Williamson DM et al. – Epidemiological studies play a key role in identifying genetic and environmental factors that are associated with complex diseases like multiple sclerosis (MS). Methodological issues arise in every study, and investigators need to be able to detect, respond to and correct problems in a timely and scientifically valid manner.

• Individuals with definite MS were identified from a prevalence study conducted in three geographic areas.
• The target number of cases was not reached, so an additional study area was added.
• Identifying clinic controls was inefficient, so controls were recruited using random digit dialing.

• In total, 276 cases and 590 controls participated, but participation rates were low, ranging from 28.4% to 38.9%.
• Only one-third (33.6%) of individuals identified in the prevalence study agreed to participate in the case–control study.
• Cases were more likely to be non-Hispanic white and older than their source populations as identified in the preceding prevalence study (P < 0.05).
• Most participants provided a blood sample for genotyping (91%; n = 789).