Presentation on theme: "Study Designs in Epidemiologic Research"— Presentation transcript:
1 Study Designs in Epidemiologic Research South Asian CardiovascularResearch Methodology WorkshopBasic EpidemiologyStudy Designs in EpidemiologicResearchThomas Songer, PhD
2 Fundamental Assumption in Epidemiology Disease doesn’t occur in a vacuumDisease is not randomly distributed throughout a populationEpidemiology uses systematic approach to study the differences in disease distribution in subgroupsAllows for study of causal and preventive factors
3 Components of Epidemiology Measure disease frequencyQuantify diseaseAssess distribution of diseaseWho is getting disease?Where is disease occurring?When is disease occurring?Formulation of hypotheses concerning causal and preventive factorsIdentify determinants of diseaseHypotheses are tested using epidemiologic studies
4 Types of primary studies Descriptive studiesdescribe occurrence of outcomeAnalytic studiesdescribe association between exposure and outcome
5 Basic Question in Analytic Epidemiology Are exposure and disease linked?EDExposureDisease
6 Basic Questions in Analytic Epidemiology Look to link exposure and diseaseWhat is the exposure?Who are the exposed?What are the potential health effects?What approach will you take to study the relationship between exposure and effect?Wijngaarden
7 Basic Research Study Designs and their Application to Epidemiology • Society will be healthier• Society can save money on health care budgets• It will improve life expectancy• It will improve the economyResponses to this question vary. As outlined below, some believe that altruistically, society should pursue disease prevention to improve health and save money. These are noble goals, but I will demonstrate later that prevention does not always save money. The desire to prevent NCDs probably is a repercussion of our efforts to prevent infectious diseases. We have had great success in preventing communicable diseases. This has led to an initiative to prevent NCDs.
8 Big Picture To prevent and control disease In a coordinated plan, look toidentify hypotheses on what is related to disease and may be causing itformally test these hypothesesStudy designs direct how the investigation is conducted
9 What designs exist to identify and investigate factors in disease?
10 Study Designs Descriptive Analytic Case report Cohort study RCT Case seriesCase-ControlstudyStudy DesignsDescriptiveEpidemiologyCase-CrossoverstudyCross-sectionalAs Koepsell has illustrated in the book, “Injury Control”, injury studies may be descriptive in nature (describing the frequency or characteristics of injury events) or analytic (testing relationships between common traits and injury). Differing forms of descriptive studies exist. These designs are outlined in the next slide.Analytic studies include experimental designs (the randomized controlled trial) and observational designs (case-control studies, cohort studies, etc.). The case-crossover study design has received a lot of attention in the injury field in the last five years.studyBefore-AfterstudyEcologic study
11 Timeframe of StudiesProspective Study - looks forward, looks to the future, examines future events, follows a condition, concern or disease into the futuretimeStudy begins here
12 Timeframe of StudiesRetrospective Study - “to look back”, looks back in time to study events that have already occurredtimeStudy begins here
13 Study Design Sequence Hypothesis formation Case reports Case series DescriptiveepidemiologyAnalyticepidemiologyAnimalstudyLabstudyClinicaltrialsHypothesis testingCohortCase-controlCross-sectional
14 Increasing Knowledge of DevelophypothesisDescriptive StudiesInvestigate it’srelationship tooutcomesCase-control StudiesIncreasing Knowledge ofDisease/ExposureDefine it’s meaningwith exposuresTo further illustrate, if one seeks to identify the etiologic factors (e.g. causal factors) behind an outcome (e.g. an injury), then each step in the epidemiologic framework provides new and important information.Descriptive studies are useful for identifying hypotheses to test in analytic studies. Case-control studies are then usually applied to evaluate if the hypothesized factor is related to the outcome of interest. Subsequently, cohort or longitudinal studies are applied to further define the importance of exposure to the causal agent for the development of the outcome.Cohort StudiesTest linkexperimentallyClinical trials
15 Descriptive Studies • Society will be healthier • Society can save money on health care budgets• It will improve life expectancy• It will improve the economyResponses to this question vary. As outlined below, some believe that altruistically, society should pursue disease prevention to improve health and save money. These are noble goals, but I will demonstrate later that prevention does not always save money. The desire to prevent NCDs probably is a repercussion of our efforts to prevent infectious diseases. We have had great success in preventing communicable diseases. This has led to an initiative to prevent NCDs.
16 Case ReportsDetailed presentation of a single case or handful of casesGenerally report a new or unique findinge.g. previous undescribed diseasee.g. unexpected link between diseasese.g. unexpected new therapeutic effecte.g. adverse events
17 Case Series Experience of a group of patients with a similar diagnosis Assesses prevalent diseaseCases may be identified from a single or multiple sourcesGenerally report on new/unique conditionMay be only realistic design for rare disorders
18 Case Series Advantages Disadvantages Useful for hypothesis generation Informative for very rare disease with few established risk factorsCharacterizes averages for disorderDisadvantagesCannot study cause and effect relationshipsCannot assess disease frequency
19 Houseboat Carbon Monoxide Poisonings on Lake Powell Study designDefinition of injuryData SourcesPopulationBiasFindingsCase seriesCO poisoningNPS EMS transport recordsLake Powell eventsmissing casesoutdoor exposuresThe first paper to examine is the MMWR paper on carbon monoxide poisonings noted at Lake Powell. This paper attempts to identify all CO poisoning events identified from the EMS records of the National Park Service from It is thus a case series study design. The study was initiated because of case reports of CO poisoning death related to houseboats on the lake. The definition of injury used was based upon information in the transport records. Cases were defined as events with either (a) symptoms of CO poisoning and laboratory elevated carboxyhemoglobin values or (b) exposure to exhaust and symptoms. By design, only injuries receiving medical attention are included in this study.The study is unique in that it found several cases of outdoor exposure to CO poisoning. CO poisoning is most often found in indoor settings. The report suggests that the placement of generators on houseboats creates a poisoning hazard. It implies causality related to these generators, but the design cannot prove it in the strict methodologic sense. Potential bias in the report may be the underascertainment of CO poisoning cases. It is not clear how accurate the NPS transport records may be.Source: Houseboat associated carbon monoxide poisonings on Lake Powell. MMWR 49(49): , December 15, 2000.
20 cases with denominator One case of unusualinjury findingCase ReportMultiple cases ofinjury findingCase SeriesDescriptiveEpidemiology StudyDescriptive study designs include case reports, case series, incidence studies, and ecologic studies. The case report is the most elementary study design in the literature. It generally describes an injury or injuries to one or two individuals that have been identified in a medical setting. There is also usually a unique feature to the noted injury (by cause, by nature of injury, etc.). The case series design is an extension of the case report. In a case series, a number of events are described. These events usually have been observed over a set period of time (such as one year) and are identified from one reporting source (e.g. a hospital).The descriptive epidemiology study is noted by the collection of injuries over a defined population base and by the use of denominator data to determine rates. The most frequent information generated from these designs are incidence rates for injuries. The ecologic study is a hypothesis generating study. Usually using group-level data, it examines if two factors are correlated with each other.Population-basedcases with denominator
21 Analytical StudiesResponses to this question vary. As outlined below, some believe that altruistically, society should pursue disease prevention to improve health and save money. These are noble goals, but I will demonstrate later that prevention does not always save money. The desire to prevent NCDs probably is a repercussion of our efforts to prevent infectious diseases. We have had great success in preventing communicable diseases. This has led to an initiative to prevent NCDs.
23 Experimental Studiestreatment and exposures occur in a “controlled” environmentplanned research designsclinical trials are the most well known experimental design. Clinical trials use randomly assigned data.Community trials use nonrandom data
24 Observational Studies non-experimentalobservational because there is no individual interventiontreatment and exposures occur in a “non-controlled” environmentindividuals can be observed prospectively, retrospectively, or currently
25 Cross-sectional studies An “observational” design that surveys exposures and disease status at a single point in time (a cross-section of the population)timeStudy only exists at this point in time
26 Cross-sectional Design factor presentNo Diseasefactor absentStudypopulationfactor presentDiseasefactor absenttimeStudy only exists at this point in time
27 Cross-sectional Studies Often used to study conditions that are relatively frequent with long duration of expression (nonfatal, chronic conditions)It measures prevalence, not incidence of diseaseExample: community surveysNot suitable for studying rare or highly fatal diseases or a disease with short duration of expression
28 Cross-sectional studies DisadvantagesWeakest observational design, (it measures prevalence, not incidence of disease). Prevalent cases are survivorsThe temporal sequence of exposure and effect may be difficult or impossible to determineUsually don’t know when disease occurredRare events a problem. Quickly emerging diseases a problem
29 Epidemiologic Study Designs Case-Control Studiesan “observational” design comparing exposures in disease cases vs. healthy controls from same populationexposure data collected retrospectivelymost feasible design where disease outcomes are rare
30 Case-Control Studies Cases: Disease Controls: No disease Case-Control studies represent one form of analytic study that provides information on the relationship between causal factors and injuries. In a case-control study, subjects who have been injured are identified and their past exposure to suspected causal factors is compared with that of controls (persons who have not been injured).Many case-control studies ascertain exposure from personal recall, using either a self administered questionnaire or an interview. The validity of such information will depend in part on the subject matter. People may be able to remember recent events quite well. On the other hand, long term recall is generally less reliable.Source: Chapter 8: Case-control and cross-sectional studies, Epidemiology for the Uninitiated
31 Case-Control Design Study begins here factor present Cases (disease) factor absentStudypopulationfactor presentControls(no disease)factor absentCase-Control DesignpresentpasttimeStudy begins here
32 Case-Control Study Strengths Limitations Less expensive and time consumingEfficient for studying rare diseasesLimitationsInappropriate when disease outcome for a specific exposure is not known at start of studyExposure measurements taken after disease occurrenceDisease status can influence selection of subjects
33 Seismic, structural, and individual factors associated with earthquake related injury Case-control studyfatal or hospital-admittedcoroners office/hospital recordsmoderate to severeLos Angeles Countycontrols identified by phonehigher risk in elderly, women, and apartmentsStudy designDefinition of injuryData SourcesSeverity of InjuryPopulationBiasFindingsMany believe that the health status of older drivers places them at greater risk for motor vehicle accidents. This study examines the association between several medical conditions and motor vehicle accidents resulting in injury. It uses the case-control study design as the method of study as crashes are rare events and several disease conditions are relatively rare in their occurrence. The study was based upon members in the Group Health Cooperative HMO. Cases were individuals who received medical care for injuries sustained in a crash where they were the driver. Accidents were identified from police reports. Controls were a random selection of HMO members who had not been injured in a crash. Collision injuries were identified from a review of the HMO database. Information on existing health conditions were also gathered from the database. All subjects were mailed a questionnaire to ascertain driving patterns, driving exposure, and health habits.Overall, the study found higher crash rates in subjects with diabetes, but not in subjects with several other medical conditions, including cardiovascular disease, neurological disease, arthritis, and depression. This study was based upon police accident reports, so events with injuries that were not reported are not included. Also, the sample sizes of subjects with several of the conditions were small (less than 10) indicating limited ability to detect small to moderate associations.Source: Koepsell TD, Wolf ME, McCloskey L, Buchner DM, Louie D, Wagner EH, Thompson RS. Medical conditions and motor vehicle collision injuries in older adults.
35 Case-Crossover Each participant is a case acting as their own control Accounts for effect of potential confounders (e.g. matches on age, sex, genetic susceptibility)Exposure status immediately before event/outcome compared with exposure some time prior to eventAcute exposures and outcomes (e.g. anger & MI; driving while using cell phone & injury)Recall of prior exposures
36 Hypothesis Testing: Case-Crossover Studies Study of “triggers” within an individual”Case" and "control" component, but information of both components will come from the same individual”Case component" = hazard period which is the time period right before the disease or event onset”Control component" = control period which is a specified time interval other than the hazard period
37 Cell phones and crashes Case-crossover studyproperty damage crashphone records, surveymoderate, no severe injuryOntariovolunteers, control time frame4 times higher risk for crash when using the phoneStudy designDefinition of injuryData SourcesSeverity of InjuryPopulationBiasFindingsAre you distracted when using a cellular telephone in a car to the extent that you crash more often? That is the basic question that this study seeks to address. This work was one of the first examples of the case-crossover study design in the injury literature. It examined a population of drivers in Toronto who brought their vehicles into a collision damage assessment center following a crash. They obtained informed consent from the drivers and got copies of their phone records. The cases served as their own controls. Case events included phone use at the time of the crash. Control events included phone use at the same time on the day before the crash. Alternative evaluation days were also considered. The data examines moderate crashes producing property damage to the cars. No serious of fatal injury crashes are included.The authors found a higher risk for crash (4 times higher) at the time of phone use. This was a fairly well done study for its time. The study subjects, though, were all volunteers and may not be representative. The driving patterns in the control period may also have been different than in the case period.Source: Redelmeier DA, Tibshirani RJ. Association between cellular telephone calls and motor vehicle collisions. NEJM 336: , 1997.N Engl J Med 1997 Feb 13;336(7):453-8
38 Epidemiologic Study Designs Cohort Studiesan “observational” design comparing individuals with a known risk factor or exposure with others without the risk factor or exposurelooking for a difference in the risk (incidence) of a disease over timebest observational designdata usually collected prospectively (some retrospective)
39 Cohort Design Study begins here disease Factor present no disease populationfree ofdiseasediseaseFactorabsentno diseaseCohort DesignpresentfuturetimeStudy begins here
40 Timeframe of StudiesProspective Study - looks forward, looks to the future, examines future events, follows a condition, concern or disease into the futuretimeStudy begins here
41 Prospective Cohort study ExposedOutcomeMeasure exposureand confoundervariablesNon-exposedOutcomeBaselineCase-control studies are perhaps the most frequent form of analytic study designs used in the injury field. These designs are very good for events that are rare in occurrence, and one could argue that severe injuries are relatively rare.Still, there are some situations where cohort study designs would be appropriate in the injury field. Most notably for less severe forms of injury. The classic design in a cohort study is shown here. The study begins by assessing baseline levels of the exposure and other variables. Study subjects are then followed on a regular basis to identify the outcome. The frequency of outcomes are tested between persons who had exposure to the possible risk factor at baseline and persons with no exposure.timeStudy begins here
42 Timeframe of StudiesRetrospective Study - “to look back”, looks back in time to study events that have already occurredtimeStudy begins here
43 Retrospective Cohort study ExposedOutcomeMeasure exposureand confoundervariablesNon-exposedOutcomeBaselineAn alternative form of the cohort study is something termed the retrospective cohort study. Other researchers may also call this a historical prospective study. This design is nearly identical to the prospective cohort study. The sequence of baseline exposure determination and longitudinal follow-up for outcomes is similar. The difference lies in the time in which the study begins. In this retrospective design, the researcher constructs the cohort study by looking back in time and placing data in the appropriate order and sequence. These studies are possible to do with large medical databases, such as the membership files of the Health Maintainance Organizations, or the medical files in the Scandinavian countries.timeStudy begins here
44 Cohort Study Strengths Limitations Exposure status determined before disease detectionSubjects selected before disease detectionCan study several outcomes for each exposureLimitationsExpensive and time-consumingInefficient for rare diseases or diseases with long latencyLoss to follow-up-- Exp. Measured before disease - so no temporal ambiguity-- Exposure measured before disease - so disease cannot influence the amount of error with which exposure status is measured-- Subject selection before disease, disease status does not influence of subjects
45 Experimental Studies investigator can “control” the exposure akin to laboratory experiments except living populations are the subjectsgenerally involves random assignment to groupsclinical trials are the most well known experimental designthe ultimate step in testing causal hypotheses
46 Experimental StudiesIn an experiment, we are interested in the consequences of some treatment on some outcome.The subjects in the study who actually receive the treatment of interest are called the treatment group.The subjects in the study who receive no treatment or a different treatment are called the comparison group.
47 Epidemiologic Study Designs Randomized Controlled Trials (RCTs)a design with subjects randomly assigned to “treatment” and “comparison” groupsprovides most convincing evidence of relationship between exposure and effectnot possible to use RCTs to test effects of exposures that are expected to be harmful, for ethical reasons
48 Experimental Design time Study begins here (baseline point) outcome RANDOMIZATIONInterventionno outcomeStudypopulationoutcomeControlno outcomeExperimental DesignbaselinefuturetimeStudy begins here (baseline point)
49 Epidemiologic Study Designs Randomized Controlled Trials (RCTs)the “gold standard” of research designsprovides most convincing evidence of relationship between exposure and effecttrials of hormone replacement therapy in menopausal women found no protection for heart disease, contradicting findings of prior observational studies
50 Randomized Controlled Trials DisadvantagesVery expensiveNot appropriate to answer certain types of questionsit may be unethical, for example, to assign persons to certain treatment or comparison groups
51 Thromboembolism and Air Travel Study designOutcomeTreatmentPopulationFindingsRCTDVTElastic hosehigh risk for DVTlower frequency of DVT in those wearing hoseThe authors found no significant association between marijuana use and the risk for injury. This is a unique study approach, but several bias’ may influence the results. One, the study population are members of an HMO, and may have a higher SES than the general population. Two, the assessment of marijuana exposure was crude and was by self-report. Three, no measures of marijuana use are available at the time of the injury.Source: Braun BL, Tekawa IS, Gerberich SG, Sidney S. Marijuana use and medically attended injury events. Annals of Emergency Medicine 32: , 1998.Angiology 52(6): , 2001