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Case-control studies
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ofa group ofpatients the characteristics - - --<-\)ntrol study compares (the cases)to a group of individuals outcome i rirnicular disease ' (the controls)' to see whether exposureto . -_ r diseaseoutcome -r _:iroroccurredmoreorlessirequently inthecasesthanthecontrols -' : : :h.I ). Such rerospective studiesdo not provide information on :t :::r alenceor incidenceof diseasebut may give clues as to which orreducethe riskof disease. -.' :. elevate

Slection of cases
-'< :lisibility criteria for casesshould be precise and unambiSuous : : liebetes mellitus lWorld Hea]th Organjzation criteriall single . _ _ glucose concenlrrli,rn >7 mmol/liLre Ur renous plasma I --,\e measured2 hours after ingestion of 75g oral glucose load :rmol/litre). [n particular,it is importantto deline whether incident .,<. pntientswho are recruitedat the time ofdiagnosis) or prevalent entering the study) -,<. pirtientswho were already diagnosedbefore . casesmay have had time to reflecl on Prevalent J be recruited. ially if the di sease -.- : hi of exposureto know n ri sk factors.espec 'lory altered their may have and , ,rell-publicized one such as cancer, citsesas many identify as to lt is important -r-:\ iour after diagnosis. can conclusions and the weight more results cany :, -.rble so that lhe to '< !.neralized to future populations.To this end, it may be necessary and to includecaseswho registries. hospitallists and disease -::.' controls were recrulted' - a.: Juring the time period when casesand _<::usetheir excluskrnmay lead to a biasedsarnpleofcases.

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ofa case{ontrol stLldy. rcprcsentation Figure16.1 Diagrammatic rcquired.it is importantk) documcnthow the controlsshouldbeselected liom all eligibleindividuals) (c.g.bt randomselection

ldentification of risk tactors

As in irny epiclemiologicalstudy. lhe poteilial risk factors should be delined betbre conducting thc study The delinition of lhese factors of interestshould be clear and unambiguous(e g in a case-controlstudy for the developmentofdiabetes mellitus, where exercise'is the factor of interest,there should be a clexr explanationot'how exerciseis to be measuredand categorized).A pilot study may help to ensure that the definition will be feasible given the need to rely on retrospectively collecreddata and/orInemory.Othertactors which may have an impact (Chapter eitherasconfounders on the outcome(i.e-case{ontrol status), 34) and/or effect modifiers,should also be listed and defined.

Selection of controls
: . * rrhcuses. rheeliEibilir)(riterir for (onlrol. shnulJllso he preci'e at entry to the study to Controls should be screened -_J unambiguous. Where possible' interest. of the disease not have they do :-.Lrre that ':trols shouldbe selected from the samesourceas cases Controls are related to one ::an selectedfrom hospitals. However, as risk f-actors ::.eir\e outcome may also be related to other diseaseoutcomes' the controls may over-selectindividuals whtr < .ction of hospital-based _:\('been exposedto the risk lactor ofinterest' and may. therefore' not to selectcontrols fiom the It is often acceptable -.i\ ir] s be appropriate. as motivatedto take part may not be they ::neral population,although be poorerin control\ mr) therelL're .rr.h stuJ). rrte\ re.pon\e and a ':rn cases. The use of neighbourhood controls may ensure that Ol note, it is -i.cs and controls are fiom similar social backgrounds. :rportant b avoid the temptation to relax the criteria fbr eligibility : .,'nlrol\ pafl-ua) lhrougha slud) timpl) lt'.peed up the procets [ -aanrilment. \lthough most case{ontrol studiesinclude only a single control tbr :J.h casek)tien referredto asa I ll case-controlstudy).it is possibleto :ilude multiple controlsfor each case (a l:n case{ontrol study)' lncreasednumbers of controls per case will provide the study with :r. aler power (Chapter l8), althoughany suchgains in powerare likely :,r be fairly srnall beyond four controls per casel Where a greater :umber of individuals are eligible to be selectedas controls than is

Matching
Many case-control studies are matched in order to select casesand controls who are as similar as possible. we may have frequency matching on a g/orp basis(i.e. the averagevalueofeach ofthe relevant potentidl risk lactors of the whole group ol casesshould be similar lo that ofthe whole group ofcontrols) orwe may have pairwise matching (i.e. eachcaseis matchedindividually to a control on an in.1ivi../Ila/basis In general. when perlbrming risk factors.). potential has similar who (i.e il thecase it is usefulto sex matchindividuals matching, individual is male, the control should also be maie), and. sometimes.patientswill be agc matched.However, it is important not b match on lhe basisof therisk factorofinterest. oron any factor that falls on the causalpathway of the disease(Chapter34), as this will remove the ability of the study to assessany relationship between the risk factor and the disease' Furthernore, it is important not to match on t()o manv tactors' as this may rest ct the availability of suitable controls Untbrtunately' matching doesmeanthat the eflect on diseascofthe variablesthat have beenusedfbr matching cannotbe studied Case-controlstudies Study design 47

Gdmes, D.A. and Schulz. K.F. (2005) Comparedlo what? Findingcontrols fbr 1429-31. -r'e {ontrol studies.ld,r.et, 365.