The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?

BACKGROUND: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT-drug development programmes before patent expiration. METHODS: We identified novel drug-radiation phase I combination trials performed between 1980 and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for each drug included: date the initial phase I trial with/without RT was opened/published, date of the published positive phase III trials, and patent expiration dates. Lag time was defined as the interval between opening of the phase I trial without RT and the opening of the phase I with RT. Linear regression was used to model how the lag time has changed over time. RESULTS: The median lag time was 6 years. The initial phase I trial with RT was typically published 2 years after the first published positive phase III trial and 11 years before patent expiration. Using a best-fit linear model, lag time decreased from 10 years for phase I trials published in 1990 to 5 years in 2005 (slope significantly non-zero, P<0.001). CONCLUSIONS: Clinical drug development with RT commences late in the life cycle of anti-cancer agents. Taking into account the additional time required for late-phase clinical trials, the delay in initiating clinical testing of drug-RT combinations discourages drug companies from further pursuing RT-based development. Encouragingly, lag time appears to be decreasing. Further reduction in lag time may accelerate RT-based drug development, potentially improving patient outcomes.

Age and gender differences in children's self- and task perceptions during elementary school.

We examined the development of children's self- and task perceptions during the elementary school years. 865 first-, second,- and fourth-grade children (ages 7-10) completed questionnaires assessing their perceptions of competence in, and valuing of, activities in several activity domains (math, reading, sports, and instrumental music). Factor analyses showed that even the first graders had differentiated self-beliefs for the various activities. These analyses also indicated that children's competence beliefs and subjective task values formed distinct factors. Analyses assessing age and gender differences in children's beliefs showed that for all the activities except sports, younger children's (particularly the first graders) perceptions of competence and subjective task values were more positive than the beliefs of the older children. Boys had more positive competence beliefs and values than did girls for sport activities, and more positive competence beliefs for mathematics. Girls had more positive competence beliefs and values than did boys for reading and music activities.

Credit and blame among American and Japanese children: normative, cultural, and individual differences.

Japanese and American 5th graders (N = 593 children, 198 American and 395 Japanese) assigned credit and blame to good and bad classroom deeds and performances. Theoretically, a morality of aspiration involves assigning more credit for a good deed than blame for a corresponding bad deed; a morality of duty involves assigning more blame than credit. In both countries academic achievement norms were most consistent with aspiration, moral norms were judged as duties, and procedural norms were intermediate. Japanese children's responses were more consistent with aspiration than those of Americans. Analyses also explored cultural versus individual differences in sanctioning. The conclusion addresses the relevance of the concept of aspiration to the study of achievement and other norms.