W 507 Epidemiology Epidemiology Scientific process that attempts

W 507 – Epidemiology

Epidemiology • Scientific process that attempts to link exposure to hazardous substances to specific health effects. • Statistical correlations developed to indicate degree of risk associated with a particular exposure pattern • Epidemiological studies tend to be complex and outside the remit of most industrial hygienists • However, important to understand the principles of epidemiology

Epidemiology • Much information is derived from animal tests, in-vitro tests and comparison with similar chemicals • However, to establish actual risks in a population an epidemiological study is often the only valid technique • Aim is to establish a link between exposure and development of disease or ill-health e. g. • Angiosarcoma of the liver and exposure to vinyl chloride monomer • Mesothelioma of the lung pleura and exposure to asbestos • However, clear evidence may not be available and many studies have limitations and deficiencies • Historical data may be unclear or not valid • Potential problems of bias or other confounding factors in selection or monitoring of groups under study

Epidemiological terms • Incidence rates • Number of new cases of ill-health or disease that occur in a population in a period of time • Commonly expressed in number of new cases per 1000 people in group under study per year • Prevalence rates • Total number of cases of ill-health or disease that exist in the population at a particular point in time • Affected by incidence of new cases but also the duration of the effects • Findings may be expressed in terms of morbidity (number of cases of illness) or of mortality (death) rates

Measures of frequency • Incidence and prevalence rates need to be compared to a reference (or control) group or population • Incidence and prevalence rates can be expressed as a ratio or ‘Standardised Mortality Ratio’ (SMR) compared to reference group • If no difference between study and reference group the SMR would be 1 • If greater incidence or prevalence rate in study group compared to reference group the SMR would be greater than 1 • (Note: some texts quote SMR’s as percentage of expected numbers of deaths or events – i. e. if no difference SMR would be 100)

Measures of frequency • Major potential difficulty is identifying a suitable reference population which must be matched to the study group in all aspects except exposure to the substance. • Potential areas of difference include • Age distribution • General health levels • e. g. working population tends to be more healthy than the general population as this includes people unable to work due to ill-health

Causation or association • Important to differentiate between causation and association • Study may show a link (association) between exposure to a substance and a health effect • This does not necessarily mean there is a direct causal link • The association may be spurious or it may be indirect through other known or unknown variables • A number of criteria have been developed (Bradford-Hill criteria) that can be examined to provide support for a causal link

Bradford-Hill Criteria • • • Strength of association Temporality Consistency Biological plausibility Coherence Specificity Dose-response relationship Experimental evidence Analogy

Bradford-Hill Criteria • None of the nine criteria provide indisputable evidence for or against a cause and effect hypothesis • Rarely will all nine points be present – however the more that are, the stronger the association • They can to a greater or lesser extent support or refute the hypothesis • Quality of study should also be assessed • Those with appropriate statistical analysis and those published in peer-reviewed journals carry more weight • Claims of causation should not be made lightly as poorly justified claims can be very misleading

Causation or association – smoking and lung cancer • Strength of association • Lung cancer rates far higher for smokers than non-smokers • Temporality • Smoking precedes onset of disease • Consistency • Different types of studies produce the same result • Biological plausibility • Theory that smoking causes tissue damage that over time could cause cancer is highly plausible • Coherence • Theory ‘makes sense’ given current knowledge

Causation or association – smoking and lung cancer • Specificity • Lung cancer is predicted by incidence of smoking • Dose-response relationship • Data showed linear relationship between amount smoked and incidence • Experimental evidence • Animal experiments using tobacco tar produced cancer in tissue • Analogy • Induced smoking in animal experiments showed increased lung cancer

Bias All epidemiological studies are subject to bias: • Selection bias in study group or control group • Information bias related to the quality and accuracy of data gathered as well as errors by the interviewer or interviewee • Confounding factors influence both the exposure and the outcome and therefore may show a spurious link Many of these factors can be controlled at the planning stage of the study

Statistical significance • It is important to determine whether the apparent link between exposure and outcome is statistically significant i. e. unlikely to have occurred by chance • Most studies define statistically significant as 95% or better confidence that the results were not due to chance – i. e. less than 5% (1 in 20) probability the association was by chance • Sometimes written as a probability of ‘p <0. 05’ • Lower the probability or significance the stronger the evidence • Establishing statistical significance is important but is not in itself enough to confirm causality. At this stage criteria developed by Bradford-Hill need to be examined

Types of epidemiological studies • Longitudinal studies • Follow a group of people over period of time with repeated observations of risk factors and health effects • Vary widely in size and duration (even decades) • Two common types of longitudinal study are cohort and case-control studies • Cross-sectional studies

Longitudinal studies • Case-control studies • Used to identify factors that may have caused a particular effect or illness • Tend to be retrospective • Study a group (the ‘cases’) who have the effect or illness and compare with another group who do not have the effect or illness (the ‘controls’) • Gather information on past exposure to the factor or substance – often difficult to get accurate data • Often difficult to avoid possible confounding factors when choosing the control group • Usually not the most robust type of study but often used to identify exposure / disease relationships that can then be investigated more fully

Longitudinal studies • Cohort studies • Tend to be prospective • Gathers data over period of time on the incidence of the effect • Study a group of people who are exposed to a particular substance • Cohort group identified before appearance of the effect • Control group identified either from the general population or from another similar cohort who have had little or no exposure to the substance in question • Potentially the most robust type of study • Tend to take a long time to complete and as such can be complex and expensive

Cross-sectional studies • Involves observation of a group of people at a particular moment in time • Can be considered as a ‘snap-shot’ of the prevalence of the effect • Group compared with a similar matched control group • Relatively quick and inexpensive • However, study only deals with a particular moment in time and cannot give information on exposure and outcome as a time dependant relationship • Not suited to an effect that is uncommon

W 507 – Epidemiology case study

Epidemiology case study • Concerns have been raised that a number of people working at a plant producing orthotoluidine have developed bladder cancer over the last few years • What information would you initially require if you were investigating the above?

Initial information required • Other chemicals used • Are all workers exposed to the ortho-toluidine – or just some groups? • What levels of exposure have occurred to ortho-toluidine? • Number of people working at the plant • Number of cases of bladder cancer • When were the cases of bladder cancer first noted? • When was ortho-toluidine first used? • What problems may there be in obtaining accurate information?

Epidemiological case study • What type of epidemiological study would you suggest for this scenario? • To evaluate whethere is an increased risk of bladder cancer a reference or control group is needed • Who would you select for this reference group?

Epidemiological case study • What sources would you use to gather information about exposure levels and occurrence of bladder cancer for the case and reference groups? • What problems may there be in getting accurate information?

Epidemiological case study • 13 cases of bladder cancer out of 1749 people who worked at plant • Expected number of cases of bladder cancer in the general population – 2. 1 per 1000 • What is the SMR (standardised mortality ratio)?

Epidemiological case study • Is this SMR (3. 5) significant or simply a random or chance occurrence? • Statistical analysis required • 95% confidence limits of SMR found to be 1. 8 – 6. 2 • Does this prove a causal link?

Epidemiological case study • What possible confounding factors may need to be considered when designing the study? • Other chemicals used • Smoking habits • Age distribution of case and reference groups

Epidemiological case study • Results of epidemiological study • See tables 1 to 3 • Animal studies show increased rates of cancer in both mice and rats • Ortho-toluidine is similar chemical structure to other aromatic amines which have shown an increased risk of bladder cancer • Use Bradford-Hill criteria to assess whethere is a causal link

Epidemiological case study • Bradford-Hill criteria • • • Strength of association Temporality Consistency Biological plausibility Coherence Specificity Dose-response relationship Experimental evidence Analogy