Small samples and increased variability-discussing the need for restricted types of randomization in exercise interventions in old age

Abstract

Background: Randomization provides an equal chance for participants to be allocated to intervention groups, in order to create an equal distribution of all variables at baseline in all groups. However, this is not guaranteed, particularly if the groups are too small, or if the researched groups consist of older adults. The aims of this commentary are to discuss the increased variability in old age which intensifies the risk of baseline inequalities, to elaborate on the need to estimate potential baseline group differences in small samples of older participants in exercise intervention, to discuss alternative procedures for creating equal groups at baseline and to provide specific guidelines for selecting the design of small studies. Main body: Small groups with increased inter-individual differences may lead to reduced power, thus differences that truly exist may not be detected, or false group differences may appear in the outcome following the treatment. Studies that focused exclusively on older adults have found increased variability in advanced age. Therefore, baseline group differences are more common in older adults as compared to younger persons, and may lead to misinterpretation of the intervention′s results. Imbalances can be reduced by covariate-adaptive randomization procedures, such as stratified permuted-block randomization or minimization. Specific guidelines are provided for selecting a randomization procedure by assessing the probability of unequal groups at baseline in typical, widely used functional tests in old age. A calculation of the required number of participants for creating equal groups for these functional tests is provided, and can be used when increasing the number of participants is possible. R-scripts specifically created for assessing the probability of unequal groups, or for determining the sample size assuring equal groups, are recommended. Conclusions: In exercise interventions assessing older adults, it is recommended to have a sample large enough for creating equal groups. If this is not possible, as is the case quite often in intervention studies in old age, it is recommended to assess the probability of inequality in the study groups and to apply an alternative randomization.