Epidemiology FINAL

Disadvantages of Crossover Studies

-It is possible that the order in which treatments are administered may affect the outcome. -Carry over effect: a carry-over is when the 'effect' of one treatment 'carries over' into the next treatment, which confounds the estimates of treatment effects. This effect can be combatted with a 'washout period' which is when participants received no treatment and the effects of the previous treatment are eliminated. -Learning effect: you cannot make a group 'unlearn' a skill in order to act as a control in a later phase of the study

REVIEW: What is the purpose of blinding?

-Keeps the identity of treatment assignments form participants and investigators. -Reduces bias in measurement of outcomes/side effects.

Matching

-Major concern is that cases and controls may differ in characteristics or exposures other than the one that has been targeted for study. -One approach is to match the cases and controls so that they are similar to the cases in certain characteristics. -Matching may be one of two types: group matching OR individual matching.

Case Control Studies Disadvantages

-Measurement of exposure may be inaccurate -Representativeness of cases and controls may be unknown -Only provides indirect estimates of risk -Data quality may be a factor (information bias) -The temporal relationship between exposure factor and outcome cannot always be ascertained.

Vaccine Development - What is Emergency Use Authorization (EUA)?

-Mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies. -We can seek out an EUA to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met, including that there are no adequate, approved, or available alternatives.

What is the proportion of attributable risk? Exposed incidence = 120.3 per 1000. Unexposed incidence = 62.9 per 1000

(120.3 - 62.9) / 120.3 = .47714 x 100 = 47.7% AR = 47.7% Interpretation: Of women who smoked during pregnancy, 47.7% of those who have a child born with LBW can attribute it directly to their exposure of smoking.

Benefits of RCTs

-Most rigorous way of determining a cause and effect relationship between treatment and outcomes. Assesses the cost-effectiveness of a treatment. -Distributing the characteristics of patients that may influence the outcome randomly between the groups in order to obtain no systematic differences between the groups.

Data Collection on Subjects

-Must have quality data collection in both treatment and control groups. If we do not, differences may be due to the completeness of the data that were collected from the study groups.

Feasibility of blinding

1. Ethics: the double-blind procedure should not result in harm or undue risk for participants. (It may be considered unethical to give repeated injections of a placebo to a control group) 2. Practicality: It may be impossible to blind some treatments. (If conducting a study about radiation therapy...how would one create a placebo?) 3. Avoidance of bias: blinded studies require extra effort such as manufacturing look-alike pills, setting up complicated coding systems, etc. (Consider the sources of bias to decide if the reduction in bias is worth the effort.)

Why is randomization important in an RCT?

1. It allows for blinding or masking of the subjects 2. So causation may be extrapolated without worrying about confounding 3. It balances out individual characteristics between groups

Information Bias

1. Limitations of Recall/Information recall 2. Recall Bias

Issues in RCT

1. Noncompliance 2. Sample size 3. Recruitment and Retention

Individuals matching (matched pairs)

A control is selected who is similar to the case in terms of the specific variable(s) of concern. Often used for hospital controls

REVIEW: What is rate adjustment/standardization?

A statistical process by which we remove the affect of different characteristics within the structure of a population in rates (incidence or mortality)

What is bias?

-"Systematic error introduced in to sampling or testing by selecting or encouraging one outcome or answer over another." -Lots of different types of bias. Bias is not always purposeful

REVIEW: What is a reference level?

-A group that we use to compare to another group -When we have a non-dichotomous exposure, we must separate the exposure into different categories/levels. We choose one category to serve as the reference level that we consider to be unexposed. -We compare all the other categories that we consider to be exposed to that reference category -Ex: underweight, healthy weight, overweight, morbidly obese

Crossover study example

A study wished to look at the effect of additional dietary fiber on cardiovascular disease risk. Participants (n=68) with high cholesterol were given dietary fiber supplementation for one month. Their fasting blood sugar, blood pressure were obtained at baseline, week 2 and week 4. Their weight was measured every week. Then for a second month they were put on a low-fat, low cholesterol diet. Again, Their fasting blood sugar, blood pressure were obtained at baseline, week 2 and week 4.

Masking/Blinding

-A procedure in which the parties involved in an experiment are kept unaware of the hypothesis being tested and/or the condition to which each participant has been assigned. -We do not want participants to know which group they have been assigned to. (important for subjective measurements such as pain) -We can mask participants by using a PLACEBO (an inert substance that looks, tastes, and smells like the treatment medication) -We also want to mask the observers or data collectors from knowing which group the participants are in to PREVENT BIAS.

Crossover RCT

-A type of randomized clinical trial in which the participants receive each treatment in a random order. -Every patient serves as his/her own control. -Often used when researchers feel it would be difficult to recruit participants -Two types: planned and unplanned

REVIEW: What is the difference between absolute and relative risk?

-Absolute risk is the probability of the outcome occurring in the TOTAL population given all possible exposures. This is measured by the overall incidence in a population. -Relative risk is the difference in the probability of the outcome occurring between TWO GROUPS. Those that have one specific exposure, and those that do not.

Multiple Controls of the Same Type

-All controls come from the same type of source (registry, hospitals, OR clinics) -Multiple controls are used because there may be a limit to the number of possible cases. -Because the number of cases cannot be increased without extending the length of the study a different option is to increase the number of controls.

Prospective Cohort Studies

-Also called 'concurrent cohort' or 'longitudinal study' -Investigator identifies the original population at the beginning of the study. -Exposure and non-exposure are ascertained during the study -Groups are then followed (concurrently) into the future, and incidence is measured. -Problems: Takes a long time to complete (Funding from grants typically only lasts between 2-5 years)

Retrospective Cohort Studies

-Also called 'historical cohort' or 'non concurrent' study -Uses historical data from the past to obtain our results sooner. **No longer prospective because we are beginning with a pre-existing population to reduce the duration of the study. **Exposure is ascertained from past records and the outcome is ascertained at the time the study began. **Retrospective is quicker because we are beginning with a pre-existing population to reduce the duration of the study!

History of RCT

-Ambroise Pare (1510-1590): unplanned trial, cauterization and topical treatment. -James Lind (1716-1794): Scottish naval physician, conducted the first ever planned clinical trial, scurvy sailors, advanced: preventative medicine and nutrition. -Austin Bradford HIll: the first published RCT in medicine was published in 1948. Hill criteria for causality.

Case Control Studies Advantages

-Can be used to study low-prevalence conditions -Relatively quick and easy to complete -Usually inexpensive -Involve smaller number of subjects -Multiple risk factors can be assessed at one time

Benefits/Advantages of Cross-Sectional studies

-Can be very suggestive of a possible exposure or risk factor for disease. -Feasible and not too time consuming -Inexpensive -Helps to estimate burden of diseases within a population -We can study multiple outcomes/exposures at once -Prompts further research

REVIEW: What are the advantages of cross-sectional study design?

-Can study multiple outcomes/exposures -Inexpensive, feasibility, not too time-consuming -Helps to estimate burden of disease -Prompts further research/suggests avenues for further research (exploratory = cross-sectional)

REVIEW: What are the disadvantages of cross-sectional study design?

-Cannot determine causality -May not be generalizable -Susceptible to other bias (confounders, recall, sample size)

Step 1: Defining the Cases (Case Control Study Steps)

-Cases should be representative of all diseased. -Correctly defining cases (disease) helps us to select cases and limit bias.

How is randomization accomplished?

-Coin toss (heads = intervention, tails = control) -Random number generation (odd numbers get the intervention, even numbers are controls)

Prospective vs. Retrospective Cohort Studies

-Designs for both prospective cohort study and retrospective are identical because we are comparing exposed and non-exposed populations. -Only difference is calendar time!! -Can be a combination of the two. -Which ever study design, the participant CANNOT have the outcome of interest at the time that exposure status is determined. You will need records from far enough in the past BEFORE the participant had the health outcome.

Efficacy Calculation

-Efficacy is the extent of the reduction in the disease caused by use of the treatment in a trial. Efficacy = ((incidence in control group - incidence in treatment group) / incidence in control group ) x 100 Interpretation: The new drug causes 20% less bone loss in our treatment group than our control group.

Purpose of RCT

-Evaluating new drugs and medical technology -Assessment of screening programs -Assessment of intervention programs -Evaluation of new ways of delivering health services

REVIEW: What are the two types of matching?

-Frequency (group): selecting the controls so that they have the proportion of a characteristic identical to that in the case group -Individual: a control is selected who is similar to the case in terms of the specific variable(s) of concern.

Cross-sectional study

-Helps us to investigate causes of disease. -Analyzes sample population at one point in time. -Exposures and outcomes are measured simultaneously. -Gives us a 'snapshot' of the population. -We CAN identify prevalent cases. We CANNOT identify incident cases. -These studies are NOT enough to determine causality, only mathematical associations. Case-control studies would be the next step to determine causality.

Problems with Matching

-If we want to match cases on too many characteristics, it may be too difficult to find appropriate controls. (gender, age, race, education, income, and geography) -Matching creates an artificially identical proportion of a factor in the control group -Overmatching: matching variables OTHER THAN ones that we are convinced are risk factors for the disease.

Expressing the Results of RCTs (randomized control trials)

-In an RCT, the risks of death or of developing a disease/complication in each group can be calculated as an incidence rate. -After doing so, the efficacy (reduction in risk) can then be calculated. -Efficacy of a treatment can be expressed in terms of the rates of developing disease between the treatment and control groups. -Calculate relative risk in the two treatment groups (A significantly lower RR in the treatment group compared to the control group indicates that the treatment IS EFFECTIVE)

Measuring the Outcome

-Includes improvement and side effects -Should be measured from the very beginning of a study. -They should be measured the same among treatments and control groups. -Potential bias: we may measure more/less carefully depending on the group membership of the participant (Masking/blinding)

Selection of Subjects in an RCT

-Inclusion criteria: Characteristics that prospective subjects MUST have if they are to be included in the study -Exclusion criteria: Characteristics that DISQUALIFY prospective subjects from participating in a study -Examples: age, sex, race/ethnicity, type and stage of disease, previous treatment history, etc. -Test of adequacy: If we have spelled out our criteria in writing, and someone not involved in the study walks in off the street and applies our criteria to the same population, will that person select the same subjects whom we would have selected?

Internal Validity and RCTs (REQUIRED!!!)

-Internal validity refers to how well an experiment is done, especially if it avoids confounding. The less chance of confounding in a study, the more internal validity in a study. -An RCT is internally valid if the randomization is properly done, steps have been taken to decrease biases, and is without any major methodologic problems (did what we said we were going to do throughout our research).

ABSOLUTE RISK IS:

the number of people experiencing an event in relation to the population at risk, and indicates the magnitude of the risk in a group of people with all exposures.

Step 6: Conclusion and Interpretation (Case Control Study Steps)

Interpret odds ratio! OR = 1 Those with (insert the case outcome) had the same odds of (insert the exposure) than those without (insert the outcome). There was no relationship between (insert the outcome) and (insert the exposure). OR >1 Those with (insert the case outcome) had (insert OR) higher odds of (insert the exposure) than those without (insert the outcome). OR < 1 Those with (insert the case condition) had (1 - OR) less/lower odds of (insert the exposure) than those without (insert the case condition).

Use of Multiple Controls

Investigators can determine how many controls will be used per case in a case-control study --> multiple controls are frequently used (could be controls of the same type of different types)

Why is attributable risk important?

It addresses how much of a risk of disease we can hope to prevent if we are able to eliminate the exposure to the agent in question.

REVIEW: Who conducted the first planned clinical trial?

James Lind

Direct adjustment

Mortality rates are so far from each other because of their differences in their population. Our adjusted mortality rate is going to be more accurate because we removed those differences in population.

REVIEW: Is a cross-sectional study design an observational or experimental study type?

Observational because there is no manipulation of events/variables

Observational vs Experimental studies

Observational: researchers observe individuals and record information about variables of interest (no manipulation of events AND the purpose is to describe some group or situation) --> Randomized controlled trial (RCT) Experimental: researchers intentionally impose treatments on individuals and measure their responses (determine cause and effect relationship AND determines whether treatment leads to positive effect) --> cohort, case-control, cross sectional, ecological

What is the appropriate measure of association for this Case-Control study.

Odds ratio

Noncompliance - Covert

Participants do not tell you that they no longer want to take part in the study.

REVIEW: What is noncompliance?

Participants who do not comply with the assigned treatment (even though they are still in the study) --> still doing some things but not following all of the directions

Triple blinding

Participants, data collectors, and data analyst are blinded.

Noncompliance - Drop ins

Patients in one group may inadvertently take the agent assigned in another.

Randomization

The process by which each subject has the same chance of being assigned to either intervention or control. -CRITICAL ELEMENT OF RANDOMIZATION = unpredictability of next assignment -Purpose: we increase comparability between groups in regard to characteristics that we are concerned about.

REVIEW: What is randomization?

The process by which each subject has the same chance of being assignment to either intervention or control.

REVIEW: Suppose you calculate a relative risk ratio for a study and find an RR = 2.7, what is the overall take away about the relationship between the exposure and outcome?

There is evidence that the exposure is a strong risk factor for the outcome

Randomized Control Trials

These trials are considered the "gold standard" design for evaluating both the effectiveness and the side effects of new forms of intervention. (AKA: randomized clinical trial, randomized trial, clinical trial, intervention study, RCT)

Treatment vs. Control

Treatment: The condition under study. Medicine, behavioral intervention (asking someone to behave a certain way), knowledge. Control: The baseline status. No treatment. (not giving treatment is UNETHICAL because you are preventing individuals from treatment)

Why not match treatment and control members?

We can only match on variables that we know about and that are measurable.

Making Comparisons - How do we determine whether a certain disease is associated with a certain exposure?

We must determine suing data obtained in case-control and cohort studies. Is there excess risk of the disease in persons who have been exposed to a certain agent? (EX: foodborne disease)

The main difference between prospective and retrospective cohort studies:

When researchers are collecting information about the exposure/outcome in relationship to the current time period.

Double blinding

When we mask both the participant and the data collectors

REVIEW: Which famous cohort study gave us the term for "risk factors"?

The Framingham Heart Study

What is effectiveness?

The ability of an intervention to have a meaningful effect on patients/individuals in normal clinical/community conditions. **We must consider how well a treatment works under 'normal' conditions vs. how it may work differently in 'real life' situations. **In RCT, we try to make ideal conditions which can be different from how people live their everyday lives.

REVIEW: What is attributable risk?

The amount or proportion of disease incidence that can be directly attributed to a specific exposure •Important because it indicates the potential for prevention if the exposure is eliminated

Assessing Preventive and Therapeutic Measures

The goal of clinical and public health professions is to modify the natural history of disease. (delay death or disability & improve health of patient or population)

REVIEW: What are the two ways that we can choose multiple controls?

1. Controls of the same type 2. Controls of different types

Steps in a Case Control Study

1. Definition of Cases 2. Selection of Cases 3. Selection of Controls 4. Ascertainment of Exposure Status 5. Analysis 6. Conclusion and Interpretation

What is an example of non-response bias? Attrition? Non Participation? Loss to follow up?

-Non-response: The participants are in the study and are actively participating, but the are not completing all of the research procedures in the way that researchers want them to. -Attrition: when participants drop out of the study or when we lose contact with them. There was no information in the prompt to indicate that this was an issue. -Non participation: when those who agree to participate in the study are significantly different from those who decided not to be in the study. This is important if these differences are ALSO related to likelihood of the exposure or outcome. There was no information in the prompt to indicate that this was the issue. -Loss-to-follow-up: significant number of participants drop out of the study

Limitations of RCTs

-Not all RCTs are created equally. Quality varies from poor to excellent. -Typically expensive and time consuming. (2-5 years) -May not always be the right study design to answer the question.

Recruitment and Retention of Study Participants

-One major challenge is recruiting eligible and willing participants. Failure to do so may yield statistically invalid results. -We need people who are willing to be in the experimental group or control group. This will prevent bias. -EXAMPLE: Study done in Tampa. Pregnant women did not know that they were taking part in a study. The doctor gave them medicine but did not tell them/get their consent. -Cash incentives may work as subtle or overt coercion which results in biases and distortion of study results. Incentives must be balanced so that they are not a form of coercion!

Framingham Study

-One of the most important and best-known prospective cohort studies on cardiovascular disease. -Began in 1948 -Framingham, MA (30,000 people lived there in 1948) -Planned to follow for 20 years -Residents were eligible if they were 30-62 years of age **Examined the study population every two years. Daily surveillance of hospitalizations at the only hospital in Framingham. **A defined population was selected on the basis of location of residence or other factors not related to the exposures in question. **RISK FACTOR

Noncompliance

-Patients may agree to be randomized but following randomization they may not comply with the assigned treatment. -Can be overt or covert.

Information Bias in Cohort Studies

-Quality and extent of information for each groups differs, likely to occur in retrospective cohort studies. Quality of info should be comparable in exposed and non-exposed groups meaning that there should be no difference in information between exposed and unexposed groups.

Breast Cancer and Progesterone Deficiency

-Retrospective Cohort study -In 1978, Cowan identified a population of women who had been patients at Johns Hopkins Infertility Clinic from 1945-1965 -All had a late first pregnancy. During infertility evaluation, detailed hormonal profiles were taken. Patients were divided into exposure groups based on their past medical records (hormonal abnormality vs. normal hormones). Both groups were followed for subsequent development of breast cancer. **This study was a cohort study because it compared exposed and unexposed persons.

Attributable Risk for the Exposed Groups

-Risk of disease is higher in exposed group. Risk of disease is NOT zero in unexposed group. -Background risk = unexposed group -Total risk in exposed group = total risk - background risk

Group matching (frequency matching)

-Selecting the controls so that they have the proportion of a characteristic identical to that in the case group. -Requires that all the cases are selected first, so that proportions can be calculated before selecting controls.

Step 4: Ascertainment/Measurement of Exposure (Case Control Study Steps)

-Set criteria for exposure and understand the methods of exposure -Collect information: observation, interviews, questionnaire, examination of records

Research study design

-Set of methods and procedures used to collect and analyze data on variables in a specific research problem -Type is determined by nature of research question, goal of research, availability of resources

Multiple Controls of Different Types

-Sometimes, we use different types of controls because our controls are not representative of the rate of exposure that is expected in the population of non-diseased persons. -To address this problem, we may add an additional control group such as "neighborhood controls"

Potential Bias in Selection of Cases

-Sources of cases. Cases can be selected from a variety of sources (hospital patients, patients in physician practices, clinic patients, disease registries, etc.) -From hospitals: risk factors unique to the hospital due to referral patterns or other factors -Selection bias from using incident cases: must often wait for new cases to be diagnosed AND prevalent cases have already been diagnosed and represent a larger number of cases available for the study. -Selection bias from using prevalent cases: risk factors that we identify in a study using prevalent cases may be related more to survival with the disease rather than to the development of the disease.

Generalizability

-The ability to apply the results obtained in our study population to a broader population. -Also called external validity. -To do so, we must know to what extent the patients we have studied are representative of the defined population. -Necessitates REPLICATION STUDIES in other populations. -At minimum, internal validity for RCTs SHOULD be established.

Attributable Risk

-The amount or proportion of disease incidence (or disease risk) that can be attributed to a specific exposure. -Important in clinical and public health practice because it address how much of a risk (incidence) of disease can we hope to prevent if we are able to eliminate the exposure to the agent in question. -AR expressed THE MOST we can hope to accomplish in reducing the risk of disease if we completely eliminate the exposure of interest.

Absolute Risk

-The incidence of a disease in a whole population. -The number of people experiencing an event in relation to the population at risk. -Absolute risk can indicate magnitude of the risk in a group of people with all exposures. **Comparison of risk is FUNDAMENTAL to epidemiology.

Advantages of a Crossover Study

-The influence of confounders are reduced because each participant serves as his/her own control. (Even in a RCT, sometimes characteristics in different groups are unbalanced. In a crossover, this becomes irrelevant.) -They are statistically efficient, requiring fewer participants

Issues/Disadvantages with Cross-Sectional Studies

-The prevalent cases in the study may not be generalizable. They do not represent all people with that disease/illness. -Identifying prevalent cases could exclude people who already died from the disease. It is hard to determine the temporal relationship because exposure and outcome are determined at the same time. -Can establish an association, but NOT causation -VERY susceptible to bias -Weaknesses of using aggregated data (occurs when inferences about the nature of individuals are deduced from inferences about the group to which those individuals belong)

Relative Risk (RR)

-The probability of an event (developing a disease) occurring in exposed people compared to the probability of the event in unexposed people. (risk in exposed / risk in unexposed) -Measures the strength of an association and the possibility of a causal relationship. -What is the ratio of the risk of disease in exposed individuals to the risk of disease in unexposed individuals? This ratio is called relative risk.

Step 3: Selecting Controls (Case Control Study Steps)

-The way controls are chosen is a major determinant of whether this conclusion is valid. -Non hospital population: Best friend control is when a case is asked to provide the name for a friend who may be more likely to participate in the study. Friends tend to be similar in age and sociodemographic variables. -Hospitalized population: selecting from hospitals may mean that controls do not represent the general population

Unplanned Crossover RCT

-This occurs when participants inadvertently end up in the opposite group than they were assigned. (ex: ÷A participant may have second thoughts about undergoing surgery and opt for medical care, therefore becoming a control) -Unplanned crossovers pose a serious challenge when analyzing data (HARD TO WORK WITH)

Step 2: Selecting Cases (Case Control Study Steps)

-This step is important because it introduce bias

Clinical Trials (4 phases)

-This study sequence has been instrumental in protecting the American public from hazardous agents for years. -Not without its political influences (both good and bad) -Ex: HIV/AIDS (it took lots of activism to change how research on this was approached)

Case-control study purpose

-To examine the possible relation of an exposure to a certain disease (cases and controls) -Collect data from groups to determine the proportion of exposure in each group -If there is an association between the exposure and disease (Prevalence of exposure should be higher in cases than in controls --> more cigarettes with cases means that there is an association)

Benefits of Randomization

-To prevent any potential biases on the part of the investigators from influencing the assignment of participants to different treatment groups. (Investigators make no decisions about which individuals are assigned to which groups.) -Randomization protects the study from conscious or unconscious bias from assignment.

Stratified Randomization

-Used to address this issue: any difference between the treatment and control group may be attributable to the difference in these characteristics. -Divide (stratify) the population into groups that differ in important ways. Select random sample from within each group.

Types of RCTs: Factorial Design

-We can use the same study if we want to look at more than one treatment compared to either no/current treatment. -We can evaluate the effects of treatment A, treatment B, both A and B, or neither A and B.

When do we use Cohort Studies?

-We must have some idea of associations of exposure to disease....so that we know what exposures to track. -Because of the long follow-up period, the cohort study is a good approach if we can minimize attrition (loss to follow-up). Easier to do when the interval between exposure and development of disease is shorter.

RCT Sample Size

-We need enough subjects to obtain meaningful results. -Increasing the sample size is one way to increase the power of a study.

Population Attributable Risk (PAR)

-What proportion of the disease incidence in the total population (including both exposed and unexposed persons) can be attributed to a specific exposure? -What would the total impact of an intervention have on the community?

REVIEW: In what situations would we use an indirect method of adjusting rates?

-When age (or other characteristics) specific rates are not available -When the population is really small, and we do not trust the mortality rates -For specific reasons such as comparing the mortality rates of different populations

Indirect rate adjustment is used when.....

-When the age (or other characteristic) specific mortality rates are not available (Such as in countries with poor vital records keeping (e.g. ages are not well recorded)) -Very small populations that could create greater error -Also used for occupational exposure (For example: Do people who work in a certain industry, such as mining or construction, have a higher mortality than people of the same age in the general population?) ***INDIRECT = EXTRA STEPS

REVIEW: What is a factorial RCT?

-When we test two different experimental variables in an RCT at the same time -Their mechanism of action must be completely separate

REVIEW: Which of the following is an example of a control in an RCT?

1. A brand-new medicine given to patients to see if it improves a health condition 2. An educational program given to people to see if it improves their knowledge about a health condition 3. A typical medicine given to patients for a health condition 4. A new surgical technique being used for the first time ANSWER IS 3!!!

Basic Deign of a RCT

1. Begin with a defined population 2. Randomized to receive new treatment or current/no treatment 3. Follow subjects in each group to see how many are improved in the new treatment group compared with how many are improved in the current treatment group. (If new treatment is associated with a better outcome, we would expect to find better outcome in more of the new treatment group than the current treatment group)

Selection Bias in Cohort Studies

1. Nonparticipation bias: Were the people who participated in a cohort study different from those who didn't? Does this difference also impact the likelihood of being exposed or unexposed? 2. Non-response bias: Sometimes study individuals are unwilling to participate in all of the study procedures. This is an issue if those who responded and hose who didn't, are different in meaningful ways that effect exposure or outcome. 3. Loss to follow-up: Participants who at one time were actively participating in the study, but have become lost at the time of follow up (EX: TOP Project - students move schools or leave the state)

Perfect Use vs. Typical Use

1. Perfect use = the highest efficacy ever researched in reputable clinical trial (ex: taking pill at the same time everyday) 2. Typical use = rate based on an analysis from reputable studies about how people typically use contraceptives (ex: condoms expire, user error, taking brith control pill at the different times everyday, human error/forgetting to take the pill)

Types of Cohort Studies

1. Prospective 2. Retrospective

AR example: What is the incidence? Exposed incidence = 120.3 per 1000. Unexposed incidence = 62.9 per 1000

120.3 - 62.9 = 57.4 AR = 57.4 per 1,000 Interpretation: For every 1000 women who smoked during pregnancy, 57.4 have a child born with LBW that can be attributed directly to their exposure of smoking.

REVIEW: What is the calculation for incidence of disease in the exposed individuals?

A / A+B

Reference Group

A characteristic or group to which an individual, group, or characteristic is compared.

PAR Example: What amount of incidence of LBW infants is due to smoking? 72 per 10000 babies Exposed incidence = 120.3 per 1000. Unexposed incidence = 62.9 per 1000

72 - 62.9 = 9.1 PAR = 9.1 Interpretation: If we could eliminate smoking among pregnant women, we would prevent 9.1 LBW births per every 1000 babies born.

Adjusted rates

Adjusting for the different ages to make a better comparison. A rate of morbidity or mortality in a population in which statistical procedures have been applied to permit fair comparisons across populations by removing the effect of the differences in the composition of various populations. **Types: direct age adjusted AND indirect age adjustment

Who completed the first unplanned RCT?

Ambroise Pare

REVIEW: What is the calculation for incidence of disease in the unexposed group?

C / C+D

Cases vs. Controls

Cases: individuals WITH the outcome of interest (ex: people with breast cancer) Controls: individuals WITHOUT the outcome of interest (ex: people who do not have breast cancer)

REVIEW: What is the purpose of a cohort study?

Compares the development of disease over time in a group of exposed individuals and a group of unexposed individuals. (finds cause and effect)

Odds Ratio

Compares the odds of exposure in the cases to the odds of exposure in the controls. Looks at relationship between exposure and outcome. Can be calculated using data from cross sectional studies, cohort studies, and case-control studies.

Exposures vs. Outcomes (in cross-sectional studies)

Exposure: Broadly applied to any factor that is the primary explanatory variable of interest. Independent variable. The CAUSE in a cause and effect relationship. Outcome: Disease, state of health, or health related event or death that we think the exposure impacts in some way. Dependent variable meaning that its value or presence depends on another variable. The EFFECT in the cause and effect relationship. Examples: Does smoking increase the risk of lung cancer? Exposure = smoking Outcome = lung cancer

Purpose of Epidemiological Studies

Determine whether there is an excess or reduced risk of a certain disease in association with a certain exposure or characteristic.

Direct vs. Indirect adjustment

Direct: mortality rates from populations of interest --> standard population age distribution Indirect: mortality rates from standard population --> population of interests age distribution

Investigator Information Bias

Epidemiology who are analyzing data may unintentionally introduce bias into their analyses and their interpretation of the findings.

Step 5: Analysis (Case Control Study Steps)

Find odds ratio! (can use cross multiple method)

The ultimate objective of carrying out an RCT is to _____________ the results beyond the study population itself.

GENERALIZE

Comparing Mortality in Different Populations

Helps us to determine what causes disproportions in different populations. Different groups have different risks for dying. Sometimes overall mortality rates (crude or unadjusted mortality) can mask these differences.

Who tests the New Drugs in the US?

In the US, the Food and Drug Administration is responsible for testing the safety and effectiveness of new drugs and medical devices. Happens in 4 different phases.

REVIEW: What is one of the benefits of randomization?

Increase comparability between the treatment and control groups.

Noncompliance - Overt

Individuals articulate in some way that they are going to stop the study (dropouts).

4 Phases of Testing New Drugs

Phase I: Clinical pharmacologic studies -Toxic and pharmacologic effects are examined, including safety, safe ranges of human dosage, and the side effects observed with the new drug. Phase II: Consists of clinical investigations of 100 to 300 patients in order to evaluate to further asses its relative safety. Phase III: Large-scale RCTs for effectiveness and relative safety/side effects of intervention. Phase IV: Certain adverse effects of drugs, such as carcinogenesis (cancer) and teratogenesis (congenital malformations), may not become apparent for many years. To monitor this, post-marketing surveillance is needed to monitor new agents as they come into general use by the public. (requires a high quality surveillance system to monitor/report adverse effects)

This phase of clinical trials in the United States are large-scale and responsible for recruiting thousands of participants (which may be difficult) in order to test for the efficacy and relative safety of materials.

Phase III

Benefits of Phase IV Studies

Phase IV studies are valuable in providing additional evidence on the benefits and help optimize the use of the new agent.

Interpreting Risk Ratio

RR = 1 -There was no relationship between the (insert the exposure) and the (insert the outcome). -Those with (insert the exposure) had the same risk of (insert the outcome) as those without (insert the exposure). RR = > 1 -Those with (insert the exposure) had (insert RR number) times the risk/increased risk of (insert the outcome) compared to those without (insert the exposure). RR = < 1 -Same rules apply for protective exposures as for odds ratios (1 - RR). Need to say how much less of risk the exposure is. -Those with (insert the exposure) had (1 - RR number) less risk/decreased risk of (insert the outcome) compared to those without (insert the exposure).

Which study design has the highest level of evidence strength?

Randomized control trial (RCT)

REVIEW: Which type of cohort study is one where the exposure status of participants is determined from records created in the past?

Retrospective cohort study

Which word did the Framingham Study originate?

Risk factor

What is Risk?

Risk is the probability of an event (such as developing a disease) occurring. There are several measures of risk: absolute risk, relative risk, attributable risk, and odds ratio.

Statistical Power

Statistical power is the probability that a statistical test will say there are no significant differences when in reality there really are none. **Power is only gained when you have a ratio of at least 1 case to 4 controls.

Examples of observational studies are _____, ______, ______.

cross-sectional, case-control study, and cohort study.

REVIEW: Why might comparing populations based on crude mortality be misleading?

differences may be masked

Analysis from reputable studies about how people normally use a new intervention or medicine is called:

effectiveness

Randomized control trials are ______.

experimental

Another word for generalizability, or the ability to apply the results obtained in a study to the wider population, is:

external validity

How to know if a study is cross-sectional:

information about both the exposure(s) of interest and the outcome(s) of interest are collected at the same time.