Quantitative benefit-risk tradeoff preferences for crohn's disease treatments - implications for regulatory decision making and disease management

In managing Crohn's disease (CD), gastroenterologists increasingly are adopting earlier, more aggressive strategies in the hope of altering the course of the disease. Biologic therapies such as the inhibitors of Tumor Necrosis Factor-alpha (TNF-), infliximab, adalimumab and certolizumab pegol, and the integrin receptor antagonist, natalizumab, offer the promise of more efficacious outcomes, but also may be associated with potential serious adverse events (SAEs) such as lymphoma and serious opportunistic infections. Thus, regulators, patients or parents and clinicians are faced with weighing the possible benefits against the possible risks of the available therapies. Several recent studies have applied stated-preference methods to quantify the willingness of Crohn's disease patients, gastroenterologists, and parents of juvenile Crohn's patients to accept treatment-related adverse-event risks in return for potential treatment benefits. Treatment preferences were elicited to estimate the annual maximum acceptable risk of treatment-related adverse events for given levels of efficacy. These studies employ a common preference-elicitation instrument, adapted as necessary for particular subject samples. In each of these studies, subjects evaluated the severity of daily symptoms and activity limitations, the frequency of flare-ups, the ability to avoid serious complications of CD, the need for oral steroids, and the risks of three potentially fatal serious adverse events (SAEs). The results of these studies provide strong evidence that adult patients, gastroenterologists, and parents of juvenile patients are willing to accept tradeoffs between treatment efficacy and risks of SAEs. However, physicians would accept more than twice as much mortality risk as patients for improvements from severe to moderate CD symptoms, while patients would tolerate 50% more risk than physicians for an improvement from moderate to mild symptoms. Physicians were unwilling to tolerate additional risk for improvements from mild symptoms to remission, while patients would tolerate an additional 15% treatment-related risk to achieve remission. The results of these studies demonstrate that adult patients and parents of juvenile patients have clear and quantifiable preferences over the benefits and risks of CD treatments. The fact that risk tolerance may differ between physicians and patients indicates a need for greater discussion of risks and benefits between physicians and their patients. In addition, understanding the risk tolerance of stakeholders in Crohn's disease management can help inform regulatory decision making, promote better communication among stakeholders, and design more effective risk management strategies.

Duke Scholars

Author F. Reed Johnson Population Health Sciences

Author Semra Ozdemir Population Health Sciences