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Evidence Based Medicine

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Question
Answer
Steps in the EBM process   Ask, Acquire, Appraise, Apply  
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Framing the question:   PICO: Patient, Intervention, Comparison, Outcome (& Type of question/study)  
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Hierarchy of Evidence   Systematic Rvw/meta; RCT; Cohort/Case-Ctrl; Case Series, case report; Letters, etc  
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Where to search the lit:   PubMed; Cochrane Collabn; Medline (OVID); ACP Journal Club; Practice Guidelines  
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Appraise: questions   Are the results of study valid? What are the results? Will the results help in caring for my pt?  
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the study of the frequency, distribution and determinants of health related states or events in specified populations   Epidemiology  
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2 assumptions of epidemiology   1: Human disease does not occur at random; 2: Factors that cause & prevent dz can be identified  
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Defn Frequency:   how many cases of the dz exist or occurred  
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Defn distribution:   who is getting the dz, where & when is it occurring (person, place & time)  
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Defn Factors/Determinants:   what causes the disease, what influences or modifies the disease (physical, biological, social, cultural, behavioral factors)  
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Measures of dz frequency   Prevalence; incidence  
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A fraction where the numerator is contained in the denominator (e.g., percentage); falls between 0 and 1   Proportion  
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Expression of the relationship btw a numerator & a denominator where the 2 usually are separate & distinct quantities, neither being included in the other; No restrictions on ranges or dimensions   Ratio  
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Total number of individuals with the outcome of interest (i.e., disease, injury, health benefit) within a defined population at a particular point or period in time   Prevalence  
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The number of persons with the disease or attribute at a specific point in time   Point Prevalence  
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Number of persons with the dz at any time during defined period   Period Prevalence  
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Number of new events or cases of an outcome of interest (i.e., dz, injury, health benefit) that develop in a population of individuals at risk during a specified interval of time   Incidence  
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Cumulative Incidence (AKA: Relative Risk)   Proportion: outcome occurring during a certain period of time  
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Incidence Rate (AKA: Incidence Density)   Ratio: outcome occurring during person-time at risk  
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Assumptions for cumulative incidence:   All study participants included in the calc for CI = observed (at risk) for the entire period; CI for specified time period infers* that the risk of dz is constant throughout that time period  
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Considered a more precise estimate of the impact of exposure in a population because it utilizes all the information about time at risk   Incidence density  
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Able to determine changes and fluctuations in risk of disease over time   Incidence density  
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Defn population at risk   Free from dz, but susceptible  
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Prevalence pool influenced by:   Incidence rate of dz; Dz Detection; recovery rate (dz duration); fatality rate  
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Methods & procedures for collecting, classifying, summarizing, & analyzing data & for making scientific inferences from such data   Statistics  
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Descriptive Statistics   Use of graphic, tabular, or numerical techniques to describe the properties of the data  
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2 types of categorical variable   nominal; ordinal  
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Categorical variable: no intrinsic order:   Nominal (e.g., race, gender, sub-types of leukemia)  
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Categorical variable: have some intrinsic order   Ordinal variable (e.g., pain severity: none, mild, moderate, severe; Education level)  
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Measures of central tendency   Means, medians, modes  
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Measures of variability   Range, standard deviation (& variance)  
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Median vs mode   median: middle value in list; mode = most frequent value  
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If variable is normally distributed:   mean, mode, median all approx the same value  
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Problems with the mean   1: outliers skew mean; 2: bimodal dist: mean not a good summary stat  
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Measure of how spread out distribution is   variance  
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Positive sq root of variance   std deviation  
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Units for std deviation   same units as the observations  
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In normal dist, there is a defined relationship between:   std deviation & percentile distribution of the observations  
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Empirical rule: Std deviation (1,2,3): percentages   68, 95, 99.7%  
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A very large group of units about which scientific inferences are to be made =   Population  
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Subset of units in the underlying population =   Sample  
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Inferential Statistics   Use of procedures to make inferences from the data (i.e., what are the implications of or what conclusions can be drawn from the data?)  
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Provides the actual numerical information used in making inferences about the population   Sample  
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Sample mean vs popn mean   Not nec same as popn; usu close to popn mean; some samples have means very diff from popn means  
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P-value = probability that …   See a difference at least this large if samples were drawn from popn with same mean  
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Defn Study Power   Probability that a study will conclude there is an association btw exposure & outcome when one truly exists  
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Defn Study Power = ability of a study to:   to detect a statistically sig diff btw groups if one truly exists; 1 - beta  
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Confidence intervals can be calculated around:   Diffs in means; diffs in proportions; odds ratios, relative risks, hazard ratios  
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Confidence interval is presented as:   1: point estimate; 2: plausible range of diffs btw which the true diff might actually lie (with 95% confidence)  
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Mann-Whitney U-Test / Wilcoxon Rank Sum test: used when?   Used to compare continuous variables; Unpaired data; Nonparametric; Tests similar hypothesis as t-test  
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Wilcoxon Signed Rank Test used for what data?   Used for paired data (e.g., before and after measurements on same individual)  
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Wilcoxon Signed Rank Test =   Non-parametric test; Tests similar hypothesis as paired t-test  
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Statistical test used to determine if there is an association between the row and column classifications   Chi squared test  
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Assumptions of t test   Normally distribd variable (bell curve); independent observations (diff people, not multiple measurements on same people); reasonably large sample size  
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t-test used to compare means of >2 groups?   No (2 groups only; otherwise: other tests)  
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Purpose of t test   to detn how likely observed diffs in means btw groups could be due to chance  
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Type I error   False positive (alpha error)  
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Type II error   False negative (beta error)  
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t-statistic corresponds to:   a given p-value  
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The bigger the t-statistic:   the smaller the p value (more stat sig)  
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Causes of larger t-statistic   Larger diff btw means; smaller variance; larger sample sizes  
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Used to compare observations that are not independent   paired t-test  
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Alternatives to t-test or paired t-test   Nonparametric tests  
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Nonparametric tests are used when:   assumptions of t-test, particularly normal dist, are not met  
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Nonparametric tests most often used when:   with small sample sizes  
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Power: Nonparametric tests vs parametric tests   Nonparametric less powerful than parametric  
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Categorical data are often presented in:   frequency tables  
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Test: compares observed frequencies to expected frequencies   Chi squared test  
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Larger chi-square statistic correlates to:   smaller p-value  
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Variations on chi square test   Fisher exact; Mantel-Haenszel  
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Fishers exact test used when:   expected frequencies in cells are small (<5)  
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Mantel-Haenszel chi-square tests for:   linear association btw the row & column variables  
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When interpreting results of a study, consider:   both the p-value and the size of the effect  
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Alternative to p-values as a way of presenting and interpreting results   confidence intervals  
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CI: single value most likely to represent the true diff btw groups =   point estimate  
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CI provides info on:   precision of the estimate; statistical significance  
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If 95% CI excludes the null value, then:   the findings are significant at p<0.05  
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CI: Greater variance results in:   wider confidence interval  
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CI: Smaller sample size results in:   wider confidence interval  
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Type I error:   Concluding that a difference exists btw groups when no difference exists  
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Type II error:   Concluding that no difference exists btw groups when a significant difference does exist  
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Alpha =   p-value  
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Study Power is intimately related to:   the sample size used in a study  
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Most studies designed with what power?   80 or 90% power  
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1-tailed vs 2-tailed test: which more conservative?   2-tailed  
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1-tailed vs 2-tailed test: which is the std in most research?   2-tailed  
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Chi squared used on what data type?   Categorical  
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AKA Prevalence study   Cross-sectional study  
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A study in which conditions are under the direct control of the investigator (e.g., randomized clinical trial, intervention study)   Experimental  
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A study that does not involve an intervention or clinical trial. Investigators observe without intervening other than to record, classify, count and statistically analyze what is observed.   Observational  
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______ studies examine the relationship between exposure and outcome with regard to the exposure preceding the outcome (“causation”)   Etiologic studies  
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______ studies describe either the exposure, the outcome, or both, but do not infer a causal relationship between the two (association)   Descriptive studies  
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A careful & detailed report of a single pt by one or more HCPs; documents unusual medical occurrences; possibly first clues in identification of new dz   Case Report  
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An expansion of a case-report which usually describes the characteristics of a number of pts; may occur within a short period of time   Case series  
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Study in which the units of analysis are populations or groups (not individuals); a study of group characteristics   Ecologic study  
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A study that examines the relationship between diseases and other variables of interest as they exist in a defined population at one particular time.   Cross-sectional study  
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Snap shot of disease prevalence in a population at one point in time   Cross-sectional study  
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Can a cross-sectional study determine a temporal relationship (i.e., exposure preceded outcome)?   No  
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Observational study: subjects selected on basis of whether they have (cases) or do not have (controls) a particular dz. Groups are compared w/respect to the proportion having a history of the exposure of interest.   Case-control study  
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Source populations for cases in case-control studies   Hospitals (Inpatient; Outpatient/Clinics); Communities (Registries; Dz Surveillance Registries)  
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Case-control studies: 2 types of matching of cases to controls   Frequency matching; individual matching  
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Case-control studies: Number of controls selected per case can be influenced by:   Cost; recruitment; small number of cases  
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Case-control studies: There is only a small increase in statistical power when the (controls:cases) ratio increases beyond:   3:1  
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Differences in the way exposure information is remembered or reported by cases (who have experienced an adverse health outcome) and controls (who have not).   Recall bias  
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2 types of odds ratio   Prevalence odds ratio; incidence odds ratio  
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Case-control studies: diagnostic criteria should minimize the likelihood that:   1: true cases are missed (sensitive); 2: false cases are included (specific)  
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A hybrid design in which a case-control study is nested in a cohort study.   Nested case-control study  
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Observational study: subjects are sampled based on presence (exposed) or absence (non-exposed) of a risk factor of interest; subjects followed over time, assess devt of dz/ outcome of interest   Cohort studies  
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Type of cohort study: investigators use historical data to reconstruct a timeline of exposure   Retrospective cohort  
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Type of cohort study: investigators identify the original population at the beginning of the study and follow them concurrently over time   Prospective cohort  
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Cohort study: fixed cohort   Exposure groups in a cohort study represent groups that are defined at the start of the follow-up or observation period. No new members are added  
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Cohort study: dynamic cohort   Study cohort gains members over time through in-migration, or loses members through out-migration  
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Best observational design to establish cause and effect relationships =   cohort study  
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The ratio of the risk of disease among the exposed to the risk among the unexposed   Relative Risk (AKA: Cumulative Incidence Ratio, Risk Ratio)  
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The ratio of the rate of disease in the exposed population to the rate in the unexposed population   Rate Ratio (AKA: Incidence Density Ratio)  
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Ecologic study: Advantages   Quick; Inexpensive; Hypothesis generating; Useful for establishing associations at an environmental level  
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Ecologic study: Disadvantages   Individual exposure information is not collected; so we don’t know if those who are exposed are actually developing the dz and vice-versa  
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Descriptive studies: Advantages   Inexpensive; Quick; Hypothesis generating; Assessment of public health interventions  
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Descriptive studies: Disadvantages   Temporal relationship cannot be determined; Incidence (risk) of disease cannot be determined; Causal link cannot be established  
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Study: subjects randomly allocated to receive new active treatment, or the std tx, or a placebo. Different tx groups are then compared to assess effectiveness of the treatment   Randomized clinical trial  
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Types of RCT   Parallel, Equivalency (parallel), Crossover, Factorial, Group allocation  
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RCT: ____-blind trial = good for trials on very sensitive topics or subjectively measured outcomes   Triple-blind  
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Randomization in RCT   Random allocation to a grp; group in which the subject is placed is random, not the subject himself; core of a RCT  
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Random Selection in RCT   Selecting subjects, at random, to be part of a study population; can be conducted in RCTs, but primarily in intervention and observational studies  
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RCT: types of randomization   Simple, blocked, stratified  
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RCT: blocked randomization requires:   a double-blind RCT design to eliminate investigator bias  
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RCT: Only disadvantage of blocked design:   analyses become more cumbersome  
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If blocked randomization is not double-blinded, then:   Block size pattern can randomly vary within a study (blocksize = 2, 4, 6, or 8)  
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Efficacy vs Effectiveness   Efficacy = can it work (under lab conditions)? Effectiveness = will it work (are results generalizable to larger population)?  
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RCTs vs Observational study: RCTs are good for:   Establishing tx efficacy; understanding effectiveness of intervention when small sample size; understanding: 1- efficacy for tx for serious/ rare dz; 2-dz pathology in a unique population  
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RCTs vs Observational study: Observational study good for:   Understanding associations in large pops; establishing need to conduct an RCT; understanding associations of prognostic factors with dz of interest prior to RCT  
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Sensitivity =   True Positives / (True Pos + False Negs)  
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Sensitivity will be higher if there are:   fewer false negatives; i.e., fewer Type II errors  
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Specificity =   True Negatives / (True Negs + False Pos)  
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Specificity will be higher if there are:   fewer false positives; i.e., fewer Type I errors  
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Positive Predictive Value (PPV) =   True Pos / (True Pos + False Pos)  
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Negative Predictive Value (PPV) =   True Negs / (True Neg + False Neg)  
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