Comment 2124 www.thelancet.com Vol 375 June 19, 2010 Testing autism interventions: trials and tribulations In The Lancet today, Jonathan Green and colleagues 1 report results from a multisite randomised trial in children with autism. The investigators compared a parent-training technique that targeted enhancement of the child’s social-communication skills (two of the three core deficits in autism) with treatment as usual. The primary outcome was the social-communication score from the Autism Diagnostic Observation Schedule (ADOS), 2 a widely used diagnostic tool. Secondary outcomes included parent–child interaction, child language, social communication, and measures of adaptive functioning. Today’s results showed no effect of the intervention on the primary outcome and positive effects on some but not all secondary measures, including parent report of language and communication and direct observation of parent–child interaction. This study furthers the field by setting a new bar for the minimum standards of rigorous methodology needed in trials that have potentially far- reaching service and policy implications. 3 Strengths include a large sample size, multisite randomised design with masked assessors, balance across treatment groups, a manualised treatment approach (including standards for fidelity and inter-rater reliability), and outcome measures that directly relate to treatment focus. Thus, in a field in which minimum study standards have made it difficult to even look for literature to answer what works for autism, this study is an achievement. At the same time, today’s study exemplifies the complexity of attempting to detect change in samples of young children with such a heterogeneous condition. There are very few positive published trials in autism, for behavioural interventions, traditional pharmaco- therapy, or complementary/alternative therapies. 4–6 Is this due to non-efficacious treatments, lack of sensitive outcome measures, or heterogeneity of autism—or perhaps all three? The lack of effects on ADOS social-communication scores with this parent-training intervention dampens optimism about its ability to exert clinically significant change in core symptoms of autism. However, Green and colleagues’ use and breastfeeding seem to differ between carriers of BRCA1 and BRCA2 mutations. 6,7 Unfortunately, the genes studied here do not provide any new clues. If attention is limited to the gene variants that have come out of the genome-wide association studies so far and to the known risk factors for breast cancer, we are unlikely to make much progress. The challenge of breast cancer prevention remains and new approaches are needed. Steven A Narod Women’s College Research Institute, Toronto, ON, Canada M5G 1N8 steven.narod@wchospital.ca I declare that I have no conflicts of interest. 1 Travis RC, Reeves GK, Green J, et al, for the Million Women Study Collaborators. Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study. Lancet 2010; published online June 2. DOI:10.1016/S0140-6736(10)60636-8. 2 Wacholder S, Hartge P, Prentice R, et al. Performance of common genetic variants in breast-cancer risk models. N Engl J Med 2010; 362: 986–93. 3 Million Women Study Collaborators. Breast cancer and hormone- replacement therapy in the Million Women Study. Lancet 2003; 362: 419–27. 4 Ravdin PM, Cronin KA, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 2007; 356: 1670–74. 5 Eisen A, Lubinski J, Gronwald J, et al, and the Hereditary Breast Cancer Clinical Study Group. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst 2008; 100: 1361–67. 6 Cullinane CA, Lubinski J, Neuhausen SL, et al. Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. Int J Cancer 2005; 117: 988–91. 7 Jernström H, Lubinski J, Lynch HT, et al. Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 2004; 96: 1094–98. Teacher works with a boy with autism Photolibrary Published Online May 21, 2010 DOI:10.1016/S0140- 6736(10)60757-X This online publication has been corrected. The correced version first appeared at thelancet.com on December 3, 2010 See Articles page 2152