Population study, objectives

The Rijnmond area is that part of the Rhine delta between Rotterdam and the North Sea. The Commission for the Safety of the Population at large (COVO) commissioned the study for six chemicals and the operations associated with them acrylonitrile, liquid ammonia, liquid chlorine, LNG, propylene, and part of a separation process (diethanolamine stripper of a hydrodesulfurizer). The study objectives were to evaluate methods of risk assessment and obtain experience with practical applications of these methods. The results were to be used to decide to what extent such methods can be used in formulating safety policy. The study was not concerned with the acceptability of risk or the acceptability of risk reducing measures. 

CSline. CSline [84] provides information on well-designed and well-executed clinical trials of drugs currently under study or in use in humans. This information includes study objectives, design, population, intervention groups, withdrawals, adverse reactions, endpoints and results, conclusions, and references. The CSline database covers more than 500 drugs currently on the market or in development. Pharmacological data from more than 2000 journal articles, congresses, and books are added each year. The product is commercially available on CD-ROM from Prous Science and is updated every 2 months. 

Phase IV. post-licensing studies in the target population, with widening of entry criteria to broaden experience in clinical practice study objectives are typically surveillance for safety or further comparisons with other therapies. The results of such trials are more likely to be used for marketing purposes than in support of applications to regulatory authorities. 

Olsson and Brandt (1980) carried out a hospital-based case-control study of Hodgkin s disease and chemical exposures in Lund, Sweden. Twenty-five consecutive male cases aged 20-65 years were included. Two neighbourhood-matched controls were selected for each case from the Swedish population register. Interviews with study subjects focused on their detailed job history, and in particular exposure to solvents. Interview data were supplemented with visits to employers in some cases. Four of the cases and none of the controls had been exposed to xylene. All exposed cases were also exposed to other solvents. [The Working Group noted the opportunity for information bias, since the interviewer was not blind to disease status or to the study objectives ]... 

The objective of any population study is to detect and quantify variation. This objective can be accomplished in many ways depending on the overall thrust of a study. Often, the aim of a study is to follow the distribution of single polymorphisms.10,11 Assaying variation in population studies also may involve the characterization of levels of variation between individuals, within populations, between populations, or over zones of contact of populations. This objective requires methods for extensive screening of many individuals for polymorphisms. 

Post-registration clinical studies must be carried out using a written protocol that will provide answers to specific research questions. The protocol must be designed to ensure scientifically meaningful results, and should contain details about study objective, study population, methodology, information to be obtained and data collection method. 

The inclusion and exclusion criteria are described in the Subject Selection part of the protocol. To a large extent, the success or failure of a particular clinical trial can often be traced back to how well these criteria were developed. Good protocol authors strive to include the most appropriate patient population to satisfy the study objective and still include those kinds of patients who will ultimately receive the drug. Therefore, selection criteria can be unreasonable and unnecessary in some cases and vague and not specific in other cases. The management of concomitant medications is particularly problematic. The protocol must attempt to define those medications that are permitted for intercurrent illnesses and those that are prohibited as they will interfere with the interpretation of the test medication. Although there are no easy answers, quality protocols are able to justify with some precision the rationale for each inclusion and criteria. How these criteria are applied is handled in the Screening for Study Entry section. 

In addition to the greater risk in patients, results in patients are frequently confounded by the effects of disease, concomitant medication, age and other variables. By contrast, healthy subjects are much more homogeneous and subjects are studied under standardised conditions. It is sometimes argued that healthy volunteers are not representative of the patient population and therefore that the studies are of less relevance. This argument fails to take into account the study objectives some questions about a drug are much more easily answered by deliberately excluding sources of variation. 

Finnish General Population Study. This study was part of follow-up studies into levels of dioxins, dibenzofiirans, and PCBs in human milk coordinated by WHO/EURO. The objectives of the study were to correlate the birth weight and sex of a child to dioxins/dibenzofurans and PCB concentrations of its mother s milk and to evaluate personal and environmental determinants that correlated with the levels of these chemicals in human milk in two areas in Finland, an urban area and a rural area (Vartiainen et al. 1998). One hundred sixty-seven random human milk samples were collected 4 weeks after delivery for 2 weeks. Information on each mother and child was gathered by a questionnaire that included questions on all relevant covariates. 

The validation parameters mentioned above must be established, as much as possible, in the same matrix as that of the samples intended to be analyzed. Every new analytical procedure will have to be validated for each type of matrix (e.g., for each type of biological fluid and for each animal species). In addition, expectations on characteristics such as precision, sensitivity, assay range, should be stated a priori depending on the intended use of the assay (target population, matrix, study objectives, etc.). 

Integration of biomarkers into clinical protocols requires incorporation of biomarker analysis into one of the study objectives. For novel biomarkers this is typically achieved by including an exploratory objective that examines the feasibility of measuring the biomarkers in the study population. Within the protocol a summary of preclinical or translational evidence for the biomarkers should be provided. When available, biomarker qualifications or letters of support from regulatory authorities should be referenced. A schedule of events describing when samples for biomarker analysis should be collected in context with all other clinical visits and tests should be included. When special collection, processing, or storage considerations are required, a separate... 

The object of developmental studies is the development of the individual, whereas the subject of population studies - the aggregate of individuals united in a population. These two lines of research have traditionally developed independently. In the analysis of specimens is estimated the condition of the body at a certain stage of development and its dynamics in time and space. The study of ontogeny itself, which often is limited to embryonic development and identify differences between individuals. 

In an initial Phase I study of Ino Ozo, an MTD of l.Smgm was seen. Common toxicities were thrombocytopenia, neutropenia, elevated liver enzymes, and the common infusion-related toxicities, with hematopoetic toxicities, especially thrombocytopenia, being the most common dose-limiting toxicity (DLT). Complete responses were observed starting at 0.8mgm . At the MTD in a heavily pretreated patient population, the objective response rates were 69% for follicular lymphoma and 33% for DLBCL as monotherapy. ... 

Evaluating treatments for conservation has to be undertaken with rigour if the results are to be useful. Too many studies have produced results, after considerable work, that have tittle validity but are applied to objects anyway (Reedy and Reedy, 1992), often with damaging effects. Unlike materials for science research, objects are rarely well characterized or their history understood. This adds uncertainty to the results of the experiment and doubts about the implications to the wider population of objects. This inevitable uncertainty must be part of any design for an experiment. Indeed the treatment of an object is a unique experiment from which lessons can be learned and added to a growing body of conservation knowledge. Fortunately, techniques for dealing with complexities and uncertainties have been well developed in other fields, such as medicine and natural history. 

H. B. Newcombe, Present state and long term objectives of the British Columbia population study, in Proceedings of the Third International Congress of Human Genetics, pp. 291-313, Johns Hopkins Press, Baltimore (1967). 

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