Final Exam Flashcards

1
Q

Selection Bias

A

“..distortions that result from procedures used to select subjects and from factors that influence study participation”

Results in a measure of association between exposure and outcome that is meaningfully different from the association had all subjects been included in the analysis

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2
Q

Confounding

A

A mixing of effects/ distortion of the exposure-disease relationship due to the effect of a third variable
Is it a confounder?
Associated with outcome
Associated with exposure
Not a causal intermediate between the two

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3
Q

What kind of bias is misclassification bias?

A

Misclassification is a form of information bias. Self-reported data frequently raises information bias concerns

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4
Q

Non-differential misclassification

A

Classification errors do not depend on the subjects’ values for any other variables.
E.g. misclassification of exposure is not dependent on outcome status and misclassification of outcome is not dependent on exposure status
Example: you use a bad measurement tool, but use it on everyone. Likely there is measurement error and it will be non-differential.
If there is a large RR in the paper and you say this is due to non-differential misclassification due to use of a bad measurement tool for example, this would be WRONG. Because we would expect the RR to be larger than what is reported.

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5
Q

What direction does non differential misclassification bias go?

A

Results in bias toward the null

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6
Q

differential misclassification bias

A

misclassification of one variable depends on the values of other variables
Example: Recall bias – mothers of children with birth defects may be more likely to report/remember all exposures during pregnancy while mothers of children without birth defects are more likely to under-report exposures due to not remembering them

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7
Q

What direction does differential misclassification bias go?

A

any direction

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8
Q

What are the causes of selection bias and give an example of such in reproductive epi

A

Participation bias, Loss to follow-up
Issue those lost are systematically different than those kept

Repro epi example: “Unhealthy” worker effect

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9
Q

5 Methodologic Issues to Always Consider

A

Confounding
Detection Bias/Diagnostic Bias
Outcome assessment differential biased on exposure status
Ex. Study will catch more miscarriages among women whose pregnancies are diagnosed earlier Goldhaber
Participation Bias (type of selection bias)
Individuals who participate are different than those who do not
Impacts internal validity of the study
If not representative of the population to which you want to generalize results, participation bias can lead to external validity issues
Recall Bias (type of information bias)
Sample Size/Power
Not a type of bias, but something to keep in mind.

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10
Q

In experimental studies, randomization makes confounding less likely. Why is that?

A

Randomization makes confounding less likely because when you randomize each individual has an equal probability of being in either group so you are more likely to get two groups that are similar except for exposure. However still opportunity for confounding that by chance one group has more obese groups that would confound results bc they have higher risk for high blood pressure, impacting results … which is more likely in the case of a small sample size. The bigger sample size will help reduce this likelihood of confounding. But it can always occur by chance.

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11
Q

Why do observational studies have increased risk of confounding?

A

Risk of observational: no control and people exposed for different reasons which increases risk for confounding.

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12
Q

Intention to Treat (ITT) biases in what direction?

A

using this type of analysis biases toward the null (see a smaller effect) because it includes participants who are not adherent as well

**THIS IS THE BEST TYPE because although not completely unbias (bc adherenece is not 100%) but if there is any bias, it is a bias toward the null and generally in science we want to bias ourselves in a conservative way bc we do not want to see an association when there is not one.

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13
Q

When do we do ITT and why?

A

At allocation, because this is where we randomize

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14
Q

Flaw of the Goldberg calcium RCT in regards to internal validity

A

Did not really do any ITT or analysis of the full enrollment. And there are more in the treatment than in the placebo group. They were not treated for the full pregnancy length so a decision to exclude them based on adherence so that creates potentially greater bias. It would be better to include the data than just exclude them.
Not taking BP pre-pregnancy – randomization should reduce imbalance of women with preexisting hypertension
Exclusion of misclassified gestational age – definitely could create bias esp if they had risk factors for BP could bias toward the null because they took them out.

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15
Q

Example of selection bias in a study on anaesthetic gas & miscarriage

A

send survey to nurses asking for reproductive history and if they work in OR or were exposed to AG
Finding: rate was 2X as high as women unexposed and statistically significant
Issue: women who were exposed with normal pregnancies responded at much lower rate

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16
Q

Why is recall bias more common in studies of miscarriage and birth defects?

A

It is not that women exaggerate but rather they recall more completely bc they are more likely to recall than women who have healthy birth and not likely to recall something they do not think is important

Direct correlation of reporting spontaneous abortion and when it occurred. The earlier it occurs, the less likely to report. Also link between how far back in time you are asking to recall – further back you go the less accurate the memory. (2 separate effects: gestational age and recall time)

*Don’t use the word “overreport” for recall because the case is actually that control participants UNDERREPORT bc their recall may be different and more difficult bc of the normal outcome

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17
Q

Why was there diagnostic bias in the goldhaber study?

A

Time of diagnosis!
The VDT test group as a whole got their pregnancies diagnosed earlier but they were able to adjust for this in the analysis which is good because if not it would have biased away from the null

Diagnostic bias occurs because early pregnancy diagnosis has a higher rates so if the cases have earlier pregnancy diagnosis than the control, they will already have a higher rate of miscarriage and this is present in the Goldhaber study

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18
Q

Participation bias affects internal and external validity. How can you avoid this?

A

You can avoid this through recruitment

  1. Particularly a problem with retrospective studies bc participation influenced by having experienced the outcome
  2. To avoid participation bias, could do a prospective study; don’t communicate outcome or exposure the study is looking for
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19
Q

How can sample size affect internal validity

A

Sample size may affect if you are able to detect a difference

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20
Q

Which bias has the greatest bias?

A

Differential misclassification has the greatest bias. Affects only one group (control or case) and biases toward or away from the null depending on the group misclassified

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21
Q

What is the healthy worker effect?

A

A reproductive study of workersfinds weak effects but compared to outside the workforce, its higher. Because those outside the workforce are more fertile by definition because on pregnancy leave, stay at home mom, etc.)

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22
Q

Prevalence of miscarriage

A

20 to 30% of all pregnancies

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23
Q

Most common reasons for miscarriage

A

Most common cause of miscarriage is chromosomal abnormalities and it increases with maternal age. Important because when studying it, a lot of it is due to a major error and therefore it is lost, so therefore in studies that look at environmental agents we have to go ahead and eliminate 40% that is due to chromosomal abnormalities

24
Q

What is common diagnostic bias in birth defects from medical record abstraction and birth certificates?

A

Abstracted from hospital records but some may not appear/are not recognized until later, i.e. cardiovascular are not recognized at birth so may check with pediatric cardiologists to verify

Birth defects noted on birth certificate records are less complete than medical records

25
Q

Why is sample size a problem in measuring birth defects in ART?

A

ART is only 1.5% of all births so it is too little to detect a difference

26
Q

What are risk factors for birth defects are also risk factors for infertility?

A

o Maternal age a risk factor for birth defects
o Nutrition
o History of birth defects
o Exposures to alcohol, pharmaceuticals
o Diabetes
*so it is difficult to determine if these risk factors increase birth defects or infertility
THIS IS CONFOUNDING BY INDICATION:
The indication for the procedure is a risk factor for the outcome

27
Q

Prevalence of infertility

A

Infertility (no conception after 12 months unprotected sex) is prevalent in 10 to 15% of couples of childbearing age. However, 75% conceive after. ( Those children born to that group are a great comparison group to match with IVF born kids)

28
Q

Is infertility a dichotomous variable?

A

o Infertility is not really a dichotomous variable – most are on a continuum where they can get pregnant but the probability is low and there is a longer time to pregnancy so that is why you have to look at the dose response relationship to see if it makes sense so there is a long enough range into the tail end so that you think it can be generalizable to those who have the extreme time to pregnancy and those who are very fertile, i.e. the heavier you are, the longer it takes to get pregnancy. So seeing that dose-response relationship is more likely to be causal and more likely to extend to those more extreme cases not observed in the study

29
Q

If you are concerned about a confounder, why would observing a dose-response relationship how does this relate to a confounder affecting your response?

A
  • Confounder has to be associated with the exposure but if the confounder is really the causal factor than you would expect a tighter relationship with your exposure of interest because if you see a dose response, then a confounder would have to follow the dose response of the exposure
  • i.e. Air pollution and SES - affluence and proximity to highway are related so when you measure communities and air pollution you have a confounder of SES. To separate it out, you look for variability within the communities to look at a gradient of pollution within a range of income and see whether the low birth weight follows the pollution or the income more closely.
30
Q

Upon what factors should you determine burden of disease?

A
  • Ability to prevent
  • Ability to treat
  • Economic cost
  • Morbidity
31
Q

How do we measure and compare severity of illness?

A

(QALY, DALY, death, dollars)
Symptoms of acute disease: itching, discharge, lesions
Longterm complications – PID, cardiovasulaly or neurologic abnormalities, ectopic pregnancy infertility, cancer or death
Communicability: transmission to sexual parrners, miscarriage, preterm labor and delivery, neonatal infection, congenital anomalies, neonatal death
Financial cost: treatment, missed productivity

32
Q

Susser’s criteria: temporality

A

Time/Temporal Sequence: Exposure occurs before outcome

If you look cross-sectionally, you cannot tell which came first.

33
Q

Susser’s criteria: consistency

A

Consistency of association upon replication

In EPI you don’t have the exact same circumstance except in RCT. Every study has a different population and a different set of confounders or different ascertainment so there are many problems in individual study but if overall you get the same answer than you have more confidence in the causal association

34
Q

Susser’s criteria: Strength of the association

A

Magnitude of the effect of the exposure (i.e. air pollution effect on asthma or cardiovascular disease is small but in weighing the evidence, weak associations may be explained away by confounding more than a strong association) (i.e. smoking has 20 fold increase risk for lung cancer so if there was a confounder, it would have to have an equal or stronger association than smoking and would also have to be associated with smoking like a gene)
1.15 is a weak association but could be statistically significant (5% likelihood it is due to chance) but it is more likely that the 1.15 is influenced by confounding or bias

35
Q

Susser’s criteria: Specificity of association

A

o Specificity rules out confounding. In the real world, multiple exposures can cause an outcome so rarely do you have specificity, but if you do – then it is more likely to causal because no other exposure can cause the outcome (i.e. asbestos and mesothelioma)
o If you don’t have specificity it doesn’t mean it’s not causal but when you have specificity it is stronger evidence for a causal relationship
 Specificity is harder to obtain when you have a lot of unknowns
o Some birth defects that are caused by certain exposure like thalomide – a particular agent that causes certain birth defects. It is easier to see what they have in common when it is a very specific outcome.
o Specificity of the exposure is harder to determine and biologically more rare.It is likely that a particular exposure will cause more than one outcome. However for infectious disease this was important. (i.e. tuberculosis is caused by specific bacteria)
o Sometimes you want to use specificity of association to explain that it is not caused by some other bias (recall bias in birth defects) so you an break down the types of birth defects and see if Tylenol has an association with a specific birth defect and if it has the same association with each specific birth defect, it is likely to be recall bias. However if it is not a case of recall it will have a specificity – association with just one type of birth defect. So this is used in design and analysis

36
Q

Susser’s criteria: Coherent explanation

A

o biologically plausible but not always possible to know – animal studies help ascertain this but sometimes the epidemiology drives the basic science (smoking & lung cancer)
o Dose response increase likelihood that this is not due to confounding because confounding would have to be closely associated with the exposure and have the same dose response relationship with the exposure and be able to cause the outcome

37
Q

Fecundity

A

Definition: Physiological capacity of an individual or couple to produce a child.
Measurement:
1. Probability of conception (fecundability)= proportion of couples who did not conceive in the previous menstrual cycle (or month) but conceived in the present cycle/month
a. Average probability of conceiving in one month is ~25%

38
Q

Fertility

A

Definition: Reproductive performance of an individual or couple, the actual production of a child.
Measurement:
1. Male fertility
a. Semen analysis: volume, concentration, motility morphology
i. Issues: can vary over seasons, conditions of collection, and large individual variability, low participation rates in semen sample studies
2. Female fertility
a. Menstrual cycle characteristics (cycle length, flow, variability)

39
Q

Infertility

A

Multiple definitions:
1. No pregnancy after unprotected intercourse for 1 year
a. Primary infertility: no previous history of conception
b. Secondary infertility: previous history of conception
c. Subfertility: “less fertile than normal”
2. Received medical intervention for pregnancy
Measurement:
1. Time to pregnancy (with unprotected intercourse)
a. Issue: studies often exclude those with unplanned pregnancies, perhaps excluding the most fertile members of the population
b. Issue: measuring coital frequency, use/misuse of contraception
c. Issue: many couples may conceive after the 12 month cutoff
Incidence
90% of couples will conceive within 12 months of unprotected intercourse.
Risk Factors
1. Male infertility
a. Mumps, birth defect, Klinefelter syndrome, obesity (maybe)
2. Female infertility
a. Polycystic ovarian syndrome, endometriosis, fibroids, Turner syndrome, low caloric intake

40
Q

Pregnancy

A

Definition: Time period from conception to birth.
Measurement:
1. Counted from first day of last menstrual period (LMP)
a. Issue: LMP often 2 weeks before conception actually occurs
2. Detection
a. Clinical pregnancy: missed menstrual period
b. Biochemical pregnancy: assess hCG level (spikes after implantation of the blastocyst in the uterus)
3. Pregnancy rate: measured as ratio of pregnancies per 1,000 women aged 15-44
a. Issues: not reportable, misses pregnancies that end in early fetal death, induced abortion
Incidence: In the U.S., estimated at 102.1 per 1,000 women

41
Q

Early Pregnancy Loss

A

Definition: Pregnancy loss before clinical detection/recognition (usually before 6 weeks gestation)
Measurement: Biochemical detection of hCG from daily urine samples of women, along with menstrual cycle diaries to detect early pregnancy and early loss.
Incidence: Estimated at 24% of all pregnancies.
Risk Factors: Chromosomal abnormalities in the fetus.

42
Q

Spontaneous abortions/miscarriages

A

Definition: Pregnancy loss that occurs between clinical detection and before 20 weeks gestation (upper limit country specific – hovers around gestational age at which fetus could survive outside the uterus).
Measurement:
1. Gestational age measured from first day of last menstrual period
a. Issue: recall, variability in time to conception
b. Issue: pregnancy loss may occur before detected and therefore will be unmeasured
2. Risk of miscarriage calculated as number of miscarriages divided by number of miscarriages and births (including still births)

Risk Factors

  1. Chromosomal abnormalities
  2. Previous history of miscarriage
  3. Maternal age
  4. Paternal age (limited evidence)
  5. Environmental and lifestyle exposures (limited evidence)
43
Q

Maternal Mortality

A

Definition: Death to a woman while pregnancy or within 41 days of the end of pregnancy, from any cause related to the pregnancy.
Measurement:
1. Calculated as ratio of maternal deaths to live births
a. Issue: difficult to assess whether deaths “related” to condition of pregnancy
Incidence: Varies widely by country – around 20 per 100,000 in developed countries, 400 per 100,000 in developing countries.
Risk Factors:
1. Poor/no access to obstetric care
a. Delays in deciding to seek care, reaching care, receiving care (“three delays” model)
2. Maternal age

44
Q

Birth Defects

A

Definition: Physical or biochemical abnormality that is present at birth and that may be inherited or the result of environmental influence
Measurement:
1. Can be detected prior to, at, or after birth (most detected within 1st year of life)
a. Some are visible, other detectable through tests
i. E.g. echocardiogram for heart defects, hearing tests, amniocentesis, genetic testing
b. Issue: incidence biased by selective survival – fetuses with major birth defects may miscarry
Incidence: Affects 1 in 33 babies born each year in the United States (120,000 babies) ~ 3% of live births
Risk Factors
1. Heritable genetic factors
2. Uncontrolled maternal diabetes
3. Medications (e.g. thalidomide, diethylstilbestrol, Accutane)
4. Nutrition (e.g. folic acid)
5. Alcohol consumption
6. Stress (animal models only)
7. Environmental causes

45
Q

Stillbirth

A

Definition: Death of a fetus mature enough to have survived outside the uterus (gestational age cutoff varies by country) – WHO recommends counting fetal death for at least 28 weeks gestation or 1,000 grams. Most US states report fetal death at 20 weeks or later gestation as stillbirths.
Measurement: Stillbirth risk is calculated as the proportion all births ending in stillbirth, gestational age calculated from LMP.
Incidence: In the US, occurs in 1 out of 160 births (.625%)
Risk Factors: Maternal age, smoking, diabetes, obesity

46
Q

Infant Mortality

A

Definition: Death to an infant in the first year of life.
Measurement: The infant mortality rate is calculated as the proportion of live births who die in the first year of life
Incidence: In the US, the IMR is 6.1 deaths per 1,000 live births.
Risk Factors:
1. Congenital malformations
2. Birth asphyxia
3. Preterm delivery
4. Social factors
5. Maternal characteristics (smoking, diabetes, obesity, Rh incompatability)
6. Child/birth characteristics (birth order, age, twins/multiple births, males)

47
Q

Preterm birth

A

Definition: Birth before 37 weeks gestation. “Very preterm” – births before 32 weeks, “extremely preterm” – births before 28 weeks.
Measurement:
1. Gestational age determined by LMP
a. Issue: LMP often 2 weeks before actual start of pregnancy, recall, variability in time from menstrual period to conception
2. Ultrasound determination: all fetuses though to have similar growth trajectory up to 20 weeks
a. Issue: can’t distinguish between certain gestational age and fetus who is large or small for gestational age
Incidence: Varies by country: 5-6% in Nordic countries, 13% in the United States,
Risk Factors
1. Reproductive tract infections
2. Multiple births
3. Maternal characteristics: smoking, low gestational weight gain/BMI, diabetes
4. Environmental exposures: lead, DDT, air pollution, occupational exposure to PCBs

48
Q

Sex ratio

A

Definition: Ratio of boys to girls at birth.
Ratio: 51 to 49 or 1.06 (males are 51% of live births)
Risk Factors:
1. Small decline in sex ratio with maternal age
2. Son preference (selective abortion of female fetuses)

49
Q

STIs

A

Definition: Infections transmitted through sexual contact. Sexually transmitted disease – when clinical symptoms manifest (“disease state”). Most common STIs/STDs: chlamydia, gonorrhea, bacterial vaginosis, hepatitis, herpes, HPV, trichomoniasis, HIV/AIDS, syphilis.
Measurement:
1. STDs: Clinical signs and symptoms
a. Pelvic examination
2. PCR/assays of genital, cervical, or urethral swabs/culture, urine samples, blood tests
Incidence/Prevalence:
1. Incidence: CDC estimates 20 million new infections per year
a. Chlamydia incidence– 446.6 per 100,000
b. Gonorrhea incidence – 106.1 per 100,000
2. Prevalence: CDC estimates 110 million prevalent infections
a. HPV prevalence – 79 million
Risk Factors
1. Unprotected intercourse
2. Multiple sexual partners
3. MSM
4. Intravenous drug use
5. Sex partner with risk factors

50
Q

Common study designs in Repro Epi

A

o Case-control studies are useful in reproductive epidemiology to study rare outcomes, as well as acute exposures
o Cohort studies are useful to study multiple outcomes or time-varying exposures

51
Q

Pros of looking at menstrual function:

A

More women have menstrual cycle than are pregnant
Menstrual function allows for more observation time; observation time limited when looking at pregnancy
Having multiple measurements is an advantage and provides for a larger sample size
• Repeated measurements, however, are not independent

52
Q

Importance of examining menstrual function:

A

Can highlight cultural differences
Can be used as a proxy for reproductive health function
Especially helpful for women who are not trying to get pregnant

53
Q

Markers of menstrual function:

A

o Cycle length (start with first day of bleeding)
o Length of the bleeding
o Volume/intensity of bleeding (usually measured with a diary)
o Regularity and intra-women variability
o Follicular phase, lack of menstrual bleeding

54
Q

Why is ovulation is difficult to measure?

A

o Can measure with urine and look for surge in LH, but would have to measure every day to pinpoint day of ovulation
o Can be estimated from 14 days before first day of LMP (last menstrual period)

55
Q

Why is menopause difficult to measure?

A

o Hard to define and can only measure retrospectively
o There is no gold standard as there is for menstrual cycle
o No predictive value for menopause because hormone levels greatly variable

56
Q

How do we measure burden of disease?

A

BURDEN OF DISEASE = (number of people with the disease) x (severity of problems cause by disease)