RSS 2012 Study designs

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A great presentation from a well versed friend in research and EBM, Dr Yaser Faden.
This is a simple introduction to study design with an accompanying workshop to simplify the different types of research study designs.

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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.
  • RSS 2012 Study designs

    1. 1. @kaimrc_edu 1
    2. 2. Observational andExperimental Study Designs Dr. Yaser Faden Asst. Professor, Dept. of OB/GYN Consultant, Maternal-Fetal Medicine Director, RTP in OB/GYN
    3. 3. What is the basis of a good research study?AN APPROPRIATE STUDY DESIGN
    4. 4. Learning Objectives By 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
    5. 5. 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.
    6. 6. Categories of Epidemiologic Studies Epidemiologic studies Observational Studies Experimental StudiesDescriptive Studies Analytic Studies RCTs Case report Case control Case Series Cohort Cross sectional studies Ecological Studies Retrospective Cohort Prospective Cohort
    7. 7. Categories of Epidemiologic Studies Observational Studies Investigators collect, record and analyze data on subjects as they naturally divide themselves by potentially significant variables ( i.e. case-control, cohort) Experimental Studies Involve some sort of control by the investigators (i.e. RCT’s)
    8. 8. Epidemiologic Study Designs Type of observational studies based on: – Type of sampling from population Based on exposure and/or disease – Temporal sequence of observation One time point, forward, backwards
    9. 9. 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 problem which is being studied
    10. 10. Descriptive Studies Are a class of epidemiologic studies which focus on characterizing morbidity or mortality of populations by person, place or time variable and have no a priori hypotheses. Examples Include – Case Report – Case Series – Some cross-sectional studies – Some ecologic studies
    11. 11. 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
    12. 12. Case series Experience of a group of patients with a similar diagnosis Cases may be identified from a single or multiple sources Generally report on a new/unique condition May be the only realistic design for rare disorders
    13. 13. Case reports and series Case report: describes an observation in a single patient. – “I had a patient with a cold who drank lots of orange juice and got better. Therefore, orange juice 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 orange juice….”
    14. 14. Case Reports / Case Series Pros – Useful for hypothesis generation – Informative for very rare diseases with few established 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
    15. 15. Cross-Sectional Studies Assess both exposure and outcome at the same time “snapshot” These are generally surveys or interviews Used to determine the prevalence of a condition (prevalence study) Used to identify possible causative factors in disease
    16. 16. Cross-sectionalstudy time Study only exists at this point in time
    17. 17. Cross-Sectional StudiesStrengths One stop, one time (snapshot) Relatively easy, quick, and inexpensive Estimates disease prevalence Useful for planning services Good design for hypothesis generation Rely on questionnaires and no follow- ups are required
    18. 18. Cross-Sectional Studies Weaknesses •Only representative of participants •Impractical if disease is rare •May not be possible to establish temporal relationship •Not a useful study for establishing causal relationships
    19. 19. Ecologic Studies Unit of analysis In most epidemiological studies, this is the individual; but in ecologic studies, this is the group. The group or the ecological unit represents an aggregate of individuals such as countries, provinces, cities, hospitals
    20. 20. Why do an ecologic study? HYPOTHESISBUILDING!The data is easy to obtain, no follow up orindividual contact is needed.An ecologic study can suggest avenues ofresearch that may cast light on an etiologicrelationship between exposure and disease HOWEVERAn ecologic study does not itselfdemonstrate that a causal relationshipexists
    21. 21. Analytic Studies Unlike descriptive studies, analytic studies are designed to test hypotheses about an exposure of interest and a particular outcome ? Exposure Outcome
    22. 22. Analytic studies Study types – Case-control studies – Cohort studies • Retrospective cohort studies • Prospective cohort studies
    23. 23. Observational Study Designs Case-control Groups determined by outcomes Cohort Studies Groups determined by risk factors
    24. 24. Back to our diagnostic puzzler You make an inquiry to the CDC about patients with these types of symptoms Yes, they have collected a few other cases like this. All were menstruating women. You have a keen interest in this new syndrome and work with the CDC and other doctors to publish a case series. You notice that one common characteristic of all of the affected women is tampon use. Is this just chance, or could it be related?
    25. 25. Case-control studies Attempt to make inference from existing observations (retrospective) Compares patients with outcome/disease with those without and attempts to identify factors that influenced that outcome (or caused that disease) Important concept: start with the result (disease) and work backwards for the cause
    26. 26. Case-Control and Cohort studies Case-Control
    27. 27. Back to our diagnostic puzzler How would you design a case-control study to test the theory that menstruation (or perhaps tampon use) is somehow connected with this new illness, which some people have started to call “toxic shock syndrome”?
    28. 28. Case-control study designExposure Disease Observer ?Menstruation Young women(tampon use) with and without TSS
    29. 29. Strengths of case control studies Rare diseases Several exposures Rapidity Low cost Small sample size Available data No ethical problem
    30. 30. Limitations of Case-Control Studies Cannot compute directly relative risk Not suitable for rare exposure Temporal relationship exposure-disease difficult to establish Biases +++ – control selection – recall biases when collecting data Loss of precision due to sampling
    31. 31. Cohort studies Studies whether exposure to a “risk factor” is associated with a subsequent “outcome” Select two populations who seem the same except for the hypothesized risk factor Follow them ahead in time and see how many have the outcome or disease Important concept: Start with the risk, then look for the outcome
    32. 32. Case-Control and Cohort studies Case-Control Prospective Cohort Retrospective Cohort
    33. 33. Prospective cohort study Disease Exposure Study starts occurrencetime Disease Study starts Exposure occurrencetime
    34. 34. Retrospective cohort studies Disease Exposure occurrence Study startstime
    35. 35. Back to our diagnostic puzzler How would you design a prospective cohort study to test the theory that tampon use by menstruating women is somehow connected with “toxic shock syndrome”?
    36. 36. Cohort study design (Prospective) Exposure Observer Disease ?Tampon use or not TSS?
    37. 37. Cohort Studies Prospective cohort studies start with the exposure, then follow patients over time Retrospective (or historical) cohort studies start with an exposure that happened some time ago, then look at the outcomes today Important point: Even though this is retrospective, it starts with the exposure or risk and then measures the outcome
    38. 38. 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
    39. 39. Weaknesses of cohort studies Large sample size Lost to follow Exposure can change Multiple exposure = difficult Ethical considerations Cost Time consuming
    40. 40. Epidemiologic Study DesignsExperimental Observational (RCTs) Analytical Descriptive Case-Control Cohort + cross-sectional & ecologic
    41. 41. Epidemiologic Study Designs Descriptive studies Examine patterns of disease Analytical studies Studies of suspected causes of diseases Experimental studies Compare treatment modalities
    42. 42. 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
    43. 43. Types of Clinical Trials Treatment trials test experimental treatments, behavioral therapies, new combinations of drugs, or new approaches to surgery or radiation therapy Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning – These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes
    44. 44. Randomization Assigned to groups by method similar to “flipping a coin” If randomization works, groups will be the same/comparable The larger the sample, the greater the likelihood of equal groups Results should show that the demographic characteristics between groups are similar If groups are similar, do not need to control for extraneous variables
    45. 45. 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 they die, are lost to follow up, or withdraw
    46. 46. Randomization Randomization Two kinds of randomization: – Random sampling • Every person in a population must have an equal chance of getting into the sample – Random assignment • Each person in a sample must have an equal chance of getting into the experimental and control group • That is, they are randomly placed in one of the groups
    47. 47. Randomization Researcher must actually go through some randomization process – For example, number each potential subject, and then pull numbers from a box or use a random table to determine assignment to a group Randomization is a very strong and positive control method Randomization can always strengthen a study
    48. 48. Homogenous Sampling Trying to make your sample as much alike is helpful in studies – because it can minimize the possibility extraneous variables have affected the results However, it also has limitations – Because it makes generalization more difficult since the study population is smaller and applies to fewer people – It can also make it more difficult to get enough people in the study So, homogenous sampling increases internal validity, but decreases external
    49. 49. Blinding Un-blinded: Everyone knows treatment Single Blinded: Researcher or patient does not know treatment Double Blinded: Neither researcher or patient knows treatment Why blinding? – Many people believe they feel better if they are given something – This is the placebo effect
    50. 50. Double Blind Example Patient: – Patient agrees that he will be randomized to one of 4 smoking cessation treatments – None of these 4 smoking cessation treatments are known to be better than the other Provider: – Providers do not know that patients are assigned to groups – Hire different people to run each group and do not tell them about the study
    51. 51. Intervention/Treatment Treatment versus placebo Treatment versus standard of care Treatments should be made to be as same as possible – For example, new drug versus sugar pill
    52. 52. Phases of Clinical Trials Phase I trials (a pilot study): Researchers test an experimental drug or treatment in a small group of people (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 experimental study drug or treatment is given to a larger group of people (100 subjects) to see if it is effective and to further evaluate its safety
    53. 53. Phases of Clinical Trials Phase III trials (RCT): The experimental study drug or treatment is given to large groups of people (200-3,000 subjects) to – Confirm its effectiveness – Monitor side effects – Compare it to commonly used treatments – Collect information that will allow the experimental drug or treatment to be used safely Phase IV trials (implementation research): – Post marketing studies – Delineate additional information, including: the drugs risks, benefits, and optimal use
    54. 54. Non-Randomized Comparison Group Next best thing to RCT Used when we cannot randomize our subjects – For example, due to cross-contamination, or facility- or community-level interventions Make sure groups are as similar as possible
    55. 55. Types of trials
    56. 56. RCT Advantages– The “gold standard” of research designs. They thus provide the most convincing evidence of relationship between exposure and effect.– Example: • trials of hormone replacement therapy in menopausal women found no protection for heart disease, contradicting findings of prior observational studies
    57. 57. RCT Advantages Best evidence study design No inclusion bias (using blinding) Controlling for possible confounders Comparable Groups (using randomization)
    58. 58. RCT Disadvantages Large trials (may affect statistical power) Long term follow-up (possible losses) Compliance Expensive Possible ethical questions
    59. 59. Epidemiologic study designs What 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 start in design, analysis and eliminating biases
    60. 60. Hierarchy of Epidemiologic Study Design Tower & Spector, 2007
    61. 61. Epidemiologic Study Designs Grimes & Schulz, 2002
    62. 62. Study DesignExamples2. A study examines 200 women with cervical cancer and 200 controls. They determine that there is an increased risk of cervical cancer with smoking Groups by Disease Case Control
    63. 63. Study Design2. A study started in 1990 and followed 1000 consecutive women who smoked in pregnancy and 2000 consecutive non smoking pregnant women. The study was completed five years after inception. They determined that there is an increase in stillbirth in smokers.Groups determined by Risk factors ie smokers Prospective Cohort
    64. 64. Study Design 3. A study compared the incidence of PET in women who had IUI with their partners semen compared to donor semen. Records for the last 10 years were reviewed. It was found that there was an increase in PET in women who had donor semen.Groups determined by Risk factors ie husband vs donor Retrospective Cohort
    65. 65. Categories of Epidemiologic Studies THANK Epidemiologic studies Observational Studies Experimental Studies YOUDescriptive Studies Analytic Studies RCTs Case report Case control Case Series Cohort Cross sectional studies Ecological Studies Retrospective Cohort Prospective Cohort

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