Issues in applying recent CPMP ‘Points to Consider’ and FDA guidance documents with biostatistical implications

The International Conference on Harmonisation guideline ‘Statistical Principles for Clinical Trials’ was adopted by the Committee for Proprietary Medicinal Products (CPMP) in March 1998, and consequently is operational in Europe. Since then more detailed guidance on selected topics has been issued by the CPMP in the form of ‘Points to Consider’ documents. The intent of these was to give guidance particularly to non‐statistical reviewers within regulatory authorities, although of course they also provide a good source of information for pharmaceutical industry statisticians. In addition, the Food and Drug Administration has recently issued a draft guideline on data monitoring committees. In November 2002 a one‐day discussion forum was held in London by Statisticians in the Pharmaceutical Industry (PSI). The aim of the meeting was to discuss how statisticians were responding to some of the issues covered in these new guidelines, and to document consensus views where they existed. The forum was attended by industry, academic and regulatory statisticians. This paper outlines the questions raised, resulting discussions and consensus views reached. It is clear from the guidelines and discussions at the workshop that the statistical analysis strategy must be planned during the design phase of a clinical trial and carefully documented. Once the study is complete the analysis strategy should be thoughtfully executed and the findings reported. Copyright © 2003 John Wiley & Sons, Ltd.     

Society's search for a legal and ethical basis of physician-assisted suicide

A review of the way physician-assisted suicide (PAS) is being addressed in the United States reveals three models, each functioning out of distinctive concepts of autonomy: (1) litigation, which utilizes philosophical autonomy; (2) legislation, which utilizes political autonomy; and (3) act of conscience by a physician, which utilizes consumer autonomy. Each model raises a correspondingly distinct set of ethical questions and challenges centered around their point of reference-the judicial system, voters, or the doctor-patient relationship. In the end, however, efforts to resolve the challenge of PAS will falter if they do not go beyond these models of autonomy. Religious institutions offer a more constructive setting for facing the life and death decisionmaking of PAS. The challenge for religion is to address PAS in solidarity with sufferers, physicians, and the community, rather than retreating into iconoclastic dogmas.     

Joint custody and co-parenting: not by law but by love

In recent years, joint custody and co-parenting of children after divorce or separation has received considerable attention. The authors advocate wider recognition of this option to sole custody and visitation, review pertinent legal and other literature, identify indications and contraindications, and briefly discuss the implications for social workers.     

Brexit: Be Careful What You Wish For?

In this paper, I focus on the British future from Brexit. The institutional form this will take is not yet fixed. However, one can consider likely outcomes based on dominant economic frameworks. From this perspective, it seems unlikely that Brexit will address the actual grievances that resulted in Brexit. These transcend European Union membership.     

Testing the Vision: Preschool Settings as Places for Meeting,Bonding and Bridging

The OECD (2006 Starting Strong II: Early Childhood Education and Care. OECD Publishing: Paris) envisions early childhood education and care settings as meeting places for diverse social groups; places that build social capital. This vision was assessed in a comparison of three preschools types: full‐fee paying, subsidised‐fee and publicly funded. The social composition within each was examined and the connectedness of the children (n = 472) who attended compared. Publicly funded preschools had more socially diverse populations. The quantity of social connectedness did not differ but children in publicly funded preschools described higher quality social relationships. Not all preschool settings are socially diverse but, where they are, the quality of relationships is highest.     

Modeling the Adenoma and Serrated Pathway to Colorectal CAncer (ASCCA)

Several colorectal cancer (CRC) screening models have been developed describing the progression of adenomas to CRC. Currently, there is increasing evidence that serrated lesions can also develop into CRC. It is not clear whether screening tests have the same test characteristics for serrated lesions as for adenomas, but lower sensitivities have been suggested. Models that ignore this type of colorectal lesions may provide overly optimistic predictions of the screen‐induced reduction in CRC incidence. To address this issue, we have developed the Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model that includes the adenoma‐carcinoma pathway and the serrated pathway to CRC as well as characteristics of colorectal lesions. The model structure and the calibration procedure are described in detail. Calibration resulted in 19 parameter sets for the adenoma‐carcinoma pathway and 13 for the serrated pathway that match the age‐ and sex‐specific adenoma and serrated lesion prevalence in the COlonoscopy versus COlonography Screening (COCOS) trial, Dutch CRC incidence and mortality rates, and a number of other intermediate outcomes concerning characteristics of colorectal lesions. As an example, we simulated outcomes for a biennial fecal immunochemical test screening program and a hypothetical one‐time colonoscopy screening program. Inclusion of the serrated pathway influenced the predicted effectiveness of screening when serrated lesions are associated with lower screening test sensitivity or when they are not removed. To our knowledge, this is the first model that explicitly includes the serrated pathway and characteristics of colorectal lesions. It is suitable for the evaluation of the (cost)effectiveness of potential screening strategies for CRC.     

Sampling schemes for price index construction: a performance comparison across the classification of individual consumption by purpose food groups

Five sampling schemes (SS) for price index construction – one cut-off sampling technique and four probability-proportional-to-size (pps) methods – are evaluated by comparing their performance on a homescan market research data set across 21 months for each of the 13 classification of individual consumption by purpose (COICOP) food groups. Classifications are derived for each of the food groups and the population index value is used as a reference to derive performance error measures, such as root mean squared error, bias and standard deviation for each food type. Repeated samples are taken for each of the pps schemes and the resulting performance error measures analysed using regression of three of the pps schemes to assess the overall effect of SS and COICOP group whilst controlling for sample size, month and population index value. Cut-off sampling appears to perform less well than pps methods and multistage pps seems to have no advantage over its single-stage counterpart. The jackknife resampling technique is also explored as a means of estimating the standard error of the index and compared with the actual results from repeated sampling.     

Migration decision-making and migration industry in the Indonesia–Malaysia corridor

ABSTRACT

This paper explores the involvement of migration industry (MI) in the migration system of Indonesia and Malaysia. The two countries share an extensive border and have much in common in culture and history but they are very different in geographical size, population and economic development, the latter being a main cause for labour migration from Indonesia to Malaysia. The changing context of government policies generates new niches for migration services taken up by formal and informal intermediaries, thereby confronting migrants with a varied migration-decision field and thresholds during their migration process. Much of the migration is legal, but a large part of it also takes place outside the control of the national governments. While taking mental processes in migration decision-making as starting point, we analyse how the MI, by way of fostering, facilitating and controlling geographic mobility and localised employment, connects to the production and negotiating of three migration decision thresholds faced by migrants.