What are the appropriate methods for analyzing patient-reported outcomes in randomized trials when data are missing?

Subjective health measurements using Patient Reported Outcomes (PRO) are increasingly used in randomized trials, particularly for patient groups comparisons. Two main types of analytical strategies can be used for such data: Classical Test Theory (CTT) and Item Response Theory models (IRT). These two strategies display very similar characteristics when data are complete, but in the common case when data are missing, whether IRT or CTT would be the most appropriate remains unknown and was investigated using simulations. We simulated PRO data such as quality of life data. Missing responses to items were simulated as being completely random, depending on an observable covariate or on an unobserved latent trait. The considered CTT-based methods allowed comparing scores using complete-case analysis, personal mean imputations or multiple-imputations based on a two-way procedure. The IRT-based method was the Wald test on a Rasch model including a group covariate. The IRT-based method and the multiple-imputations-based method for CTT displayed the highest observed power and were the only unbiased method whatever the kind of missing data. Online software and Stata® modules compatibles with the innate mi impute suite are provided for performing such analyses. Traditional procedures (listwise deletion and personal mean imputations) should be avoided, due to inevitable problems of biases and lack of power.

Effects of essential amino acids on food and water intake of rats.

This study examined the effects of selected groups of essential amino acids (EAAs), given by gavage, on short-term food and water intake. Amino acid groups were selected on the basis of their common physiologic functions in relation to current hypotheses on the role of amino acids in food intake control, and the quantities given were based on the proportions in 1.5 g of the EAA content of albumin. The complete EAA mixture (1.5 g) suppressed food intake by an average of 60 and 37% during the 1st and 2nd h of feeding, respectively, but had no influence on feeding in the subsequent 12 h. Total daily (14 h) intake was decreased by 9%. With the exception of the aromatic amino acid (Phe + Tyr + Trp, 0.34 g) group, all groups significantly decreased food intake by a comparable magnitude (32%) during the 1st h. In this time period, rats given the EAAs, Arg + Met + Val (0.38 g), and Arg + His + Lys (0.44 g) mixtures increased their water intake, whereas intake by rats given the Phe + Tyr + Trp + Thr (0.46 g) and Ile + Leu + Val (0.45 g) mixtures was unchanged. Thus, the food intake suppression caused by EAAs was not accounted for by an equal effect of its component amino acid groups. As well, food intake suppression by amino acid groups was not explained by increased water consumption, nor was it simply related to the quantity of nitrogen provided by the treatment.