How to assess the external validity of therapeutic trials: a conceptual approach

Background External validity of study results is an important issue from a clinical point of view. From a methodological point of view, however, the concept of external validity is more complex than it seems to be at first glance. Methods Methodological review to address the concept of external validity. Results External validity refers to the question whether results are generalizable to persons other than the population in the original study. The only formal way to establish the external validity would be to repeat the study for that specific target population. We propose a three-way approach for assessing the external validity for specified target populations. (i) The study population might not be representative for the eligibility criteria that were intended. It should be addressed whether the study population differs from the intended source population with respect to characteristics that influence outcome. (ii) The target population will, by definition, differ from the study population with respect to geographical, temporal and ethnical conditions. Pondering external validity means asking the question whether these differences may influence study results. (iii) It should be assessed whether the study's conclusions can be generalized to target populations that do not meet all the eligibility criteria. Conclusion Judging the external validity of study results cannot be done by applying given eligibility criteria to a single target population. Rather, it is a complex reflection in which prior knowledge, statistical considerations, biological plausibility and eligibility criteria all have plac

The importance of parental knowledge in the association between ADHD symptomatology and related domains of impairment

Parents of children with ADHD experience several difficulties while raising their children and report lower levels of knowledge about their children’s life and behaviors. A recent study found that low levels of parental knowledge mediated the association between ADHD symptoms and risk-taking behavior (RTB) in adolescents. The current study aimed to investigate this previous finding further by replicating it, by taking peer influence into account as additional social factor of importance and by extending it and also investigate the role of parental knowledge in the association between ADHD symptoms and homework problems. Three studies were performed: study 1 (N=234) replicated previous work on parental knowledge mediating the association between ADHD symptoms and RTB, study 2 (pre-registered, N=313) added peer influence, and study 3 (pre-registered, N=315) assessed whether parental knowledge mediated the association between ADHD symptoms and homework behavior. Parental knowledge consistently mediated the association between ADHD symptoms on one hand and RTB and homework problems on the other, and also predicted stronger resistance to peer influence. Because parental knowledge was repeatedly linked to ADHD-related problems, it seems promising to include parental knowledge in treatment of ADHD-related problems in adolescents, by improving the parent-child relationship. Future studies should test more directly how improvement of the parent-child relationship can be used to optimize parental knowledge, which in its turn reduces ADHD-related problems

Effect of immune system stimulation and divergent selection for residual feed intake on digestive capacity of the small intestine in growing pigs

Residual feed intake (RFI) is a measure of feed efficiency that reflects differences in the efficiency of the use of feed for maintenance and growth. The consequences of genetic selection for RFI on intestinal nutrient digestion capacity, particularly during immune system stimulation (ISS), are poorly documented. Our objective was to evaluate the impact of ISS and genetic selection for RFI on apparent ileal digestibility (AID) of nutrients, and intestinal nutrient transport and barrier function

Total cost estimation for implementing genome-enabled selection in a multi-level swine production system

Background: Determining an animal’s genetic merit using genomic information can improve estimated breeding value (EBV) accuracy; however, the magnitude of the accuracy improvement must be large enough to recover the costs associated with implementing genome-enabled selection. One way to reduce costs is to genotype nucleus herd selection candidates using a low-density chip and to use high-density chip genotyping for animals that are used as parents in the nucleus breeding herd. The objective of this study was to develop a tool to estimate the cost structure associated with incorporating genome-enabled selection into multi-level commercial breeding programs. Results: For the purpose of this deterministic study, it was assumed that a commercial pig is created from a terminal line sire and a dam that is a cross between two maternal lines. It was also assumed that all male and female selection candidates from the 1000 sow maternal line nucleus herds were genotyped at low density and all animals used for breeding at high density. With the assumptions used in this analysis, it was estimated that genome-enabled selection costs for a maternal line would be approximately US$0.082 per weaned pig in the commercial production system. A total of US$0.164 per weaned pig is needed to incorporate genome-enabled selection into the two maternal lines. Similarly, for a 600 sow terminal line nucleus herd and genotyping only male selection candidates with the low-density panel, the cost per weaned pig in the commercial herd was estimated to be US$0.044. This means that US$0.21 per weaned pig produced at the commercial level and sired by boars obtained from the nucleus herd breeding program needs to be added to the genetic merit value in order to break even on the additional cost required when genome-enabled selection is used in both maternal lines and the terminal line. Conclusions: By modifying the input values, such as herd size and genotyping strategy, a flexible spreadsheet tool developed from this work can be used to estimate the additional costs associated with genome-enabled selection. This tool will aid breeders in estimating the economic viability of incorporating genome-enabled selection into their specific breeding program