analysis of quality of life and PRO measures in cancer randomized control trials,” which outlines how to analyze data.

These are recommendations of the SISAQOL [Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life] consortium. These two papers, in addition to the FDA guidance, can provide an idea if somebody plans a study incorporating PROs.