Study designs 2013


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Introduction to research designs by Dr. Yaser Faden

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  • Not all prospective trials are placebo-controlled, however. A non-controlled trial might identify potential subjects, give them all a treatment, and then see how they do. Such open-label single arm trials cannot control for placebo effects or experimenter biases, and again results should be considered preliminary. Open or uncontrolled trials are not useless, however. The outcome of subjects in such trials can be compared to historical controls, and if a significant result is apparent (along with safety) can be used to justify a larger and more rigorous trial. Controlled trials have one or more comparison groups in the trial itself – different groups of subjects receive different treatments or no treatment. All subjects can be followed in same manner. Control groups allow the experimenter to make sure that all the subjects have the same disease or symptoms, that they receive known treatments, and many variables (such as other treatments they may be receiving, severity at inclusion, age, sex, race, etc.) can be accounted for.
  • Study designs 2013

    1. 1. Introduction to Study DesignsDr. Yaser FadenAsst. Professor, Dept. of OB/GYNConsultant, Maternal-Fetal MedicineDirector, RTP in OB/GYN
    2. 2. What is the basis of a goodresearch study?AN APPROPRIATE STUDYDESIGN
    3. 3. Learning ObjectivesBy the end of this session, you will be able to:Distinguish between observational and experimental studiesDescribe the key characteristics of experimental, cohort,case-control, cross-sectional, and ecologic studiesList the advantages and disadvantages of each type of studydesignIdentify the design of a particular study by reading anabstractDiscuss the factors that determine when a particular designis indicated
    4. 4. DiagnosticPuzzlerYou are a practicing physician in the 1970’s.Your patient is a very ill 24 year old womanwho is hospitalized for fever, low bloodpressure, and a rash, including peeling of thehands. Your review of symptoms is positiveonly for menstruation. You treat her in theintensive care unit. You feel fortunate that shesurvived, but are uneasy because you neverreally knew what was wrong with her.
    5. 5. Categories ofCategories ofEpidemiologic StudiesEpidemiologic StudiesEpidemiologic studiesObservational Studies Experimental StudiesDescriptive Studies Analytic StudiesCase reportCase SeriesCross sectional studiesCase controlCohortRCTsEcological StudiesRetrospective Cohort Prospective Cohort
    6. 6. Categories of EpidemiologicStudiesObservational StudiesInvestigators collect, record and analyzedata on subjects as they naturally dividethemselves by potentially significantvariables ( i.e. case-control, cohort)Experimental StudiesInvolve some sort of control by theinvestigators (i.e. RCT’s)
    7. 7. Epidemiologic Study DesignsType of observational studies based on:– Type of sampling from populationBased on exposure and/or disease– Temporal sequence of observationOne time point, forward, backwards
    8. 8. Exposure and OutcomeExposure– Refers to the potential risk factor• Can be exposure such as tobacco smoke• Can be behavior (e.g.. sedentary lifestyle)• Can be attribute ( e.g.. SES)Outcome– Is the disease or other health related problemwhich is being studied
    9. 9. Descriptive Studies Are a class of epidemiologic studies which focuson characterizing morbidity or mortality ofpopulations by person, place or time variable andhave no a priori hypotheses. Examples Include– Case Report– Case Series– Some cross-sectional studies– Some ecologic studies
    10. 10. Case ReportsDetailed presentation of a single caseGenerally report a new or unique finding– Previous undescribed disease– Unexpected link between diseases– Unexpected new therapeutic effect– Adverse events
    11. 11. Case seriesExperience of a group of patients with asimilar diagnosisCases may be identified from a single ormultiple sourcesGenerally report on a new/unique conditionMay be the only realistic design for raredisorders
    12. 12. Case reports and seriesCase report: describes an observation in asingle patient.– “I had a patient with a cold who drank lots oforange juice and got better. Therefore, orangejuice may cure colds.”Case series: same thing as a case report,only with more people in it.– “I had 10 patients with a cold who drank orangejuice….”
    13. 13. Case Reports / Case SeriesPros– Useful for hypothesis generation– Informative for very rare diseases with fewestablished risk factors– Easy to understand– Can be written up in short period of timeCons– Cannot study cause and effect relationship– Cannot assess disease frequency
    14. 14. Cross-Sectional StudiesAssess both exposure and outcome atthe same time “snapshot”These are generally surveys orinterviewsUsed to determine the prevalence of acondition (prevalence study)Used to identify possible causativefactors in disease
    15. 15. Study only exists at this point in timetimeCross-sectionalstudy
    16. 16. StrengthsOne stop, one time (snapshot)Relatively easy, quick, andinexpensiveEstimates disease prevalenceUseful for planning servicesGood design for hypothesis generationRely on questionnaires and no follow-ups are requiredCross-Sectional StudiesCross-Sectional Studies
    17. 17.  Weaknesses•Only representative of participants•Impractical if disease is rare•May not be possible to establish temporalrelationship•Not a useful study for establishing causalrelationshipsCross-Sectional StudiesCross-Sectional Studies
    18. 18. Analytic Studies Unlike descriptive studies, analytic studies aredesigned to test hypotheses about an exposure ofinterest and a particular outcomeExposure Outcome?
    19. 19. Analytic studiesStudy types– Case-control studies– Cohort studies• Retrospective cohort studies• Prospective cohort studies
    20. 20. Observational Study DesignsCase-controlGroups determined by outcomesCohort StudiesGroups determined by risk factors
    21. 21. Back to our diagnostic puzzler You make an inquiry to the CDC about patientswith these types of symptoms Yes, they have collected a few other cases likethis. All were menstruating women. You have a keen interest in this new syndromeand work with the CDC and other doctors topublish a case series. You notice that one common characteristic of allof the affected women is tampon use. Is this justchance, or could it be related?
    22. 22. Case-control studiesAttempt to make inference from existingobservations (retrospective)Compares patients with outcome/diseasewith those without and attempts toidentify factors that influenced thatoutcome (or caused that disease)Important concept: start with the result(disease) and work backwards for thecause
    23. 23. Case-Control and Cohort studiesCase-Control
    24. 24. Back to our diagnostic puzzlerHow would you design a case-controlstudy to test the theory thatmenstruation (or perhaps tampon use)is somehow connected with this newillness, which some people have startedto call “toxic shock syndrome”?
    25. 25. Case-control study designExposure Disease Observer?Menstruation Young women(tampon use) with and without TSS
    26. 26. Strengths of case control studies Rare diseases Several exposures Rapidity Low cost Small sample size Available data No ethical problem
    27. 27. Limitations ofCase-Control Studies Cannot compute directly relative risk Not suitable for rare exposure Temporal relationship exposure-disease difficultto establish Biases +++– control selection– recall biases when collecting data Loss of precision due to sampling
    28. 28. Cohort studiesStudies whether exposure to a “riskfactor” is associated with a subsequent“outcome”Select two populations who seem the sameexcept for the hypothesized risk factorFollow them ahead in time and see howmany have the outcome or diseaseImportant concept: Start with the risk,then look for the outcome
    29. 29. Case-Control and Cohort studiesProspective CohortRetrospective CohortCase-Control
    30. 30. timeExposure Study startsDiseaseoccurrenceProspective cohort studyExposureDiseaseoccurrencetimeStudy starts
    31. 31. Retrospective cohort studiesExposuretimeDiseaseoccurrence Study starts
    32. 32. Back to our diagnostic puzzlerHow would you design a prospectivecohort study to test the theory thattampon use by menstruating womenis somehow connected with “toxicshock syndrome”?
    33. 33. Cohort study design(Prospective)Exposure Observer Disease?Tampon use or not TSS?
    34. 34. Cohort StudiesProspective cohort studies start with theexposure, then follow patients over timeRetrospective (or historical) cohort studiesstart with an exposure that happened sometime ago, then look at the outcomes todayImportant point: Even though this isretrospective, it starts with the exposure orrisk and then measures the outcome
    35. 35. Strengths of cohort studies Can directly measure– incidence in exposed and unexposed groups– true relative risk Well suited for rare exposure Temporal relationship exposure-disease is clear Less subject to selection biases
    36. 36. Weaknesses of cohort studies Large sample size Lost to follow Exposure can change Multiple exposure = difficult Ethical considerations Cost Time consuming
    37. 37. Epidemiologic Study DesignsExperimental ObservationalDescriptiveAnalyticalCase-Control Cohort+ cross-sectional & ecologic(RCTs)
    38. 38. Descriptive studiesDescriptive studiesExamine patterns of diseaseAnalytical studiesAnalytical studiesStudies of suspected causes of diseasesExperimental studiesExperimental studiesCompare treatment modalitiesEpidemiologic Study Designs
    39. 39. Randomized Control Trial(RCT) Gold standard of all studies Prospective Two or more groups assigned by randomization Baseline measurements on all groups Give different treatments Measure outcome
    40. 40. Types of Clinical Trials Treatment trials test experimental treatments,behavioral therapies, new combinations of drugs,or new approaches to surgery or radiationtherapy Prevention trials look for better ways to preventdisease in people who have never had the diseaseor to prevent a disease from returning– These approaches may include medicines, vitamins,vaccines, minerals, or lifestyle changes
    41. 41. Randomization Assigned to groups by method similar to“flipping a coin” If randomization works, groups will be thesame/comparable The larger the sample, the greater the likelihoodof equal groups Results should show that the demographiccharacteristics between groups are similar If groups are similar, do not need to control forextraneous variables
    42. 42. Randomization Sometimes we cannot randomize people (e.g., cross-contamination or “system” interventions) Can randomize hospitals, or units instead– For example, testing clinical reminder systems Once randomized, always randomized Subjects are treated as part of that group, even if theydie, are lost to follow up, or withdraw
    43. 43. Randomization Randomization Two kinds of randomization:– Random sampling• Every person in a population must havean equal chance of getting into the sample– Random assignment• Each person in a sample must have anequal chance of getting into theexperimental and control group• That is, they are randomly placed in oneof the groups
    44. 44. Randomization Researcher must actually go through somerandomization process– For example, number each potential subject, and then pullnumbers from a box or use a random table to determineassignment to a group Randomization is a very strong and positive controlmethod Randomization can always strengthen a study
    45. 45. Homogenous Sampling Trying to make your sample as much alike ishelpful in studies– because it can minimize the possibility extraneousvariables have affected the results However, it also has limitations– Because it makes generalization more difficult since thestudy population is smaller and applies to fewer people– It can also make it more difficult to get enough peoplein the study So, homogenous sampling increases internalvalidity, but decreases external
    46. 46. Blinding Un-blinded: Everyone knows treatment Single Blinded: Researcher or patient does not knowtreatment Double Blinded: Neither researcher or patient knowstreatment Why blinding?– Many people believe they feel better if they are givensomething– This is the placebo effect
    47. 47. Double Blind Example Patient:– Patient agrees that he will be randomized to one of 4smoking cessation treatments– None of these 4 smoking cessation treatments areknown to be better than the other Provider:– Providers do not know that patients are assigned togroups– Hire different people to run each group and do nottell them about the study
    48. 48. Intervention/TreatmentTreatment versus placeboTreatment versus standard of careTreatments should be made to beas same as possible– For example, new drug versus sugar pill
    49. 49. Phases of Clinical Trials Phase I trials (a pilot study): Researchers test anexperimental drug or treatment in a small group ofpeople (5-60 subjects) for the first time to– Evaluate its safety– Determine a safe dosage range– Identify side effects Phase II trials (a larger pilot study): The experimentalstudy drug or treatment is given to a larger group ofpeople (100 subjects) to see if it is effective and to furtherevaluate its safety
    50. 50. Phases of Clinical Trials Phase III trials (RCT): The experimental study drug ortreatment is given to large groups of people (200-3,000subjects) to– Confirm its effectiveness– Monitor side effects– Compare it to commonly used treatments– Collect information that will allow the experimental drug ortreatment to be used safely Phase IV trials (implementation research):– Post marketing studies– Delineate additional information, including: the drugs risks,benefits, and optimal use
    51. 51. Non-Randomized ComparisonGroupNext best thing to RCTUsed when we cannot randomize oursubjects– For example, due to cross-contamination, or facility-or community-level interventionsMake sure groups are as similar aspossible
    52. 52. Types of trials
    53. 53. RCT Advantages– The “gold standard” of research designs.They thus provide the most convincingevidence of relationship between exposure andeffect.– Example:• trials of hormone replacement therapy inmenopausal women found no protection forheart disease, contradicting findings ofprior observational studies
    54. 54. RCT Advantages Best evidence study design No inclusion bias (using blinding) Controlling for possible confounders Comparable Groups (using randomization)
    55. 55. RCT DisadvantagesLarge trials (may affect statisticalpower)Long term follow-up (possible losses)ComplianceExpensivePossible ethical questions
    56. 56. Epidemiologic study designsWhat type of study to choose depends on: What is the research question/ objective Time available for study Resources available for the study Common/rare disease Type of outcome of interest Quality of data from various sources Often there are multiple approaches which will all work Choosing an established design gives you a huge head startin design, analysis and eliminating biases
    57. 57. Hierarchy of Epidemiologic Study DesignHierarchy of Epidemiologic Study DesignTower & Spector, 2007
    58. 58. Epidemiologic Study DesignsGrimes & Schulz, 2002
    59. 59. Study DesignExamples1. A study examines 200 women withcervical cancer and 200 controls. Theydetermine that there is an increasedrisk of cervical cancer with smokingGroups by DiseaseCase Control
    60. 60. Study Design2. A study started in 1990 and followed 1000consecutive women who smoked inpregnancy and 2000 consecutive nonsmoking pregnant women. The study wascompleted five years after inception. Theydetermined that there is an increase instillbirth in smokers.Groups determined by risk factors ie smokersRetrospective Cohort
    61. 61. Categories ofCategories ofEpidemiologic StudiesEpidemiologic StudiesEpidemiologic studiesObservational Studies Experimental StudiesDescriptive Studies Analytic StudiesCase reportCase SeriesCross sectional studiesCase controlCohortRCTsEcological StudiesRetrospective Cohort Prospective CohortTHANKTHANKYOUYOU