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).