Guidelines Call for Patient-Reported Outcomes in Clinical Trials

Clinical trial research outcomes need to be more patient-centered and integrate more patient-reported outcomes, according to a new set of research principles designed by the American College of Hematology (ASH) and US Food & Drug Administration (FDA).

The guidelines, published in two articles in the most recent issue of Blood Advances, asserts that patient-reported outcomes (PROs) and other outcomes need to be included when designing clinical trials for sickle cell disease treatments.

Sickle cell disease (SCD) is a blood disorder in which the red blood cells take on a curved, sickle shape rather than the typical round shape. SCD causes a number of symptoms in patients, including acute pain, joint or organ damage, impaired cognitive function, and reduced life expectancy.

Currently, there are only four FDA-approved treatments for SCD, although the medical industry is on the precipice of more advancing therapies.

"There are a number of investigational drugs in development that target different manifestations of SCD," said Julie Panepinto, MD, MSPH, FAAP, professor of pediatric hematology at Medical College of Wisconsin/Children's Wisconsin.

"However, there are no clear standardized endpoints for evaluating the effect of therapies on clinical outcomes and patient well-being,” Panepinto, who is also co-chair of ASH’s Guideline Oversight Committee and co-chair of this specific guideline workshop, added.

Panepinto, alongside Ann Farrell, MD, director of the FDA's Division of Hematology Products and co-chair of the workshop, convened seven panels over two days, during which clinicians, investigators, and individuals with SCD reviewed key information about SCD clinical trials.

Specifically, the panels conducted literature reviews and evidence assessments to judge different approaches to clinical trial measurement when developing SCD treatments. The seven panels were responsible for identifying different research endpoints in SCD clinical trials.

These goals are critical as the medical industry sees new and innovative strategies for treating SCD.

"These changes have greatly impacted the discussion the Agency is having with the pharmaceutical industry as new clinical trials are designed," Farrell pointed out. "We need endpoints that better reflect the patient experience of their disease in the current healthcare system."

Panepinto echoed those sentiments.

"What's happening in SCD is really exciting and many of us feel we are on the cusp of identifying multiple disease-modifying therapies," Dr. Panepinto said. "The field is exploding, so we want to be sure we are measuring relevant endpoints for researchers, clinicians, and patients because that helps us advance the field and get new therapies approved."

Foremost, the guidelines point to PROs as key research endpoints. PROs to be included in clinical trial design include ones regarding pain, affect, and function of different treatments. Clinical trials should also look at pain outside the scope of PROs, including by assessing healthcare utilization, analgesic use, and physical function.

The guidelines also suggest clinical trial developers consider cognitive and brain function issues as well as outcomes related to organ failure. Additionally, researchers should look at biomarkers and different evidence of a cure to SCD.

Finally, the guidelines point out room to investigate SCD treatments in low-income and low-resource areas, including sub-Saharan Africa. Data should likewise be put in the context of the social determinants of health, including early childhood experiences, mortality, and growth and development.

As noted above, these guidelines were developed as a part of diverse panels, taking into consideration the viewpoints of clinicians, patients, caregivers, and the researchers themselves. Multidisciplinary panels were essential to creating realistic and comprehensive clinical trial guidelines.

"The papers document the wide-ranging discussions held by researchers, patients, caregivers, international experts, pharmaceutical industry and government to understand where we are in terms of defining clinical trial endpoints for current use and those for future development that will serve patients best," Farrell concluded.