Topic 9 - Study Designs

Question 1

A study design plans for selecting study _____ and obtaining _____ about them

Answer 1

A study design plans for selecting study subjects and obtaining data about them

Question 2

A descriptive study is a study undertaken without a specific ________.

Answer 2

A descriptive study is a study undertaken without a specific hypothesis

Question 3

An Observational studies (AKA Analytical studies)
* Test a __________: Concerned with an ________ causing a certain ______ (disease)
* _____ is an important characteristic of these studies: One of _____ criteria for causation

Answer 3

• Test a hypothesis: Concerned with an exposure causing a certain outcome (disease)
• Time is an important characteristics of these studies: One of Hill’s criteria for causation

Question 4

Experimental studies

• Test the effect of an _______ (e.g. therapy, challenge)
• ______ or _____ setting
• Non-_______ and ________

Answer 4

• Test the effect of an intervention (e.g. therapy, challenge)
• Laboratory or Field setting
• Non-randomized and Randomized

Question 5

What is a research synthesis?

Answer 5

• Research Synthesis
• Non-systematic reviews, Systematic reviews, and Meta-analyses

Question 6

Descriptive studies describe?

Answer 6

Attributes

Question 7

Explanatory studies explains?

Answer 7

Associations

Question 8

Repeated associations are a summary of?

Answer 8

Summary of what consistently changes disease status ?

Question 9

List the study designs in order from least to greatest strength of evidence?

Answer 9

Cohort = best amount of info (almost a control trial - due to different arms and groups being monitored over time)

Question 10

Case reports are used for:
______ (or very _____) cases
- _____ or _____ condition
- _______/____ manifestation or _______ of a common condition
- Could help to build _________

Answer 10

Single (or very few) cases
- Rare or new condition
- Unusual/new manifestation or management of a common condition
- Could help to build hypothesis

Question 11

Case series describe the _______ course of a condition shared by a ______ of subjects
- Document the ____/_____/______
- ________ estimation when representative of cases in the population

Answer 11

Case series describe the clinical course of a condition shared by a group of subjects
- Document the Who/When/Where
- Prognosis estimation when representative of cases in the population

Question 12

Surveys describe the _______ & ________ of a condition in a population at a point in time
- Focus on _____ feature at the time
- Requires proper _______ protocol and collection of information (___________)
- ________ valid when representative sampling

Answer 12

Describe the frequency & distribution of a condition in a population at a point in time
- Focus on one single feature at the time
- Requires proper sampling protocol and collection of information (questionnaire)
- Extrapolation valid when representative sampling

not looking at risk factors, only looking at presence, or lack thereof, of disease

Question 13

Case-control
* Investigating ____ factors for _____ diseases
* …you can also think about _______
situations

Answer 13

Case-control
* Investigating risk factors for rare
diseases
* …you can also think about outbreak
situations

Question 14

This case below is an example of what type of study design?

Perfect dataset with medical records
for every dog in a country and details
about exposure in first year of life
* Risk of bladder cancer
* Benzidine + : 32 per 100,000
* Benzidine - : 20 per 100,000
* Risk Ratio = 1.6
* Odds Ratio = 1.55
* (60 x 278,943) / (57 x 188,940)

Answer 14

Case-control

Contd.

• Instead, enroll ALL dogs with bladder
  cancer and a sample of dogs who did
  not
• Can’t calculate risk of bladder in E+
  or E- because we don’t know the
  size of the population at risk
• Risk in E+ is definitely not 24%
  of the population (60 / 249)
• OR = 1.55
• (60 x 279) / (57x189)

Question 15

Answer 15

Once you collect first few cases, go back in time and ask them questions related to past: where did you eat, go, etc. anything you think led to them testing positive.

Question 16

What are the advantages of case-control studies?

Answer 16

• Efficient with rare diseases
• Quick to undertake
• Cheaper than other studies

Question 17

What are the disadvantages of case-control studies?

• No information on disease ____ or ______ in the studied population
• Reliant on _________ of study participants
• Difficult to ensure _________ selection of control group

Answer 17

• No information on disease risk or incidence in the studied population
• Reliant on recollection of study participants
• Difficult to ensure unbiased selection of control group

Question 18

What are cross sectional studies?

Answer 18

Sample of individuals from a population taken at a single or relatively short period of time
* “Snap-shot” in time

Often requires
* Surveys (sampling strategy)
* Questionnaires

Question 19

Answer 19

Seeing what is occurring at a single moment in time.
Look for breed, age, sex, risk factors, exposure to anything you think might be related to disease.

Question 20

What are the advantages of an observational studies?

• _______ to undertake
• Can estimate ____ (________)
• ________ than other studies
  
  • No ________-___ period

Answer 20

• Quick to undertake
• Can estimate risk (prevalence)
• Cheaper than other studies
  
  • No follow-up period

Question 21

What are the disadvantages of cross-sectional studies?

• No information on disease ______ in the studied population
• Not suitable for diseases of ______ duration
  
  • Imagine a X-sec study for milk fever!
    
    • First 24-hrs post-parturition
• Difficult to investigate _______/_____ relationships
• Don’t know if E__ occurred before D__

Not good for ____ studies because if you are showing up randomly for a moment in time, you are most likely not going to get anything.

Answer 21

• No information on disease incidence
  in the studied population
• Not suitable for diseases of short
  duration
  
  • Imagine a X-sec study for milk fever!
    
    • First 24-hrs post-parturition
• Difficult to investigate cause/effect
  relationships
• Don’t know if E+ occurred before D+

Not good for rare studies because if you are showing up randomly for a moment in time, you are most likely not going to get anything.

Question 22

What are cohort studies?

• Comparing disease ______ over _____ among groups (cohorts) with different ______
• ________ or _________

Answer 22

• Comparing disease incidence over time among groups (cohorts) with different exposures
• Prospective or Retrospective

Question 23

Answer 23

Observational studies
More powerful studies go forward in time
Less powerful studies go back in time b/c they get history charts

Question 24

What are the advantages of cohort studies?

• Absolute incidence of disease in E__and E__
• Exposure is recorded _______ disease
• Well-suited for _____ exposures (but must be a fairly _______ disease; if doctor is doing a rare treatment for a common disease)
  
  • No need to reflect E__ or E___ prevalence from population

Answer 24

• Absolute incidence of disease in E+
  and E-
• Exposure is recorded BEFORE disease
• Well-suited for rare exposures (but must be a fairly common disease; if doctor is doing a rare treatment for a common disease)
  
  • No need to reflect E+ or E- prevalence from population

Question 25

What are the disadvantages of cohort studies? * ______ follow-up period * _________ * Losses to follow-up are problems * Introduce potential _____ * Rare diseases require ______ groups

Answer 25

* Long follow-up period * Expensive * Losses to follow-up are problems * Introduce potential bias * Rare diseases require LARGE groups

Question 26

What are some examples of hybrid studies?

Answer 26

Nested case-control Case-crossover Panel Repeated survey

Question 27

What is an ecological study? Unit of analysis is a _____ (e.g. cities, state, countries, etc.) * Summary measures of ______ and summary measures of ______ are compared and inference is made at the individual level *Never take these results seriously?

Answer 27

Unit of analysis is a group (e.g. cities, state, countries, etc.) * Summary measures of exposure and summary measures of outcomes are compared and inference is made at the individual level *Never take these results seriously?

Question 28

What are the advantages of ecological studies? * Extremely _____ and _______ to perform * Provide clues about associations between?

Answer 28

* Extremely quick and inexpensive to perform * Provide clues about associations between E+ and D+

Question 29

What are the disadvantages of ecological studies? * Extremely prone to ______!!!! * “Ecological ________” * Assumption that an observed relationship in ________ data will hold at the ________ level!

Answer 29

* Extremely prone to bias!!!! * “Ecological Fallacy” * Assumption that an observed relationship in aggregated data will hold at the individual level!

Question 30

Answer 30

Questions should be of individuals, not of the entire country. Pointless!

Question 31

Question 32

What is the difference in regards to intervention between observational and experimental studies ?

Answer 32

Intervention Observational = no Experimental = yes

Question 33

Experimental (intervention) studies utilize ________ settings to reduce _______.

Answer 33

Experimental (intervention) studies utilize controlled settings to reduce variation.

Question 34

What are the pros of experimental studies? Pros: Stronger evidence of ________ * ________ * Confounders are fixed by ______ or controlled by ________ allocation

Answer 34

Pros: Stronger evidence of causation * Prospective * Confounders are fixed by design or controlled by random allocation

Question 35

What are the cons of experimental studies? Cons: _________ range of hypothesis * ______ or _____ factors investigated * Not always ‘___-____’ (_____)

Answer 35

Cons: Limited range of hypothesis * Single or few factors investigated * Not always ‘do-able’ (ethics)

Question 36

What is a lab experimental study? _________ allocation Strict controlled ‘__-_____’ conditions Pros: _________ level of evidence (for causation) Cons: _____-to-________ level of relevance to ‘real-world’ Very ________, ____ & ______ intensive

Answer 36

Controlled allocation Strict controlled ‘in-house’ conditions Pros: Highest level of evidence (for causation) Cons: Low-to-moderate level of relevance to ‘real-world’ Very expensive, time & labour intensive

Question 37

What is a controlled trial experimental study?

Answer 37

Controlled allocation ‘Real-world’ conditions Pros: Very high level of evidence (for causation) Highest level of relevance to ‘real world’ Cons: Very expensive, time & labour intensive

Question 38

Answer 38

Homogenous: make all subjects the same to control environment as much as possible Randomization is crucial

Question 39

What are controlled trials?

Answer 39

Question 40

Controlled trials * The study of an _________ (treatment, preventive factor) allocated (________) among animals _________ exposed to disease * Goal is to test an ________

Answer 40

Controlled trials * The study of an intervention (treatment, preventive factor) allocated (randomly) among animals naturally exposed to disease * Goal is to test an intervention

Question 41

What are the essential features of controlled trials? * Comparison group (__________ treatment) * Often a ‘control’ group = ______ * ____________ allocation * Addresses issues with selection ______ * _________ (AKA masking) * Addresses issues with _______ and selection _____

Answer 41

* Comparison group (alternative treatment) * Often a ‘control’ group = placebo * Random allocation * Addresses issues with selection bias * Blinding (AKA masking) * Addresses issues with information and selection bias

Question 42

Answer 42

Population has to have a condition and then see if the condition remains or goes away over time. Want the doctors and patients to be blind to treatment

Question 43

What are the issues can arise in a controlled trial study? * Bias towards ___________... * Hawthorn effect: * Participants in trial tend to ______ many behaviors, regardless of _________ * Placebo effect: * A _______ effect that cannot be attributed to the _______ of the placebo itself Both of these effects ________ the condition of patients without them being the real treatment. Unfortunately makes it more difficult for study to find the _____ effects.

Answer 43

* Bias towards improvement... * Hawthorn effect: * Participants in trial tend to change many behaviors, regardless of intervention * Placebo effect: * A beneficial effect that cannot be attributed to the properties of the placebo itself Both of these effects improve the condition of patients without them being the real treatment. Unfortunately makes it more difficult for study to find a real effectl.

Question 44

Answer 44

The higher on the y axis, the better you get. Just b/c in study they get better --> hawthorne effect thinking when they take something they will feel better --> placebo

Question 45

Looking for lameness scores in dogs with secondary arthritis. Asking owners if lameness was getting better over time vs. pressure plate in animal and if it was making condition better or worse? owners saying animal getting better even though they were not

Question 46

What are controlled trials? * Measuring ________ effect * Intention-to-treat * All ________ patients and _______ allocated to treatment are included in the analysis “once randomized, always analyzed” * Per-protocol * Includes only those patients who completed the treatment _________ allocated (as per the ______)

Answer 46

Controlled trials * Measuring treatment effect * Intention-to-treat * All enrolled patients and randomly allocated to treatment are included in the analysis “once randomized, always analyzed” * Per-protocol * Includes only those patients who completed the treatment originally allocated (as per the protocol)

Question 47

Question 48

What are other terms used to refer to controlled trials?

Answer 48

Question 49

Answer 49

Intervention control group as comparison group is important looking for improvement of disease condition

Question 50

Answer 50

B/c treatment, you expect patients in treatment group to have a lower risk of disease compared to the placebo group.

Question 51

How do you calculate a risk ratio?

Answer 51

Question 52

Risk ratio in a controlled trial is called?

Answer 52

Risk difference (attributable risk) * AKA: Attributable Risk Reduction (ARR)

Question 53

What is the Number needed to treat (NNT)?

Answer 53

Tells you on average how many people need this treatment in order to cure one person. Number needed to treat (NNT) * Average number of patients who need to be treated to prevent one additional bad outcome * “Number of patients that need to be treated for one to benefit compared with a control in a controlled trial” * It is the inverse of the RD

Question 54

Question 55

Question 56

What can happen in controlled trials?

Answer 56

* Loss to follow-up (a type of selection bias) * Losses should be minimal (<20%) * Were they equal in both groups? * If losses were related to the exposure and also to the outcome = BIAS (untestable) Make sure you don't lose anyone along the way. Worry when we have reached 20% loss in a group. Need to make sure you are losing the same number in each group, if not matching then you need to worry about bias EXAMPLE If patients who didn’t respond to treatment died (or dropped out) before the end of the study, the treatment effect could look much better than it actually is! b/c it would only effect people who did not respond

Question 57

Randomize: allocating patients uniformly across treatment groups Blind: removes potential selection bias If you do both, everything should be fine Relisten to randomize

Question 58

What is a narrative review?

Answer 58

Very qualitative in nature. * Subjective (reviewer bias) * No details on how studies were selected for inclusion * Tend to weight studies equally (or subjectively) * No quantitative summary * Conducted by subject-matter experts * Pre-conceived notions? * Suitable for obtaining a broad overview of an area * Not for decision-making!

Question 59

What is a systematic review? * Systematic review (best option for __________ data) --> Features * _______ question * Written protocol for review (________ and ________) * Explicit (replicable) methods; meaning search terms are well defined. * Thorough literature _______ * _________ data extraction tool * Does not require subject matter ______ --> Purpose * Ensure ____ evidence considered * Minimize potential for _____ in drawing conclusions * Identify _____ in knowledge – precursor of research * ______ decision

Answer 59

* Systematic review (best option for reviewing data) --> Features * Specific question * Written protocol for review (transparent and repeatable) * Explicit (replicable) methods; meaning search terms are well defined. * Thorough literature review * Standard data extraction tool * Does not require subject matter expertise --> Purpose * Ensure all evidence considered * Minimize potential for bias in drawing conclusions * Identify gaps in knowledge – precursor of research * Policy decision

Question 60

Controlled trials get more points

Question 61

If you are able to extract data from each study (odds ratio, animal from each study) --> pool together --> metaanalysis (qualitative review on steroids)

Question 62

* Qualitative * Weighting of studies based on assessment of quality of methods

Question 63

* Quantitative * “Meta-analysis”... see next section * Weighting of studies based on precision of results * Options to include study quality * Quantitative outcome (multiple)

Question 64

What are the steps of a systematic review?

Answer 64

Qualitative review is still considered a systematic review because you went through all of the steps

Answer 65

Answer 66

Answer 67

Question 68

Meta-analysis is the statistical methodology used to combine data from ___ or ____ studies that have addressed the ___ question “The statistical analysis of a _____ collection of analysis results from _____ studies for the purpose of ______ the findings” – Glass, 1976

Answer 68

* Meta-analysis is the statistical methodology used to combine data from two or more studies that have addressed the same question “The statistical analysis of a large collection of analysis results from individual studies for the purpose of integrating the findings” – Glass, 1976

Question 69

What are the objectives of a meta-analysis? * Provide an overall ________ of an association * Explore sources of _______ in the observed effect across studies

Answer 69

* Provide an overall estimate of an association * Explore sources of variation in the observed effect across studies

Question 70

What are the advantages of a meta-analysis? * Ensures that all data _______ and appropriate _____ * Gain in _______ power * Allows for ______, non-________ results to contribute * Document _______ in study results * Investigate ______ for variability * _______ impacts of potential _____

Answer 70

* Ensures that all data considered and appropriate weight * Gain in statistical power * Allows for small, non-significant results to contribute * Document variability in study results * Investigate reasons for variability * Quantify impacts of potential bias

Question 71

Types of Meta-analysis: 1. _________ estimates 2. ________ patient data --> What can you measure? - ________ outcomes!!! - ____, ____, ____ - _____ Difference and _______ Mean Difference - _______ trials are best!

Answer 71

Types of Meta-analysis: 1. Summary estimates 2. Individual patient data --> What can you measure? - Quantitative outcomes!!! - OR, RR, RD - Mean Difference and Standardized Mean Difference - Controlled trials are best!

Question 72

How does meta-analysis pool weight across studies? * _________ average treatment effects * Study weighted by their _______ * More _____ = more _____! * Example: Effect of bovine somatotropin (rBST) on risk ratio for clinical mastitis * 1.27 (95%CI: 1.13-1.43)

Answer 72

* Weighted average treatment effects * Study weighted by their precision * More precise = more weight! * Example: Effect of bovine somatotropin (rBST) on risk ratio for clinical mastitis * 1.27 (95%CI: 1.13-1.43)

Question 73

What is an extra-advantages of a meta-analysis Use a ________ plot to see when you gained sufficient evidence over time to make decision!

Answer 73

Use a cumulative plot to see when you gained sufficient evidence over time to make decision!

Answer 74

as you have smaller sample sizes, your standard error gets wider;. RR < 1 --> no effect (small sample sizes). Studies without effects do not tend to get published, whihc keads to publication bias.

Question 75

Meta-analysis * Applicable for many study designs * Traditionally used with RCTs * More standardized with clearly defined intervention/comparison groups * Observational studies * Possible, but more difficult * Issues with heterogeneity * More prone to biases * Diagnostic test evaluation * Estimate DSe and DSp

Question 76

Meta-analysis are applicable to many study designs.

Answer 76