How best to assess new celiac disease therapies?

Last Updated: 2016-11-16

By Reuters Staff

NEW YORK (Reuters Health) - Two patient-reported outcome measures, and morphometric histology, are the best outcome measures for trials of celiac disease therapies, according to a new systematic review.

Dr. Vipul Jairath of the University of Western Ontario in London, Ontario, Canada and colleagues found the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) were the most appropriate measures available for defining primary end points in celiac disease registration trials.

Several new drugs are under development for treating celiac disease, Dr. Jairath and his team note in their report, published online October 31 in Gut. "These novel opportunities for drug development also pose substantial challenges for selection of appropriate end points to measure disease activity and response to treatment in clinical trials in order to support labeling claims," they add.

The researchers analyzed 286 studies to assess the operating properties of all available scoring indices used to measure celiac disease activity, and their potential usefulness for measuring clinical trial outcomes. They evaluated five patient-reported outcome (PRO) scales, six histological indices and four endoscopic indices for content and construct validity, reliability, responsiveness and feasibility using US Food and Drug Administration (FDA) guidelines.

Three of the five patient-reported outcomes met most evaluative criteria, but only the CDSD and the CeD PRO are FDA approved.

None of the histologic or endoscopic scores had content validity. Reliability and responsiveness were better for quantitative morphometric histologic analysis than for qualitative scales. While serologic markers are useful for celiac disease diagnosis, the authors state, "their prognostic significance is unknown and they have not been FDA approved for use as a monitoring tool for celiac disease activity due to lack of supportive data for this purpose."

The use of PROs as outcome measures for chronic disease is in line with the shift from disease-oriented to patient-centered care that the FDA recommends, Dr. Jairath and colleagues note. However, they add, PROs have limitations including subjectivity as well as the fluctuation of individual patients' symptoms, while the change in PRO that would constitute a clinically meaningful response has not been defined. Acceptable values for number needed to treat and number needed to harm also need to be defined for celiac disease drugs, they add.

"Further work is needed to determine the optimal choice and configuration of end points for celiac disease trials," the researchers conclude.

Dr. Jairath did not respond to an interview request by press time.

SOURCE: http://bit.ly/2fFQ8II

Gut 2016.