The Epinhood (TEH)

CALIBRATION Adjustment of an instrument or its measurements so the distribution of measurements matches a standard. In multicenter studies, calibration ensures a common standard and therefore comparability of measurements.

CALIPER MATCHING See matching.

CAMPBELL COLLABORATION An independent international nonprofit organization that aims to help people make well-informed decisions about the effects of interventions in the social, behavioral, and educational arenas. An international network of social scientists that produces and disseminates systematic reviews of research evidence on the effectiveness of social interventions. Also known as “C2” because of its relation- ship with the Cochrane Collaboration. http://www.campbellcollaboration.org.

CANADIAN MORTALITY DATABASE A large set of computer-stored death statistics; personal identifiers and causes of all deaths in Canada since 1950 have been computer- stored, with the death certificates preserved on microfiche. This database and record linkage have been used in some important historical cohort studies. See also National Death Index.

CANCER EPIDEMIOLOGY A branch or subspecialty of epidemiology that studies fac- tors influencing the occurrence (e.g., incidence, population distribution) of neoplastic and preneoplastic diseases and related disorders. Primary outcomes include incidence, prevalence, survival, and mortality from all types of cancers.

As mentioned below, epidemiology studies all types of diseases and health-related events in populations; hence, this dictionary includes only a few examples of definitions of some disease-based subspecialties of epidemiology. See also carcinogenesis; cardiovascular epidemiology; environmental epidemiology; molecular epidemiology; neuroepidemiology.

CANCER MORTALITY:INCIDENCE RATIO (Syn: cancer MIR, cancer mortality-to-inci- dence ratio) The ratio of mortality to incidence for each of several cancer sites being considered in a study. It is one diagnostic technique among several that can be used to gain some sense of cancer data quality; its main use is in studies of the natural history and survival rates of malignancies. Because not all patients with cancer die of cancer, the number of new cases in any one year should exceed cancer deaths in that same year, and—if cancer mortality and incidence are reported accurately—the ratio between the two should be proportional to the known survival for each specific site. For example, cancers with poor survival, such as pancreatic cancer, would be expected to have an

CANCER REGISTRY See register.

CAPTURE-RECAPTURE METHOD A method of estimating the size of a target population or a subset of this population that uses overlapping and presumably incomplete but intersecting sets of data about that population.50,51 The method originated in wildlife biology, where it relied on tagging and releasing captured animals and then recapturing them. The method was adopted in veterinary epidemiology and later in vital statistics (census taking) and epidemiology. If two independent sources or population estimates are available, with (a) cases found by both, (b) cases found only by the first source, or (c) cases found only by the second source, the maximum likelihood population estimate is the product of the total in each source divided by the total found in both sources, i.e., (a + b) × (a + c) / a. If the two sources are positively (negatively) dependent, the result will be biased toward an underestimate (overestimate). If three or more sources are available, log-linear methods can sometimes be used to model the degrees of depend- ency among the sources. Although the capture-recapture methods have some limi- tations, they are useful to estimate numbers of cases and numbers at risk in elusive populations, such as homeless people and sex workers. See also snowball sampling.

CARCINOGEN A substance or agent that can cause cancer. Also, a physical, chemical, or biological agent that may induce or otherwise participate in the causation of cancer. A carcinogen may or may not be mutagenic. Some compounds do not bind to DNA and are not mutagenic, yet they are carcinogenic in animal models and in humans. Carcino- gens act through genotoxic and nongenotoxic mechanisms. “Complete carcinogens” [e.g., some polycyclic aromatic hydrocarbons (PAHs)] can induce both somatic (acquired) mutations in genes through DNA binding (tumor “initiation” phase) and subsequent out- growth of irreversibly transformed cells (tumor “promotion” phase). In the early 1980s, carcinogenic PAHs were shown to induce activating mutations in ras genes. Today, about 200 different chemical compounds and mixtures are officially recognized as “known” or “anticipated to be” human carcinogens. See also procarcinogen; TCDD.

The International Agency for Research on Cancer (IARC) classifies carcinogens as follows:

Sufficient evidence. A positive causal relationship has been established between exposure and occurrence of cancer.
Limited evidence. A positive association has been observed between exposure to the agent and cancer for which a causal interpretation is credible, but chance, bias, or confounding cannot be ruled out.

Inadequate evidence. Available studies are of insufficient quality, consistency, or statistical power to permit a conclusion regarding the presence or absence of a causal relationship.
Evidence suggesting lack of carcinogenicity. Several adequate studies covering the full range of doses to which humans are known to be exposed are mutually consistent in not showing a positive association between exposure to the agent and any studied cancer at any level of exposure.

Overall evaluation: Taking all the evidence into account, the agent is assigned to one of the following categories:

Group 1: The agent is carcinogenic to humans.
Group 2: At one extreme, the evidence for human carcinogenicity is almost sufficient (group 2A, probably carcinogenic); at the other, there are no human data but there is experimental evidence of carcinogenicity (group 2B, possibly carcinogenic).
Group 3: The agent is not classifiable as to its human carcinogenicity.
Group 4: The agent is probably not carcinogenic to humans.

CARCINOGENESIS The process by which cancer is produced. Carcinogenesis is a multi- stage process driven by carcinogen-induced accumulation of genetic and epigenetic damage in susceptible cells, which gain a selective growth advantage and undergo clonal expansion as the result of activation of (proto)oncogenes and inactivation of tumor suppressor genes. Accumulation of genetic and epigenetic alterations is hence a key causal process linking environment exposure and the occurrence of diseases of complex etiology.

The traditional stages of carcinogenesis are as follows:
Initiation. The primary step of tumor induction; the irreversible transformation of a cell’s growth-regulatory processes whereby the potential for unregulated growth is established, usually through genetic damage by a chemical or physical carcinogen. Promotion. The second stage, in which a promoting agent induces an initiated cell to divide abnormally.
Progression. Transition of initiated promoted cells to a phase of unregulated growth and invasiveness, frequently with metastases and morphological changes in the cancer cells.

Research in molecular epidemiology often generates evidence that clarifies aspects of the carcinogenic process (e.g., the mutational spectra of chemical and physical carcinogens in critical genes are of interest to define endogenous and exogenous carcinogenic mechanisms).

CARDIOVASCULAR EPIDEMIOLOGY A branch or subspecialty of epidemiology that studies factors influencing the occurrence of diseases that affect the cardiovascular sys- tem, like coronary heart disease and stroke. Primary outcomes include incidence, preva- lence, survival, and mortality from cardiovascular diseases. Established and putative risk factors include individual-level behavioral factors (e.g., diet, smoking, physical activity) and psychosocial risk factors (e.g., social support, depression) as well as macro-, aggregate-, or higher-level socioeconomic factors and processes (e.g., geographic and economic characteristics of neighborhoods or cities).

As mentioned below, epidemiology studies all types of diseases and health-related events in populations; hence, this dictionary includes just some examples of definitions for a few disease-based and exposure-based branches or subspecialties of epidemiology. See also clinical epidemiology; environmental epidemiology; molecular epidemiology; pharmacoepidemiology.

CARRIER A person or animal harboring a specific infectious agent in the absence of discernible clinical disease and serves as a potential source of infection. The carrier state may occur in an individual with an infection that is inapparent throughout its course (known as a healthy or asymptomatic carrier) or the carrier state may exist only during the incubation period, convalescence, and postconvalescence of an individual with a clinically recognizable disease (known as an incubatory carrier or convalescent carrier).

CARRYING CAPACITY FOR HUMANS In a community of subsistence farmers, the carrying capacity denotes the maximum number of people that a hectare of land can support sustainably in an average year at a practicable level of technology and at a specified standard of living—commonly mere survival. For example, if a hectare of land grows 1 ton of maize and 250 kg will feed one person for a year, the carrying capacity of that land is four people to the hectare. There is uncertainty about the earth’s carry- ing capacity: some experts argue that there is abundant unused capacity, while others believe that the earth is already exceeding its carrying capacity.

CARRYING CAPACITY FOR OTHER SPECIES The maximum sustainable size of a resident population in a given ecosystem.

CARRYOVER EFFECT

1. A bias that may occur when the effects of an exposure persist into a subsequent period when a second exposure of interest is acting.
   
2. In a crossover clinical trial the effect of the treatment given in the first period may continue (“carryover”) into the second treatment period.
   
3. Treatments may be randomly allocated to paired organs (eyes, arms, hips, kidneys) if treatments act only locally. However, contamination may occur if there is a carryover effect of the experimental treatment to the control organ of the pair.14
   

CARTOGRAM A diagrammatic map on which epidemiological or statistical information is presented visually; examples include isodemographic and choroplethic maps.

CASE A particular disease, health disorder, or condition under investigation found in an individual or within a population or study group. As often non-strictly used in the health sciences, a person having a particular disease, disorder, or condition (e.g., a case of cancer, a case in a case-control study). A variety of criteria may be used to identify cases, e.g., individual physicians’ diagnoses, registries and notifications, abstracts of clinical records, surveys of the general population, population screening, and reporting of defects, as in a dental record. The epidemiological definition of a case is not necessarily the same as the ordinary clinical definition.

CASE, AUTOCHTHONOUS In infectious disease epidemiology, a case of local origin. Literally, “native where it arises.” See also case, imported; case, indigenous.

CASE-BASE STUDY A variant of the case-control design in which the controls are drawn from the same study base as the cases, regardless of their disease status.12,53 Cases of the disease of interest are identified, and a sample of the entire base population (cases and noncases) forms the controls. This design provides for estimation of the risk ratio or rate ratio without any rare disease assumption. Specific examples include the case- cohort study and the density case-control study.

CASE-CASE STUDY A type of study in which cases of a given disease with a specific characteristic are compared with other cases with the same disease but without the characteristic; the latter may be, for instance, an acquired (somatic) genetic alteration or an inherited genetic variant. The aim is to identify etiological or susceptibility factors specific to the subset of cases with the characteristic.54 The design is also used in infectious disease epidemiology to detect different transmission ways between subtypes of one disease.55–57 It is also useful to analyze infectious disease outbreaks: exposures of an outbreak cluster are compared with exposures among individuals infected by another subtype of the same disease. See also case-only study.

CASE-COHORT STUDY A variant of the case-control design in which the controls are drawn from the same cohort as the cases regardless of their disease status. Cases of the disease of interest are identified, and a sample of the entire starting cohort (regardless of their outcomes) forms the controls. This design provides an estimate of the risk ratio without any rare disease assumption.12,31 A type of case-base study. See also density case-control study; nested case-control study.

CASE, COLLATERAL A case occurring in the immediate vicinity of a case that has been the subject of an epidemiological investigation; a term used mainly in malaria control programs, equivalent to the term contact as used in infectious disease epidemiology.

CASE, IMPORTED In infectious disease epidemiology, a case that has entered a region by land, sea, or air transport, in contrast to one acquired locally. See also case, autochtonous.

CASE, INDIGENOUS In infectious disease epidemiology, a case in a person residing in the area.

CASE, INDUCED In malaria epidemiology, a case occurring in a person who has received a transfusion of blood containing malaria parasites; the term is generalizable to other conditions that can be transmitted by infected blood (e.g., HIV, hepatitis C).

CASE CLASSIFICATION In surveillance epidemiology, gradations in the likelihood of being a case (e.g., suspected/probable/confirmed); a useful method when early report- ing of cases is important (e.g., Ebola hemorrhagic fever) and where there are difficulties in making a definitive diagnosis, (e.g., because specialized laboratory tests are required) or when the diagnosis is based on a scoring system, as with multiple sclerosis.

CASE-COMPARISON STUDY A term considered a synonym for case-control study in the past.

CASE-COMPEER STUDY Another term that in the past was considered a synonym for case-control study.

CASE-CONTROL STUDY (Syn: case-referent study) The observational epidemiological study of persons with the disease (or another outcome variable) of interest and a suit- able control group of persons without the disease (comparison group, reference group). The potential relationship of a suspected risk factor or an attribute to the disease is examined by comparing the diseased and nondiseased subjects with regard to how fre- quently the factor or attribute is present (or, if quantitative, the levels of the attribute) in each of the groups (diseased and nondiseased).12,31

It is not correct to call “case-control study” any comparison of a group of people having a specific outcome with another group free of that outcome.10 The case-control study used to be called “retrospective” because, conceptually, it goes from disease onset backwards to the postulated causal factors. Yet cases and controls in a case-control study are often accumulated prospectively: the conduct of the study starts before cases have been diagnosed and, as each new case is diagnosed and identified, it is entered in the study. Subjects in a randomized controlled trial should not be described as cases and controls.

CASE-CROSSOVER DESIGN A variant of the case-only study. An observational ana- logue of a crossover study. It can be used when a brief exposure triggers an outcome or causes a transient rise in the risk of a disease with an acute onset (e.g., to assess the effect of medication use on the short-term risk of myocardial infarction). 12,58 One key difference between a traditional case-control study and the case-crossover design is that in the latter latter each case serves as its own matched control. The exposure status

Case definition 32

of each case is assessed during different time windows, and the exposure status at the time of case occurrence is compared to the status at other times. Conditions to be met include the following:

1. Acute cases are needed, an abrupt outcome applies best.
   
2. Crossover in exposure status. There must be a sufficient number of individuals who crossed from higher to lower exposure level and vice-versa.
   
3. Brief and transient exposures. The exposure or its effects must be short-lived.
   
4. Selection of control time periods must be unrelated to any general trends in
   exposure.
   

Properly applied, the design allows estimation of the rate ratio without need for a rare

disease assumption. See also case-time control study.
CASE DEFINITION A set of criteria (not necessarily diagnostic criteria) that must be

fulfilled in order to identify a person as representing a case of a particular disease. It is different from case diagnosis. Case definition can be based on geographic, clinical, laboratory, or combined clinical and laboratory criteria or on a scoring system with points for each criterion that matches the features of the disease. Where the diagnosis is based on a scoring system (e.g., multiple sclerosis), it is important to abide by the system for surveillance purposes and in deciding whether to include or exclude cases in an epidemiological study.59

CASE FATALITY RATE The proportion of cases of a specified condition that are fatal within a specified time.

This definition can lead to paradox when more persons die of the disease than develop it during a given period. For instance, chemical poisoning that is slowly but inexorably fatal may cause many persons to develop the disease over a relatively short period of time, but the deaths may not occur until some years later and may be spread over a period of years during which there are no new cases. Thus, in calculating the case fatality rate, it is necessary to acknowledge that the time dimension varies: it may be brief (e.g., covering only the period of stay in a hospital); of finite duration (e.g., 1 year); or of longer duration still. The term case fatality rate is then better replaced by a term such as survival rate or by the use of a survivorship table. See also attack rate; survivorship study.

CASE FINDING

1. (Syn: Contact tracing). A standard procedure in the control of certain contagious diseases (e.g., tuberculosis and sexually transmitted diseases) whereby diligent efforts are made to locate and treat persons who have had close or intimate contact with a known case. Also, seeking persons who have been exposed to risk of other potentially harmful factors, like toxic substances, epidemic conditions, or outbreaks such as food poisoning.
   
2. Secondary prevention through early clinical detection of cases among persons using health services for other reasons (e.g., checking blood pressures of all patients who attend a physician’s office).
   

33 Case-specular study

CASE HISTORY STUDY

1. In clinical medicine, a case report or a report on a case series.
   
2. A term considered a synonym for case-control study in the past.
   

CASE IMPACT NUMBER See impact numbers
CASE INVESTIGATION In surveillance epidemiology, examination to determine whether

an individual is or is not involved in an epidemic, especially an index case.
CASE-MIX INDEX (CMI) A measure of the complexity of illness.Among hospital patients, it is based on the relative severity indexes assigned to a diagnosis-related group. A high CMI indicates a high proportion of complex cases and justifies higher rates of

reimbursement in medical care insurance systems such as Medicare.
CASE-ONLY STUDY A method that analyzes data from a case series. It may be seen as an epidemiological equivalent of the “thought experiment” used by theoretical physi- cists. It is used in the case-crossover study, in case-specular designs, and in molecular and genetic epidemiology to assess relationships between environmental exposures

and genotypes.60 See also case-case study.
CASE REFERENT STUDY See case-control study.
CASE REPORTS Detailed descriptions of a few patients or clinical cases (frequently,

just one sick person) with an unsual disease or complication, uncommon combinations of diseases, an unusual or misleading semiology, cause or outcome (maybe a surpris- ing recovery …). They often are preliminary observations that are later refuted. They cannot estimate disease frequency or risk (e.g., for lack of a valid denominator). How- ever, as Pierre Charles Alexandre Louis, Claude Bernard, Thomas Lewis, Austin Brad- ford Hill, and many others have shown (e.g., more recently, Jan P. Vandenbroucke or Gordon Guyatt, or organizations like the Cochrane Collaboration), many problems worthy of investigation in medicine are first identified by observations at the bedside.61 Indeed, case reports may thoughtfully integrate clinical, anatomopathological, genetic, pathophysiological, biochemical, or molecular information and reasoning; they may thus build a sound mechanistic or pragmatic hypothesis and help set the foundation for microbiological studies and for larger clinical and epidemiological studies. They may also properly raise a suspicion of a new adverse drug event, and they are an important means of surveillance for rare clinical events. They help us to reflect on and learn from medical error.62,63

CASE SERIES A collection of patients with common characteristics used to describe some clinical, pathophysiological, or operational aspect of a disease, treatment, or diagnostic procedure. Some are similar to the larger case reports and share the vir- tues of this design. The number of subjects does not attenuate the limitations of the design. A case series does not include a comparison group and is often based on prevalent cases and on a sample of convenience.62 Common selection biases and con- founding severely limit their power to make causal inferences. See also inception cohort.

CASE-SPECULAR STUDY A type of case-only study that obtains the actual distribu- tion of exposure among the dwellings of the cases and a reflected or “specular” exposure distribution, which is what the exposure distribution would have been if the dwellings had been placed on the opposite side of the street. From these two distributions (i.e., the actual and the specular distribution) and some assumptions, including a rare dis- ease assumption, a relative risk estimate for the effect of exposure can be calculated, much as it can for a case-control study, albeit with different assumptions. For example,

Case study 34

the distance of each case’s front door from an electrical wire is matched with the distance

from the same wire of a hypothetical front door located exactly across the street.64 CASE STUDY A detailed analysis of the occurrence, development, and outcome of a par- ticular problem or innovation, often over a period of time. A detailed description of a

concrete situation requiring ethical analysis, judgment, and—sometimes—action. CASE-TIME-CONTROL DESIGN A design in which exposure of cases and controls dur- ing one period is compared in matched-pair analyses to their own exposure during

another period of similar length.65 See also case-crossover study.
CASUISTRY A method of reasoning and decision making, especially in ethics, based on experience with and decisions about similar cases in the past. This contrasts with ethical decision making that is more strongly based on ethical principles. Medical casuistics is

the study of cases of disease.
CAT-AND-WHISKERS PLOT See box-and-whiskers plot.
CATASTROPHE THEORY A branch of mathematics dealing with large changes in the

total system that may result from small changes in a critical variable in the system. An example is the sudden change in the physical state of water into steam or ice with rise or fall of temperature beyond a critical level. Certain epidemics, gene frequencies, and behavioral phenomena in populations may abide by the same mathematical rule. Herd immunity is an example. See also chaos theory.

CATCHMENT AREA Region from which the clients of a particular health facility are drawn. Such a region may be well or ill defined.

CATEGORIZATION One way of organizing information on objects or ideas. The process of recognition, differentiation, and understanding of objects by grouping into catego- ries, usually for statistical analysis or graphic representation. Category is from late Latin categoria—a division within a system of classification. See also taxonomy; ontology; directory; cataloguing; clustering.

CAUSAL CRITERIA or CAUSAL CONSIDERATIONS Considerations (often called “criteria”) that help to guide judgments about causality and to make causal infer- ences.6,9,10,14,66,67 Examples close to epidemiology include John Stuart Mill’s Canons, the “rules” of David Hume, Evans’s postulates, Henle-Koch postulates, or Hill’s criteria of causation.

CAUSAL DIAGRAM (Syn: causal graph, path diagram) A graphical display of causal rela- tions among variables, in which each variable is assigned a fixed location on the graph (called a node) and in which each direct causal effect of one variable on another is represented by an arrow with its tail at the cause and its head at the effect.68 Direct noncausal associations are usually represented by lines without arrowheads. Graphs with only directed arrows (in which all direct associations are causal) are called directed graphs. Graphs in which no variable can affect itself (no feedback loop) are called acyclic. Algorithms have been developed to determine from causal diagrams which sets of variables are sufficient to control confounding and for when control of variables leads to bias.69,70

CAUSAL INFERENCE The thought processes and methods that assess or test whether a relation of cause to effect does or does not exist. See also association; Hill’s criteria of causation; probability of causation; properties of a cause; verification.

CAUSALITY The relating of causes to the effects they produce. The property of being causal. The presence of cause. Ideas about the nature of the relations of cause and effect. The potential for changing an outcome (the effect) by changing an antecedent (the cause). Most of clinical, epidemiological, and public health research concerns cau- sality. In the health and life sciences, causality is often established by integration of bio- logical, clinical, epidemiological, and social evidence, as appropriate to the hypothesis at stake. Several types of causes can be distinguished.66,67 A cause is termed “necessary” when it must always precede an effect. This effect need not be the sole result of the one cause. A cause is termed “sufficient” when it inevitably initiates or produces an effect.

CAUSATION OF DISEASE, FACTORS IN The following factors have been differenti- ated, although they are not mutually exclusive:

1. predisposing factors are those that prepare, sensitize, condition, or otherwise create a situation such as a level of immunity or state of susceptibility so that the host tends to react in a specific fashion to a disease agent, personal interaction, environmental stimulus, or specific incentive. Examples include age, sex, marital status, family size, educational level,previous illness experience,presence of concurrent illness,dependency, working environment, and attitudes toward the use of health services. These factors may be “necessary” but are rarely “sufficient” to cause the phenomenon under study.
   
2. enablingfactorsarethosethatfacilitatethemanifestationofdisease,disability,ill- health, or the use of services or conversely those that facilitate recovery from illness, maintenance or enhancement of health status, or more appropriate use of health services. Examples include income, health insurance coverage, nutrition, climate, housing, personal support systems, and availability of medical care. These factors may be “necessary” but are rarely “sufficient” to cause the phenomenon under study.
   
3. precipitating factors are those associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others if several are involved and one may often be regarded as “necessary.” Examples include exposure to specific disease, amount or level of an infectious organism, drug, noxious agent, physical trauma, personal interaction, occupational stimulus, or new awareness or knowledge.
4. reinforcing factors are those tending to perpetuate or aggravate the presence of a disease, disability, impairment, attitude, pattern of behavior, or course of action.They may tend to be repetitive, recurrent, or persistent and may or may not necessarily be the same or similar to those categorized as predisposing, enabling, or precipitating. Examples include repeated exposure to the same noxious stimulus (in the absence of an appropriate immune response) such as an infectious agent, work, household, or interpersonal environment, presence of financial incentive or disincentive, personal satisfaction or deprivation. See also probability of causation.

CAUSE-DELETED LIFE TABLE A life table constructed using death rates lowered by eliminating the risk of dying from a specified cause; its most common use is to calculate the gain in life expectancy that would result from the elimination of one cause. See also competing risk.

CAUSE, PROPERTIES See properties of a cause.

CAUSES, COMPONENTS See component causes.

CAUSES IN PUBLIC HEALTH SCIENCES In epidemiology and other population sciences, causes include contextual factors, even if such factors can seldom be manipu- lated experimentally to produce change,71,72 given the following facts: causes operate at upper, aggregate, and distal levels as well as across macro- and micro-levels (climate, geographic location, diet); some causes are fairly constant or inmutable conditions (as gender); others show large variations across time and space in the extent to which they change in an individual’s lifecourse (educational and occupational achievement, social mobility and status, income, living arrangements).16 Hence, causes of individual and population health often change with global and local societal processes, and many act in specific periods of susceptibility (as in utero), often with long latencies, or throughout life. None of these characteristics per se excludes or refutes causality. Research on the causes of diseases is a “natural meeting place” for basic science (whose focus is knowl- edge on biological mechanisms), clinical sciences, and epidemiology (which aims at gen- erating knowledge useful for primary prevention). See also strategy, “population.”

CAUSES OF DEATH See death certificate.

CAUSE-SPECIFIC RATE A rate that specifies events, such as deaths, according to their cause.

CCS See case-control study.

CDC Centers for Disease Control and Prevention. An agency of the U.S. Public Health Service (www.cdc.gov).

CENSORING

1. Loss or attrition of subjects from a follow-up study; the occurrence of the event of interest among such subjects is uncertain after a specified time when it was known that the event of interest had not occurred; it is not known, however, if or when the event of interest occurred subsequently. Such subjects are described as censored. For example, in a follow-up study with myocardial infarction as the outcome of interest, a subject who has not had an infarct but is killed in a traffic crash in year 6 is described as censored as of year 6, since it cannot be known when, if ever, he might have had an infarct at a later year of follow-up. This is censoring by competing risk; other varieties include loss to follow-up and termination of the study. Examination of data for censoring requires the use of special analytical methods, such as life table analysis.12,31

2. Observations with unknown values from one end or a particular interval of a frequency distribution. Left-censored data come from the left-hand portion, or low end, and right-censored data come from the right-hand portion, or high end, of the distribution.

CENSUS An enumeration of a population, originally intended for purposes of taxation and military service. Ancient civilizations such as the Romans conducted censuses; Jesus of Nazareth was born in Bethlehem because Mary and Joseph had gone there to be counted in a Roman census. Census enumeration of a population usually records identities of all persons in every place of residence, with age or birth date, sex, occupa- tion, national origin, language, marital status, income, and relationship to head of house- hold in addition to information on the dwelling place. Many other items of information may be included, e.g., educational level (or literacy) and health-related data such as permanent disability. A de facto census allocates persons according to their location at the time of enumeration. A de jure census assigns persons according to their usual place of residence at the time of enumeration.

CENSUS TRACT An area for which details of population structure are separately tabu- lated at a periodic census; normally it is the smallest unit of analysis of census tabula- tions. Census tracts are chosen because they have well-defined boundaries, sometimes the same as local political jurisdictions, sometimes defined by conspicuous geographical features such as main roads or rivers. In urban areas census tracts may be further sub- divided (e.g., into city blocks), but published tables do not contain details to this level. Census tracts are usually relatively homogenous in demographic, socioeconomic, and ethnic composition.

CENTILE See quantiles.

CESSATION EXPERIMENT Controlled study in which an attempt is made to evaluate the termination of an exposure to risk such as a living habit that is considered to be of etiological importance.

CHAINS OF RISK A sequence of linked exposures that increase (or decrease) disease risk because one negative (or positive) experience or exposure tends to lead to another and then another. See also life course.

CHANCE

1. Frequency probability.
2. Accidental, unanticipated, unplanned, fortuitous, serendipitous (e.g., a chance finding during data dredging). See also fortuitous.
3. In ordinary use, the possibility that an event will happen (e.g., “There is a chance that
   she will survive”). Prospect, probability, likelihood. An opportunity.
   

CHAOS THEORY Branch of mathematics dealing with events and processes that cannot be predicted by conventional mathematical theorems or laws because small, localized perturbations have widespread general consequences. Examples include long-range weather changes and turbulence in fast-flowing water. The unpredictable course of some epidemics and metastases in many kinds of cancer accord with chaos theory.

CHART The medical dossier of a patient. See also information system; medical record.

CHECK DIGIT A single digit, derived from a multidigit number such as a case identification number, that is used as a screening test for transcription errors.

CHEMOPROPHYLAXIS The administration of a chemical, including antibiotics, to pre- vent the development of an infection or to slow progression of the disease to a clinically manifest form. Applicable to infectious and noninfectious diseases.

CHEMOTHERAPY The use of a chemical to treat a clinically recognizable disease or to limit its further progress.

CHILD DEATH RATE The number of deaths of children age 1–4 years in a given year per 1000 children in this age group. This is a useful measure of the burden of preventable communicable diseases in the child population.

CHILD MORTALITY RATE (Syn: under-5 mortality rate) Health indicator used by the United Nations Children’s Fund (formerly the United Nations International Chil- dren’s Emergency Fund, or UNICEF), the United Nationd Development Programme (UNDP), and other international agencies. It is computed as an annual rate, dividing the death count of children under age 5 by the count of live births in the same year and expressing the result per thousand. Therefore it is not an age-specific mortality rate, since the denominator is not the size of the child population under age 5. This rate is preferable to the child death rate, which is more difficult to determine in communities where the age of young children may not be known precisely.

CHILD NUTRITION, MEASURES OF UNCF defines several aspects of infant and child nutrition:

Stunting A measure of protein-energy malnutrition, indicated by low height for age or failure to achieve expected stature.

Underweight A composite measure of protein-energy malnutrition, indicated by low weight for age.

Wasting A measure of protein-energy malnutrition that occurs when a child’s weight for height falls significantly below what is expected in the reference population; an indicator of current malnutrition.

CHI-SQUARE (c2) DISTRIBUTION A variable is said to have a chi-square distribution with K degrees of freedom if it is distributed like the sum of the squares of K independent random variables, each of which has a normal distribution with mean zero and variance one.

CHI-SQUARE (c2) TEST Any statistical test based on comparison of a test statistic to a chi-square distribution. The oldest and most common chi-square tests are for detecting whether two or more population distributions differ from one another; these tests usu- ally involve counts of data and may involve comparison of samples from the distribu- tions under study or the comparison of a sample to a theoretically expected distribution. The Pearson chi-square test is probably the best known; another is the Mantel- Haenszel test. (Statisticians disagree about the terminal letter; most of those who contributed to the discussion of this entry prefer chi-square rather than chi-squared. Either usage is acceptable.)

CHOROPLETHIC MAP A method of mapping to display quantitative information (e.g., rates) in defined jurisdictions such as counties or states; an example is a color-coded atlas of cancer mortality.

CHRISOMS This word, which appears in Bills of Mortality, means infants who die before formal baptism: therefore the number recorded in Bills of Mortality can be used to estimate (albeit inaccurately) neonatal death rates in studies of historical demography and epidemiology.

CHRONIC

1. Referring to a health-related state, lasting a long time.

2. Referring to exposure, prolonged or long-term, often with specific reference to low intensity.

3. The U.S. National Center for Health Statistics defines a “chronic” condition as one of 3 months’ duration or longer.

CHRONOBIOLOGY The study of biological processes that possess periodicity (e.g., circa- dian rhythms, the menstrual cycle).

CIOMS Council for International Organizations of the Medical Sciences. See also cohort study, historical.

CIRCULAR EPIDEMIOLOGY Needlessly repetitive epidemiological studies that merely reiterate what has already been done and demonstrated unequivocally.73

CIRCULAR REASONING

1. Reasoning that requires that the conclusion be used to support one of the premises. Circularity may be a problem in definitions.74
   
2. An argument whose conclusion is implicitly assumed in one of the premises.
   

As with the assessment of a temporal relationship, detection of circular reasoning in a research study may need to be based on a complex and subtle assessment of the study design, conduct, and analysis.

CLASS A term used in the theory of frequency distributions.The total number of observations made upon a particular variate may be grouped into classes according to convenient divisions of the variate range in order to make subsequent analyses less laborious or for other reasons. A group so determined is called a class. The variate values that determine the upper and lower limits of a class are called class boundaries, the interval between them is the class interval, and the frequency falling into the class is the class frequency. See also set; social class.

CLASSIFICATION

1.Assignment to predesignated classes on the basis of perceived common characteristics.

2. A means of giving order to a group of disconnected facts.

Ideally, a classification should be characterized by (1) naturalness—the classes correspond to the nature of the thing being classified, (2) exhaustiveness—every member of the group will fit into one (and only one) class in the system, (3) usefulness— the classification is practical, (4) simplicity—the subclasses are not excessive, and (5) constructability—the set of classes can be constructed by a demonstrably systematic procedure. See also categorization; taxonomy.

CLASSIFICATION OF DISEASES Arrangement of diseases into groups having com- mon characteristics. Useful in efforts to achieve standardization, and therefore compa- rability, in the methods of presentation of mortality and morbidity data from different sources. May include a systematic numerical notation for each disease entry. Examples include the International Classification of Diseases (ICD) and the See Interna- tional Classification of Primary Care, Second Edition Revised (ICPC-2-R). See also family of classifications.

CLASS INTERVAL The difference between the lower and upper limits of a class.

CLASTOGENIC That causes damage to chromosomes. See also mutagenic; aneugenic.

CLINICAL DECISION ANALYSIS Application of decision analysis in a clinical setting, often to assess probabilities of outcomes of alternative decisions (e.g., surgical pro- cedures or drug treatment for myocardial ischemia). It considers three aspects of the decision: choices (options available to the patient), chances (probabilities of outcome for each choice), and values (quantitative expression of the desirability of different outcomes). It can be applied to small numbers of cases and even to a single patient. A method to systematically assess available treatment options, possible outcomes, and the desirability of each possible outcome. See also decision analysis; n-of-one study.

CLINICAL ECOLOGY An outdated term for the study of environmental hypersensi- tivity. Also an earlier name for environmental medicine.

CLINICAL ECONOMICS The application of cost-benefit and cost-effectiveness analytic techniques in a clinical setting or to clinical problems.

CLINICAL EPIDEMIOLOGY The application of epidemiological knowledge, reasoning, and methods to study clinical issues and improve clinical care. In practice, unfortunately, “clinical” is often restricted to “medical” (“medical epidemiology” is also a completely acceptable and commonly used term). Research often addresses etiological, mechanis- tic, diagnostic, therapeutic, and prognostic medical issues, is conducted in clinical set- tings, is led by clinicians, and has patients as the subjects of study. Clinical epidemiology uses epidemiological principles mostly to aid decision making involving sick individu- als, although the wider context is also considered.9,10,14,61–63,75 See also clinical decision analysis; n-of-one study.

CLINICAL IMPORTANCE See significance, clinical.

CLINICAL PREDICTION RULE A set of criteria used to estimate the probability of a specific outcome or outcomes, particularly in a group of patients.62 See also clinical decision analysis.

CLINICAL SIGNIFICANCE See significance, clinical.

CLINICAL STUDY (Syn: clinical investigation) An investigation involving persons and aiming to understand or control disease and other health states in persons. Often—but not exclusively—carried out on patients, by physicians, and in a health care setting. Problems found worthy of investigation in caring for patients are frequently taken to the laboratories; yet the nature and purpose of the investigation often remains clinical, and the laboratory results must be tested again on actual persons—eventually by integrating epidemiological and statistical reasoning with clinical, pathophysiological, and microbiological (e.g., genetic) reasoning.61 See also case reports; clinical epidemiology; individual thinking; integrative research.

CLINICAL TRIAL (Syn: therapeutic trial) A research activity that involves the administration of a test regimen to humans to evaluate its efficacy and safety. The term is subject to wide variation in usage, from the first use in humans without any control treatment to a rigorously designed and executed experiment involving random allocation of test and control treatments. Four phases of clinical trials are distinguished:

Phase I trial It is the first test of a drug (or a candidate vaccine) in a small group of humans to determine its safety and mode of action. It usually involves fewer than 100 healthy volunteers. The focus is on safety and pharmacological profiles; it may also assess dose and route of administration.

Phase II trial Pilot efficacy studies. Initial trial to examine efficacy, usually in 200 to 500 volunteers; with vaccines, the focus is on immunogenicity, and with drugs, on demonstration of safety and efficacy in comparison to existing regimens. Usually but not always, subjects are randomly allocated to the study and control groups.

Phase III trial Extensive clinical trial. This phase is intended for complete assessment of safety and efficacy. It involves larger numbers of patients with the disease or condition of interest, sometimes thousands: it uses random allocation to study and control groups.

Phase IV trial Conducted after the regulatory authority has approved registration and marketing begins. The common aim is to estimate the incidence of rare adverse reactions and other potential effects of long-term use in real life; it may also study new uses and indications. It is part of postmarketing surveillance, which also includes observational studies. See also community trial.

CLINICAL TRIAL, NEGATIVE See negative study; null study.

CLINICAL TRIAL, SPLIT-MOUTH A design used frequently in oral research: the mouth is divided into two or more subunits. Active and control (comparison) treatments are applied to the subunits (e.g., to the left and right sides). Treatments are compared within each patient. The design may reduce interpatient variability, much as in a crossover clinical trial. See also carryover effect.

CLINIMETRICS The domain concerned with indexes, rating scales, and other expres- sions used to describe or measure symptoms, physical signs, and other distinctly clinical phenomena in clinical medicine.75 Such measurements are an essential part of many microbiological, clinical, and epidemiological studies. See also clinical epidemiology.

CLOSED COHORT A population in which membership begins at a defined time or with a defined event and ends only through occurrence of the study outcome or the end of eligibility for membership. An example is a population of women in labor being studied to determine the vital status of their offspring (i.e., whether live or stillborn).

CLOSED POPULATION A population that gains no new members and loses members only to death. Compare closed cohort.

CLUSTER Aggregations of relatively uncommon events or diseases in space and/or time in amounts that are believed or perceived to be greater than could be expected by chance. Putative disease clusters are often perceived to exist on the basis of anecdotal evidence, and much effort may be expanded by epidemiologists and biostatisticians in assessing whether a true cluster of disease exists

CLUSTER ANALYSIS A set of statistical methods used to group variables or observations into interrelated subgroups (e.g., to detect clusters in routine surveillance of disease).

CLUSTERING (Syn: disease cluster, time cluster, time-place cluster) A closely grouped series of events or cases of a disease or other health-related phenomena with well- defined distribution patterns in relation to time or place or both. The term is normally used to describe aggregation of relatively uncommon events or diseases (e.g., leukemia, multiple sclerosis).

CLUSTER SAMPLING A sampling method in which each unit selected is a group of persons (all persons in a city block, a family, etc.) rather than an individual.

CNN APPROACH “Condoms, Needle exchange, Negotiation.” A set of strategies aim- ing to combat the HIV/AIDS pandemic, other sexually transmitted diseases, and other blood-borne infections. Harm reduction approaches to reducing the rate of HIV trans- mission through the adoption of safer sex and through risk reduction in intravenous drug users by provision of clean needles. See also ABC Approach.

COCARCINOGEN A substance that enhances the effect of a carcinogen.

COCHRANE COLLABORATION An international organization of clinicians, epidemiologists, patients, and others that aims to help health professionals make well-informed decisions about health care by preparing, maintaining, disseminating, and promot- ing the accessibility of systematic reviews of the effects of health care interventions. Cochrane Reviews are prepared and updated by collaborating authors working in a Cochrane Collaborative Review Group and using explicitly defined methods to mini- mize the effects of bias; where appropriate and feasible, meta-analysis is used to reduce imprecision. The collaboration honors Archibald L. Cochrane, who advocated prefer- ence (including financial advantage) for interventions that have been assessed and

found to be effective and efficient (www.cochrane.org). See also effectiveness.

COCHRAN-MANTEL-HAENSZEL TEST See Mantel-Haenszel test.

CODE A numerical and/or alphabetical system for classifying information (e.g., about diagnostic categories).

CODING Translation of information (e.g., questionnaire responses) into numbered categories for entry in a data processing system.

CODE OF CONDUCT A formal statement of desirable conduct that research workers and/or practitioners are expected to honor; there may be penalties for violation. Exam- ples include the Hippocratic Oath, the Nürnberg (Nuremberg) Code, and the Helsinki Declaration, which govern requirements for research on human subjects. See also guidelines.

COEFFICIENT OF CONCORDANCE A measure of the agreement among several rankings or categories.

COEFFICIENT OF VARIATION The ratio of the standard deviation to the mean. This is meaningful only if the variable is measured on a ratio scale. See measurement scale.

COERCION Excessive pressure or influence to force or entice a person to act in a given way (e.g., to enroll in a research study or a public health program). May be exercised by offering excessive incentives, applying social pressure, using authority figures, or other- wise manipulating the vulnerable person or group.37 See also informed consent.

COGNITIVE DISSONANCE The state of having inconsistent thoughts, beliefs, perceptions (i.e., cognitions), or attitudes, especially as relating to behavioral decisions and attitude change.76 The drive to reduce dissonance in one’s system of beliefs may lead to surprising strategies of belief formation and retention.77 A theory that addresses competing or contradictory elements of cognition and behavior (e.g., why do people continue smoking when they know that smoking damages health?). Dissonance reduction may be attained through a change in behavior (e.g., quit smoking), in attitude or in beliefs.78

COGNITIVE DISSONANCE BIAS A form of interpretive bias that occurs when the belief in a given mechanism increases rather than decreases in the face of contradictory evidence.79 See also confirmation bias.

COHERENCE The extent to which a hypothesized causal association fits with preexist- ing theory and knowledge.67 Biological coherence requires more than just biological plausibility or compatibility with biological knowledge derived from studies of nonhuman species or experimental systems.

COHERENCE, EPIDEMIOLOGICAL The extent to which a biological, clinical, or social observation is coherent with epidemiological evidence. A criterion for causal inference in the biological and clinical sciences, approximately but not fully reciprocal to the criterion of biological plausibility in epidemiological causal inference.80

COHORT (From Latin cohors, warriors, the tenth part of a legion)

1. The component of the population born during a particular period and identified
   by period of birth so that its characteristics (e.g., causes of death and numbers still
   living) can be ascertained as it enters successive time and age periods.
   
2. The term “cohort” has broadened to describe any designated group of persons who are followed or traced over a period of time, as in cohort study (prospective study).
   See also birth cohort; historical cohort study.
   

COHORT ANALYSIS The tabulation and analysis of morbidity or mortality rates in relation to the ages of a specific group of people (cohort) identified at a particular period of time and followed as they pass through different ages during part or all of their life span. In certain circumstances (e.g., studies of migrant populations), cohort analysis may be performed according to duration of residence of migrants in a country, rather than year of birth, in order to relate health or mortality experience to duration of exposure. The aim is to detect age, period, and generation effects. Age-period-cohort models can be fitted to distinguish these effects; because of the dependency among the three factors, they require assumptions in order to estimate the parameters of the model. See also accumulation of risk; birth cohort; developmental and life course epidemiology.

COHORT COMPONENT METHOD A method of population projection that takes the population distributed by age and sex at a base date and carries it forward in time on the basis of separate allowances for fertility, mortality, and migration.

COHORT EFFECT See generation effect.

COHORT INCIDENCE See incidence.

COHORT SLOPES (Syn: graphical cohort analysis) Arrangement of data so that when plotted graphically, lines connect points representing the age-specific rates for popula- tion segments from the same generation of birth (see diagram). These slopes represent changes in rates with age during the life experience of each cohort.

COHORT STUDY (Syn: concurrent, follow-up, incidence, longitudinal, panel, prospec- tive study) The analytic epidemiological study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the occurrence of a given disease or other outcome.9–12 The main feature of cohort study is observation of large numbers over a long period (commonly years), with comparison of incidence rates in groups that differ in exposure levels. The alternative terms for a cohort study (i.e., follow-up, longitudinal, and prospective study) describe an essential feature of the method, which is observation of the population for a sufficient number of person-years to generate reliable incidence or mortality rates in the population subsets. This generally implies study of a large population, study for a prolonged period (years), or both. The denominators used for analysis may be persons or person-time.81 See also cohort analysis.

COHORT STUDY, HISTORICAL (Syn: historical prospective study, nonconcurrent prospective study, prospective study in retrospect) A cohort study conducted by reconstructing data about persons at a time or times in the past. This method uses existing records about the health or other relevant aspects of a population as it was at some time in the past and determines the current (or subsequent) status of mem- bers of this population with respect to the condition of interest. Different levels of past exposure to risk factor(s) of interest must be identifiable for subsets of the population. record linkage systems are often used in historical cohort studies. Growing public concern about protection of privacy threatens such studies, which in the past have often made very valuable contributions to scientific understanding of disease causation. Ethi- cal reviewers of research proposals for historical cohort studies increasingly require the investigators to obtain the informed consent of persons whose archived records are to be used in the study. If the study involves very large numbers and/or some or all of the persons are dead or cannot be traced, it is obviously not feasible to obtain their informed consent. Guidelines such as those composed by the Council for International Organizations of Medical Sciences (CIOMS) recommend that the informed consent requirement be waived in such circumstances.

COINTERVENTION In a randomized controlled trial, the application of additional diagnostic or therapeutic procedures to members of either or both the experimental and the control groups.

COLD CHAIN A system of protection against high environmental temperatures for heat- labile vaccines, sera, and other active biological preparations. Unless the cold chain is preserved, such preparations are inactivated and immunization procedures, etc., will be ineffective. Preservation of the cold chain is an integral part of the WHO expanded program on immunization in tropical countries.

COLLAPSIBILITY Equality of stratum-specific measures of association or effect with the crude (collapsed), unstratified measure. Often, lack of collapsibility is equated with confounding but may instead signal inappropriate stratification (as in berkson’s bias and some forms of selection bias). See confounding bias.

COLLIDER A variable directly affected by two or more other variables in the causal diagram.68,69,82 In the following “inverted fork” X → C ← Y the arrow represents a direct effect of the tail variable on the head variable; C is then called a collider on the X-C-Y pathway in the graph, and stratifying on C will tend to change the association of X and Y.

COLLINEARITY Very high correlation among variables.

COLONIZATION See infection.

COMMENSAL Literally, eating together (sharing the same table). An organism that lives harmlessly in the gut. See also xenobiotic.

COMMON DISEASE GENETIC AND EPIGENETIC HYPOTHESIS The CDGE hypothesis argues that in addition to genetic variation, epigenetics provides an added layer of variation that might mediate the relationship between genotype and internal and exter- nal environmental factors. This epigenetic component may help to explain the marked increase in common diseases with age as well as the frequent discordance of diseases between monozygotic twins.83

COMMON GOOD Shared values or benefits deemed to be good, either explicitly or tac- itly, for individuals and for society. Although the definition is critical for public health, in complex democratic societies it may be difficult to achieve consensus on certain “goods.” For epidemiological and public health practice, elements of the larger public good include health itself as social value, and the broader value of “assuring conditions under which people can be healthy.”37 See also public health.

COMMON SOURCE EPIDEMIC (Syn: common vehicle epidemic) See epidemic, common source.

COMMON VEHICLE SPREAD Transmission of a disease agent (infectious pathogen, toxic chemical, etc.) from a source that is common to those who acquire the disease. Common vehicles include air, water, food, injected substances. Legionellosis is an exam- ple of common vehicle spread in air that has passed through air conditioning equipment contaminated by the causal organism. HIV disease and hepatitis B and C can be spread among illicit drug users by the common vehicle of contaminated needles and syringes. Cholera and many other waterborne diseases are spread by the common vehicle of contaminated water. The principal modes of foodborne common vehicle spread were sonorously summarized by an anonymous author (probably Sir Andrew Balfour) in Memoranda on Medical Diseases in Tropical and Subtropical Areas,84 published by the British War Office in 1914–1918: “. . . careless carriers, contact cases, chiefly cooks, dirty drinking water, the dust of dried dejecta and the repulsive regurgitation, dangerous droppings, and filthy feet of faecal-feeding flies fouling food.” The work has not lacked chances to be revised often in later wars.

COMMUNICABLE DISEASE (Syn: infectious disease) An illness due to a specific infec- tious agent or its toxic products that arises through transmission of that agent or its products from an infected person, animal, or reservoir to a susceptible host, either directly or indirectly through an intermediate plant or animal host, vector, or the inanimate environment. See also transmission of infection.

COMMUNICABLE PERIOD The time during which an infectious agent may be transferred directly or indirectly from an infected person to another person, from an infected animal to humans, or from an infected person to an animal, including arthropods. See also transmission of infection.

COMMUNITARIAN ETHICS An approach to ethics emphasizing communal values, the common good, or social goals. Closely aligned with the cooperative virtues and a community’s shared understanding of life. Need not be pitted against individual rights.36,85,86

COMMUNITY A group of individuals organized into a unit or manifesting some unifying trait or common interest; loosely, the locality or catchment area population for which a service is provided or, more broadly, the state, nation, or body politic.

COMMUNITY DIAGNOSIS The process of appraising the health status of a community, including assembly of vital statistics and other health-related statistics and of informa- tion pertaining to determinants of health, such as prevalence of tobacco smoking, and examination of the relationships of these determinants to health in the specified com- munity. The term may also denote the findings of this diagnostic process. Community diagnosis may attempt to be comprehensive or may be restricted to specific health con- ditions, determinants, or subgroups. J. N. Morris identified community diagnosis as one of the uses of epidemiology.87

COMMUNITY HEALTH See public health. COMMUNITY MEDICINE

1. The study of health and disease in the population of a specified community. The goal is to identify health problems and needs, to identify means by which these needs may be met, and to evaluate the extent to which health services meet these needs.
   
2. The practice of medicine concerned with communities (or specified populations) rather than individuals; this includes the above elements and the organization and provision of health care at a community (or specified population) level.
   

COMMUNITY NEED ASSESSMENT A method of identifying the needs of the commu- nity so that corrective measures can be taken.

COMMUNITY-ORIENTED PRIMARY HEALTH CARE Integration of community medi- cine with the primary health care of individuals. The primary health care practitioner or team is responsible for health care both at the individual and the community or population levels. See also public health; social medicine.

COMMUNITY TRIAL Experiment in which the unit of allocation to receive a preven- tive, therapeutic, or social intervention is an entire community or political subdivision. Examples include the trials of fluoridation of drinking water and of heart disease pre- vention in North Karelia (Finland) and California. See also clinical trial; experiment; experimental epidemiology.

COMORBIDITY Disease(s) that coexist(s) in a study participant in addition to the index condition that is the subject of study.

COMPARISON GROUP Any group to which the index group is compared. Usually synonymous with control group. Use of this term is preferably restricted to randomly allocated groups.

COMPETING CAUSE In considering a particular cause of death (or other inevitable out- come), one must take account of other causes, which are commonly called competing causes. When a previously common cause of death becomes rare, competing causes must become more prominent. For instance, among young adults, pneumonia and other infections were a common cause of death until about midway through the twentieth century; their control has brought to prominence some competing causes of death, such as cancers and suicide.

COMPETING RISK An event that removes a subject from being at risk for the outcome under investigation. For example, in a study of smoking and cancer of the lung, a subject who dies of coronary heart disease is no longer at risk of lung cancer; in this situation, coronary heart disease is a competing risk.

COMPLETED FERTILITY RATE The number of children born alive per woman in a cohort of women by the end of their childbearing years. See also total fertility rate.

COMPLETING THE CLINICAL PICTURE The use of epidemiology to define all modes of presentation of a disease and all possible outcomes. One of the “uses of epidemiology” identified by J. N. Morris.87

COMPLETION RATE The proportion or percentage of persons in a survey for whom complete data are available for analysis. See also response rate.

COMPLEX TRAIT (Syn: polygenic trait, multifactorial trait) Any phenotype that results from the effect of multiple genes at two or more loci, often from environmental influ- ences as well.23

COMPLIANCE See adherence.

COMPONENT CAUSES Multiple causes (not necessarily risk factors) that act jointly to cause a given effect. They do so in different combinations, each combination of compo- nent causes capable of giving rise to particular effects. No component cause is sufficient to produce the effect. In some processes (e.g., diseases), one of the component causes is necessary, but in other instances this is not so (i.e., none of the component causes may be necessary). The frequency of the components of a sufficient cause influences their relative strength. This heuristic model is useful when it also integrates the analysis of antecedent causes, the sequence and time order of causal events, and causal processes that operate at different levels.12,66–69,88

COMPOSITE INDEX An index, such as the Apgar score or the tumor/nodes/metastases (TNM) system to stage cancer, that contains contributions from categories of several different variables.

COMPOSITIONAL EFFECTS Effects of individual-level factors (i.e., characteristics of individuals within a group or area, such as individual income) on individual-level out- comes after accounting for the effects of relevant group- or area-level factors (referred to as contextual effects). They are estimated using multilevel analysis.89 See also causes in public health sciences.

COMPRESSION OF MORBIDITY A term describing abbreviation of the average period of life when chronic illness or disability affects physical, mental, or social func- tion. In theory, as health promotion and disease prevention become more efficacious, this period of long-term morbidity is compressed into a smaller proportion of the total life span. Empirical observations in several countries have failed to demonstrate the phenomenon. Others envisage an expansion of morbidity or a state of balance. See also rectangularization of mortality.

CONCORDANCE Pairs or groups of individuals of identical phenotype. In twin studies, a condition in which both twins exhibit or fail to exhibit a trait under investigation.

CONCORDANT A term used in twin study to describe a twin pair in which both twins exhibit a certain trait and in matched pair analysis when the pairs match.

CONCURRENT STUDY See cohort study.

CONDITIONAL PROBABILITY The probability of an event given that another event has occurred. If D and E are two events and P (…) is “the probability of (…),” the conditional probability of D given that E occurs is denoted P(D|E), where the vertical slash is read “given” and is equal to P(D and E)/P(E). The event E is the “conditioning event.” Conditional probabilities obey all the axioms of probability theory. See also Bayes’ Theorem; probability theory.

CONFIDENCE INTERVAL (CI) The conventional form of an interval estimate, computed in statistical analyses, based on the theory of frequency probability. If the under- lying statistical model is correct and there is no bias, a confidence interval derived from a valid analysis will, over unlimited repetitions of the study, contain the true parameter with a frequency no less than its confidence level (often 95% is the stated level, but other levels are also used).12

CONFIDENCE LIMITS The upper and lower boundaries of the confidence interval.

CONFIDENTIALITY The obligation not to disclose information; the right of a person to withhold information from others. Information in medical records, case registries, and other data files and bases is generally confidential, and epidemiologists are required to obtain permission before being given access to it. This may be the informed consent of the person to whom the records relate or the permission of an institutional review board. Epidemiologists have an obligation to preserve confidentiality of information they obtain during their studies. See also informed consent; privacy.

CONFIRMATION BIAS A form of bias that may occur when evidence that supports one’s preconceptions is evaluated differently from evidence that challenges these convictions.34 The tendency to test one’s beliefs or conjectures by seeking evidence that might confirm or verify them and to ignore evidence that might disconfirm or refute them.90 See also consistency.

CONFLICT OF INTEREST Compromise of a person’s objectivity when that person has a vested interest (e.g., in peer review, in the outcome of a study). It occurs when the person could benefit financially or in other ways (e.g., promotion, tenure, prestige) from some aspect of a study, report, or other professional activity. Conflicts of interest are not limited to research settings. See also disclosure of interests.

CONFOUNDING (From the Latin confundere, to mix together) Loosely, the distortion of a measure of the effect of an exposure on an outcome due to the association of the exposure with other factors that influence the occurrence of the outcome. Confounding occurs when all or part of the apparent association between the exposure and outcome is in fact accounted for by other variables that affect the outcome and are not them- selves affected by exposure.5–12 See also confounding bias.

CONFOUNDING BIAS (Syn: confounding)

1. Bias of the estimated effect of an exposure on an outcome due to the presence of a common cause of the exposure and the outcome. Example: The effect of aspirin use on the risk of stroke will be confounded if aspirin is more likely to be prescribed to individuals with heart disease, which is hence both an indication for treatment and a risk factor for the disease. Heart disease may be a risk factor for stroke if it has a direct causal effect on stroke (heart disease is then the common cause of aspirin use and stroke) or if atherosclerosis causes both heart disease and stroke (atherosclerosis is then the common cause).
   
2. Bias of the estimated effect of an exposure on an outcome due to baseline differences among exposure groups in the risk factors for the outcome, or differences in potential
   

outcomes.91 Unlike the first definition, this definition includes biases produced by selection when the selection occurred prior to the exposure of interest (e.g., m-bias82 and confounding by indication). Confounding bias is often equated with lack of collapsibility, but the latter concept is purely numerical, not causal.

CONFOUNDING BY INDICATION A type of confounding bias that occurs when a symptom or sign of disease is judged as an indication (or a contraindication) for a given therapy and is therefore associated both with the intake of a drug or medical procedure (or its avoidance) and with a higher probability of an outcome. The reason to initiate treatment, assessed by a health professional or by the patient, is thus associated both with the prescription of a drug (or with self-medication) and with a higher probability of a particular outcome—usually adverse. Confounding by indication generally arises in a common clinical situation and in full coherence with clinical logic: before beginning to take a given drug patients who are prescribed the drug have a poorer prognosis (or a higher risk of a disease-related adverse outcome) than patients who do not receive the drug. Confounding by indication stems from an initial lack of similarity in the prog- nostic expectations of treated and nontreated subjects.92 It shares some features with “susceptibility bias,” “procedure selection bias,” protopathic bias, and selection bias.

CONFOUNDING, NEGATIVE Confounding that produces a downward bias in the effect estimate. Alternatively, confounding that dillutes, underestimates, obscures, or attenu- ates (rather than exaggerates or overestimates) the estimated effect of an exposure on an outcome. These alternative definitions often coincide for causal factors but are opposites for preventive factors; hence the term can be confusing.

CONFOUNDING, POSITIVE Confounding that produces an upward bias in the effect estimate. Alternatively, confounding that creates, overestimates, or exaggerates (rather than underestimates) the estimated effect of an exposure on an outcome. These alterna- tive definitions often coincide for preventive factors but are opposites for causal factors; hence the term can be confusing.

CONFOUNDING VARIABLE, CONFOUNDER A variable that can be used to decrease confounding bias when properly adjusted for. The identification of confounders requires expert or substantive knowledge about the causal network of which exposure and outcome are part (e.g., pathophysiological and clinical knowledge). Attempts to select confounders solely based on observed statistical associations may lead to bias.12,31,69,93

CONNECTION Something that can be shown to make a difference: an observed change in state (the effect) is consequent on change in an independent antecedent state (the cause) and not vice versa. One of the three essential properties of a cause specified by David Hume, along with association and time order. It requires the elimination of alternative explanations (e.g., confounding).9,71 See also direction.

CONSANGUINE Related by a common ancestor within the previous few generations.

CONSENT BIAS A type of selection bias in epidemiological and clinical studies caused by the process of asking for informed consent (e.g., to be interviewed for the study, to access medical records, to store biological specimens). The sample of subjects, records, or specimens included in the study is systematically different from the original sample.

CONSISTENCY

1. Close conformity between the findings in different samples, strata, or populations, or at different times or in different circumstances, or in studies conducted by different methods or investigators. Consistency may be examined in order to study an effect modifier. Consistency of results on replication of studies is an important criterion in judgments of causality. See also confirmation bias; Hill’s criteria of causation.

1. In statistics, an estimator is said to be consistent if the probability of its yielding
   estimates close to the true value approaches 1 as the sample size grows larger.
   
2. A potential or counterfactual outcome under exposure level a is said to be consistent when, for each individual actually exposed to level a, its value equals that of the
   observed outcome.
   

CONSORT Consolidated Standards of Reporting Trials. An evidence-based and structured approach to reporting clinical trials. Its central features include a checklist and a flow diagram spelling out the important features of the trial [i.e., protocol, methods, participant (subject) assignment, masking procedures, details of analysis, participant flow, results, and follow-up]. The aim is to improve the quality of reporting of rand- omized trials (www.consort-statement.org and http://www.cochrane.dk).94,95 See also moose; quorom; stard; strobe.

CONTACT, DIRECT A mode of transmission of infection between an infected host and a susceptible host. Direct contact occurs when skin or mucous surfaces touch, as in shaking hands, kissing, and sexual intercourse. See also contagion; transmission of infection.

CONTACT, INDIRECT A mode of transmission of infection involving fomites or vectors. Vectors may be mechanical (e.g., filth flies) or biological (when the disease agent under- goes part of its life cycle in the vector species). See also transmission of infection.

CONTACT, PRIMARY Person(s) in direct contact or associated with a communicable disease case.

CONTACT, SECONDARY Person(s) in contact or associated with a primary contact.

CONTACT (OF AN INFECTION) A person or animal that has been in such association with an infected person or animal or a contaminated environment as to have had opportunity to acquire the infection.

CONTACT TRACING See case finding.

CONTAGION The transmission of infection by direct contact, droplet spread, or contaminated fomites. These are the modes of transmission specified by Fracastorius (1484–1553) in De Contagione (1546). Contemporary usage is sometimes looser, but use of this term is best restricted to description of infection transmitted by direct contact.

CONTAGIOUS Transmitted by contact; in common usage, “highly infectious.”

CONTAINMENT The concept of regional eradication of communicable disease, first pro- posed by Soper in 1949 for the elimination of smallpox.96 Containment of a worldwide communicable disease demands a globally coordinated effort, so that countries that have effected an interruption of transmission do not become reinfected following importation from neighboring endemic areas.

CONTAMINATION

1. The presence of an infectious, toxic, or otherwise harmful agent (radioactive material, biological or chemical compounds) on or in the body—also on or in clothes, bedding, toys, medical devices, surgical instruments or dressings, other objects; in air, water, and food; or on buildings or land. Pollution may be deemed distinct from contamination: the agent causing the pollution or present in the polluted environment is noxious but not necessarily infectious. Contamination of a body surface does not imply a carrier state. See also source of infection; transmission of infection.

2. The situation that exists when a population being studied for one condition or factor also possesses other conditions or factors that modify results of the study. In a randomized controlled trial, the application of the experimental procedure to members of the control group or failure to apply the procedure to members of the experimental group.

CONTAMINATION, DATA In computing, the intentional or accidental alteration of data (e.g., in a computer system).

CONTEXTUAL ANALYSIS Analysis of contextual effects.

CONTEXT

1. The location of a person by time and place; the latter refers to both geographical location and to group membership (e.g., in terms of family, friends, age, class, ethnicity, residence, gender). Context may affect exposure to risk and the individual’s response strategies.16
   
2. In linguistics, the text surrounding a word; knowledge of the context allows the reader to gain a better understanding of what the word means.
   

CONTEXTUAL EFFECTS Effects of group- or area-level factors (e.g., neighborhood poverty) on individual-level outcomes after accounting for the effects of relevant individual-level confounders (referred to as compositional effects). They are estimated using multilevel analysis.89 See also integrative research.

CONTINGENCY TABLE A tabular cross-classification of data such that subcategories of one characteristic are indicated horizontally (in rows) and subcategories of another characteristic are indicated vertically (in columns). Tests of association between the characteristics in the columns and rows can be readily applied. The simplest contingency table is the fourfold or 2 × 2, table. Contingency tables may be extended to include several dimensions of classification.

CONTINGENT VARIABLE See intermediate variable.

CONTINUING SOURCE EPIDEMIC (OUTBREAK) An epidemic in which new cases of disease occur over a long period, indicating persistence of the disease source.

CONTINUOUS DATA, CONTINUOUS VARIABLE Data (variable) with a potentially infinite number of possible values along a continuum (e.g., height, weight, enzyme output).

CONTOUR PLOT Diagrammatic presentation, usually computer-generated, of data involving three variables, one each on the horizontal and vertical axes and a third rep- resented by lines of constant value. It can be used in epidemiology to show the distribution of concentration of environmental contaminants. See also perspective plot.

CONTROL

1. (v.) To regulate, restrain, correct, restore to normal.
   
2. (v.) To adjust for or take into account extraneous influences or observations.
   
3. (n. or adj.) Applied to many communicable and some noncommunicable conditions,
   control means ongoing operations or programs aimed at reducing incidence and/or
   prevalence, or eliminating such conditions.
   
4. (n.) As used in the expressions case-control study and randomized control(led) trial,
   control means person(s) in a group that is used for reference in comparison to a case
   group or a treated group, respectively. See control group.
   
5. (adj.) The expression control variable refers to an independent variable other than
   the hypothetical causal variable that has a potential effect on the dependent variable and is subject to control by analysis.
   

CONTROL GROUP, CONTROLS Subjects with whom comparison is made in a case- control study, a randomized controlled trial, or other epidemiological study. The use of the noun control to describe the reference group in a case-control study and in a randomized controlled clinical trial may be confusing. One essential distinction is that there is no intervention in the lives of the controls in a case-control study, whereas controls in a randomized controlled trial may be asked to undergo a procedure or regimen that may affect their health; their informed consent is therefore essential. Consent may not be required (save to gain access to medical records) to study controls in a case-control study. Another essential difference is that controls in a case-control study are often defined as noncases or by other postexposure events, making them especially susceptible to selection bias. Selection of appropriate controls is crucial to the validity of epidemiological and clinical studies.

CONTROLS, HISTORICAL Persons or patients used for comparison who had the condition or treatment under study at a different time, generally at an earlier period than the study group or cases. Historical controls are often unsatisfactory because other factors affecting the condition under study may have changed to an unknown extent in the time elapsed.

CONTROLS, HOSPITAL Persons used for comparison who are drawn from the popula- tion of patients in a hospital. If wrongly chosen, hospital controls may be a source of selection bias.

CONTROLS, MATCHED Controls who are selected so that they are similar to the study group, or cases, in specific characteristics. Some commonly used matching variables are age, sex, race, and socioeconomic status.5,12,97 See also matching.

CONTROLS, NEIGHBORHOOD Persons used for comparison who live in the same locality as cases and therefore may resemble cases in environmental and socioeconomic criteria.

CONTROLS, SIBLING Persons used for comparison who are the siblings of cases and therefore share genetic makeup.

CONVENIENCE SAMPLE See sample.

COORDINATES In a two-dimensional graph, the values of ordinate and abscissa that define the locus or position of a point.

CORDON SANITAIRE The barrier erected around a focus of infection. Used mainly in the isolation procedures applied to exclude cases and contacts of life-threatening communicable diseases from society. Mainly of historical interest.

CORRELATION The degree to which variables change together. How closely two (or more) variables are related.

CORRELATION COEFFICIENT A measure of association that indicates the degree to which two variables have a linear relationship. This coefficient, represented by the letter r, can vary between +1 and –1; when r = +1, there is a perfect positive linear relation- ship in which one variable varies directly with the other; when r = –1, there is a perfect negative linear relationship between the variables. The measure can be generalized to quantify the degree of linear relationship between one variable and several others, in which case it is known as the multiple correlation coefficient. Kendall’s tau, Spearman’s rank correlation, and Pearson’s product moment correlation tests are special varieties with applications in clinical and epidemiological research.98,99 Lack of correlation does not imply lack of relation, only lack of linear relation on the scale used to assess the cor- relation; therefore the use of correlation as a synonym for relation or association can be misleading. There are also several problems associated with attempting to interpret correlation coefficients as measures of effect, among them that the correlation coefficient depends on the standard deviations of the causal and outcome variable. It can therefore vary greatly across populations and subgroups, even if the increase in the mean outcome, risk, or rate produced by exposure is identical across populations and subgroups.

CORRELATION, INTRACLASS A measure of the degree of relationship between two variables that presents the proportion of intersubject variance with respect to total variance (e.g., it compares the variance between patients to the total variance, including both between- and within-patient variance). It is used, for example, to assess interraterreliability or the reproducibility of a diagnostic test.

CORRELATION, NONSENSE A meaningless correlation between two variables. Non- sense correlations sometimes occur when social, environmental, or technological changes have the same trend as incidence or mortality rates. An example is the cor- relation between the birthrate and the density of storks in parts of Holland. See also association, fortuitous; confounding bias; ecological fallacy.

COST The value of resources engaged in a service.100

COST, AVERAGE The average cost per unit; equals the total costs divided by the units of production.

COST, AVOIDED Costs caused by a health problem that are avoided by a health care intervention. Estimating avoided costs is one way to assess the value of benefits of health care interventions; sometimes known as benefits.

COST-BENEFIT ANALYSIS An analysis of the economic and social costs of medical care and the benefits of reduced loss of net earnings owing to the prevention of premature death or disability. The general rule for the allocation of funds in a cost-benefit analysis is that the ratio of marginal benefit (the benefit of preventing an additional case) to marginal cost (the cost of preventing an additional case) should be equal to or greater than 1. The benefit-cost ratio is the ratio of net present value of measurable benefits to costs. Calculation of a benefit-cost ratio is used to assess the economic feasibility or success of a public health program.

COST, DIRECT Those costs borne by the health care system, the community, and patients’ families (e.g., costs of diagnosis and treatment).

COST-EFFECTIVENESS ANALYSIS This form of analysis seeks to determine the costs and effectiveness of an activity or to compare similar alternative activities to determine the relative degree to which they will obtain the desired objectives or outcomes. The preferred action or alternative is one that requires the least cost to produce a given level of effectiveness or that provides the greatest effectiveness for a given level of cost. In the health care field, outcomes are measured in terms of health status.

COST, FIXED Costs that, within a defined period, do not vary with the quantity produced (e.g., overhead costs of maintaining a building).

COST, INCREMENTAL The difference between marginal costs of alternative interventions.

COST, INDIRECT Lost productivity caused by disease and borne by the individual, the family, society, or the employer.

COST, INTANGIBLE Costs of pain, grief, suffering, loss of leisure time; the cost of a life is usually included in case of death.

COST, OPPORTUNITY See opportunity cost.

COST, TOTAL All costs incurred in producing a set quantity of service.

COSTS, MARGINAL The additional costs from an increase in an activity. The additional cost incurred as a result of the production of one extra unit of output; the increase is equal to the cost of the next unit produced.

COST-UTILITY ANALYSIS A form of economic evaluation in which the outcomes of alternative procedures or programs are expressed in terms of a single “utility-based” unit of measurement. A widely used utility-based measure is the quality-adjusted life year (QALY). See also utility.

COUNTERFACTUAL DEFINITION A measure of effect in which at least one of two circumstances in the definition of variables must be contrary to fact.12 An example is a hypothetical control group that represents what the distribution of exposure would have been if past events had been different from what they actually were. In a case- specular study design, the counterfactual control group comprises (imaginary) dwellings on the opposite side of the street from the dwellings occupied by the cases. The purpose is to assess what the exposure would have been in these hypothetical dwellings. The counterfactual difference in past exposure must be defined precisely to facilitate unambiguous calculation of variables in the hypothetical control group.101

COUNTERFACTUAL LOGIC Deductive reasoning that involves counterfactual premises or conditions (premises or conditions that are known to be contrary to fact). For exam- ple, in a thought experiment, an entity imagining that it had been exposed to the change agent is compared with the same entity had there been no exposure; or an entity that had no exposure to the change agent is compared with the same entity imagining that it had been exposed.102 See also potential outcome.

COUNTERMATCHING A matching procedure for case-control studies nested within a cohort when exposure status is known for all cohort members and information about confounders is acquired only on a sample of paired cases and controls; “countermatching” to each exposed case an unexposed control, and vice versa, may improve the efficiency of the study.103

COVARIATE A variable that is possibly predictive of the outcome under study. A covariate may be of direct interest to the study or may be a confounding variable or effect modifier.

COVERAGE A measure of the extent to which the services rendered cover the potential need for these services in a community. It is expressed as a proportion in which the numerator is the number of services rendered and the denominator is the number of instances in which the service should have been rendered.

Example:

COX MODEL See proportional hazards model.

CREATIVITY

1. The ability to produce ideas, policies and objects (including “knowledge objects”) that are both novel or original and worthwhile or appropriate (i.e., useful, attractive, meaningful, and valid).90
   
2. In epidemiological research, the capacity of a set of studies to harmonize relevance, validity, meaning, innovation, feasibility, and precision—ideally, beauty
3. and simplicity as well. An epidemiological study reflects creativity to the extent that it generates knowledge that is relevant, new, valid, practical, and precise. Complexity may be a plus; it need not clash with simplicity and elegance. Relevance may be social, environmental, sanitary, clinical, biological, methodological, ethical, technological, intellectual…. Studies may blend, weave, knit, or weld such qualities in extraordinarily different ways.

A public health policy or program shows creativity when it is relevant, meaningful, useful, and attractive for populations, persons, and institutions… when it is innovative, imaginative, simple… if effective and efficient in abating harmful determinants of health and significantly improving important health indicators. It may be morally and socially relevant if it increases freedom, justice, education, equity, or social cohesion. It needs be culturally, environmentally, and economically sustainable… Creativity is an importat value for epidemiology and the other health, life, and social sciences.104

CRITERION A principle or standard by which something is judged. See also standard.

CRITICAL APPRAISAL Application of rules of evidence to a study to assess the validity of the data, completeness of reporting, methods and procedures, conclusions, compliance with ethical standards, etc. The rules of evidence vary with circumstances. See also hierarchy of evidence.

CRITICAL PERIOD See sensitive period.

CRITICAL TIME WINDOW (Syn: etiologically relevant exposure period) The period during which exposure to a causal factor is relevant to causation of a disease.

CRITICAL POPULATION SIZE The theoretical minimum host population size required to maintain an infectious agent. This size varies depending on the agent and demo- graphic, social, and environmental conditions (hygiene, ambient temperature, etc.) and, in the case of vector-borne diseases, the conditions required for survival and propaga- tion of the vector species.

CRONBACH’S ALPHA (Syn: internal consistency reliability) An estimate of the correlation between the total score across a series of items from a rating scale and the total score that would have been obtained had a comparable series of items been employed.

CROSS-CULTURAL STUDY A study in which populations from different cultural back- grounds are compared.

CROSS-DESIGN SYNTHESIS A method for evaluating outcomes of medical interventions developed by the U.S. General Accounting Office (GAO).105 It is conducted by pooling databases such as the results of a randomized controlled trial (RCT) and of routinely treated patients; the latter databases may come from hospital discharge statis- tics and other sources. Thus it is a variation of meta-analysis.106 This method is claimed to be more relevant to daily practice than some RCTs because it includes outcomes of patients in categories not included in RCTs; however, the validity of the databases should be carefully assessed.

CROSS–INFECTION Infection of one person with pathogenic organisms from another and vice versa. Not the same as nosocomial infection, which occurs in a health care set- ting; cross-infection can occur anywhere (e.g., in military barracks, schools, workplaces).

CROSS-LEVEL BIAS Biases occurring in ecological studies owing to aggregation at the population level of causes and/or effects that do not aggregate, operate, or interact at the individual level.107 See also ecological fallacy, aggregative fallacy, atomistic fallacy.

CROSSOVER CLINICAL TRIAL, CROSSOVER EXPERIMENT A method of compar- ing two (or more) treatments or interventions in which subjects, upon completion of one treatment, are switched to the other. In the case of two treatments, A and B, half the patients are randomly allocated to receive these in the order “A first, then B,” and half to receive them in the order “B first, then A.” The outcomes cannot be perma- nent changes (e.g., they can be symptoms, functional capacity). A “washout” phase is often needed before beginning the second treatment. The analysis will have to check whether a carryover effect was present. If the biological and clinical bases of the trial are coherent, the results will be unbiased and the design will help reduce “noise” and sample size requirements. See also case-crossover study; n-of-one study.

CROSS-PRODUCT RATIO See odds ratio.

CROSS-SECTIONAL STUDY (Syn: disease frequency survey, prevalence study) A study that examines the relationship between diseases (or other health-related characteris- tics) and other variables of interest as they exist in a defined population at one particu- lar time. The presence or absence of disease and the presence or absence of the other variables (or, if they are quantitative, their level) are determined in each member of the study population or in a representative sample at one particular time. The relationship between a variable and the disease can be examined (1) in terms of the prevalence of disease in different population subgroups defined according to the presence or absence (or level) of the variables and (2) in terms of the presence or absence (or level) of the variables in the diseased versus the nondiseased. Note that disease prevalence rather than incidence is normally recorded in a cross-sectional study.31 The temporal sequence of cause and effect cannot necessarily be determined in a cross-sectional study. See also morbidity survey.

CROSS-VALIDATION A statistical method for model development and testing based on splitting the data set into a training sample to which a model is fit, and test sample on which the model is tested. In modern applications, this process is repeated many times using different (possibly random) splits of the data, and the final model is derived by synthesizing over the results from each split. Cross-validated models tend to exhibit far better generalizability (out-of-sample performance) than conventionally fitted models. See also jacknife; machine learning; overfitting.

CRUDE DEATH RATE See death rate.

CULTURE

1. In microbiology, the growth of an organism in or on a nutrient medium.
   
2. In social science, a set of beliefs; values; intellectual, artistic, and religious characteristics; customs, etc., common to and characteristic of a community or nation. Culturally determined characteristics include language, acceptable gender roles and
   occupations, and much health-related behavior.108
   

CUMULATIVE DEATH RATE The proportion of a group that dies over a specified time interval. It is the incidence proportion of death. This may refer to all deaths or to deaths from a specific cause or causes. If follow-up is not complete on all persons, the proper estimation of this rate requires the use of methods that take account of censoring. Distinct from force of mortality.

CUMULATIVE INCIDENCE, CUMULATIVE INCIDENCE RATE (Syn: incidence propor- tion, average risk) The number or proportion of a group (cohort) of people who experi- ence the onset of a health-related event during a specified time interval; this interval is generally the same for all members of the group, but, as in lifetime incidence, it may vary from person to person without reference to age.

CUMULATIVE INCIDENCE RATIO The ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed.

CUSUM Acronym for cumulative sum (of a series of measurements). A way to demonstrate a change in trend or direction of a series of measurements.109 Calculation begins with a reference figure (e.g., the expected average measurement). As each new meas- urement is observed, the reference figure is subtracted, and a cumulative total is pro- duced by adding each successive difference; this cumulative total is the CUSUM.

CUT POINT An arbitrarily chosen point or value in an ordered sequence of values used to separate the whole into parts. Commonly the cut point divides a distribution of val- ues into parts that are arbitrarily designated as within or beyond the range considered normal. For example, a cut point of 85, 90, or 95 mm Hg differentiates normal from high blood pressure. Synonym: cutoff point.

CYCLICITY, SEASONAL The annual cycling of incidence on a seasonal basis. Certain acute infectious diseases, if of greater than rare occurrence, peak in one season of the year and reach the low point 6 months later (or in the opposite season). The onset of some symptoms of some chronic diseases also may show this amplitudinal cyclicity. Demographic phenomena, such as marriages, births, and mortality from all causes and certain specific causes may also exhibit seasonal cyclicity. See also chronobiology.

CYCLICITY, SECULAR Fluctuation in disease incidence over a period longer than a year. For instance, in large, unimmunized populations, measles tends to have a 2-year cycle of high and low incidence. Empirical observations of secular and seasonal cycles of infectious diseases were the basis for epidemic theory (e.g., the mass action principle). Mass immunization programs, by raising herd immunity levels, have eliminated many such cycles.

CYST COUNT See worm count.