Functional Dyspepsia: Can We Get the Trial Design Right?

By Nimish B. Vakil, MD, AGAF, clinical professor of medicine at the University of Wisconsin School of Medicine and Public Health and member of the scientific advisory board for the American Gastroenterological Association (AGA) Center for Diagnostics and Therapeutics. Dr. Vakil will serve as co-chair of the 2016 AGA Drug Development Conference.

This blog is the last in a series on drug development in gastroenterology, from the American Gastroenterological Association Center for Diagnostics and Therapeutics. If you’re interested in learning more about drug development in this area, join the center for its first Drug Development Conference, Oct. 27-28, 2016, in Washington, DC. The other blogs in the series address GERD, EoE and Gastroparesis.

Functional dyspepsia

is a very common condition in clinical practice throughout the world. Despite years of effort, no specific therapy exists for this disorder. Initial attempts at treatment focused on acid inhibition and treatment of H. pylori infection with modest success. A large number of patients fail to respond to either of these measures and there are few options that are evidence-based.   Trial design in functional dyspepsia has been hampered by the disease definition that can be too inclusive or too restrictive. Regulatory definitions of functional dyspepsia exclude patients with overlapping symptoms of

gastroesophageal reflux disease

and

irritable bowel syndrome

, which reduce the size of the study population and create a situation that cannot be translated into clinical practice. Recent research has shown that patients may meet the criteria of more than one functional disorder but that the symptoms of one may predominate. The more disorders that overlap, the more profound the effect of the symptoms on the patient’s quality of life and functional status. Trials in functional dyspepsia have had difficulty recruiting patients because overlapping conditions are excluded and therefore the patients with the most severe symptoms are not eligible to participate. Clinical trials with new drugs have had to focus on patients with milder symptoms in whom a therapeutic response is difficult to show. Poor enrollment in trials, the difficulty of showing a response in a narrow subset of patients with mild symptoms have created an environment where drug development for this disorder is not pursued with as much vigor as one might expect for such a common condition.   We need a consensus on an operational definition of functional dyspepsia for use in clinical trials that is clinically meaningful. The goals of treatment - including the definition of success and failure - need clarification so that drug development and treatment trials can emerge. Only then will we have the trial design “right” for functional dyspepsia.