Challenges and Opportunities in Developing Neurologic Therapies - Page 3

Measures of efficacy and safety. Neurologic conditions often have subjective evaluations for measuring severity or progression of disease. Evaluations might include level of cognitive or physical function, which can be subject to variation in reporting by patients or investigators. Though modern diagnostic instruments (i.e., neurological or psychiatric scoring tools, PROs, and imaging) are precise to cope with these difficulties, an improvement would be beneficial. Cost effectiveness. It is no longer sufficient to demonstrate efficacy and safety for a drug license to be approved. The need to demonstrate cost-effectiveness of new treatments has become “the fourth hurdle after quality of manufacture, safety, and efficacy” (Hall, 2010). Keeping in mind the economical challenges for the health care systems of aging populations, it is obvious that means to measure cost-effectiveness of new treatments became standard in the development of CNS treatments. Subject recruitment and retention. Each neurologic condition creates specific challenges for patients, and many of these challenges affect ability to enroll in clinical trials. Pat ients with cognitive impairment may have difficulty providing informed consent. Patients with physical immobility can find frequent hospital visits and evaluations conducted in clinical trials particularly taxing. Having restrictive inclusion criteria for clinical trials increases time, costs, and risks associated with drug development (Craven, 2011). Dr. Stacy remarks that many studies are “compromised by small sample sizes due to difficulties associated with recruitment and retention of eligible patients.” Dr. Jan Wallace of WallaceRanch Consulting further comments that “patients with slowly progressive disease require too much time to demonstrate efficacy, whereas patients with rapidly progressive disease may benefit from treatments that may not be appropriate or safe for patients with less aggressive disease.” Safety issues. Dr. Wallace points out that the potency of current drugs has increased. But greater potency increases the risk of side effects. There is generally greater acceptance of side effects caused by drugs that treat lifethreatening diseases such as cancer. However, patients with neurologic conditions that are disabling but not immediately life-threatening have a lower tolerance for uncomfortable or debilitating side effects. A leading reason for failure of neurologic drug candidates is an association with life-threatening and other undesirable side effects (Steinmetz, 2009).