16 General Concepts of Epidemiology II

Dr. Shilpi Gupta

epgp books

 

General Concepts of Epidemiology

 

Study Design

 

Experimental Studies

Randomized Control Trials And

Case Crossover Trials

 

Observational Studies

Cohort Studies

Case Control Studies

Cross Sectional Studies

Ecologic Studies

 

Important Terms

Randomization,

Blinding,

Placebo,

Equipoise,

Intention-To-Treat

 

Learning Objectives

  • Describe The Difference Between Experimental And Non-Experimental (Observational)Study Designs
  • Characteristics Of Different Observational Studies
  • Explain The Purpose Of Randomization
  • Characterize Randomize Control Trials And Clinical Cross Over Study Designs
  • Identify Advantages And Disadvantages Of Randomized Control Trials
  • Defining Blinding, Equipoise, Placebo, And Intention-To-Treat

 

The Evidence For Evidence-Based Research Is All Collected Via Research, Which Uses A Variety Of Study Designs. Different Study Designs Provide Information Of Different Quality. Of Course, We Always Try To Use The Best Possible Design, But Sometimes This Is Not Practical Or Ethically Acceptable (You Cannot Do An Experiment To Expose Some People To A Harmful Substance To See What Effect It Has). Therefore, You Need To Understand The Strengths And Limitations Of Each Type Of Study Design, As Applied To A Particular Research Purpose. Epidemiological Studies Can Be Classified As Either Observational Or Experimental.

  1. Observation Studies

In Observational Studies, The Researcher Observes And Systematically Collects Information, But Does Not Try To Change The People (Or Animals, Or Reagents) Being Observed. In An Experiment, By Contrast, The Researcher Intervenes To Change Something (E.G., Gives Some Patients A Drug) And Then Observes What Happens. In An Observational Study There Is No Intervention, For Example, A New Drug Treatment. An Important Difference Between Observational And Experimental Study Design Is The ‘Randomly Assigned Exposure’.

 

Examples of Observational Studies:

  • A Survey Of Drinking Habits Among Students;
  • To Follow Diabetes Patients Over Time. Some Of Whom Smoke Tobacco And Some Who Don’t And Then Look At Their Rate Cardio Vascular Disease.

Examples of Experiments:

  • Giving One Type Of Drug Therapy To Experimental Group And Comparing Them Control Group.
  • Warning One Group Of Students That You Are Going To Take Blood Alcohol Levels Next Monday To Test For Alcohol, And Comparing Their Levels To Another Group That You Did Not Warn.

When Do You Do An Observational Study?

  • When You Merely Want To Collect Descriptive Information: “Is The Incidence Of Diabetes Rising?”
  • When You Want To Report On The Causes Of A Problem Without Disturbing The Natural Setting (Risk Factors For Causing Obesity In Certain Population)
  • When You Can’t Do An Experiment: “How Fast Does The Earth Move Around The Sun?”
  • When It’s Not Acceptable To Do An Experiment: “How Much Does Not Wearing A Condom Increase The Likelihood Of HIV Infection?”

 

Type of Observational Studies:

1.1 Cross-Sectional

1.2 Cohort

1.3 Case-Control

1.4 Ecologic

 

1.1 Cross-Sectional Study Design: In A Cross-Sectional Study, The Frequency Of A Particular Exposure(S) And / Or Outcome(S) In A Defined Population Is Measured At A Particular Point In Time. A Key Aspect Of Cross Sectional Study Design Is That The Exposure And Outcome Are Assessed At The Same Point Of Time Within The Specified Study Population. For Example, If You Conducted A Study In 2015 To Study The Risk Factors For Obesity In New Delhi. You First Define Your Study Population. For Example, All Adolescent Ages 12-17 In Schools Of South Delhi. You Will Then Survey All The Adolescents 12-17 Years From School Of South Delhi And Ask Them About The Exposures To Obesity For Example, How Frequent They Exercise, Their Eating Habits, Sleep Etc. At The Same Time We Will Also Take Measurements To Assess Their Obesity Status. So Here You Collect Information About Both Exposure And Outcome At The Same Time. This Is In Contrast To Both Case Control And Cohort Study.

Cross Sectional Studies Are Often Used To Define Occurrence Of A Health Outcome (Disease) Or Exposure In The Population. The Measure Used To Define This Occurrence Is Prevalence. To Calculate Prevalence, The Numerator Include All Existing Cases In A Population Group I.E. Prevalent Cases. While Denominator Include All Existing Persons In The Study Population Including Both Prevalent Cases And Non Cases.

Some Cross Sectional Studies Are Used To Characterize The Prevalence Of A Disease In A Specified Population In A Specific Time Period. And Some To Obtain Data On Prevalence Of Exposure And Disease To Study The Association Between Outcome And Exposure. The Prevalent Odds Ratio And Prevalence Ratio Are Commonly Used Measures Of Association When Data Are Obtained From Cross Sectional Studies.

 

Limitations Of Cross Sectional Study:

  • – Prevalence Is Influenced By Incident Rate And Duration Of A Health Outcome. For Example, Person Who Survived Longer With A Health Outcome Or Disease Would Be More Likely To Be Counted In The Numerator Of A Prevalence Proportion. Short Term Survivors Are Not As Likely To Be Counted, As They Are By Definition Around For A Shorter Time.
  • – Sometimes There Are Issues With Interpreting The Cross Sectional Studies. As Data On Both

Exposure And Outcome Are Collected At The Same Time So It Is Difficult To Assess Whether Exposure Preceded The Disease.

 

1.2 Cohort Study Design: Cohort Refers To A Group Of People Sharing Common Characteristics. Example Of Common Characteristics Are Geographic Location, Occupation, Socioeconomic Status, Age, Gender Etc. With The cohort Study Design Researchers Follow An At-Risk Population Over Time And Evaluate Exposures Over Time And Determine The Subsequent Risk Or Rate Of Disease Or Health Outcome. These Are Like Surveys, But Extend Over Time. This Allows You To Study Changes And To Establish The Time-Sequence In Which Things Occur. Therefore, You Can Use This To Study Causes.

 

For Example, You Could Draw A Sample Of People (Medical Students, For Example) Who Do Not Have The Disease You Are Interested In, And Collect Information On The Factor You Have Hypothesized To Be A Cause Of The Disease. Maybe You Want To See Whether Using A Cell Phone Leads To Brain Cancer. So, Collect Information On How Many Minutes Each Student Uses Their Phone Each Week (You Might Get Permission To Obtain This From Their Phone Company Bills), And Collect This Information Over A Long Time, And Then Eventually Collect Information On Who Gets Brain Cancer. You Could Then See Whether The Cases Of Brain Cancer Arose Among The People Who Used Their Cell Phones Most Often. In Technical Terms, You Record The Incidence Of Cancer Among Those Who Use Their Phones More Than A Pre-Determined Amount And Compare This To The Incidence In The Non-Users.

 

A Common Measure Of Disease Occurrence In Cohort Study Is A Risk Or A Rate. Since Cohort Studies Are Chosen To Be Free Of The Outcome Of Interest At The Outset, Only New Health Outcome Events Such As Diseases, Behavior Change Or Even Improvement In Health Are Considered.

 

For Risk: The Total Number of Disease Free Persons In The Cohort Is Denominator. For Rate, We Only Count Person-Time At Risk In The Denominator. This Is Estimated By Calculating The Amount Of Time Each Person Contributes To The Study Free Of Disease.

 

Cohort Study Population Can Be Open Or Closed. In An Open Study Population, Individuals Are Allowed To Join The Study At Any Point In Time From Beginning To The End Within Limitations. In Closed Cohort, Entire Cohort Is Formed At The Beginning Of The Study And The Cohort Is Closed To New Participants. An Open Study Population Collects Person-Time. And Open Study Design Is Also Less Prone To Problems Of Sample Size, Because Study Participants Contribute Person Time Even If They Were Part Of Study For Short Duration Of Time. There Are Two Type Of Cohort Study:

 

  • – Retrospective Study And
  • – Prospective Study

They Are Classified According To Their Temporal Sequence. Retrospective And Prospective Refers To The Time The Investigator Initiated The Study And Start Collecting The Data. In Retrospective Study Cohort Is Formed In the Past. The Prospective Study Starts Now and Goes In Future. In Prospective Study, The Investigator Obtain Baseline Exposure Data In Real Time, And Then Follow The Cohort Member During The Time After Baseline Exposure To Measure The Occurrence Of Disease.

 

Advantage and Disadvantages of Cohort Study Design

  • – The Advantages Of This Study Design Is That It Allow Direct Estimate Of Risk Or Rates. Investigator May Specifically Seek Out Individuals For The Study With The Exposure That Is Not Typical Among The General Population.
  • – The Ability To Assess The Effect Of Rare Exposure Is The Advantage Of Cohort Study.
  • – Cohort Study Can Also Be Useful For Assessing Multiple Outcomes.
  • – The Big Disadvantage Is That They Are Expensive.
  • – They Are Also Time Consuming.
  • – Resource Intensive: Our Ability To Detect Relatively Small Differences In Risk And Rates Between Exposed And Unexposed Groups Is Primarily Influenced By The Number Of Health Outcomes In Each Group, Rather Than Number Of Person In Exposed Group. Thus If There Are Relatively Few Person In An Exposure Category, We May Need A Very Long Period Of Follow Up To Observe Sufficient Numbers Of Rarer Outcomes In Order To Detect Difference Across Level Of Exposures. This Accounts For Considerable Cost And Time Needed To Properly Conduct Cohort Study.
  • – If Outcomes Are Very Rare, Then The Size Of The Cohort Groups May Be Too Large To Effectively Detect A Difference Between Study Groups. Example Of Rare Outcomes Includes Certain Cancers Such As Leukaemia Or Kidney Cancer.
  • – Loss T Follow Up Occurs When We Cannot Determine The Outcome For Some Measures Of The Cohort During The Entire Course Of Follow Up. If Losses Are Greater In Exposed Or Unexposed Groups Or Vice Versa, We May Obtain A Biased Estimate Of Risk Ratio Or Rate Ratio.

1.3 Case Control Study: Case Control Study Are An Efficient And Common Epidemiologic Study Design To Study Rare Diseases Where Rare Is Defined As Prevalence Of Less Than 10%. In A Case Control Study Researcher Begins By Selecting Diseased Individuals Known As Cases.

 

Researcher Also Select A Group Of Individuals Without A Disease Known As Controls. Case Control Studies Proceeds Logistically From Effect I.E. Disease (Or Health Outcome) To the Cause Or Exposure. As The Researcher Look Back In Time To See What The Exposure Was In Both The Case And Control Group. So There Are Three Key Steps In Conducting Case Control Study:

  1. Define And Select Cases
  2. Define And Select Controls
  3. Compare Exposure Prevalence

Since In Case-Control Design You Cannot Calculate Incidence Of Disease (Because The Cases Already Had Disease When You Began) Nor Can You Calculate Prevalence, (Because It Was You Who Decided How Many Cases And How Many Controls To Choose, And This Determined The Apparent Prevalence In The Study), So Rate And Risk Cannot Be Calculated Directly For Case Control Studies. Instead We Use A Measure Called Odds Ratio. Odds Ratio Is Simply The Odds Of Exposure For Cases Divided By Odds Of Exposure For Controls. The Odds Ratio Represents The Streaks Of An Association Between Exposure And Outcome.

 

Advantages and Disadvantages:

  • – It’s A Most Efficient Design for Rare Diseases.
  • – It Takes Less Time.
  • – It Also Uses Few Recourses And Money.
  • – It Can Examine Multiple Exposures.
  • – It’s Likely to Be Replicable in Other Populations.
  • – If Sampled Accurately, Odds Ratio Provides The Estimates Of Risk Or Rate Ratio.
  • There Could Be Some Biases In Selection Of Subjects, Measurement Of Exposures And Analysis.
  • Case Control Study Does Not Provide The Direct Estimate For The Risk Or Rate Ratio.
  • Also They Are Not Good For Rare Exposure.
  • The Time Sequence Between Exposure And Outcome Is Uncertain.

 

1.4 Ecologic Study Design: In Ecologic Study Design, Data Related To Exposure And Outcomes Are Collected At Groups Rather Than Individuals Level. Generally Ecologic Studies Uses Group Level of Measurements. For Example, Exposure Measurement Would Be Yearly Average Air Pollution Air Concentration In Five Different Cities. Sometimes, The Health Outcome Occurrence Or Proportion Or Rates Are Known Only At The Group Level. For Example, The Yearly Mortality Or Death Rate From Lung Disease In These Same Cities With Measured Air Pollution Levels; Obesity Prevalence Among Low Income Preschool Children By State In India.

 

Advantages and Disadvantages Of Ecologic Study Design:

  • – Group Level Data on Exposure and Outcome Are Often Available Publically In State and National Data Bases I.E. Census Data, Mortality Etc. So Ecologic Studies Have Lower Cost And Are Convenient.
  • – Ecologic Studies Are Useful For Evaluating Impact Of Community Level Interventions, For Example, Fluoridation Of Water, Mass Media Campaign, and Seatbelt Laws Etc. We Can Compare Outcomes At Community Level Before And After The Intervention.
  • – The Major Limitation Of Ecologic Study Design Is ‘Ecologic Fallacy’which Conclude That the Association At The Group Level Between Exposure And Outcome Is True At The Individual Level, When This May Not Be True. The Reason For This Fallacy Is That We Don’t Know The Length Between Exposure And Health Outcome Among Individuals Within Each Group I.E. We Don’t Know The Number Of Diseased Person Who Were Exposed Or Non-Exposed In High Exposure Group Nor In Low Exposure Group. What We Found At The Group Level May Not Be True At The Individual Level.

Let’s Consider A Hypothetical Example That Air Pollution Is Higher In Calcutta Than In Delhi. But Mortality from Lung Disease In Lower In Calcutta Than Delhi. We May Come To The Fallacious Conclusion That Air Pollution Protects Against Lung Diseases. The Explanation Might Be That Persons Dying With Lung Diseases In Delhi May Have Moved From High Pollution Cities. We Don’t Know The Cumulative Exposures Of Cases And Non Cases In Either Cities.

  • – In Ecologic Study, We Cannot Be Confident That Exposure Precedes Outcome.
  • – In Ecologic Studies, We Don’t Know What Happen To The Individual People. Thus Migration

Into And Out Of Community Can Bias the Interpretation of Ecologic Study.

  1. Experimental Study Designs

In Experimental Study Designs, A Sample Of Patients With The Condition, And Who Meet Other Selection Criteria, Are Randomly Allocated To Receive Either The Experimental Treatment, Or The Control Treatment (Commonly The Standard Treatment For The Condition). The Experimental And Control Groups Are Then Followed For A Set Time, And Relevant Measurements Are Taken To Indicate The Results (Or ‘Outcomes’) In Each Group. Experimental Studies Are Gold Standards For Inferring Causality.

There Are Two Types Of Experimental Studies:

 

2.1 Randomized Control Trials: In RCT, Treatment Such As A New Drug, Would Be Randomly Allocated To Half Of The Study Subject And Other Half Would Receive A Placebo Or The Current Standard Of Care Or Medication For The Disease. An Example Of Randomized Control Trial Would Be A Study Comparing Two Different Treatments For Arthritis. Subjects Would Be Randomized To One Of The Two Arthritis Treatments.

 

RCT Are Often Used To Test New Drug Or Treatment. Intervention And Control Groups Are Comparable In All Aspects Except The Intervention Itself, For Example Proportion Of Female And Age Distribution Would Be Same In Both Intervention And Control Group. Randomization Provides The Strongest Evidence For Causal Inference. It Basically Allow Us To Say If Everything Else Is The Same, What Is The Effect Of Exposure On Outcome?

 

Key Advantages of Rcts:

  • Randomization Reduces The Influence Of Other Determinant Of Exposure And Outcomes I.E. Confounding.
  • This Study Design Provides Strong Evidence For Causality Or Causal Inference.
  • Since Investigator Assign The Exposure Or Medical Treatment, The Time Or Temporal Relationship Between Exposure And Outcome Is Clear.

Disadvantages of Rcts:

  • Rcts Can Be Costly
  • Sometimes Rcts Have Issues With External Validity Or Generalizability. People Who Participate In The RCT May Be Very Different From Rest Of The Population, Thus The Affect Seen In The Participants May Not Be Generalized To Rest Of The Population At Large.
  • Rcts Usually Focus On A Specific Narrow Question Related To A certain Treatment Or Medication And A Specific Comparison With Another Treatment Or Exposure.
  • In Addition, There Are Ethical Issue With Randomizing Treatments Or Exposures. For

 

Example, It Would Be Unethical To Randomize People To Be Exposed To A Known Toxic Substance Such As Water Containing High Level Of Lead, Arsenic Etc.

 

2.2 Clinical Case Crossover Trials: In These Trials, Subjects Switch From One Treatment To Another After A Certain Period Of Time. They Quote/Unquote, Crossover To The Other Treatment Or Exposure. As We Don’t Want The Effect Of First Treatment To Carry Over When A Person Switches To Another Treatment, There Is Usually A Period In Between The Two Exposures Called Wash-Out Period, When No Exposure Or Treatment Is Given. The Order That Exposure Or Treatment Would Be Given Is Randomized But The Same Participants Are Involved In Each Part Of The Trial. Note That If The Person Changes In Some Meaningful Way Over Time For Example If A Woman Were To Get Pregnant During The Study, This May Affect The Study Results. For This Reason, Shorter Intervention Effects Are Preferred For Studies In Crossover Trails.

 

Example Of Crossover Trial: In A Study (Steiner Et Al, 1996), Researcher Wanted To Study The Effect Of Aged Garlic On Blood Lipid. Study Participants Were Men Ages 32 To 68 With Moderately High Cholesterol. The Men In The Study Were Randomized To Take A Dietary Supplement Either Containing Garlic Or A Placebo Over A Six Month Period. Blood Tests Were Recorded Then The Each Participant Was Switched To The Other Supplement For A Time, After Which Blood Test Were Recorded Again. The Test Result Showed That Garlic Supplements Appeared To Reduce Cholesterol And Blood Pressure.

 

There Are Both Individual And Community Experimental Studies. An Example Of An Individual Experimental Study Is Where One Group Receive Drug Aimed At Curing Cancer In An At Risk Group While Another At Risk Group Receive Placebo Drug. An Example Of Community.

Intervention Study Is A Colon Cancer Screening Program That Was Implemented In Nine Districts And Seven Control District Who Did Not Receive Screening Program.

 

  1. Important Terms Related To Experimental Study Designs

3.1 Randomization

Randomization Is Usually Done By Using Either Computer Or Some Other Method To Assign Groups To Receive Exposure, Or Treatment Or Another. Randomization Helps To Prevent Chance Or Biasness In The Study. It Is The Most Important Component Of Experimental Study Design.

 

Blinding Is Done, In Order To Reduce Assessment Based Biasness In The Study.It Is Technique Used In Experimental Studies To Conceal Certain Information From Different People Involved In The Experimental Study. Knowing Certain Information Could Lead To Biases In The Study.

 

For Instance, You Might Want To Conceal Information From The Researcher. This Researcher Might Be Very Much Invested In Cancer Related Medication But The Result May Show That Medication Doesn’t Work. Knowing Which Group Has Received Medication Could Result In Biased Assessment By The Researcher. Or If You Want To Conceal Information From The Subject, If The Subject Knows That They Received The Medication, And Think That The Medication Is Working. They May Report There Symptoms, Activity Levels, Or Level Of Depression Differently Than If They Didn’t Know Whether They Got The Medication Or Not. Or If You Want To Blind Both The Researcher And The Subject Until The Research Is Complete. There Are Four Different Type Of Blinding In Studies:

  1. Non-Blinded Study: Where Everyone Knows Who Received The Interventions, Both The Subject Themselves, The Researcher And The Statistical Analyst
  2. Single Blinded Study: Where One Category Of Person Is Blinded, Either The Subject Or The Researcher Or The Statistical Analyst.
  3. Double Blinded Study: Where Both The Tester And Subjects Are Blinded.
  4. Triple Blinded Study: Where Everyone Is Blinded Including The Subject, The Researcher And Statistical Analyst

3.3 Equipoise

It Refers To The Genuine Uncertainty About The Benefits Or Harms Of The Treatment Or Exposure. If We Are Sure That One Treatment Is Better Than Another, Then We Should Not Randomized To A Treatment That Is Known To Be Inferior.

3.4 Placebo

Placebos Are Sham Treatment That Appear Identical To The Real Treatment But Lack The Active Agents. Placebo Are Used In Order For The Different Groups To Not Realized If They Are Exposed Or Unexposed Which Could Affect Participants Behavior Or Health Outcome.

3.5 Compliance/Adherence

It Refers To Whether Or Not Participants Follow Treatment Medications, Recommendations As Some Participants may Not Stick With Their Assigned Treatment Or Exposure.

3.6 Intentions-To-Treat Analysis

It Refers To When Subjects Are Analyzed According To Their Randomized Treatment, Regardless Of Whether They Actually Got Or Took The Treatment.

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