The Rheumatoid Arthritis Drug Development Model: a case study in Bayesian clinical trial simulation

The development of a new drug is a major undertaking and it is important to consider carefully the key decisions in the development process. Decisions are made in the presence of uncertainty and outcomes such as the probability of successful drug registration depend on the clinical development programmme. The Rheumatoid Arthritis Drug Development Model was developed to support key decisions for drugs in development for the treatment of rheumatoid arthritis. It is configured to simulate Phase 2b and 3 trials based on the efficacy of new drugs at the end of Phase 2a, evidence about the efficacy of existing treatments, and expert opinion regarding key safety criteria. The model evaluates the performance of different development programmes with respect to the duration of disease of the target population, Phase 2b and 3 sample sizes, the dose(s) of the experimental treatment, the choice of comparator, the duration of the Phase 2b clinical trial, the primary efficacy outcome and decision criteria for successfully passing Phases 2b and 3. It uses Bayesian clinical trial simulation to calculate the probability of successful drug registration based on the uncertainty about parameters of interest, thereby providing a more realistic assessment of the likely outcomes of individual trials and sequences of trials for the purpose of decision making. In this case study, the results show that, depending on the trial design, the new treatment has assurances of successful drug registration in the range 0.044–0.142 for an ACR20 outcome and 0.057–0.213 for an ACR50 outcome. Copyright © 2009 John Wiley & Sons, Ltd.     

Financial Responsibilities Toward Older Parents and Stepparents Following Divorce and Remarriage

We assessed beliefs about adult children’s responsibilities to financially assist parents and stepparents following later-life divorce and remarriage using a multiple-segment factorial vignette with a national sample (N = 1,121). Ordered logistic regression analyses indicated that beliefs about financial responsibilities to older adults declined after marital transitions, and responsibilities to assist stepparents were more tenuous than to parents. Beliefs about intergenerational responsibilities were affected by adult children’s financial resources and by changes in older adults’ marital statuses. Kinship obligation norms, the adult children’s financial resources, and reciprocity norms were the most common reasons used to explain beliefs about responsibilities to financially assist older parents and stepparents, but these reasons became less salient following divorce and remarriage of the older adult. After marital transitions, beliefs about intergenerational financial responsibilities were more often based on the older adult’s culpability for being in a position of need, relationship quality, and diminished kinship obligations.     

Benefits of cultural matching in foster care

Sixty-one foster parents from a central Canadian province participated in a telephone interview that included the question: “What are the benefits of fostering children who have the same values, beliefs and traditions as you?” A total of 51 unique responses were obtained and grouped together by 13 foster parents. Multidimensional scaling and cluster analysis were used to analyze the grouping data. Foster parents described five themes: expand on held values, child feels secure, smooth transitions, low stress and more in common. There were similarities and differences between the perspectives of foster parents interviewed and the literature. Implications for future research are discussed.     

Integrity of the Marriage and Family Therapy Research Literature: Perceptions and Recommendations

Reports of falsification, fabrication, plagiarism, and other violations of research integrity across the sciences are on the increase. Joining with other disciplines to actively protect the integrity of the marriage and family therapy (MFT) research literature is of utmost importance to both the discipline and the future of the profession. To inform the issues raised, results are presented of an informal survey among MFT clinical members on their perceptions about the literature together with their preferences for how best to protect its integrity. This article initiates an important discussion about the honesty of MFT research.     

Proximate industrial activity and psychological distress

This paper examines the role that gender, occupational status, and family status play in moderating the effect of industrial activity on the psychological well-being of nearby residents. Using a unique spatial assessment of industrial activity and an environmental risk/social stressor framework in conjunction with individual-level data from the Detroit Area Study (DAS) and demographic data from the U.S. census, we find that residents of neighborhoods in close proximity to industrial activity report elevated levels of psychological distress compared to residents of neighborhoods removed from this type of activity. These influences are more pronounced among women but gender differences are also contingent upon occupational and family statuses. We show that specific combinations of work and family statuses make persons particularly vulnerable to the influence of this environmental stressor and women are two and a half times more likely than men to have these vulnerable statuses. This study makes an important contribution to the environmental health literature because it reminds researchers of the fundamental influence of social roles when examining the link between environmental risks and mental health.     

Race/ethnic differences in respiratory problems among a nationally-representative cohort of young children in the United States

Using data from a nationally-representative cohort of young children in the United States, we ask the following: (1) Are there race/ethnic and birth weight differentials in the likelihood of developing respiratory problems by age three in a nationally representative birth cohort? (2) To what extent does birth weight, vis-á-vis other key sociodemographic risk factors, mediate race/ethnic differentials in reported respiratory problems? (3) Does the effect of birth weight on respiratory problems risk differ by race? We find that non-Hispanic black children are 1.7 times as likely as non-Hispanic white children to be reported to have respiratory problems by age three, while the risk for Hispanic children is similar to that of non-Hispanic white children. Birth weight is also very strongly related to respiratory problem risk. Specifically, children born at very low weights (500–1499 g) have four times the odds of having respiratory problems of heavier children. Statistical controls for birth weight decrease the black-white differential by about 20%, while additional controls for sociodemographic factors reduce the race differential by an additional 35%. Finally, the net effect of birth weight is different for black and white children: whereas birth weight affects the risk of respiratory problems for black children only at low weights (<1500 g), it remains an important predictor of excess risk for white children up to 3500 g.

     

The effects of sampling strategies on the small sample properties of the logit estimator

Empirical researchers face a trade-off between the lower resource costs associated with smaller samples and the increased confidence in the results gained from larger samples. Choice of sampling strategy is one tool researchers can use to reduce costs yet still attain desired confidence levels. This study uses Monte Carlo simulation to examine the impact of nine sampling strategies on the finite sample performance of the maximum likelihood logit estimator. The results show stratified random sampling with balanced strata sizes and a bias correction for choice-based sampling outperforms all other sampling strategies with respect to four small-sample performance measures.