Are patients with Hodgkin lymphoma and high-grade non-Hodgkin lymphoma in clinical therapy optimization protocols representative of these groups of patients in Germany?

BACKGROUND: Improvement of lymphoma therapy is largely driven by clinical therapy optimization protocols (TOPs). It is unclear, however, whether the patients treated in clinical TOP are representative for all patients. PATIENTS AND METHODS: TOP participants were compared with nonstudy patients in a population-based approach. The study included patients with Hodgkin lymphoma (HL) and high-grade non-Hodgkin lymphoma (hgNHL). Incident cases (N = 743) were ascertained in a large population-based epidemiologic survey. Each patient's status with respect to exclusion criteria of the pertinent TOP was abstracted from primary data sources. TOP participants were identified on the basis of the trial databases. Baseline characteristics and risk factor prevalence were compared between nonstudy and TOP patients. RESULTS: Eligible for the respective TOPs were 64.1% of all incident HL patients and 29.6% of all hgNHL patients in the population. Main exclusion criterion was age (HL: 15.2%; hgNHL: 27.4%). Only 71 HL patients (23.0%) and 11 hgNHL patients (3.4%) had actually been enrolled in the respective TOPs. CONCLUSIONS: TOP participants do not represent all patients with hgNHL and HL in the population. TOP inclusion criteria caused considerable selection among the participants. Further investigation is required to clarify possible limitations for the application of the outcomes observed in TOP patients for all patients with these diseases.

[Smoking as potential confounder in german epidemiological studies: standardization of assessment, quantification, and analysis]. / Rauchen als möglicher Confounder in epidemiologischen Studien: Standardisierung der Erhebung, Quantifizierung und Analyse.

Tobacco smoking is one of the most frequently examined risk factors in epidemiological studies due to the high frequency of smoking in the population and its high risk potential. This paper discusses the issue of standardization of the assessment of tobacco exposure in German epidemiological studies based on a suggestion of the working group "Epidemiological methods" of the German Society of Epidemiology (DGEpi), the German Society of Social Medicine and Prevention (DGSMP), and German Society of Medical Informatics, Biometry and Epidemiology (GMDS) together with the working group "Epidemiology in the workplace" of the DGEpi and the German Society of Occupational and Environmental Medicine (DGAUM). The main element is a short questionnaire for German adults for the assessment of tobacco smoking in epidemiological studies where smoking is a potential confounder. In addition, information on the consideration of intermittent periods of non-smoking, a very short questionnaire for medical examinations in the workplace or non-responder interviews as well as the quantification and statistical modelling of smoking are presented. A brief discussion of scientific problems and questionnaires related to the exposure to environmental tobacco smoke is given.

[The problem of response in epidemiologic studies in Germany (Part II)]. / Zum Problem der Response in epidemiologischen Studien in Deutschland (Teil II).

The first part of this paper introduced various definitions of response and discussed their significance in the context of different study types. This second part addresses incentives as a method to increase response and evaluates the impact of non response or delayed response on the validity of the study results. Recruitment aims at minimising the proportion of refusal. To achieve this, incentives can be used and potential participants can be contacted in a sequence of increasing intensity. The effectiveness of different incentives was investigated within the pretest of the German survey on children and adolescents by the Robert Koch Institute. A low response is often interpreted in terms of non-response bias. This assumption, however, is as incorrect as would be opposite conclusion, that a high response guarantees valid results. Any study of the influence of nonresponse requires information on non-responders. The comparison between early and late responders as an indirect method to evaluate systematic differences between participants and non-participants by wave analysis is demonstrated within the Northern Germany Leukaemia and Lymphoma study (NLL). The German guidelines for Good Epidemiologic Practice recommend to solicit a minimum of information on the principal hypotheses of a study from non-participants. The example of a population-based health survey (Cooperative Health Research in the Region of Augsburg, KORA) illustrates how information on non-responders within a quantitative non-responder analysis can be achieved and used for the estimation of prevalences. Recommendations how to deal with the response in epidemiological studies in Germany are suggested.

[The problem of response in epidemiological studies in Germany (part I)]. / Zum Problem der Response in epidemiologischen Studien in Deutschland (Teil I).

To achieve high response rates in German epidemiological studies is growing more difficult. Low response in epidemiological studies may decrease the acceptance of the results. Response, however, is not identical with the quality of a study. In the first part of this paper various definitions of response (contact, cooperation, response, recruitment proportions) are introduced and discussed in the context of different study designs with reference to practical examples. A population-based survey such as the Study of Health in Pomerania (SHIP) investigates the distribution of risk factors and health-related endpoints. Surveys should yield representative results which can be generalised to apply to the entire population (external validity). This study design usually requires large participitation proportions. In a prospective cohort study such as the European Investigation into Cancer and Nutrition (EPIC) the emphasis is on internal validity. A stable study population willing to participate in regular follow-ups is a primary recruitment goal. If the response in a case-control study such as the Northern Germany Leukaemia and Lymphoma Study (NLL) is low, the priority is to achieve approximately equal response proportions for cases and controls. Simultaneous public relation and media activities can improve participitation in a study. Multidimensional strategies combining public communications, cooperation with local and regional officials and frequent press and media coverage are emphasised. The second part of this paper will discuss methods to quantify the effects of the response proportions on the validity of the study results.

[Biological markers in epidemiology: concepts, applications, perspectives (part I)]. / Biologische Marker in der Epidemiologie: Begriffe, Anwendungen, Perspektiven (Teil I).

The inclusion of biomarkers in epidemiological research provides new possibilities for exposure assessment and the study of early structural or functional changes and pre-clinical stages of diseases. At the same time issues of validity, reliability, and quality control as well as logistics require special attention. Usually epidemiological studies become more expensive with regard to time and cost. Interdisciplinary collaboration between epidemiology, basic research, and laboratory research is crucial. A prerequisite for this collaboration are agreements on definitions, methods and procedures. The definition of "biomarker" and a description of previous uses of biomarkers in epidemiological studies are presented in the first part of this paper. The second part addresses genetic markers and markers of individual sensitivity and susceptibility. We will end with a discussion about the possible future of biomarkers in epidemiology.

[Biological Markers in Epidemiology: Concepts, applications, Perspectives (Part II)]. / Biologische Marker in der Epidemiologie: Begriffe, Anwendungen, Perspektiven (Teil II).

The first part of this paper outlined terms and definitions in the context of the application of biological markers in epidemiological studies. Cardiovascular epidemiology served as an example for their historical development. The second part focusses on DNA-based biomarkers, practical and methodological dimensions of the use of biomarkers in analytic epidemiological studies as well as requirements in respect of validity and quality assurance. Most genetic polymorphisms have no impact on health. However, some can be used as biomarkers for individual sensitvity to exposures and susceptibility for specific diseases. The Human Genome Project has brought about a quantum leap in the development of genetic markers. The practical implications cannot presently be assessed with certainty. However, present and future research programmes of gene-environment interactions depend on "traditional" epidemiological study designs, methods, and concepts. Ethical principles and data protection requirements apply equally to genetic and molecular epidemiology as do the "Guidelines for Good Epidemiological Practice".