What does it mean? Looking beyond group differences in clinical research

Abstract

It is usual practice for scientific papers to focus on the description of groups of subjects in terms of their mean scores on a particular measure and to assess differences between these groups by comparing these means using standard statistical tests. When we read that, ‘‘compared to a control group, those with a particular disorder or problem scored significantly higher on a symptom questionnaire’’, or ‘‘performed less well on a particular neuropsychological task’’, or that ‘‘those patients treated with an active treatment had lower symptom scores at the end of the trial than those treated with a placebo’’, we are able to make certain assumptions about that disorder or treatment. If we are interested in the strength of an effect we will often look to the effect size for an answer. There is no doubt that incorporating information derived from such comparisons is not only appropriate but forms the basis of evidencebased clinical practice. However, sometimes it is informative to look beyond the means and consider the heterogeneity and inter-individual variability that is often seen across many levels of analysis including symptoms, cognition and more basic causal processes. Andres and colleagues (this issue) compared cognitive functioning in a group of adolescents with anorexia nervosa to a matched group of healthy controls. Interestingly, despite measuring performance across a wide range of tasks assessing multiple cognitive domains, the two groups differed on only one task, the Rey Complex figure Task, but not on any of the other measures. From this one could conclude that adolescents with anorexia nervosa have only very limited cognitive impairments. However, in addition to comparing the two groups using mean scores Andres and colleagues also identified those individuals who were cognitively impaired on two or more tasks. From this perspective they found that significantly more of those with anorexia had significant cognitive impairment compared to the healthy controls (30 vs. 7%). While this still means that most of the anorexic subjects were not impaired, there were clearly a significant minority who had significant problems. One great strength of this study, and something that makes these findings even more relevant, is the way that the authors worked very hard to recruit a homogeneous patient group. Previous studies in this field included a much broader group of individuals with a wide range of eating disorders. This, of course, makes it difficult to know whether differences between individuals are a consequence of diagnostic heterogeneity rather than heterogeneity within the clinical phenotype. However, here we have a well-characterised patient cohort with a short duration of illness all of whom were in the acute phase of their illness. This clearly indicates that the neuropsychological heterogeneity, which was found in this group of adolescents and which is similar to that previously demonstrated in less well-defined cohorts of adults with anorexia nervosa is related to the disorder itself rather than to some broader associated factors. Analogous findings have been reported across several other disorders. Perhaps the best researched example within child and adolescent mental health is attention deficit/hyperactivity disorder (ADHD) where several groups of authors have highlighted the considerable cognitive heterogeneity found within ADHD samples. Nigg et al. [4] described data from three independent sites that suggested while many neuropsychological tasks can differentiate those with ADHD from healthy controls, only a D. Coghill (&) Division of Neuroscience, Medical Research Institute, College of Medicine, Dentistry and Nursing, Ninewells Hospital and Medical School, Dundee, UK e-mail: d.r.coghill@dundee.ac.uk