1. Epidemiologic Study Designs Chapter 4

2. Learning Objectives Define the general meaning of “study design” Distinguish descriptive from analytic study designs Discuss the rationale, strengths, and weaknesses of the various study designs Distinguish observational from experimental studies Define internal and external validity Identify the six primary activities and three types of meta-analysis

3. Study Designs At the heart of an investigation of any environmental health problem is the research or study design. A study design is the program that directs the researcher along the path of systematically collecting, analyzing and interpreting results It allows for descriptive assessment of events and for statistical inference concerning relationships between exposure and disease and defines the domain for generalizing the results Study designs in epidemiology are either implicit or explicit

4. Descriptive Study Designs Descriptive study designs focus on assessing a sample without making inferences or causal statements. A descriptive study assists us in : 1) providing information about a disease or condition 2) providing clues to identify a new disease or adverse health effect 3)identifying the extent of the public health problem 4) obtaining a description of the public health problem that can be easily communicated 5) identifying the population at greatest risk 6) assisting in planning resource allocation 7) identifying avenues for future research that can provide insights about an etiologic relationship between an exposure and outcome

5. Epidemiologic descriptive study designs

7. Case Study The aim of a case study is to provide a complete understanding of a problem or situation It includes describing the characteristics of a person or group of people, the setting or community (cultural norms, community values, motives, etc.), the circumstance, and the problem Case studies are useful for obtaining an in-depth understanding of how and why questions The Centers for Disease Control and Prevention defines “cluster” as “an unusual aggregation, real or perceived of health events that are grouped together in time and space and that are reported to a health agency”

8. Epidemiologic evaluations of clusters have resulted in many triumphs in infectious and noninfectious disease control Well-known examples: The investigation of cases of pneumonia at the Bellevue-Stratford Hotel in Philadelphia in 1976 The 1981 report that seven cases of Pneumocysticcarinii pneumonia had occurred among young homosexual men in Los Angeles Angiosarcomea among vinyl chloride workers Neurotoxicity and infertility in kepone workers Dermatitis and skin cancer in persons wearing radioactively contaminated gold rings Adenocarcinoma of the vagina and maternal consumption of diethylstilbestrol Phocomelia and consumption of thalidomide Salmonella meningitis in children Under one year of age in Taiwan

9. Cross-sectional Study A cross-sectional study involves simultaneous measurement of exposure and outcome factors at a specific point in time for a defined group of individuals. Cross-sectional studies may be thought of as a “snapshot” of at the frequency and characteristics of exposure and outcome factors in a group at a specific point in time Cross-sectional studies provides data that reflect the prevalence of an exposure or outcome in a selected group

10. Ecologic Study An ecologic study involves making comparisons between populations Ecologic studies are often appropriate in environmental settings. Ex. Injuries are often associated with characteristics in the environment and may best be controlled be group-focused rather than efforts to change individual behaviors. In talking about an ecologic study, it is important to have an understanding of the concepts and rationale underlying this type of study.

11. Ecologic measures into three types: Aggregate measures-summaries of observations based on individual with a Environmental measures-physical characteristics of a place such as a home or work site for members of a group. Often individual exposure (or dose) levels remain unmeasured. Global measures-attributes of groups for which no analogue at the individual level exists

12. Type of ecologic analysis performed depends on whether the unit of analysis variables in the study is on the individual level or group level. If data are collected on the individual level, a value for each variable is measured for every person in the study. If collected on the ecologic level, a value for each variable is measured for the group in the study

13. Research may involve completely ecologic analysis, partially ecologic analysis, or multi-level analysis: Completely ecologic analysis-the units of analysis on all variables are ecologic measures, such as the proportion exposed, the rate of injury, or the rate of disease. The association may be made at the county level Partially ecologic analysis-a combination of individual-and group level data in the analysis. For example, infant birth weight may be associated with environmental exposure to biogas from a landfill. Multilevel analysis- a modeling technique that combines information at two or more levels. For example, an individual-level analysis within each group could be performed.

14. In an analytic ecologic study, the ecologic association is assessed between the aggregate exposure level and the rate of the injury/disease for many groups The steps goes through to conduct an analytic ecologic study: 1. Develop a hypothesis regarding exposure and outcome 2. Define and select the ecologic units to be compared 3. Obtain summary measures of exposure and outcome 4. Plot the data for each ecologic unit of a graph 5. Determine if the hypothesized relationship exists

15. Time-trend designs can also be classified as exploratory or analytic (or time series), a comparison of injury/disease rates over it is made for a population in a single geographic area Age-period-cohort analysis is a special type of exploratory time-trend analysis. In an analytic time-trend analysis, the ecologic association between average exposure and change and disease rate change is made for a population in a single geographic area

16. Analytic Study Designs Analytic study designs are distinct from descriptive study designs I that they utilize a comparison group that has been explicitly collected Analytic study designs in environmental epidemiology are based on the comparison of individuals who are classified according to exposure and injury/disease status. The unit of analysis is the individual Analytic study designs fit into two general categories, observational and experimental In observational studies, researchers evaluate the strength of the relationship between an exposure and health-related state or event

17. In experimental studies some of the participants in the study are deliberately manipulated for the purpose of studying an intervention effect If the intervention being assessed is an environmental exposure being investigated for its adverse health effects, clearly it would be unethical to assign the intervention Most environmental investigations include both descriptive and analytic studies The descriptive study describes distributions of health-related states and events in the population The analytic study examines associations with the ultimate goal to establish cause-effect relationships Experimental studies typically come last because of their comparatively high cost, difficulty in execution, and narrow focus

18. Epidemiologic analytic study designs

20. Experimental Study The randomized blinded controlled experimental study is considered to be the “gold standard” in epidemiology because it is an effective design for controlling confounding and bias Randomization of sufficiently large numbers creates a situation where confounding by unmeasured variables is equally likely between groups Blinding the intervention eliminates unintended interventions Blinding the outcome eliminates the ascertainment bias The strongest design is a between-group design where outcomes are compared between two or more groups of people receiving different levels of the intervention A within-group design may also be used where the outcome in a single group is compared before and after the assignment of an intervention The within-group design is susceptible to confounding from time-related factors such as climate-related conditions but may be adjusted for in the analysis Applying the experimental study design for assessing physical, chemical, biological, and psychosocial environments poses ethical challenges

21. Cohort Study In cohort studies, people are followed over time in order to describe the incidence or the natural history of a health outcome. As time passes, the number of potential health outcomes associated with a specific exposure increases Cohort studies are characterized by identifying exposure levels and then following over time, with the health outcome of interest assessed in the future Cohort studies are observational studies that have their unique strengths and weaknesses.

22. Cohort studies can be either prospective or retrospective. In a prospective cohort, the study begins by making measurements of exposure at baseline, following the cohort over time, and then measuring selected outcomes according to exposure status A retrospective cohort is the same as a prospective cohort except assembly of the exposure and outcome variables all happened in the past In other words, a historical cohort is reconstructed with data on the exposure variable, measured in the past, and data on the outcome variable, measured in the past after some follow-up period The strength of a prospective cohort design is that is provides better control over exposure and outcome measures than in a retrospective cohort

23. In environmental epidemiology it is often convenient to compare cohorts from two separate populations It is also convenient to compare the outcomes for people exposed to a potential risk factor at a work site or location with people in the general population

25. Case-Control Study In a case-control study, the presence of a potential risk factor is compared between those with and those without the health problem of interest. The study begins by identifying cases and controls and then investigating whether the cases were more likely to have been exposed than the controls A nested case-control study (case-cohort study) is a case-control study “nested” within a cohort study Levels of the risk factor are compared between cases and a sample of non-cases Yet to carry out a nested case-control study, samples or records of interest must be available from before the outcome condition occurred

27. Case-Crossover Design Case-crossover design involves comparing the exposure status of a case immediately before its occurrence with that of the same case at a prior time It is appropriate where individual exposures are intermittent, the disease occurs abruptly and the incubation period for detection is short, and the induction period is short Individuals serve as their own controls, with the analytic unit being time-where the time just before the acute event is the “case” time compared with some other time, referred to as the “control” time Assumes that there are no confounding time-related factors, or that they are adjusted for in the analysis A time-related factor-is also assumed not to be present

29. Case-crossover designs may also be used for injury research, but there are challenges 1st-occupational injuries often require selected conditions to occur Hence identifying the person-time at risk, may be a challenge, and only a subset of an individual’s person-time at risk may be a considered for the study 2nd-exposure information may not be available prospectively because most injuries are relatively rare, making prospective data collection inefficient in may settings Hence retrospective patient self-reporting of exposure may be necessary but it is prone to recall bias 3rd-identifying control periods may be a challenge that is similar to the time when the injury occurs, yet for which the exposure is uncorrelated

30. Observational versus Experimental Study The observational design involves the science and planning of how information will be assembled, described, and related. In an observational study, researchers observe events for individuals in the study without altering them. The experimental design involves the science and planning of how an experiment will be conducted in order to obtain valid and reliable results. In an experimental study, researchers evaluate the effects fo an assigned intervention on an outcome. If an observational study design is selected, several questions should be answered: Should the observation be taken at a point in time or should the same subjects be studied over time Should you begin with the outcome and then consider past events or begin with exposure and follow subjects forward in time to evaluate events that have not yet occurred

31. Observational studies are limited by confounding and bias, and basing causal inference on these studies is more difficult than with experimental studies Especially in environmental epidemiologic studies where the numbers are often small and the exposure is misclassified or poorly measured Cohort studies evaluating long-term exposure may be ethical once a physical, chemical, biological, or psychosocial environment has been identified When the exposure is identified and people are informed of the environmental contaminant, people will naturally leave the polluted area and the study of duration is no longer feasible

32. Casual inference is strongest when based on experimental studies, followed by cohort studies The prospective cohort study is better than the retrospective cohort study, the nested case-control study, or the case-crossover study because there is better control over exposure and outcome measures Casual inference based on cohort and case-control studies is stronger than when based on cross-sectional or ecological studies because a comparison (control) group is involved

33. Study Subjects The study subjects are persons that are the object of scientific investigation Selecting the study subjects involves two primary decisions 1st decision-involves deciding Defining the study population essentially involves identifying those individuals best for answering the research question 2nd decision involves how to obtain a sample of the population for descriptive and analytic evaluation

35. Validity The validity of an investigation is that component of accuracy reflecting the level of systematic error in the study. Two types of validity: external validity and internal validity. External validity refers to the extent the results of a study are relevant to people who are not part of the study (representatives) Internal validity is the extent the results of a study are not attributable to bias or confounding A high response rate to questionnaires, minimized information bias, and proper control of potential confounders is often determined when designing the study.

37. For example, incentives may ensure an adequate response rate, proper training may minimize interviewer bias, and information gathered on potential confounders at the time of data collection can allow for their adjustment in the analysis In environmental epidemiologic studies, samples of people selected for inclusion into the study are restricted by calendar time and geography Restriction by time, location, and other factors, as commonly done in environmental epidemiologic studies, minimizes the threat of confounding by these factors, thereby improving the internal validity of the study

38. Meta-Analysis It is the process or technique of synthesizing research results by using various statistical methods to retrieve, select, and combine results from previous separate but related studies Considered a more comprehensive or developed study because it is a systematic comparison of studies that results in the integration of several studies into one analysis. While a review summarizes similar studies, meat-analysis combines similar studies to analyze the aggregated information in order to identify consistency of studies,

39. Meta-analysis is also used to aggregate subsets of studies, such as information based on age or sex. A meta-analysis of subsets is less successful in establishing causal relationships because meta-analysis does not allow the selection of subsets to be randomized. Meta-analysis of subsets does provide information in moderator variables Moderator variable can be thought of as a thrid factor that influences the direction or magnitude of a causal association between an exposure and outcome

40. For a meta-analysis to establish a causal relationship depends on both the research designs of each primary study and on the 6 methods of meta-analysis 1. Assessing evidence that a relationship or law, exists and that it is relatively non-artificial 2. Examining the form of a relationship 3. Analyzing the causal or key conceptual components of the independent variable and the key components of the dependent variable 4. Assessing the scope of a relationship 5. Analyzing the mediating processes that underlie a relationship 6. Developing a model that counts for the variance among study outcomes

41. Researchers use one or many of these methods to accomplish 3 main outcomes or types of meta-analysis: 1. Integration of individual studies that all examined a single empirical relation 2. Assessment of the generability of empirical relationships or associations 3. Examination of the effect of new theoretical concepts that had not been considered in the primary-level studies