Natural history studies follow patients for several years in order to understand the natural course a disease takes as it progresses. This type of study can offer insights as to how to treat a particular disease. The main study referred to in the Lancet article, “Challenges ahead for trials in Friedreich’s ataxia,” followed 605 people with FA over two years.
Data from this study showed that clinical trials for FA likely need at least 180 participants and two years. However, most clinical trials in FA have been much shorter, and have included fewer people. And although these trials showed promising results in terms of drug benefits, these benefits have been too small to lead to approved therapies.
“With the results of the various natural history studies in Friedreich’s ataxia now available, it seems likely that these therapeutic studies were underpowered, being either too small or too short,” wrote the authors. They added that the therapeutic benefits of the drugs being tested in these trials could have been overestimated — and the higher frequency of assessment visits in clinical trials compared to natural history studies might have enhanced practice effects. This suggests that the number of participants needed for a good clinical trial might be even higher than estimated by natural history studies.
“All of these issues add to the difficulty of successfully implementing clinical trials in Friedreich’s ataxia,” they concluded.
FA, a rare inherited disease that causes nervous system damage and movement problems, results form an increase in the number of GAA repeats in the frataxin gene. It usually begins in childhood and leads to impaired muscle coordination (ataxia) that worsens over time. Although rare, FA is the most common form of hereditary ataxia, affecting about 1 in every 50,000 people in the United States. Both male and female children can inherit the disorder.
One interesting finding from natural history studies was that the more GAA repeats there were in the frataxin gene, the earlier a patient develops FA. The article’s authors suggest that classifying participants in a clinical trial according to the number of GAA repeats in their frataxin gene might improve the design and outcome of future clinical trials.