1.
Comparison of results from different imputation techniques for missing data from an anti-obesity drug trial.
Jørgensen, AW, Lundstrøm, LH, Wetterslev, J, Astrup, A, Gøtzsche, PC
PloS one. 2014;(11):e111964
Abstract
BACKGROUND In randomised trials of medical interventions, the most reliable analysis follows the intention-to-treat (ITT) principle. However, the ITT analysis requires that missing outcome data have to be imputed. Different imputation techniques may give different results and some may lead to bias. In anti-obesity drug trials, many data are usually missing, and the most used imputation method is last observation carried forward (LOCF). LOCF is generally considered conservative, but there are more reliable methods such as multiple imputation (MI). OBJECTIVES To compare four different methods of handling missing data in a 60-week placebo controlled anti-obesity drug trial on topiramate. METHODS We compared an analysis of complete cases with datasets where missing body weight measurements had been replaced using three different imputation methods: LOCF, baseline carried forward (BOCF) and MI. RESULTS 561 participants were randomised. Compared to placebo, there was a significantly greater weight loss with topiramate in all analyses: 9.5 kg (SE 1.17) in the complete case analysis (N = 86), 6.8 kg (SE 0.66) using LOCF (N = 561), 6.4 kg (SE 0.90) using MI (N = 561) and 1.5 kg (SE 0.28) using BOCF (N = 561). CONCLUSIONS The different imputation methods gave very different results. Contrary to widely stated claims, LOCF did not produce a conservative (i.e., lower) efficacy estimate compared to MI. Also, LOCF had a lower SE than MI.
2.
Circulating ACE is a predictor of weight loss maintenance not only in overweight and obese women, but also in men.
Wang, P, Holst, C, Wodzig, WK, Andersen, MR, Astrup, A, van Baak, MA, Larsen, TM, Jebb, SA, Kafatos, A, Pfeiffer, AF, et al
International journal of obesity (2005). 2012;(12):1545-51
Abstract
BACKGROUND Circulating angiotensin-converting enzyme (ACE) was identified as a predictor of weight loss maintenance in overweight/obese women of the Diogenes project. OBJECTIVE To investigate whether ACE acted also as a predictor in men of the Diogenes study and to compare it with that in women. DESIGN Subjects, who lost ≥ 8% of body weight induced by low-caloric diet in an 8-week weight loss period, were assigned to weight loss maintenance with dietary intervention for 6 months. SUBJECTS 125 overweight/obese healthy men from eight European countries who completed whole intervention. MEASUREMENTS Concentrations and activity of serum ACE at baseline and after the 8-week weight loss, in addition to anthropometric and physiological parameters. RESULTS Serum ACE concentration decreased by 11.3 ± 10.6% during the weight loss period in men. A greater reduction is associated with less body weight regain during the maintenance period (r=0.227, P=0.012). ACE change was able to predict a weight regain ≤ 20% after 6 months, with an odds ratio of 1.59 (95% confidence interval (CI): 1.09-2.33, P=0.016) for every 10% reduction, which was independent of body mass index and weight loss. The prediction power was weaker in men than in women, but without a significant sex difference (P=0.137). In pooled subjects (N=218), the odds ratio was 1.96 (95% CI: 1.46-2.64, P<0.001). CONCLUSIONS A greater reduction of ACE during weight loss is favorable for weight maintenance in both men and women. This can offer useful information for personalized advice to improve weight loss maintenance. It also confirms the role of ACE in the metabolic pathways of weight regulation.
3.
Micronutrient intake in overweight subjects is not deficient on an ad libitum fat-reduced, high-simple carbohydrate diet.
Vasilaras, TH, Astrup, A, Raben, A
European journal of clinical nutrition. 2004;(2):326-36
Abstract
OBJECTIVE To investigate whether subjects consuming a fat-reduced, high-simple carbohydrate diet (SCHO) are at greater risk of micronutrient inadequacy than subjects consuming a fat-reduced, high-complex carbohydrate (CCHO) or a normal-fat diet (control, CD). DESIGN A 6-month randomised controlled dietary intervention trial with a parallel design. METHODS In total, 46 overweight (BMI: 24.4-36.3 kg/m(2)) subjects (19 males, 27 females) aged 21-54 y consumed one of three ad libitum diets: SCHO, CCHO, or CD. Nutrient intake was assessed by a 7-day weighed food record. RESULTS Self-reported energy intake did not differ between diet groups. The lowest intake of vitamin B(12) was found in the SCHO group vs CCHO (P=0.025) and vs. CD (P=0.012). In men, zinc intake was lower on the SCHO diet compared to the CD diet (P=0.018). The recommendations for zinc and vitamin B(12) were, however, met by all the diet groups. No other diet differences were observed. Intake of several micronutrients were insufficient in all three diet groups, although in most cases comparable to average Danish intakes. CONCLUSION Zinc intake in men and vitamin B(12) intake in the combined gender groups were lower on a fat-reduced, simple carbohydrate-rich diet compared to a habitual, normal-fat diet, but not below recommended levels.