Causation & Study Design: HIV & AIDS Flashcards
(68 cards)
1
Q
Study designs
- Which study design is reflected in each? (A-D)
A
- Which study design is reflected in each? (A-D)
- A = Cross-Sectional
- B = Case-control
- C = Cohort
- D = Randomised Control Trial
2
Q
Study designs
- Which study design is reflected in each? (A-D)
A
- Which study design is reflected in each? (A-D)
- A = Cross-Sectional
- B = Case-control
- C = Cohort
- D = Randomised Control Trial
3
Q
Study designs
- Which study design is reflected in each? (A-D)
A
- Which study design is reflected in each? (A-D)
- A = Cross-Sectional
- B = Case-control
- C = Cohort
- D = Randomised Control Trial
4
Q
Study designs
- Which study design is reflected in each? (A-D)
A
- Which study design is reflected in each? (A-D)
- A = Cross-Sectional
- B = Case-control
- C = Cohort
- D = Randomised Control Trial
5
Q
Cross-sectional study
- A defined population is surveyed to simultaneously measure
- …/ … status
- …
- Sample selected using inclusion and exclusion criteria
- Different to case-control (sample selected based on outcome status)
- Different to cohort (sample based on exposure status)
- Could be general population or clinic-based
- Prevalence is reported for the population as a whole, and often for subgroups
A
- A defined population is surveyed to simultaneously measure
- Disease/ condition status (e.g. infertility)
- Exposure (e.g. sedentary lifestyle, alcohol intake)
- Sample selected using inclusion and exclusion criteria
- Different to case-control (sample selected based on outcome status)
- Different to cohort (sample based on exposure status)
- Could be general population or clinic-based
- Prevalence is reported for the population as a whole, and often for subgroups
6
Q
Cross-sectional study
- A defined population is surveyed to simultaneously measure
- Disease/ condition status (e.g. infertility)
- Exposure (e.g. sedentary lifestyle, alcohol intake)
- Sample selected using … and … criteria
- Different to case-control (sample selected based on outcome status)
- Different to cohort (sample based on exposure status)
- Could be general … or …-based
- Prevalence is reported for the population as a whole, and often for subgroups
A
- A defined population is surveyed to simultaneously measure
- Disease/ condition status (e.g. infertility)
- Exposure (e.g. sedentary lifestyle, alcohol intake)
- Sample selected using inclusion and exclusion criteria
- Different to case-control (sample selected based on outcome status)
- Different to cohort (sample based on exposure status)
- Could be general population or clinic-based
- Prevalence is reported for the population as a whole, and often for subgroups
7
Q
Cross-sectional study
- A defined population is surveyed to simultaneously measure
- Disease/ condition status (e.g. infertility)
- Exposure (e.g. sedentary lifestyle, alcohol intake)
- Sample selected using inclusion and exclusion criteria
- Different to case-control (sample selected based on … status)
- Different to cohort (sample based on exposure status)
- Could be general population or clinic-based
- Prevalence is reported for the population as a …, and often for …
A
- A defined population is surveyed to simultaneously measure
- Disease/ condition status (e.g. infertility)
- Exposure (e.g. sedentary lifestyle, alcohol intake)
- Sample selected using inclusion and exclusion criteria
- Different to case-control (sample selected based on outcome status)
- Different to cohort (sample based on exposure status)
- Could be general population or clinic-based
- Prevalence is reported for the population as a whole, and often for subgroups
8
Q
Cross-sectional study
- A defined population is surveyed to simultaneously measure
- Disease/ condition status (e.g. infertility)
- … (e.g. sedentary lifestyle, alcohol intake)
- Sample selected using inclusion and exclusion criteria
- Different to case-control (sample selected based on outcome status)
- Different to cohort (sample based on … status)
- Could be general population or clinic-based
- Prevalence is reported for the population as a whole, and often for subgroups
A
- A defined population is surveyed to simultaneously measure
- Disease/ condition status (e.g. infertility)
- Exposure (e.g. sedentary lifestyle, alcohol intake)
- Sample selected using inclusion and exclusion criteria
- Different to case-control (sample selected based on outcome status)
- Different to cohort (sample based on exposure status)
- Could be general population or clinic-based
- Prevalence is reported for the population as a whole, and often for subgroups
9
Q
Cohort study
- Used to
- calculate … (new onset cases of a disease/condition/outcome)
- identify … (risk factors) for particular outcome
- Participants selected into exposed vs non-exposed group (no allocation made by the researcher)
- Two groups as similar as possible (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- At study end, relative numbers of new disease occurrences compared across groups
- Retrospective or prospective
A
- Used to
- calculate incidence (new onset cases of a disease/condition/outcome)
- identify exposures (risk factors) for particular outcome
- Participants selected into exposed vs non-exposed group (no allocation made by the researcher)
- Two groups as similar as possible (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- At study end, relative numbers of new disease occurrences compared across groups
- Retrospective or prospective
10
Q
Cohort study
- Used to
- calculate incidence (new onset cases of a disease/condition/outcome)
- identify exposures (risk factors) for particular outcome
- Participants selected into … vs non-… group
- Two groups as … as possible (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- At study end, relative numbers of new disease occurrences compared across groups
- Retrospective or prospective
A
- Used to
- calculate incidence (new onset cases of a disease/condition/outcome)
- identify exposures (risk factors) for particular outcome
- Participants selected into exposed vs non-exposed group (no allocation made by the researcher)
- Two groups as similar as possible (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- At study end, relative numbers of new disease occurrences compared across groups
- Retrospective or prospective
11
Q
Cohort study
- Used to
- calculate … (new onset cases of a disease/condition/outcome)
- identify exposures (risk factors) for particular outcome
- Participants selected into exposed vs non-exposed group (no allocation made by the researcher)
- Two groups as similar as possible (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- At study end, relative numbers of new disease occurrences compared across …
- Retrospective or prospective
A
- Used to
- calculate incidence (new onset cases of a disease/condition/outcome)
- identify exposures (risk factors) for particular outcome
- Participants selected into exposed vs non-exposed group (no allocation made by the researcher)
- Two groups as similar as possible (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- At study end, relative numbers of new disease occurrences compared across groups
- Retrospective or prospective
12
Q
Cohort study
- Used to
- calculate incidence (… … cases of a disease/condition/outcome)
- identify exposures (… …) for particular outcome
- Can be …spective or ….spective
A
- Used to
- calculate incidence (new onset cases of a disease/condition/outcome)
- identify exposures (risk factors) for particular outcome
- Can be retrospective or prospective
13
Q
Case-control study
- Used to identify relevant … (not used to calculate …)
- Two groups of participants are selected – one with condition (cases) and one without (controls)
- Controls selected to be as similar as possible to the cases (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- Always …→Past exposure/s in both groups
- E.g. interview/survey, historical records
A
- Used to identify relevant exposures (not used to calculate incidence)
- Two groups of participants are selected – one with condition (cases) and one without (controls)
- Controls selected to be as similar as possible to the cases (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- Always retrospective→Past exposure/s in both groups
- E.g. interview/survey, historical records
14
Q
Case-control study
- Used to identify relevant exposures (not used to calculate incidence)
- Two groups of participants are selected – one with condition (…) and one without (…)
- Controls selected to be as … as possible to the … (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- Always retrospective→Past exposure/s in both groups
- E.g. interview/survey, historical records
A
- Used to identify relevant exposures (not used to calculate incidence)
- Two groups of participants are selected – one with condition (cases) and one without (controls)
- Controls selected to be as similar as possible to the cases (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- Always retrospective→Past exposure/s in both groups
- E.g. interview/survey, historical records
15
Q
Case-control study
- Used to identify relevant exposures (not used to calculate incidence)
- Two groups of participants are selected – one with condition (cases) and one without (controls)
- Controls selected to be as similar as possible to the cases (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential …) at selection
- Exposures of interest are … … or matched at selection
- Always retrospective→Past exposure/s in both groups
- E.g. interview/survey, historical records
A
- Used to identify relevant exposures (not used to calculate incidence)
- Two groups of participants are selected – one with condition (cases) and one without (controls)
- Controls selected to be as similar as possible to the cases (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- Always retrospective→Past exposure/s in both groups
- E.g. interview/survey, historical records
16
Q
Case-control study
- Used to identify relevant exposures (not used to calculate …)
- Two groups of participants are selected – one with condition (cases) and one without (controls)
- Controls selected to be as similar as possible to the cases (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- Always retrospective→… …/s in both groups
- E.g. interview/survey, historical records
A
- Used to identify relevant exposures (not used to calculate incidence)
- Two groups of participants are selected – one with condition (cases) and one without (controls)
- Controls selected to be as similar as possible to the cases (e.g. age, gender, occupation, stage of illness, etc.)
- Variables not of interest are matched (i.e. potential confounders) at selection
- Exposures of interest are not measured or matched at selection
- Always retrospective→Past exposure/s in both groups
- E.g. interview/survey, historical records
17
Q
Cohort studys can be retrospective or prospective, but case-control studies are always …
A
retrospective
18
Q
RCT
- Used to test the … and …/… of interventions
- Participants selected and then randomly allocated to either receive the intervention of interest or to receive a control (or no) intervention
- Random allocation should ensure that the two groups are essentially identical before provision of intervention or control
- Outcomes are compared across the two groups at the end of the trial
A
- Used to test the safety and efficacy/effectiveness of interventions
- Participants selected and then randomly allocated to either receive the intervention of interest or to receive a control (or no) intervention
- Random allocation should ensure that the two groups are essentially identical before provision of intervention or control
- Outcomes are compared across the two groups at the end of the trial
19
Q
RCT
- Used to test the safety and efficacy/effectiveness of interventions
- Participants selected and then … allocated to either receive the …. of interest or to receive a …
- Random allocation should ensure that the two groups are essentially identical before provision of intervention or control
- Outcomes are compared across the two groups at the end of the trial
A
- Used to test the safety and efficacy/effectiveness of interventions
- Participants selected and then randomly allocated to either receive the intervention of interest or to receive a control (or no) intervention
- Random allocation should ensure that the two groups are essentially identical before provision of intervention or control
- Outcomes are compared across the two groups at the end of the trial
20
Q
RCT
- Used to test the safety and efficacy/effectiveness of interventions
- Participants selected and then randomly allocated to either receive the intervention of interest or to receive a control (or no) intervention
- Random allocation should ensure that the two groups are essentially … before provision of intervention or control
- Outcomes are … across the two groups at the end of the trial
A
- Used to test the safety and efficacy/effectiveness of interventions
- Participants selected and then randomly allocated to either receive the intervention of interest or to receive a control (or no) intervention
- Random allocation should ensure that the two groups are essentially identical before provision of intervention or control
- Outcomes are compared across the two groups at the end of the trial
21
Q
RCT
- Used to test the … and …/effectiveness of interventions
- Participants selected and then randomly allocated to either receive the intervention of interest or to receive a control (or no) intervention
- … allocation should ensure that the two groups are essentially identical before provision of intervention or control
- Outcomes are compared across the two groups at the end of the trial
A
- Used to test the safety and efficacy/effectiveness of interventions
- Participants selected and then randomly allocated to either receive the intervention of interest or to receive a control (or no) intervention
- Random allocation should ensure that the two groups are essentially identical before provision of intervention or control
- Outcomes are compared across the two groups at the end of the trial
22
Q
Why do we need to think about causation?
A
23
Q
Differences between study designs
A
24
Q
Differences between study designs
- List in order (top to bottom) - Cohort, Cross-sectional, Case control, RCT, Case Study
A
25
Which study design gives the best evidence for causal association?
RCT
26
A ... is a variable that influences both the dependent variable and independent variable causing a spurious association
A **confounder** is a variable that influences both the dependent variable and independent variable causing a spurious association
27
_Confounding_
* Influences both ... and ...
* Influences both **exposure** and **disease**
28
_Causal criteria_
* ... postulates – causal factors in infectious disease
* ...-Hill criteria – causal factors in sickness, injury and occupation
* **Koch’s** postulates – causal factors in infectious disease
* **Bradford**-Hill criteria – causal factors in sickness, injury and occupation
29
_Causal criteria_
* Koch’s ... – causal factors in ... disease
* Bradford-... criteria – causal factors in ..., injury and occupation
* Koch’s **postulates** – causal factors in **infectious** disease
* Bradford-**Hill** criteria – causal factors in **sickness**, injury and occupation
30
_Causal criteria_
* Koch’s postulates – causal factors in ... disease
* Bradford-Hill criteria – causal factors in sickness, ... and occupation
* Koch’s postulates – causal factors in **infectious** disease
* Bradford-Hill criteria – causal factors in sickness, **injury** and occupation
31
_Causal criteria_
* ... postulates – causal factors in infectious disease
* Bradford-Hill criteria – causal factors in sickness, injury and ...
* **Koch’s** postulates – causal factors in infectious disease
* Bradford-Hill criteria – causal factors in sickness, injury and **occupation**
32
_Bradford-Hill criteria_
33
_Bradford-Hill criteria_
34
_Bradford-Hill criteria_
35
_Koch’s postulates_
36
_Koch’s postulates_
* The bacteria must be ... in ... case of the disease.
* The bacteria must be isolated from the host with the disease and grown in pure culture.
* The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host.
* The bacteria must be recoverable from the experimentally infected host.
* The bacteria must be **present** in **every** case of the disease.
* The bacteria must be isolated from the host with the disease and grown in pure culture.
* The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host.
* The bacteria must be recoverable from the experimentally infected host.
37
_Koch’s postulates_
* The bacteria must be present in every case of the disease.
* The bacteria must be ... from the host with the disease and ... in pure culture.
* The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host.
* The bacteria must be recoverable from the experimentally infected host.
* The bacteria must be present in every case of the disease.
* The bacteria must be **isolated** from the host with the disease and **grown** in pure culture.
* The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host.
* The bacteria must be recoverable from the experimentally infected host.
38
_Koch’s postulates_
* The bacteria must be present in every case of the disease.
* The bacteria must be isolated from the host with the disease and grown in pure culture.
* The specific disease must be ... when a pure culture of the bacteria is inoculated into a ... susceptible host.
* The bacteria must be recoverable from the experimentally infected host.
* The bacteria must be present in every case of the disease.
* The bacteria must be isolated from the host with the disease and grown in pure culture.
* The specific disease must be **reproduced** when a pure culture of the bacteria is inoculated into a healthy susceptible host.
* The bacteria must be recoverable **from** the experimentally infected host.
39
_Koch’s postulates_
* The bacteria must be present in every case of the disease.
* The bacteria must be isolated from the host with the disease and grown in pure culture.
* The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host.
* The bacteria must be ... from the ... infected host.
* The bacteria must be present in every case of the disease.
* The bacteria must be isolated from the host with the disease and grown in pure culture.
* The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host.
* The bacteria must be **recoverable** from the **experimentally** infected host.
40
_HIV/AIDS_
* ... ... Virus infection / Acquired Immune Deficiency Syndrome (HIV/AIDS)
* A spectrum of conditions caused by infection with the ... ... Virus (HIV)
* HIV targets cells within the immune system, causing immunodeficiency→disease and opportunistic infections which would typically normally be neutralised
* Discovered in 1981 in USA – the AIDS crisis
* Global pandemic, responsible for at least 35 million deaths worldwide; c. 350,000 men and women in the USA died between 1987 and 1998
* **Human Immunodeficiency Virus** infection / Acquired Immune Deficiency Syndrome (HIV/AIDS)
* A spectrum of conditions caused by infection with the **Human Immunodeficiency Virus** (HIV)
* HIV targets cells within the immune system, causing immunodeficiency→disease and opportunistic infections which would typically normally be neutralised
* Discovered in 1981 in USA – the AIDS crisis
* Global pandemic, responsible for at least 35 million deaths worldwide; c. 350,000 men and women in the USA died between 1987 and 1998
41
_HIV/AIDS_
* Human Immunodeficiency Virus infection / Acquired Immune Deficiency Syndrome (HIV/AIDS) A spectrum of conditions caused by infection with the Human Immunodeficiency Virus (HIV)
* HIV targets cells within the immune system, causing ...→disease and opportunistic infections which would typically normally be ...
* Discovered in 1981 in USA – the AIDS crisis
* Global pandemic, responsible for at least 35 million deaths worldwide; c. 350,000 men and women in the USA died between 1987 and 1998
* Human Immunodeficiency Virus infection / Acquired Immune Deficiency Syndrome (HIV/AIDS) A spectrum of conditions caused by infection with the Human Immunodeficiency Virus (HIV)
* HIV targets cells within the immune system, causing **immunodeficiency**→disease and opportunistic infections which would typically normally be **neutralised**
* Discovered in 1981 in USA – the AIDS crisis
* Global pandemic, responsible for at least 35 million deaths worldwide; c. 350,000 men and women in the USA died between 1987 and 1998
42
_HIV/AIDS_
* Human Immunodeficiency Virus infection / Acquired Immune Deficiency Syndrome (HIV/AIDS) A spectrum of conditions caused by infection with the Human Immunodeficiency Virus (HIV)
* HIV targets cells within the immune system, causing immunodeficiency→disease and opportunistic infections which would typically normally be neutralised
* Discovered in ... in USA – the AIDS crisis
* Global pandemic, responsible for at least ... million deaths worldwide; c. 350,000 men and women in the USA died between 1987 and 1998
* Human Immunodeficiency Virus infection / Acquired Immune Deficiency Syndrome (HIV/AIDS) A spectrum of conditions caused by infection with the Human Immunodeficiency Virus (HIV)
* HIV targets cells within the immune system, causing immunodeficiency→disease and opportunistic infections which would typically normally be neutralised
* Discovered in **1981** in USA – the AIDS crisis
* Global pandemic, responsible for at least **35** million deaths worldwide; c. 350,000 men and women in the USA died between 1987 and 1998
43
_HIV/AIDS_
* Human Immunodeficiency Virus infection / Acquired Immune Deficiency Syndrome (HIV/AIDS) A spectrum of conditions caused by infection with the Human Immunodeficiency Virus (HIV)
* HIV targets cells within the immune system, causing immunodeficiency→disease and ... infections which would typically normally be neutralised
* Discovered in 1981 in USA – the AIDS crisis
* Global ..., responsible for at least 35 million deaths worldwide; c. 350,000 men and women in the USA died between 1987 and 1998
* Human Immunodeficiency Virus infection / Acquired Immune Deficiency Syndrome (HIV/AIDS) A spectrum of conditions caused by infection with the Human Immunodeficiency Virus (HIV)
* HIV targets cells within the immune system, causing immunodeficiency→disease and **opportunistic** infections which would typically normally be neutralised
* Discovered in 1981 in USA – the AIDS crisis
* Global **pandemic**, responsible for at least 35 million deaths worldwide; c. 350,000 men and women in the USA died between 1987 and 1998
44
_AIDS: Contribution of study designs_
* ... ... help when disease is new, when first cases are being discovered
* After this - which study design?
* Then -
* **Case studies** help when disease is new, when first cases are being discovered
* After this - which study design - **Cross-sectional**
* Then - **Case control**
45
_AIDS: Contribution of study designs_
* Which study design for each?
* **Case studies**
* **Cross-sectional**
* **Case control**
46
_AIDS Cohort studies_
* Immediately after initial recognition of AIDS, epidemiologists in the United States, Denmark, and the Netherlands established cohort studies of ... men, injection drug users, and people with ...
* Then the larger Multicenter AIDS Cohort Study (MACS) which was launched in 1984
* 1) describe the early pathophysiologic events in the course leading to AIDS-related conditions [and] AIDS...,
* 2) define and quantify the factors suspected of initiating or modulating the immunopathologic process leading to AIDS...,
* [and] 3) provide access to a repository of biologic specimens with detailed epidemiologic data for investigators with promising ideas for research
* Immediately after initial recognition of AIDS, epidemiologists in the United States, Denmark, and the Netherlands established cohort studies of **homosexual** men, injection drug users, and people with **hemophilia**
* Then the larger Multicenter AIDS Cohort Study (MACS) which was launched in 1984
* 1) describe the early pathophysiologic events in the course leading to AIDS-related conditions [and] AIDS...,
* 2) define and quantify the factors suspected of initiating or modulating the immunopathologic process leading to AIDS...,
* [and] 3) provide access to a repository of biologic specimens with detailed epidemiologic data for investigators with promising ideas for research
47
_AIDS Cohort studies_
* Immediately after initial recognition of AIDS, epidemiologists in the United States, Denmark, and the Netherlands established cohort studies of homosexual men, injection drug users, and people with hemophilia
* Then the larger Multicenter AIDS Cohort Study (...) which was launched in ...
* 1) describe the early pathophysiologic events in the course leading to AIDS-related conditions [and] AIDS...,
* 2) define and quantify the factors suspected of initiating or modulating the immunopathologic process leading to AIDS...,
* [and] 3) provide access to a repository of biologic specimens with detailed epidemiologic data for investigators with promising ideas for research
* Immediately after initial recognition of AIDS, epidemiologists in the United States, Denmark, and the Netherlands established cohort studies of homosexual men, injection drug users, and people with hemophilia
* Then the larger Multicenter AIDS Cohort Study (**MACS**) which was launched in **1984**
* 1) describe the early pathophysiologic events in the course leading to AIDS-related conditions [and] AIDS...,
* 2) define and quantify the factors suspected of initiating or modulating the immunopathologic process leading to AIDS...,
* [and] 3) provide access to a repository of biologic specimens with detailed epidemiologic data for investigators with promising ideas for research
48
_AIDS Cohort studies_
* Immediately after initial recognition of AIDS, epidemiologists in the United States, Denmark, and the Netherlands established cohort studies of homosexual men, injection drug users, and people with hemophilia
* Then the larger Multicenter AIDS Cohort Study (MACS) which was launched in 1984
* 1) describe the early ... events in the course leading to AIDS-related conditions [and] AIDS...,
* 2) define and quantify the ... suspected of initiating or modulating the immunopathologic process leading to AIDS...,
* [and] 3) provide access to a repository of biologic specimens with detailed epidemiologic data for investigators with promising ideas for research
* Immediately after initial recognition of AIDS, epidemiologists in the United States, Denmark, and the Netherlands established cohort studies of homosexual men, injection drug users, and people with hemophilia
* Then the larger Multicenter AIDS Cohort Study (MACS) which was launched in 1984
* 1) describe the early **pathophysiologic** events in the course leading to AIDS-related conditions [and] AIDS...,
* 2) define and quantify the **factors** suspected of initiating or modulating the immunopathologic process leading to AIDS...,
* [and] 3) provide access to a repository of biologic specimens with detailed epidemiologic data for investigators with promising ideas for research
49
_AIDS Cohort studies_
* Immediately after initial recognition of AIDS, epidemiologists in the United States, Denmark, and the Netherlands established cohort studies of homosexual men, injection drug users, and people with hemophilia
* Then the larger Multicenter AIDS Cohort Study (MACS) which was launched in 1984
* 1) describe the early pathophysiologic events in the course leading to AIDS-related conditions [and] AIDS...,
* 2) define and quantify the factors suspected of initiating or modulating the ... process leading to AIDS...,
* [and] 3) provide access to a repository of biologic ... with detailed epidemiologic data for investigators with promising ideas for research
* Immediately after initial recognition of AIDS, epidemiologists in the United States, Denmark, and the Netherlands established cohort studies of homosexual men, injection drug users, and people with hemophilia
* Then the larger Multicenter AIDS Cohort Study (MACS) which was launched in 1984
* 1) describe the early pathophysiologic events in the course leading to AIDS-related conditions [and] AIDS...,
* 2) define and quantify the factors suspected of initiating or modulating the **immunopathologic** process leading to AIDS...,
* [and] 3) provide access to a repository of biologic **specimens** with detailed epidemiologic data for investigators with promising ideas for research
50
_The contribution of MACS_
* Over 1,500 papers, 4 which have been cited more than 1000 times;
* Fahey et al. (1990), in which researchers validated serum levels of neopterin and β2-microglobulin, in combination with the CD4 T-cell count, as biomarkers of AIDS risk;
* Dean et al. (1996), in which they described the profound protection against HIV infection by a genetic variant of a co-receptor for HIV on CD4 T-cells;
* Mellors et al. (1996), in which the authors identified the level of HIV circulating in plasma (i.e., HIV viral load) as a strong prognostic indicator; and
* Mellors et al. (1997), in which they established the combined measurement of HIV viral load and CD4 T- cell count as a highly accurate predictor of prognosis.
* MACS is being combined with a ...-focused cohort WIHS-CISS which still continues to date.
* Over 1,500 papers, 4 which have been cited more than 1000 times;
* Fahey et al. (1990), in which researchers validated serum levels of neopterin and β2-microglobulin, in combination with the CD4 T-cell count, as biomarkers of AIDS risk;
* Dean et al. (1996), in which they described the profound protection against HIV infection by a genetic variant of a co-receptor for HIV on CD4 T-cells;
* Mellors et al. (1996), in which the authors identified the level of HIV circulating in plasma (i.e., HIV viral load) as a strong prognostic indicator; and
* Mellors et al. (1997), in which they established the combined measurement of HIV viral load and CD4 T- cell count as a highly accurate predictor of prognosis.
* MACS is being combined with a **female**-focused cohort WIHS-CISS which still continues to date.
51
_The contribution of MACS_
* Over 1,500 papers, 4 which have been cited more than 1000 times;
* Fahey et al. (1990), in which researchers validated serum levels of neopterin and β2-microglobulin, in combination with the CD4 T-cell count, as biomarkers of AIDS risk;
* Dean et al. (1996), in which they described the profound protection against HIV infection by a genetic variant of a co-receptor for HIV on CD4 T-cells;
* Mellors et al. (1996), in which the authors identified the level of HIV circulating in plasma (i.e., HIV viral load) as a strong prognostic indicator; and
* Mellors et al. (1997), in which they established the combined measurement of HIV viral load and CD4 T- cell count as a highly accurate predictor of prognosis.
* MACS is being combined with a female-focused cohort WIHS-CISS which still continues to date.
* Over 1,500 papers, 4 which have been cited more than 1000 times;
* Fahey et al. (1990), in which researchers validated serum levels of neopterin and β2-microglobulin, in combination with the CD4 T-cell count, as biomarkers of AIDS risk;
* Dean et al. (1996), in which they described the profound protection against HIV infection by a genetic variant of a co-receptor for HIV on CD4 T-cells;
* Mellors et al. (1996), in which the authors identified the level of HIV circulating in plasma (i.e., HIV viral load) as a strong prognostic indicator; and
* Mellors et al. (1997), in which they established the combined measurement of HIV viral load and CD4 T- cell count as a highly accurate predictor of prognosis.
* MACS is being combined with a female-focused cohort WIHS-CISS which still continues to date.
52
_Causation and confounding_
* Close association between male circumcision and HIV/AIDS prevalence
* 1) male circumcision causes a reduction in the chance of contracting HIV/AIDS
* OR
* 2) some other factor increases chance of being uncircumcised and chance of contracting HIV/AIDS
53
_Causation and cofounding - HIV/AIDs and male circumcision_
* Close association between male circumcision and HIV/AIDS prevalence
* 1) male circumcision ... a ... in the chance of contracting HIV/AIDS
* OR
* 2) some other ... increases chance of being ... and chance of contracting HIV/AIDS
* Can it tell us if either, or both or not?
* Close association between male circumcision and HIV/AIDS prevalence
* 1) male **circumcision** causes a **reduction** in the chance of contracting HIV/AIDS
* OR
* 2) some other **factor** increases chance of being **uncircumcised** and chance of contracting HIV/AIDS
* **Can't tell us - RCT come in handy here**
54
_Causation and confounding - Male circumcision and HIV/AIDS_
* Analytic - experimental
* 3 RCTs; South Africa (N= 3274), Uganda (N= 4996), and Kenya (N= 2784) Does Adult male circumcision reduce risk of HIV acquisition in men?
* RR of 0.50 at 12 months [CIs 0.34, 0.72]
* Meta-analysis secondary outcomes (Cochrane Review)
* Suggested only one sig. difference in sexual behaviour in one trial (circumcised men 1 more sexual contact at 12m)
* Why?
* Foreskin increases risk of micro tears during sex
* Foreskin provides hospitable environment for pathogen survival
* Analytic - experimental
* 3 RCTs; South Africa (N= 3274), Uganda (N= 4996), and Kenya (N= 2784) **Adult male circumcision reduces risk of HIV acquisition in men by c. 60%**
* RR of 0.50 at 12 months [CIs 0.34, 0.72]
* Meta-analysis secondary outcomes (Cochrane Review)
* Suggested only one sig. difference in sexual behaviour in one trial (circumcised men 1 more sexual contact at 12m)
* Why?
* Foreskin increases risk of micro tears during sex
* Foreskin provides hospitable environment for pathogen survival
55
_Causation and confounding - Male circumcision and HIV/AIDS_
* Analytic - experimental
* 3 RCTs; South Africa (N= 3274), Uganda (N= 4996), and Kenya (N= 2784) Does Adult male circumcision reduce risk of HIV acquisition in men?
* Analytic - experimental
* 3 RCTs; South Africa (N= 3274), Uganda (N= 4996), and Kenya (N= 2784) **Adult male circumcision reduces risk of HIV acquisition in men by c. 60%**
* RR of 0.50 at 12 months [CIs 0.34, 0.72]
* Meta-analysis secondary outcomes (Cochrane Review)
* Suggested only one sig. difference in sexual behaviour in one trial (circumcised men 1 more sexual contact at 12m)
* Why?
* Foreskin increases risk of micro tears during sex
* Foreskin provides hospitable environment for pathogen survival
56
_Causation and confounding - Male circumcision and HIV/AIDS_
* Analytic - experimental
* 3 RCTs; South Africa (N= 3274), Uganda (N= 4996), and Kenya (N= 2784) Adult male circumcision reduces risk of HIV acquisition in men by c. 60%
* RR of 0.50 at 12 months [CIs 0.34, 0.72]
* Meta-analysis secondary outcomes (... Review)
* Suggested only ... sig. difference in sexual behaviour in one trial
* Why?
* Foreskin increases risk of micro tears during sex
* Foreskin provides hospitable environment for pathogen survival
* Analytic - experimental
* 3 RCTs; South Africa (N= 3274), Uganda (N= 4996), and Kenya (N= 2784) Adult male circumcision reduces risk of HIV acquisition in men by c. 60%
* RR of 0.50 at 12 months [CIs 0.34, 0.72]
* Meta-analysis secondary outcomes (**Cochrane** Review)
* Suggested only **one** sig. difference in sexual behaviour in one trial (circumcised men 1 more sexual contact at 12m)
* Why?
* Foreskin increases risk of micro tears during sex
* Foreskin provides hospitable environment for pathogen survival
57
_Causation and confounding - Male circumcision and HIV/AIDS_
* Analytic - experimental
* 3 RCTs; South Africa (N= 3274), Uganda (N= 4996), and Kenya (N= 2784) Adult male circumcision reduces risk of HIV acquisition in men by c. 60%
* RR of 0.50 at 12 months [CIs 0.34, 0.72]
* Meta-analysis secondary outcomes (Cochrane Review)
* Suggested only one sig. difference in sexual behaviour in one trial (circumcised men 1 more sexual contact at 12m)
* Why?
* Foreskin increases risk of ... ... during sex
* Foreskin provides ... environment for pathogen ...
* Analytic - experimental
* 3 RCTs; South Africa (N= 3274), Uganda (N= 4996), and Kenya (N= 2784) Adult male circumcision reduces risk of HIV acquisition in men by c. 60%
* RR of 0.50 at 12 months [CIs 0.34, 0.72]
* Meta-analysis secondary outcomes (Cochrane Review)
* Suggested only one sig. difference in sexual behaviour in one trial (circumcised men 1 more sexual contact at 12m)
* Why?
* Foreskin increases risk of **micro tears** during sex
* Foreskin provides **hospitable** environment for pathogen **survival**
58
_Koch's posulates - HIV/AIDS_
59
_Koch's posulates - HIV/AIDS_
60
_Bradford-Hill criteria - HIV/AIDS_
61
_Bradford-Hill criteria - HIV/AIDS_
62
_Bradford-Hill criteria - HIV/AIDS_
63
_Summary - Causation and Study Design - HIV/AIDS_
* Four key types of study design- ....
* ... (3) = analytic-observational, ... = analytic-experimental, ... = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* Koch’s postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; Strength of association, Consistency, Specificity, Temporality, Biological gradient, Plausibility, Coherence, Experimental evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
* **Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT**
* **Cross-sectional, cohort, case control = analytic-observational, RCT = analytic-experimental, RCT = best**
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* Koch’s postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; Strength of association, Consistency, Specificity, Temporality, Biological gradient, Plausibility, Coherence, Experimental evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
64
_Summary - Causation and Study Design - HIV/AIDS_
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, ...
* Cross-sectional, cohort, case control = analytic-observational, ... = analytic-experimental, ... = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* ... postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* ...-Hill criteria; Strength of association, Consistency, Specificity, Temporality, Biological gradient, Plausibility, Coherence, Experimental evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, **RCT**
* Cross-sectional, cohort, case control = analytic-observational, **RCT** = analytic-experimental, **RCT** = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* **Koch’s** postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* **Bradford**-Hill criteria; Strength of association, Consistency, Specificity, Temporality, Biological gradient, Plausibility, Coherence, Experimental evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
65
_Summary - Causation and Study Design - HIV/AIDS_
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT
* Cross-sectional, cohort, case control = analytic-..., RCT = analytic-..., RCT = best
* evidence for ... ... between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing ... the other to happen
* Koch’s postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; Strength of association, Consistency, Specificity, Temporality, Biological gradient, Plausibility, Coherence, Experimental evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT
* Cross-sectional, cohort, case control = analytic-**observational**, RCT = analytic-**experimental**, RCT = best
* evidence for **causal** **association** between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing **caused** the other to happen
* Koch’s postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; Strength of association, Consistency, Specificity, Temporality, Biological gradient, Plausibility, Coherence, Experimental evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
66
_Summary - Causation and Study Design - HIV/AIDS_
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT
* Cross-sectional, cohort, case control = analytic-observational, RCT = analytic-experimental, RCT = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* Koch’s postulates; presence of ... in diseased organism, microorganism can be ... and cultured, introduction of microorganism to ... organism leads to disease, microorganism can be ... from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; Strength of association, Consistency, Specificity, Temporality, Biological gradient, Plausibility, Coherence, Experimental evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT
* Cross-sectional, cohort, case control = analytic-observational, RCT = analytic-experimental, RCT = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* Koch’s postulates; presence of **microorganism** in diseased organism, microorganism can be **isolated** and cultured, introduction of microorganism to **healthy** organism leads to disease, microorganism can be **re-isolated** from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; Strength of association, Consistency, Specificity, Temporality, Biological gradient, Plausibility, Coherence, Experimental evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
67
_Summary - Causation and Study Design - HIV/AIDS_
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT
* Cross-sectional, cohort, case control = analytic-observational, RCT = analytic-experimental, RCT = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* Koch’s postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; ... of association, Consistency, ..., Temporality, Biological gradient, ..., Coherence, ... evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT
* Cross-sectional, cohort, case control = analytic-observational, RCT = analytic-experimental, RCT = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* Koch’s postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; **Strength** of association, Consistency, **Specificity**, Temporality, Biological gradient, **Plausibility**, Coherence, **Experimental** evidence, Analogy
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
68
_Summary - Causation and Study Design - HIV/AIDS_
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT
* Cross-sectional, cohort, case control = ...-observational, RCT = ...-experimental, RCT = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* Koch’s postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; Strength of association, Consistency, Specificity, ..., ... gradient, Plausibility, ..., Experimental evidence, ...
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
* Four key types of study design- cross-sectional, cohort (retro/prospective), case control, RCT
* Cross-sectional, cohort, case control = **analytic**-observational, RCT = **analytic**-experimental, RCT = best
* evidence for causal association between exposure/s and outcome/s
* When a study finds an association between one thing and another thing, it does not mean one thing caused the other to happen
* Koch’s postulates; presence of microorganism in diseased organism, microorganism can be isolated and cultured, introduction of microorganism to healthy organism leads to disease, microorganism can be re-isolated from inoculated, disease organism and identified as identical to the original agent
* Bradford-Hill criteria; Strength of association, Consistency, Specificity, **Temporality**, **Biological** gradient, Plausibility, **Coherence**, Experimental evidence, **Analogy**
* We can use different study designs to satisfy causal factors and determine the likelihood of an exposure being causative of a disease outcome
