Are better endpoints and better design of clinical trials needed?

For the clinician it is important to know whether a new drug works, and how the new drug performs against other drugs. However, new drugs are typically tested in placebo-controlled trials without active comparison. New drugs are often tested in a population with high levels of disease activity. Clinicians, however, may also seek the optimal treatment for patients with persistent moderate levels of disease activity. An answer may come from clinical trials that compare two effective drugs in patients with moderate disease activity. A main consequence, however, is that trial endpoints are needed that can detect small but relevant differences in efficacy. An ideal endpoint for trials in rheumatic diseases may be a marker that continually follows short-term changes in the disease process. The levels of the marker should be strongly associated with long-term outcome, thus prognosticating the future. When it can be measured truly and feasible, the marker would be useful as an endpoint in trials and for supporting treatment decisions in clinical practice.     

Living longer--but better?

The highest attained age has increased by about 20 years since the beginning of the 19th century. In the course of the 1990s, more than ten individuals reached 115 years or more, including Jeanne Calment who attained the age of 122 years. In low-mortality countries, the number of centenarians has doubled every decade since 1950. This dramatic increase was mainly due to periodical effects related to the drastic fall in mortality among the elderly. The fact that centenarians are survivors does not mean that they are healthy. A high prevalence of comorbidity is found, and many centenarians have survived major diseases thanks to medical treatment and surgery. It is, however, possible that the comorbidity is less serious than in younger elderly. Certain personality traits may also be important in surviving health-threatening conditions. Furthermore, a number of biological and cognitive functions seem to be well-preserved in several centenarians. The influence of the apoE-gene and other genes involved in fundamental mechanisms illustrates that with advancing age and increasing mortality even small risks may have a substantial effect on survival to 100 years. A small proportion of long-livers may be considered as relatively autonomous, and this proportion will probably increase in the future. We are living longer and seem to postpone the terminal dependent phase to higher ages. Longevity may thus be perceived as part of our postmodern condition with its mix of pleasure and suffering.