Bad Science: Cause and Consequence.

Scientific progress is dependent on accumulation of quality data with appropriate data analysis. Unfortunately, there are a troubling number of accounts describing an inability to replicate published work. Some explanations are lack of access to proprietary reagents and equipment, or lack of expertise and know how. However, it is clear that there are many publications that are fatally flawed, and it is difficult to ascertain which ones they are, but there are clues. Many articles are improperly controlled, resulting in false-positive or -negative results. Reagents and procedures are used without verifying their specificity. There is also confirmation bias, a tendency to seek and find conclusions that we like, which is exacerbated by faithful acceptance by readers of the publication record without assessment of merit. These and other issues have slowed progress, resulted in waste of scarce funds, and even put patients at risk when clinical decisions are made according to flawed data. Solving these and related problems requires recognition of the problem and better training. We also need to take personal responsibility for not only our own work, but also for the accuracy of information in the scientific domain.

Genetic variations of orosomucoid genes associated with serum alpha-1-acid glycoprotein level and the pharmacokinetics of paclitaxel in Japanese cancer patients.

Alpha-1-acid glycoprotein (AGP) encoded by orosomucoid genes (ORM1 and ORM2) is an acute-phase response protein and functions as a drug-binding protein that affects pharmacokinetics (PK)/pharmacodynamics of binding drugs. To explore the effects of genetic variations of ORMs and a role of AGP on paclitaxel (PTX) therapy, we analyzed the duplication and genetic variations/haplotypes of ORMs in 165 Japanese cancer patients and then investigated their associations with serum AGP levels and the PK parameters of PTX. No effects of ORM duplications on serum AGP levels at baseline or PK of PTX were observed, but close associations of ORM1 -559T > A with the increases of AGP levels and area under the curve (AUC) of PTX metabolites were detected. In addition, a significant correlation between the serum AGP level and the AUCs of PTX metabolites was observed, suggesting that AGP may function as a carrier of PTX from the blood into the liver via putative receptors. This study provided useful information on the possible clinical importance of ORM genetic polymorphisms and a novel role of AGP in PTX therapy.