Last month, The Lancet published an article describing a recent phase III clinical trial in totally blind patients. The study evaluated the efficacy of a new medical intervention called tasimelteon for non-24-hour sleep-wake disorders.1
The science behind these conditions is simple. Circadian rhythm sleep-wake disorders result from discordance between an individual’s environment and the sleep-wake cycle. In the case of circadian rhythms, perhaps the most important component of one’s environment is light. In fact, phototherapy is generally the first treatment for patients with this type of sleep disorder. For blind patients, however, they cannot detect this key environmental stimulus, nor can they respond to this first-line therapy.
Melatonin is a hormone produced within the human body, and it has a strong impact on sleep and circadian rhythms. While its mechanism is complex, levels of the hormone are, in part, inversely correlated with light exposure. Higher interaction with light-emitting devices can lower melatonin levels, and levels increase when light becomes dim.
Tasimelteon is a melatonin agonist regulated by the FDA, and it is the drug studied in the phase III clinical trial referenced above. In one component of the trial, researchers enrolled 84 patients to receive either tasimelteon or a placebo to treat their sleep disorders. The results of the study showed that after one month, once-daily tasimelteon entrained 20 percent of patients to a circadian rhythm, as compared to 3 percent in the placebo group. Patients needed to continue taking the drug daily to maintain these effects. Withdrawal of tasimelteon resulted in renewed sleep-wake disorders in 80 percent of patients, but if patients continued taking the drug daily, 90 percent continued to have normal circadian sleep.
Though interesting from a purely clinical research perspective, the importance of this trial goes beyond that. The most intriguing part about this particular intervention is that it targets a problem considered rare in the general population. But specifically within the blind community, this “rare” condition is, in fact, common.
During our medical school education, we learn about an incredible array of diseases, and so often, the incidences of these diseases are described in the context of “normal” patients: patients with intact senses, healthy lifestyles and no genetic predispositions. This is an understandable approach to education; there is so much information to learn. Thus, in our early training, it is irrational to attempt to learn every nuance of every disease.
As we progress, however, it is important to continue to learn and recognize the unique needs within every patient population. This perspective will be crucial in transitioning from students to doctors.
Physicians do not simply save lives; they also improve quality of life. The above study is indicative of the fact that we must be cognizant that just because a disease is rare overall does not mean there are not patient populations more strongly affected and in need of improved care. By being aware of the complexities of different patient populations, doctors of all specialties can become better providers.
1. Lockley, S.W., et al., Tasimelteon for non-24-hour sleep–wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials. The Lancet.