PUBLIC HEALTH MAnERS Causation and Causal Inference in Epidemiology Kenneth J. Rothman. DrPH. Sander Greenland. MA, MS, DrPH. C Stat fixed. In other words, a cause of a disease Concepts of cause and causal inference are largely self-taught from early learn- ing experiences. A model of causation that describes causes in terms of suffi- event is an event, condition, or characteristic cient causes and their component causes illuminates important principles such that preceded the disease event and without as multicausality, the dependence of the strength of component causes on the which the disease event either would not prevalence of complementary component causes, and interaction between com- have occun-ed at all or would not have oc- ponent causes. curred until some later time. Under this defi- Philosophers agree that causal propositions cannot be proved, and find flaws or nition it may be that no specific event, condi- practical limitations in all philosophies of causal inference. Hence, the role of logic, tion, or characteristic is sufiicient by itself to belief, and observation in evaluating causal propositions is not settled. Causal produce disease. This is not a definition, then, inference in epidemiology is better viewed as an exercise in measurement of an of a complete causal mechanism, but only a effect rather than as a criterion-guided process for deciding whether an effect is pres- component of it. A "sufficient cause," which ent or not. (4m JPub//cHea/f/i. 2005;95:S144-S150. doi:10.2105/AJPH.2004.059204) means a complete causal mechanism, can be defined as a set of minimal conditions and What do we mean by causation? Even among eral. The tendency to identify the switch as events that inevitably pT'oduce ciisease; "mini- those who study causation as the object of their the unique cause stems from its usual i-ote as mal" implies that all ofthe conditions or work, the concept is largely self-taught, cob- the final factor that acts in the causal mecha- events are necessar}' to tliat occurrence. In bled together fioni early experiences. As a nism. The wiring can be considered part of disease etiology, the completion of a sufficient youngster, each person develops and tests an the causal mechanism, but once it is put in cause may be considered equivalent to the inventory of causal explanations that brings place, it seldom warrants further attention. onset of disease. (Onset here refers to the meaning to perceived events and Ihat ulti- The switch, however, is often the only part of onset of the earliest stage of the disease pro- mately leads to more control of those events. the mechanism that needs to be activated to cess, rather than the onset of signs or symp- toms,) For biological effects, most and some- Because our first appreciation ofthe con- obtam the effect of turning on the light. The times all of the components of a sufficient cept of causation is based on our own direct effect usually occurs immediately after turn- cause are unknown.' observations, the resulting concept is limited ing on the switch, and as a result we slip into by the .scope of those obsei-vations. We typi- the fi^ame of thinking in which we identify the For example, tobacco smoking Ls a cause of cally observe causes with effects that are im- switch as a unique cause. The inadequacy of lung cancer, but by itself it is not a sufficient mediately apparent. For example, when one this assumption is emphasized when the bulb cause. First the term smoking is too imprecise turns a light switch to the "on" position, one goes bad and needs to he replaced, 'lliese to be used in a causal description. One must normally sees the instant efTect of the light concepts of causation that are established specify the type of smoke (e.g., cigarette. going on. Nevertheless, the causal mechanism empirically early in life are too rudimentary cigar, pipe), whether it is filtered or unfiltered, for getting a light to shine involves more to serve well as the basis for scientific theo- the manner and frequency of inhalation, and than turning a light switch to "on." Suppose ries. To enlarge upon them, we need a more the onset and duration of smoking. More im- a storm has downed the electric lines to the general conceptual model that can serve as a portantly, smoking, even defined explicitly, building, or the witnng is faulty, or the bulb common stalling point in discussions of will not cause cancer in everyone. Appar- is burned out—in any of these cases, turning causal theories. ently, there are some people who, by virtue the switch on wili have no efFect One cause of their genetic makeup or previous experi- ofthe light going on is having the switch in SUFFICIENT AND COMPONENT ence, are susceptible to the effects of smok- the proper position, but along with it we CAUSES ing, and others who are not. These suscepti- must have a supply of power to the circuit, hiWty factors are other components in the good wiring, and a working bulb. When all The concept and definition of causation various causa] mechanisms through which other factors are in place, turning the switch engender continuing debate among philoso- smoking causes lung cancer. will cause the light to go on, but if one or phers. Nevertheless, researchers interested in Figure 1 provides a schematic diagram of more of the other factors is lacking, the light causal phenomena must adopt a working defi- sufficient causes in a hypothetical individual, will not go on. nition. We can define a cause of a specific dis- Kach constellation of component causes rep- Despite the tendency to consider a switch ease event as an antecedent event, condition, resented in Figure 1 is minimally sufficient to as the unique cause of turning on a light, the or characteristic that was necessary for the produce the disease: that is, there is no redun- complete causal mechanism is more intricate, occun'ence of the disease at the moment it dant or extraneous component cause. Kach and the switch is only one component of sev- occun-ed, given that other conditions are one is a necessary part of that specific causal S144 I Public Health Matters ( Peer Reviewed I Rothman and Greenland American Journai of Public Heaith | Supplement 1, 2005. Vol 95, No, SI PUBLIC HEALTH MAHERS disease frequency produced by introducing tbe factor into a population. Tbis cbange may be measured in absolute or relative terms. In eitber case, tlie strength of an effect may bave tremendous public health significance, bul it may have little biological signili :ance. Tbe reason is that given a spedfic causal mechanism, any ol' the component causes can have strong or weak efTects. Tbe aetua! iden- tity of tbe constituent components of tbe causal mecbanism amounts to the biology of causation. In contrast, the strengtb of a fac- One Causal Mechanism Single Component Cause tor's effect depends on the time-specific distri- bution of its causal complements in the popu- FIGURE l-Three sufficient causes of disease. lation. Over a span of time, tbe strengtb of tbe effect of a given factor on the occurrence of a given disease may change, because tbe prevalence of its causal complements in vari- mechanism. A specific component cause may sertion tbat tbere are nearly always some ous causal mechanisms may also cbange. play a role in one, two, or all three of the genetic and some environmental component The causal mechanisms in which the factor causal mechanisms pictured. causes in every causa! mecbanism, Tbus, and its complements act could remain un- even an event sucb as a fall on an icy patb changed, however. MULTiCAUSAUTY leading to a broken bip is part of a compli- cated causal mecbanism tbat involves many The model of causation implied by component causes. INTERACTION AMONG CAUSES Figure 1 illuminates several important princi- Tbe importance of multicausality is tbat ples regaRJiiig causes. Perhaps the most im- most identified causes are neitber necessar}' Tbe causal pie model posits tbat several portant of these principles is self-evident from nor sufficient to produce disease, Nevertbe- causal components act in concert to produce the model: A given disease can be caused by less, a cause need not be eitber necessary or an effect. "Acting in concert" does not neces- more than one causal mechanism, and ever}' sufficient for its removal to result in disease sarily imply that factors must act at tbe same causal mechanism involves tbe joint action of prevention. If a component cause tbat is nei- dme. Consider tbe example above of tbe per- a multitude of component causes. Consider tber necessary nor sufficient is blocked, a sub- son wbo sustained trauma to the head that as an example the cause of a broken bip. Sup- stantial amount of disease may be prevented, resulted in an equilibrium disturbance, pose tbat someone experiences a naumatie Tbat tbe cause is not necessary implies tbat wbieh led, years later, to a fall on an icy injury to the bead tbal leads to a permanent some disease may still occur after tbe cause path. Tbe earlier head trauma played a disturbance in equilibrium. Many years later, is blocked, but a component cause wili never- causal role in tbe later hip fracture: so did the faulty equilibrium plays a causal role in a theless be a necessary cause for some of the the weatber conditions on the day of tbe fall tbat occui"s wbile tbe person is walking cases tbat occur, Tbat tbe component cause is fracture. If both of tbese factors played a on an icy patb.