Epidemiological studies
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Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and
determinants In mathematics, the determinant is a scalar value that is a function of the entries of a square matrix. It characterizes some properties of the matrix and the linear map represented by the matrix. In particular, the determinant is nonzero if and ...
of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidence-based practice by identifying risk factors for disease and targets for preventive healthcare. Epidemiologists help with study design, collection, and statistical analysis of data, amend interpretation and dissemination of results (including
peer review Peer review is the evaluation of work by one or more people with similar competencies as the producers of the work ( peers). It functions as a form of self-regulation by qualified members of a profession within the relevant field. Peer revie ...
and occasional systematic review). Epidemiology has helped develop methodology used in clinical research, public health studies, and, to a lesser extent,
basic research Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied rese ...
in the biological sciences. Major areas of epidemiological study include disease causation, transmission,
outbreak In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
investigation, disease surveillance, environmental epidemiology, forensic epidemiology,
occupational epidemiology Occupational epidemiology is a subdiscipline of epidemiology that focuses on investigations of workers and the workplace. Occupational epidemiologic studies examine health outcomes among workers, and their potential association with conditions in ...
, screening,
biomonitoring In analytical chemistry, biomonitoring is the measurement of the body burden of toxic chemical compounds, elements, or their metabolites, in biological substances. Often, these measurements are done in blood and urine. Biomonitoring is performed ...
, and comparisons of treatment effects such as in clinical trials. Epidemiologists rely on other scientific disciplines like
biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...
to better understand disease processes, statistics to make efficient use of the data and draw appropriate conclusions,
social science Social science is one of the branches of science, devoted to the study of societies and the relationships among individuals within those societies. The term was formerly used to refer to the field of sociology, the original "science of so ...
s to better understand proximate and distal causes, and
engineering Engineering is the use of scientific principles to design and build machines, structures, and other items, including bridges, tunnels, roads, vehicles, and buildings. The discipline of engineering encompasses a broad range of more speciali ...
for exposure assessment. ''Epidemiology'', literally meaning "the study of what is upon the people", is derived , suggesting that it applies only to human populations. However, the term is widely used in studies of zoological populations (veterinary epidemiology), although the term " epizoology" is available, and it has also been applied to studies of plant populations (botanical or plant disease epidemiology). The distinction between "epidemic" and "endemic" was first drawn by
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...
, to distinguish between diseases that are "visited upon" a population (epidemic) from those that "reside within" a population (endemic).Carol Buck, Alvaro Llopis; Enrique Nájera; Milton Terris (1998) ''The Challenge of Epidemiology: Issues and Selected Readings''. Scientific Publication No. 505. Pan American Health Organization. Washington, DC. p. 3. The term "epidemiology" appears to have first been used to describe the study of epidemics in 1802 by the Spanish physician Villalba in ''Epidemiología Española''. Epidemiologists also study the interaction of diseases in a population, a condition known as a syndemic. The term epidemiology is now widely applied to cover the description and causation of not only epidemic, infectious disease, but of disease in general, including related conditions. Some examples of topics examined through epidemiology include as high blood pressure, mental illness and
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
. Therefore, this epidemiology is based upon how the pattern of the disease causes change in the function of human beings.


History

The Greek physician
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...
, known as the father of
medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...
, sought a logic to sickness; he is the first person known to have examined the relationships between the occurrence of disease and environmental influences. Hippocrates believed sickness of the human body to be caused by an imbalance of the four humors (black bile, yellow bile, blood, and phlegm). The cure to the sickness was to remove or add the humor in question to balance the body. This belief led to the application of bloodletting and dieting in medicine.Merril, Ray M., PhD, MPH. (2010): ''An Introduction to Epidemiology'', Fifth Edition. Chapter 2: "Historic Developments in Epidemiology". Jones and Bartlett Publishing He coined the terms ''endemic'' (for diseases usually found in some places but not in others) and '' epidemic'' (for diseases that are seen at some times but not others).


Modern era

In the middle of the 16th century, a doctor from Verona named Girolamo Fracastoro was the first to propose a theory that these very small, unseeable, particles that cause disease were alive. They were considered to be able to spread by air, multiply by themselves and to be destroyable by fire. In this way he refuted
Galen Aelius Galenus or Claudius Galenus ( el, Κλαύδιος Γαληνός; September 129 – c. AD 216), often Anglicized as Galen () or Galen of Pergamon, was a Greek physician, surgeon and philosopher in the Roman Empire. Considered to be one ...
's miasma theory (poison gas in sick people). In 1543 he wrote a book '' De contagione et contagiosis morbis'', in which he was the first to promote personal and environmental
hygiene Hygiene is a series of practices performed to preserve health. According to the World Health Organization (WHO), "Hygiene refers to conditions and practices that help to maintain health and prevent the spread of diseases." Personal hygiene refer ...
to prevent disease. The development of a sufficiently powerful microscope by Antonie van Leeuwenhoek in 1675 provided visual evidence of living particles consistent with a germ theory of disease. During the
Ming Dynasty The Ming dynasty (), officially the Great Ming, was an imperial dynasty of China, ruling from 1368 to 1644 following the collapse of the Mongol-led Yuan dynasty. The Ming dynasty was the last orthodox dynasty of China ruled by the Han peo ...
, Wu Youke (1582–1652) developed the idea that some diseases were caused by transmissible agents, which he called ''Li Qi'' (戾气 or pestilential factors) when he observed various epidemics rage around him between 1641 and 1644. His book ''Wen Yi Lun'' (瘟疫论,Treatise on Pestilence/Treatise of Epidemic Diseases) can be regarded as the main etiological work that brought forward the concept. His concepts were still being considered in analysing SARS outbreak by WHO in 2004 in the context of traditional Chinese medicine. Another pioneer,
Thomas Sydenham Thomas Sydenham (10 September 1624 – 29 December 1689) was an English physician. He was the author of ''Observationes Medicae'' which became a standard textbook of medicine for two centuries so that he became known as 'The English Hippocrate ...
(1624–1689), was the first to distinguish the fevers of Londoners in the later 1600s. His theories on cures of fevers met with much resistance from traditional physicians at the time. He was not able to find the initial cause of the smallpox fever he researched and treated.
John Graunt John Graunt (24 April 1620 – 18 April 1674) has been regarded as the founder of demography. Graunt was one of the first demographers, and perhaps the first epidemiologist, though by profession he was a haberdasher. He was bankrupted later in li ...
, a haberdasher and amateur statistician, published ''Natural and Political Observations ... upon the Bills of Mortality'' in 1662. In it, he analysed the mortality rolls in
London London is the capital and List of urban areas in the United Kingdom, largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary dow ...
before the
Great Plague The Black Death (also known as the Pestilence, the Great Mortality or the Plague) was a bubonic plague pandemic occurring in Western Eurasia and North Africa from 1346 to 1353. It is the most fatal pandemic recorded in human history, causi ...
, presented one of the first
life tables In actuarial science and demography, a life table (also called a mortality table or actuarial table) is a table which shows, for each age, what the probability is that a person of that age will die before their next birthday ("probability of deat ...
, and reported time trends for many diseases, new and old. He provided statistical evidence for many theories on disease, and also refuted some widespread ideas on them. John Snow is famous for his investigations into the causes of the 19th-century cholera epidemics, and is also known as the father of (modern) epidemiology. He began with noticing the significantly higher death rates in two areas supplied by Southwark Company. His identification of the Broad Street pump as the cause of the Soho epidemic is considered the classic example of epidemiology. Snow used chlorine in an attempt to clean the water and removed the handle; this ended the outbreak. This has been perceived as a major event in the history of public health and regarded as the founding event of the science of epidemiology, having helped shape public health policies around the world. However, Snow's research and preventive measures to avoid further outbreaks were not fully accepted or put into practice until after his death due to the prevailing Miasma Theory of the time, a model of disease in which poor air quality was blamed for illness. This was used to rationalize high rates of infection in impoverished areas instead of addressing the underlying issues of poor nutrition and sanitation, and was proven false by his work. Other pioneers include Danish physician Peter Anton Schleisner, who in 1849 related his work on the prevention of the epidemic of neonatal tetanus on the
Vestmanna Islands Vestmannaeyjar (, sometimes anglicized as Westman Islands) is a municipality and archipelago off the south coast of Iceland. The largest island, Heimaey, has a population of 4,414, most of whom live in the archipelago's main town, Vestmannaeyj ...
in
Iceland Iceland ( is, Ísland; ) is a Nordic island country in the North Atlantic Ocean and in the Arctic Ocean. Iceland is the most sparsely populated country in Europe. Iceland's capital and largest city is Reykjavík, which (along with its s ...
. Another important pioneer was Hungarian physician
Ignaz Semmelweis Ignaz Philipp Semmelweis (; hu, Semmelweis Ignác Fülöp ; 1 July 1818 – 13 August 1865) was a Hungarian physician and scientist, who was an early pioneer of antiseptic procedures. Described as the "saviour of mothers", he discovered that t ...
, who in 1847 brought down infant mortality at a Vienna hospital by instituting a disinfection procedure. His findings were published in 1850, but his work was ill-received by his colleagues, who discontinued the procedure. Disinfection did not become widely practiced until British surgeon Joseph Lister 'discovered'
antiseptics An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...
in 1865 in light of the work of Louis Pasteur. In the early 20th century, mathematical methods were introduced into epidemiology by
Ronald Ross Sir Ronald Ross (13 May 1857 – 16 September 1932) was a British medical doctor who received the Nobel Prize for Physiology or Medicine in 1902 for his work on the transmission of malaria, becoming the first British Nobel laureate, and the ...
, Janet Lane-Claypon,
Anderson Gray McKendrick Lt Col Anderson Gray McKendrick DSc FRSE (8 September 1876 – 30 May 1943) was a Scottish military physician and epidemiologist who pioneered the use of mathematical methods in epidemiology. Irwin (see below) commented on the quality of his wo ...
, and others. In a parallel development during the 1920s, German-Swiss pathologist
Max Askanazy Max Askanazy (24 February 1865, Stallupönen, East Prussia – 23 October 1940, Geneva, Switzerland) was a German-Swiss pathologist. In 1890 he received his medical doctorate from the University of Königsberg, where he worked for several years ...
and others founded the International Society for Geographical Pathology to systematically investigate the geographical pathology of cancer and other non-infectious diseases across populations in different regions. After World War II,
Richard Doll Sir William Richard Shaboe Doll (28 October 1912 – 24 July 2005) was a British physician who became an epidemiologist in the mid-20th century and made important contributions to that discipline. He was a pioneer in research linking smoking ...
and other non-pathologists joined the field and advanced methods to study cancer, a disease with patterns and mode of occurrences that could not be suitably studied with the methods developed for epidemics of infectious diseases. Geography pathology eventually combined with infectious disease epidemiology to make the field that is epidemiology today. Another breakthrough was the 1954 publication of the results of a British Doctors Study, led by
Richard Doll Sir William Richard Shaboe Doll (28 October 1912 – 24 July 2005) was a British physician who became an epidemiologist in the mid-20th century and made important contributions to that discipline. He was a pioneer in research linking smoking ...
and
Austin Bradford Hill Sir Austin Bradford Hill (8 July 1897 – 18 April 1991) was an English epidemiologist and statistician, pioneered the randomised clinical trial and, together with Richard Doll, demonstrated the connection between cigarette smoking and lung ...
, which lent very strong statistical support to the link between tobacco smoking and
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...
. In the late 20th century, with the advancement of biomedical sciences, a number of molecular markers in blood, other biospecimens and environment were identified as predictors of development or risk of a certain disease. Epidemiology research to examine the relationship between these
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
s analyzed at the molecular level and disease was broadly named "
molecular epidemiology Molecular epidemiology is a branch of epidemiology and medical science that focuses on the contribution of potential genetic and environmental risk factors, identified at the molecular level, to the etiology, distribution and prevention of disease ...
". Specifically, " genetic epidemiology" has been used for epidemiology of germline genetic variation and disease. Genetic variation is typically determined using DNA from peripheral blood leukocytes.


21st century

Since the 2000s,
genome-wide association studies In genomics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an observational study of a genome-wide set of genetic variants in different individuals to see if any varian ...
(GWAS) have been commonly performed to identify genetic risk factors for many diseases and health conditions. While most molecular epidemiology studies are still using conventional disease diagnosis and classification systems, it is increasingly recognized that disease progression represents inherently heterogeneous processes differing from person to person. Conceptually, each individual has a unique disease process different from any other individual ("the unique disease principle"), considering uniqueness of the exposome (a totality of endogenous and exogenous / environmental exposures) and its unique influence on molecular pathologic process in each individual. Studies to examine the relationship between an exposure and molecular pathologic signature of disease (particularly
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
) became increasingly common throughout the 2000s. However, the use of molecular pathology in epidemiology posed unique challenges, including lack of research guidelines and standardized statistical methodologies, and paucity of interdisciplinary experts and training programs. Furthermore, the concept of disease heterogeneity appears to conflict with the long-standing premise in epidemiology that individuals with the same disease name have similar etiologies and disease processes. To resolve these issues and advance population health science in the era of molecular
precision medicine Precision, precise or precisely may refer to: Science, and technology, and mathematics Mathematics and computing (general) * Accuracy and precision, measurement deviation from true value and its scatter * Significant figures, the number of digi ...
, "molecular pathology" and "epidemiology" was integrated to create a new interdisciplinary field of " molecular pathological epidemiology" (MPE), defined as "epidemiology of molecular pathology and heterogeneity of disease". In MPE, investigators analyze the relationships between (A) environmental, dietary, lifestyle and genetic factors; (B) alterations in cellular or extracellular molecules; and (C) evolution and progression of disease. A better understanding of heterogeneity of disease
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
will further contribute to elucidate
etiologies Cause, also known as etiology () and aetiology, is the reason or origination of something. The word ''etiology'' is derived from the Greek , ''aitiologia'', "giving a reason for" (, ''aitia'', "cause"; and , ''-logia''). Description In medicine, ...
of disease. The MPE approach can be applied to not only neoplastic diseases but also non-neoplastic diseases. The concept and paradigm of MPE have become widespread in the 2010s. By 2012, it was recognized that many pathogens' evolution is rapid enough to be highly relevant to epidemiology, and that therefore much could be gained from an interdisciplinary approach to infectious disease integrating epidemiology and molecular evolution to "inform control strategies, or even patient treatment." Modern epidemiological studies can use advanced statistics and
machine learning Machine learning (ML) is a field of inquiry devoted to understanding and building methods that 'learn', that is, methods that leverage data to improve performance on some set of tasks. It is seen as a part of artificial intelligence. Machine ...
to create predictive models as well as to define treatment effects.


Types of studies

Epidemiologists employ a range of study designs from the observational to experimental and generally categorized as descriptive (involving the assessment of data covering time, place, and person), analytic (aiming to further examine known associations or hypothesized relationships), and experimental (a term often equated with clinical or community trials of treatments and other interventions). In observational studies, nature is allowed to "take its course", as epidemiologists observe from the sidelines. Conversely, in experimental studies, the epidemiologist is the one in control of all of the factors entering a certain case study."Principles of Epidemiology." Key Concepts in Public Health. London: Sage UK, 2009. Credo Reference. 1 August 2011. Web. 30 September 2012. Epidemiological studies are aimed, where possible, at revealing unbiased relationships between exposures such as alcohol or smoking, biological agents,
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
, or
chemicals A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wit ...
to mortality or
morbidity A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
. The identification of causal relationships between these exposures and outcomes is an important aspect of epidemiology. Modern epidemiologists use informatics as a tool. Observational studies have two components, descriptive and analytical. Descriptive observations pertain to the "who, what, where and when of health-related state occurrence". However, analytical observations deal more with the 'how' of a health-related event.
Experimental epidemiology An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a ...
contains three case types: randomized controlled trials (often used for a new medicine or drug testing), field trials (conducted on those at a high risk of contracting a disease), and community trials (research on social originating diseases). The term 'epidemiologic triad' is used to describe the intersection of ''Host'', ''Agent'', and ''Environment'' in analyzing an outbreak.


Case series

Case-series may refer to the qualitative study of the experience of a single patient, or small group of patients with a similar diagnosis, or to a statistical factor with the potential to produce illness with periods when they are unexposed. The former type of study is purely descriptive and cannot be used to make inferences about the general population of patients with that disease. These types of studies, in which an astute clinician identifies an unusual feature of a disease or a patient's history, may lead to a formulation of a new hypothesis. Using the data from the series, analytic studies could be done to investigate possible causal factors. These can include case-control studies or prospective studies. A case-control study would involve matching comparable controls without the disease to the cases in the series. A prospective study would involve following the case series over time to evaluate the disease's natural history. The latter type, more formally described as self-controlled case-series studies, divide individual patient follow-up time into exposed and unexposed periods and use fixed-effects Poisson regression processes to compare the incidence rate of a given outcome between exposed and unexposed periods. This technique has been extensively used in the study of adverse reactions to vaccination and has been shown in some circumstances to provide statistical power comparable to that available in cohort studies.


Case-control studies

Case-control studies select subjects based on their disease status. It is a retrospective study. A group of individuals that are disease positive (the "case" group) is compared with a group of disease negative individuals (the "control" group). The control group should ideally come from the same population that gave rise to the cases. The case-control study looks back through time at potential exposures that both groups (cases and controls) may have encountered. A 2×2 table is constructed, displaying exposed cases (A), exposed controls (B), unexposed cases (C) and unexposed controls (D). The statistic generated to measure association is the
odds ratio An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
(OR), which is the ratio of the odds of exposure in the cases (A/C) to the odds of exposure in the controls (B/D), i.e. OR = (AD/BC). If the OR is significantly greater than 1, then the conclusion is "those with the disease are more likely to have been exposed," whereas if it is close to 1 then the exposure and disease are not likely associated. If the OR is far less than one, then this suggests that the exposure is a protective factor in the causation of the disease. Case-control studies are usually faster and more cost-effective than
cohort studies A cohort study is a particular form of longitudinal study that samples a cohort (a group of people who share a defining characteristic, typically those who experienced a common event in a selected period, such as birth or graduation), performing ...
but are sensitive to bias (such as
recall bias Recall may refer to: * Recall (bugle call), a signal to stop * Recall (information retrieval), a statistical measure * ''ReCALL'' (journal), an academic journal about computer-assisted language learning * Recall (memory) * ''Recall'' (Overwatc ...
and selection bias). The main challenge is to identify the appropriate control group; the distribution of exposure among the control group should be representative of the distribution in the population that gave rise to the cases. This can be achieved by drawing a random sample from the original population at risk. This has as a consequence that the control group can contain people with the disease under study when the disease has a high attack rate in a population. A major drawback for case control studies is that, in order to be considered to be statistically significant, the minimum number of cases required at the 95% confidence interval is related to the odds ratio by the equation: :\text = A+C = 1.96^2 (1+N) \left(\frac\right)^2 \left(\frac\right) \approx 15.5 (1+N) \left(\frac\right)^2 where N is the ratio of cases to controls. As the odds ratio approaches 1, the number of cases required for statistical significance grows towards infinity; rendering case-control studies all but useless for low odds ratios. For instance, for an odds ratio of 1.5 and cases = controls, the table shown above would look like this: For an odds ratio of 1.1:


Cohort studies

Cohort studies A cohort study is a particular form of longitudinal study that samples a cohort (a group of people who share a defining characteristic, typically those who experienced a common event in a selected period, such as birth or graduation), performing ...
select subjects based on their exposure status. The study subjects should be at risk of the outcome under investigation at the beginning of the cohort study; this usually means that they should be disease free when the cohort study starts. The cohort is followed through time to assess their later outcome status. An example of a cohort study would be the investigation of a cohort of smokers and non-smokers over time to estimate the incidence of lung cancer. The same 2×2 table is constructed as with the case control study. However, the point estimate generated is the relative risk (RR), which is the probability of disease for a person in the exposed group, ''P''e = ''A'' / (''A'' + ''B'') over the probability of disease for a person in the unexposed group, ''P''''u'' = ''C'' / (''C'' + ''D''), i.e. ''RR'' = ''P''e / ''P''u. As with the OR, a RR greater than 1 shows association, where the conclusion can be read "those with the exposure were more likely to develop the disease." Prospective studies have many benefits over case control studies. The RR is a more powerful effect measure than the OR, as the OR is just an estimation of the RR, since true incidence cannot be calculated in a case control study where subjects are selected based on disease status. Temporality can be established in a prospective study, and confounders are more easily controlled for. However, they are more costly, and there is a greater chance of losing subjects to follow-up based on the long time period over which the cohort is followed. Cohort studies also are limited by the same equation for number of cases as for cohort studies, but, if the base incidence rate in the study population is very low, the number of cases required is reduced by .


Causal inference

Although epidemiology is sometimes viewed as a collection of statistical tools used to elucidate the associations of exposures to health outcomes, a deeper understanding of this science is that of discovering ''causal'' relationships. " Correlation does not imply causation" is a common theme for much of the epidemiological literature. For epidemiologists, the key is in the term inference. Correlation, or at least association between two variables, is a necessary but not sufficient criterion for the inference that one variable causes the other. Epidemiologists use gathered data and a broad range of biomedical and psychosocial theories in an iterative way to generate or expand theory, to test hypotheses, and to make educated, informed assertions about which relationships are causal, and about exactly how they are causal. Epidemiologists emphasize that the "one cause – one effect" understanding is a simplistic mis-belief. Most outcomes, whether disease or death, are caused by a chain or web consisting of many component causes. Causes can be distinguished as necessary, sufficient or probabilistic conditions. If a necessary condition can be identified and controlled (e.g., antibodies to a disease agent, energy in an injury), the harmful outcome can be avoided (Robertson, 2015). One tool regularly used to conceptualize the multicausality associated with disease is the
causal pie model In the field of epidemiology, the causal mechanisms responsible for diseases A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to ...
.


Bradford Hill criteria

In 1965,
Austin Bradford Hill Sir Austin Bradford Hill (8 July 1897 – 18 April 1991) was an English epidemiologist and statistician, pioneered the randomised clinical trial and, together with Richard Doll, demonstrated the connection between cigarette smoking and lung ...
proposed a series of considerations to help assess evidence of causation, which have come to be commonly known as the " Bradford Hill criteria". In contrast to the explicit intentions of their author, Hill's considerations are now sometimes taught as a checklist to be implemented for assessing causality. Hill himself said "None of my nine viewpoints can bring indisputable evidence for or against the cause-and-effect hypothesis and none can be required ''sine qua non''." # Strength of Association: A small association does not mean that there is not a causal effect, though the larger the association, the more likely that it is causal. # Consistency of Data: Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect. # Specificity: Causation is likely if a very specific population at a specific site and disease with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship. # Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and expected effect, then the effect must occur after that delay). # Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence. # Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge). # Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such aboratoryevidence cannot nullify the epidemiological effect on associations". # Experiment: "Occasionally it is possible to appeal to experimental evidence". # Analogy: The effect of similar factors may be considered.


Legal interpretation

Epidemiological studies can only go to prove that an agent could have caused, but not that it did cause, an effect in any particular case: In United States law, epidemiology alone cannot prove that a causal association does not exist in general. Conversely, it can be (and is in some circumstances) taken by US courts, in an individual case, to justify an inference that a causal association does exist, based upon a balance of probability. The subdiscipline of forensic epidemiology is directed at the investigation of specific causation of disease or injury in individuals or groups of individuals in instances in which causation is disputed or is unclear, for presentation in legal settings.


Population-based health management

Epidemiological practice and the results of epidemiological analysis make a significant contribution to emerging population-based health management frameworks. Population-based health management encompasses the ability to: * Assess the health states and health needs of a target population; * Implement and evaluate interventions that are designed to improve the health of that population; and * Efficiently and effectively provide care for members of that population in a way that is consistent with the community's cultural, policy and health resource values. Modern population-based health management is complex, requiring a multiple set of skills (medical, political, technological, mathematical, etc.) of which epidemiological practice and analysis is a core component, that is unified with management science to provide efficient and effective health care and health guidance to a population. This task requires the forward-looking ability of modern risk management approaches that transform health risk factors, incidence, prevalence and mortality statistics (derived from epidemiological analysis) into management metrics that not only guide how a health system responds to current population health issues but also how a health system can be managed to better respond to future potential population health issues. Examples of organizations that use population-based health management that leverage the work and results of epidemiological practice include Canadian Strategy for Cancer Control, Health Canada Tobacco Control Programs, Rick Hansen Foundation, Canadian Tobacco Control Research Initiative. Each of these organizations uses a population-based health management framework called Life at Risk that combines epidemiological quantitative analysis with demographics, health agency operational research and economics to perform: * ''Population Life Impacts Simulations'': Measurement of the future potential impact of disease upon the population with respect to new disease cases, prevalence, premature death as well as potential years of life lost from disability and death; * ''Labour Force Life Impacts Simulations'': Measurement of the future potential impact of disease upon the labour force with respect to new disease cases, prevalence, premature death and potential years of life lost from disability and death; * ''Economic Impacts of Disease Simulations'': Measurement of the future potential impact of disease upon private sector disposable income impacts (wages, corporate profits, private health care costs) and public sector disposable income impacts (personal income tax, corporate income tax, consumption taxes, publicly funded health care costs).


Applied field epidemiology

Applied epidemiology is the practice of using epidemiological methods to protect or improve the health of a population. Applied field epidemiology can include investigating communicable and non-communicable disease outbreaks, mortality and morbidity rates, and nutritional status, among other indicators of health, with the purpose of communicating the results to those who can implement appropriate policies or disease control measures.


Humanitarian context

As the surveillance and reporting of diseases and other health factors become increasingly difficult in humanitarian crisis situations, the methodologies used to report the data are compromised. One study found that less than half (42.4%) of nutrition surveys sampled from humanitarian contexts correctly calculated the prevalence of malnutrition and only one-third (35.3%) of the surveys met the criteria for quality. Among the mortality surveys, only 3.2% met the criteria for quality. As nutritional status and mortality rates help indicate the severity of a crisis, the tracking and reporting of these health factors is crucial. Vital registries are usually the most effective ways to collect data, but in humanitarian contexts these registries can be non-existent, unreliable, or inaccessible. As such, mortality is often inaccurately measured using either prospective demographic surveillance or retrospective mortality surveys. Prospective demographic surveillance requires much manpower and is difficult to implement in a spread-out population. Retrospective mortality surveys are prone to selection and reporting biases. Other methods are being developed, but are not common practice yet.


Validity: precision and bias

Different fields in epidemiology have different levels of validity. One way to assess the validity of findings is the ratio of false-positives (claimed effects that are not correct) to false-negatives (studies which fail to support a true effect). To take the field of genetic epidemiology, candidate-gene studies produced over 100 false-positive findings for each false-negative. By contrast genome-wide association appear close to the reverse, with only one false positive for every 100 or more false-negatives. This ratio has improved over time in genetic epidemiology as the field has adopted stringent criteria. By contrast, other epidemiological fields have not required such rigorous reporting and are much less reliable as a result.


Random error

Random error is the result of fluctuations around a true value because of sampling variability. Random error is just that: random. It can occur during data collection, coding, transfer, or analysis. Examples of random errors include poorly worded questions, a misunderstanding in interpreting an individual answer from a particular respondent, or a typographical error during coding. Random error affects measurement in a transient, inconsistent manner and it is impossible to correct for random error. There is a random error in all sampling procedures. This is called
sampling error In statistics, sampling errors are incurred when the statistical characteristics of a population are estimated from a subset, or sample, of that population. Since the sample does not include all members of the population, statistics of the sample ( ...
. Precision in epidemiological variables is a measure of random error. Precision is also inversely related to random error, so that to reduce random error is to increase precision. Confidence intervals are computed to demonstrate the precision of relative risk estimates. The narrower the confidence interval, the more precise the relative risk estimate. There are two basic ways to reduce random error in an epidemiological study. The first is to increase the sample size of the study. In other words, add more subjects to your study. The second is to reduce the variability in measurement in the study. This might be accomplished by using a more precise measuring device or by increasing the number of measurements. Note, that if sample size or number of measurements are increased, or a more precise measuring tool is purchased, the costs of the study are usually increased. There is usually an uneasy balance between the need for adequate precision and the practical issue of study cost.


Systematic error

A systematic error or bias occurs when there is a difference between the true value (in the population) and the observed value (in the study) from any cause other than sampling variability. An example of systematic error is if, unknown to you, the
pulse oximeter Pulse oximetry is a noninvasive method for monitoring a person's oxygen saturation. Peripheral oxygen saturation (SpO2) readings are typically within 2% accuracy (within 4% accuracy in 95% of cases) of the more accurate (and invasive) reading o ...
you are using is set incorrectly and adds two points to the true value each time a measurement is taken. The measuring device could be precise but not accurate. Because the error happens in every instance, it is systematic. Conclusions you draw based on that data will still be incorrect. But the error can be reproduced in the future (e.g., by using the same mis-set instrument). A mistake in coding that affects ''all'' responses for that particular question is another example of a systematic error. The validity of a study is dependent on the degree of systematic error. Validity is usually separated into two components: * Internal validity is dependent on the amount of error in measurements, including exposure, disease, and the associations between these variables. Good internal validity implies a lack of error in measurement and suggests that inferences may be drawn at least as they pertain to the subjects under study. *
External validity External validity is the validity of applying the conclusions of a scientific study outside the context of that study. In other words, it is the extent to which the results of a study can be generalized to and across other situations, people, stim ...
pertains to the process of generalizing the findings of the study to the population from which the sample was drawn (or even beyond that population to a more universal statement). This requires an understanding of which conditions are relevant (or irrelevant) to the generalization. Internal validity is clearly a prerequisite for external validity.


Selection bias

Selection bias occurs when study subjects are selected or become part of the study as a result of a third, unmeasured variable which is associated with both the exposure and outcome of interest. For instance, it has repeatedly been noted that cigarette smokers and non smokers tend to differ in their study participation rates. (Sackett D cites the example of Seltzer et al., in which 85% of non smokers and 67% of smokers returned mailed questionnaires.)
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It is important to note that such a difference in response will not lead to bias if it is not also associated with a systematic difference in outcome between the two response groups.


Information bias

Information bias (epidemiology), Information bias is bias arising from systematic error in the assessment of a variable. An example of this is recall bias. A typical example is again provided by Sackett in his discussion of a study examining the effect of specific exposures on fetal health: "in questioning mothers whose recent pregnancies had ended in fetal death or malformation (cases) and a matched group of mothers whose pregnancies ended normally (controls) it was found that 28% of the former, but only 20% of the latter, reported exposure to drugs which could not be substantiated either in earlier prospective interviews or in other health records". In this example, recall bias probably occurred as a result of women who had had miscarriages having an apparent tendency to better recall and therefore report previous exposures.


Confounding

Confounding has traditionally been defined as bias arising from the co-occurrence or mixing of effects of extraneous factors, referred to as confounders, with the main effect(s) of interest. A more recent definition of confounding invokes the notion of ''counterfactual'' effects. According to this view, when one observes an outcome of interest, say Y=1 (as opposed to Y=0), in a given population A which is entirely exposed (i.e. exposure ''X'' = 1 for every unit of the population) the risk of this event will be ''R''A1. The counterfactual or unobserved risk ''R''A0 corresponds to the risk which would have been observed if these same individuals had been unexposed (i.e. ''X'' = 0 for every unit of the population). The true effect of exposure therefore is: ''R''A1 − ''R''A0 (if one is interested in risk differences) or ''R''A1/''R''A0 (if one is interested in relative risk). Since the counterfactual risk ''R''A0 is unobservable we approximate it using a second population B and we actually measure the following relations: ''R''A1 − ''R''B0 or ''R''A1/''R''B0. In this situation, confounding occurs when ''R''A0 ≠ ''R''B0. (NB: Example assumes binary outcome and exposure variables.) Some epidemiologists prefer to think of confounding separately from common categorizations of bias since, unlike selection and information bias, confounding stems from real causal effects.


The profession

Few universities have offered epidemiology as a course of study at the undergraduate level. One notable undergraduate program exists at
Johns Hopkins University Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hemisphere. It consi ...
, where students who major in public health can take graduate-level courses, including epidemiology, during their senior year at the Bloomberg School of Public Health. Although epidemiologic research is conducted by individuals from diverse disciplines, including clinically trained professionals such as physicians, formal training is available through Masters or Doctoral programs including Master of Public Health (MPH),
Master of Science A Master of Science ( la, Magisterii Scientiae; abbreviated MS, M.S., MSc, M.Sc., SM, S.M., ScM or Sc.M.) is a master's degree in the field of science awarded by universities in many countries or a person holding such a degree. In contrast t ...
of Epidemiology (MSc.), Doctor of Public Health (DrPH), Doctor of Pharmacy (PharmD),
Doctor of Philosophy A Doctor of Philosophy (PhD, Ph.D., or DPhil; Latin: or ') is the most common degree at the highest academic level awarded following a course of study. PhDs are awarded for programs across the whole breadth of academic fields. Because it is ...
(PhD), Doctor of Science (ScD). Many other graduate programs, e.g.,
Doctor of Social Work The Doctor of Social Work (DSW) is a professional doctorate in social work, it is the highest academic award available in the field of social work, and most offer advanced training in a professional area of practice including but not limited to; ...
(DSW), Doctor of Clinical Practice (DClinP), Doctor of Podiatric Medicine (DPM), Doctor of Veterinary Medicine (DVM), Doctor of Nursing Practice (DNP), Doctor of Physical Therapy (DPT), or for clinically trained physicians, Doctor of Medicine (MD) or Bachelor of Medicine and Surgery (MBBS or MBChB) and
Doctor of Osteopathic Medicine Doctor of Osteopathic Medicine (DO or D.O., or in Australia DO USA) is a medical degree conferred by the 38 osteopathic medical schools in the United States. DO and Doctor of Medicine (MD) degrees are equivalent: a DO graduate may become lice ...
(DO), include some training in epidemiologic research or related topics, but this training is generally substantially less than offered in training programs focused on epidemiology or public health. Reflecting the strong historical tie between epidemiology and medicine, formal training programs may be set in either schools of public health and medical schools. As public health/health protection practitioners, epidemiologists work in a number of different settings. Some epidemiologists work 'in the field'; i.e., in the community, commonly in a public health/health protection service, and are often at the forefront of investigating and combating disease outbreaks. Others work for non-profit organizations, universities, hospitals and larger government entities such as state and local health departments, various Ministries of Health,
Doctors without Borders Doctor or The Doctor may refer to: Personal titles * Doctor (title), the holder of an accredited academic degree * A medical practitioner, including: ** Physician ** Surgeon ** Dentist ** Veterinary physician ** Optometrist *Other roles ** ...
, the Centers for Disease Control and Prevention (CDC), the
Health Protection Agency The Health Protection Agency (HPA) was a non-departmental public body in the United Kingdom. It was an organisation that was set up by the UK government in 2003 to protect the public from threats to their health from infectious diseases and envi ...
, the World Health Organization (WHO), or the
Public Health Agency of Canada The Public Health Agency of Canada (PHAC; french: Agence de la santé publique du Canada, ASPC) is an agency of the Government of Canada that is responsible for public health, emergency preparedness and response, and infectious and chronic dis ...
. Epidemiologists can also work in for-profit organizations such as pharmaceutical and medical device companies in groups such as market research or clinical development.


COVID-19

An April 2020 University of Southern California article noted that "The
coronavirus epidemic The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identifie ...
... thrust epidemiology – the study of the incidence, distribution and control of disease in a population – to the forefront of scientific disciplines across the globe and even made temporary celebrities out of some of its practitioners."


See also

* * * * * * * * * * * * * * * * * * * * * * * * * * * *


References


Citations


Sources

* Clayton, David and Michael Hills (1993) ''Statistical Models in Epidemiology'' Oxford University Press. * Miquel Porta, editor (2014) "A dictionary of epidemiology", 6th edn, New York: Oxford University Press
A Dictionary of Epidemiology
* Morabia, Alfredo, editor. (2004) A History of Epidemiologic Methods and Concepts. Basel, Birkhauser Verlag. Part I
A History of Epidemiologic Methods and ConceptsA History of Epidemiologic Methods and Concepts
* Smetanin P, Kobak P, Moyer C, Maley O (2005). "The Risk Management of Tobacco Control Research Policy Programs" The World Conference on Tobacco OR Health Conference, 12–15 July 2006, Washington DC. * Szklo M, Nieto FJ (2002). "Epidemiology: beyond the basics", Aspen Publishers. * Robertson LS (2015). Injury Epidemiology: Fourth Edition. Free online at nanlee.net * Rothman K., Sander Greenland, Lash T., editors (2008). "Modern Epidemiology", 3rd Edition, Lippincott Williams & Wilkins.
Olsen J, Christensen K, Murray J, Ekbom A. An Introduction to Epidemiology for Health Professionals. New York: Springer Science+Business Media; 2010


External links


The Health Protection Agency

The Collection of Biostatistics Research Archive



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