Written by Or, Sean Rose A newly published research study, titled “Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football’” diagnosed CTE in 110 of 111 former NFL players, and overall in 177 of 202 former football players with varying amounts of playing exposure. This is an important study because it included the largest number of CTE cases in football players ever published. However, it's important to put these results into the right context. Understanding two different research principles is necessary when interpreting the results: levels of scientific evidence and selection bias. There are multiple levels of scientific evidence, from weak to strong. Opinion and anecdotal findings (for example, when a doctor notices a pattern in a few of his/her patients) are the weakest types of evidence. Randomized trials and compilations of multiple trials are the strongest. A case series: which means that the people included in the study were chosen based on their medical condition, is considered to be one of the weaker types of This study is a case series because the football players were already known or suspected to have CTE. Case series are unable to establish a cause-effect relationship or the incidence of a disease. "Selection bias" means that the people who are included in a study are not randomly chosen, and the group chosen is not representative of the population that needs to be studied. For example, if you want to know what percentage of students at a school have strep throat, you would bias the results by only testing those students complaining of a sore throat. In this study, the player or his family chose to donate his brain to be studied for CTE, likely because he was having symptoms and other brain problems before he died. Farmer football players who do not have symptoms before dying are less likely to donate their brains to be studied for CTE. Keeping in mind these two research principles, it becomes clear that focusing on the percentage of football players diagnosed with CTE in this study is misleading. The high frequency of CTE in this group of patients could represent the high degree of selection bias. As the authors of this study acknowledge, “Caution must be used in interpreting the high frequency of CTE in this sample, and estimates of prevalence cannot be concluded or implied from this sample." Much more research, involving study types with stronger scientific evidence, is needed to determine the risk factors for developing CTE. Studying a random group of former football players' brains, or following a group of youth football players through their years of participation, would provide that stronger evidence. As we await the results of ongoing research in these areas, we should be thoughtful in the way we handle the current evidence. CTE does develop in some football players, as well as other athletes and non-athletes who are exposed to repetitive head impacts. We don't know the degree of risk, but it is reasonable to assume that there is a dose effect (i.e. more head impacts increase your risk). Taking results from studies of NFL players and applying them to children is problematic. In the current study, CTE was not seen in any individuals who only played football in grade school, and seen at a low frequency in those who only played through high school. It is also important to note that the current study findings have not been replicated in better designed studies. For example, in a study of over 400 individuals (average age 68) who played high school football from 1946-1956, there was no increased risk of dementia or other neurodegenerative diseases compared to classmates who did not play a contact sport.¹ The bottom line is that while concern about CTE in former NFL players may be an appropriate response to this study, putting it into the right context highlights the need to conduct substantially more research using different stud y designs before we make dramatic conclusions and statements about CTE and contact sports participation in general. 1. Savica R, Parisi JE, Wold LE, Josephs KA, Ahlskog JE. High school football and risk of neurodegeneration a community-based study. Mayo Clinic Proc. 2012;87:335-340.