Mechanisms of change in control group drinking in clinical trials of brief alcohol intervention: Implications for bias toward the null JUDITH A. BERNSTEIN 1,2 , EDWARD BERNSTEIN 1,2 & TIMOTHY C. HEEREN 3 1 Department of Community Health Sciences, Boston University School of Public Health, Boston, USA, 2 Department of Biostatistics, Boston University School of Public Health, Boston, USA, and 3 Department of Emergency Medicine, Boston University School of Medicine, Boston, USA Abstract Issues. Reductions in control group consumption over time that are possibly related to research design affect the impact of brief alcohol interventions (BAI) in clinical settings. Approach. We conducted a systematic review to identify research design factors that may contribute to control group change, strategies to limit these effects and implications for researchers. Studies with control group n > 30 were selected if they published baseline and outcome consumption data, conducted trials in clinical settings in Anglophone countries and did not censor gender or age. Key Findings. Among 38 studies cited in 20 reviews through October 2009, 16 met criteria (n = 31–370). In 54%, controls received alcohol specific handouts, advice and/or referral. Both the number and depth of assessments were highly variable. The percentage change in consumption ranged from -0.10 to -0.84 (mean -0.32), and effect size from 0.04 to 0.70 (mean 0.37). Published data were insufficient for meta-analysis. Implica- tions. Researchers should consider strategies to reduce the impact of research design factors, such as procedures to enhance sample diversity, blind subjects to study purpose to limit social desirability bias, reduce the number and depth of instruments (assessment reactivity), and finally, analytic techniques to decrease the impact of outliers and regression to the mean. Conclusions. This review identifies problems with retrospective analysis of predictors of control group change, and underscores the need to design prospective studies to permit identification, quantification and adjustment for potential sources of bias in BAI trials. [Bernstein JA, Bernstein E, Heeren TC. Mechanisms of change in control group drinking in clinical trials of brief alcohol intervention: Implications for bias toward the null. Drug Alcohol Rev 2010;29;498–507] Key words: brief alcohol interventions, control group drinking reductions, regression to the mean. Introduction and Aims Two decades ago teams of clinicians, psychologists and alcohol researchers began systematic testing of the notion that brief alcohol intervention (BAI) in the clini- cal setting with problem drinkers could decrease alcohol consumption and improve health status.Twenty meta-analyses later, short-term reductions in consump- tion and clinically meaningful health benefits have been fully documented in health-care settings, principally in primary care [1–20]. However, open questions remain about long-term effects, mechanisms of change, best practices, and applicability of results across diverse settings and sub-populations.The field has come of age, ‘middle age’ according to Babor and colleagues [21], and with maturity comes the responsibility to examine the quality of the scientific evidence and explore remaining methodologic issues. Perhaps the most puzzling of these emerging meth- odologic concerns is the degree to which control groups in studies of BAI reduce alcohol consumption over time. Effect sizes for clinical BAI are small, typically a mean difference of four drinks less per week (38 g), a decrease of 12% [13]. It has become almost a conven- tion for published reports to suggest that the impact of BAI and treatment may be larger than researchers are Judith A. Bernstein PhD, Professor, Edward Bernstein MD, Professor, Timothy C. Heeren PhD, Professor. Correspondence to Dr Judith A. Bernstein, Department of Community Health Services, Boston University School of Public Health and Department of Emergency Medicine, Boston University School of Medicine, 801 Massachusetts Avenue (403b), Boston, MA 02118, USA.Tel: +1 617 414 1415; Fax: +1 617 638 5370; E-mail jbernste@bu.edu Received 19 October 2009; accepted for publication 17 January 2010. REVIEW Drug and Alcohol Review (September 2010), 29, 498–507 DOI: 10.1111/j.1465-3362.2010.00174.x © 2010 Australasian Professional Society on Alcohol and other Drugs