Bradford-Hill criteria
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The Bradford Hill criteria, otherwise known as Hill's criteria for causation, are a group of nine principles that can be useful in establishing
epidemiologic 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 proper ...
evidence of a
causal relationship Causality (also referred to as causation, or cause and effect) is influence by which one event, process, state, or object (''a'' ''cause'') contributes to the production of another event, process, state, or object (an ''effect'') where the ca ...
between a presumed cause and an observed effect and have been widely used in
public health Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the det ...
research. They were established in 1965 by the English epidemiologist Sir
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 ...
. In 1996, Fredricks and Relman remarked on Hill's criteria in their seminal paper on
microbial pathogenesis Microbial pathogenesis is a field of microbiology started at least as early as 1988, with the identification of the triune Falkow's criteria aka molecular Koch's postulates. In 1996 Fredricks and Relman proposed a seven-point list of "Molecular Gui ...
.


Definition

In 1965, the English statistician Sir
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 set of nine criteria to provide
epidemiologic 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 proper ...
evidence of a
causal relationship Causality (also referred to as causation, or cause and effect) is influence by which one event, process, state, or object (''a'' ''cause'') contributes to the production of another event, process, state, or object (an ''effect'') where the ca ...
between a presumed cause and an observed effect. (For example, he demonstrated the connection between cigarette smoking and lung cancer.) The list of the criteria is as follows: # Strength (
effect size In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, the ...
): 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 ( reproducibility): Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect. # Specificity: Causation is likely if there is 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 (
dose–response relationship The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure tim ...
): 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 In sociology and especially the sociological study of religion, plausibility structures are the sociocultural contexts for systems of meaning within which these meanings make sense, or are made plausible. Beliefs and meanings held by individuals a ...
: 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 use of analogies or similarities between the observed association and any other associations. Some authors consider, also, Reversibility: If the cause is deleted then the effect should disappear as well.


Debate in epidemiology

Bradford Hill's criteria had been widely accepted as useful guidelines for investigating causality in
epidemiological Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidenc ...
studies but their value has been questioned because they have become somewhat outdated. In addition, their method of application is debated. Some proposed options how to apply them include: # Using a
counterfactual Counterfactual conditionals (also ''subjunctive'' or ''X-marked'') are conditional sentences which discuss what would have been true under different circumstances, e.g. "If Peter believed in ghosts, he would be afraid to be here." Counterfactual ...
consideration as the basis for applying each criterion. # Subdividing them into three categories: ''direct'', ''mechanistic'' and ''parallel'' evidence, expected to complement each other. This operational reformulation of the criteria has been recently proposed in the context of evidence-based medicine. # Considering confounding factors and
bias Bias is a disproportionate weight ''in favor of'' or ''against'' an idea or thing, usually in a way that is closed-minded, prejudicial, or unfair. Biases can be innate or learned. People may develop biases for or against an individual, a group ...
. # Using Hill’s criteria as a guide, but not considering them to give definitive conclusions. # Separating causal association and
interventions ''Interventions'' is a book by Noam Chomsky, an American academic linguist and political activist. Published in May 2007, ''Interventions'' is a collection of 44 op-ed articles, post-9/11, from September 2002, through March 2007. The book's sub ...
, because interventions in public health are more complex than can be evaluated by use of Hill’s criteria An argument against the use of Bradford Hill criteria as exclusive considerations in proving causality is that the basic mechanism of proving causality is not in applying specific criteria—whether those of Bradford Hill or counterfactual argument—but in scientific common sense deduction. Others argue that the specific study from which data has been produced is important, and while the Bradford Hill criteria may be applied to test causality in these scenarios, the study type may rule out deducing or inducing causality, and the criteria are only of use in inferring the best explanation of this data. Debate over the scope of application of the criteria includes, whether they can be applied to
social sciences 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 ...
. The argument proposes that there are different motives behind defining causality; the Bradford Hill criteria applied to complex systems such as
health sciences The following outline is provided as an overview of and topical guide to health sciences: Health sciences are those sciences which focus on health, or health care, as core parts of their subject matter. Health sciences relate to multiple ac ...
are useful in prediction models where a consequence is sought; explanation models as to why causation occurred are deduced less easily from Bradford Hill criteria because the instigation of causation, rather than the consequence, is needed for these models.


Examples of application

Researchers have applied Hill’s criteria for causality in examining the evidence in several areas of epidemiology, including connections between ultraviolet B radiation,
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
and
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 ...
, vitamin D and
pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...
and
neonatal An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
outcomes, alcohol and cardiovascular disease outcomes,
infections An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
and risk of stroke,
nutrition Nutrition is the biochemical and physiological process by which an organism uses food to support its life. It provides organisms with nutrients, which can be metabolized to create energy and chemical structures. Failure to obtain sufficient ...
and
biomarkers 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, pa ...
related to disease outcomes, and sugar-sweetened beverage consumption and the prevalence of
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 ...
and obesity-related diseases. They have also been used in non-human epidemiological studies, such as on the effects of
neonicotinoid Neonicotinoids (sometimes shortened to neonics ) are a class of neuro-active insecticides chemically similar to nicotine, developed by scientists at Shell and Bayer in the 1980s. The neonicotinoid family includes acetamiprid, clothianidin, din ...
pesticides on
honey bees A honey bee (also spelled honeybee) is a eusocial flying insect within the genus ''Apis'' of the bee clade, all native to Afro-Eurasia. After bees spread naturally throughout Africa and Eurasia, humans became responsible for the current cosm ...
. Their use in
quality improvement Quality management ensures that an organization, product or service consistently functions well. It has four main components: quality planning, quality assurance, quality control and quality improvement. Quality management is focused not o ...
of health care services has been proposed, highlighting how quality improvement methods can be used to provide evidence for the criteria. Since the description of the criteria, many methods to systematically evaluate the evidence supporting a causal relationship have been published, for example the five evidence-grading criteria of the
World Cancer Research Fund World Cancer Research Fund International is a not-for-profit association related to cancer prevention research related to diet Diet may refer to: Food * Diet (nutrition), the sum of the food consumed by an organism or group * Dieting, the del ...
(Convincing; Probable; Limited evidence – suggestive; Limited evidence – no conclusion; Substantial effect on risk unlikely).What the Continuous Update Conclusions Mean
American Institute for Cancer Research, n.d., retrieved 13 June 2017


See also

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References

{{Reflist, 30em Epidemiology Diseases and disorders Causality