Genetics Research Flashcards
Medical Genetic Research
- experimental studies
- higher quality
- lower volume of evidence
- shorter interval between time of intervention to outcome
- individual decision-making
Public Health Genomics Research
- quasi-experimental studies
- lower quality
- higher volume of evidence
- longer interval between time of intervention to outcome
- group decision-making
Incidence
- rate
- # new cases/population at risk
- measured over period of time
Prevalence
- # new cases/# people in population
- measured at specified time point/time period
Experimental Studies
- researcher controls who is exposed and who is not
- provide strongest evidence of causal association between exposure and disease/outcome
Observational Studies
- researcher simply observe what happens to those exposed
- exposure can occur by choice or by chance
Prospective Studies
data collected before disease/outcome occurred
Retrospective Studies
data collected after disease/outcome occurred
Longitudinal Studies
occur over a span of time
Cross-Sectional Studies
looks at one point in time
Ecologic Studies
type of cross-sectional study that looks at how community is exposed
Cohort Studies
- sampling population based on exposure to calculate relative risk
- longitudinal study as cohort followed over time
- compared exposed and non-exposed individuals with respect to outcome
Case-Control Studies
- sampling population based on outcome to calculate odds ratio
- cases have outcome and controls do not but could have gotten it
- cross-sectional study as data collected at one point in time
Randomized Clinical Trials
- experiments designed to look for cause and effect relationships
- type of cohort study
- assignment of exposure to participant is randomized
- single blind: study participants do not know group they’re in
- double blind: study participants and researchers assessing outcomes don’t know groups
Internal Validity
- how well exposure and outcome measure
- how well study population selected and controlled
- was study designed well to reduce error
Random Error
probability that observed result is due to chance
Bias
systematic error committed by investigator during course of study
Confounding
association due to a third factor that is both related to the exposure and the outcome but is not an intermediate step in causal pathway between exposure and outcome
External Validity
generalizability of results to other groups
Effect Modifier
- third variable alters effect of exposure on disease
- synergistic effect: positive interaction
- antagonistic effect: negative interaction
Relative Risk
- incidence in exposed/incidence in non-exposed
- (TP / (TP+FP))/(FN / (FN+TN))
- RR = 1, risk in exposed is equal to risk in non-exposed
- RR > 1, risk in exposed > risk in non-exposed
- RR < 1, risk in exposed < risk in non-exposed
Attributable Risk
- how much exposure actually causing outcome
- incidence in exposed-incidence in non-exposed
- (TP / (TP+FP)) - (FN / (FN+TN))
Odds Ratio
- measure of association between exposure and outcome; odds a case was exposed compared to control
- odds cases exposed/odds controls exposed
- TPTN/FPFN
- OR = 1, no association
- OR > 1, positive association, risk factor
- OR < 1, negative association, protective factor
Phase I Clinical Trials
assesses safety and effects of drug using small study group of healthy volunteers
Phase II Clinical Trials
tests efficacy of drug and placebo introduced for comparative results
Phase III Clinical Trials
randomized and blind testing to allow for more detailed understanding of drug’s effectiveness, benefits, risks; FDA approval requested
Phase IV Clinical Trials
monitors long-term effectiveness and compares drugs with others on market; determines cost-effectiveness and drug approved for consumer sale
Null Hypothesis
intervention will have no effect
Alternative Hypothesis
- intervention will have an effect, either good or bad (two-tailed test)
- intervention will help (one-tailed test)
Equipoise
ethical principle where must be genuine uncertainty about which treatment better
Alpha
probability of making type I error
Beta
probability of making type II error
Type I Error
concluding treatment makes a difference when it really does not
Type II Error
concluding treatment does not make a difference when it really does
Power
- 1-beta
- probability of correctly concluding treatment makes difference or probability of detecting difference when it exists
- small alpha means larger beta and smaller power
Quantitative Research
- means for testing objective theories by examining the relationship among variables
- variables measured on instruments so numbered data can be analyzed using statistical procedures
Qualitative Research
- means for exploring and understanding meaning individuals/groups ascribed to social or human problems
- process of research involves emerging questions and procedures, collecting data in participants’ settings, analyzing data inductively, building from particulars to general themes, and making interpretation of meaning of data
- often longitudinal
Mixed Methods Research
- approach to inquiry that combines or associates both qualitative and quantitative forms of research
- intermethod mixing: use of more than one method of data collection
- intramethod mixing: use of single method of data collection to obtain qualitative and quantitative data
Literature Review
- surveys scholarly articles, books, and other sources relevant to particular issue, area of research, or theory providing a description, summary, and critical evaluations of each work
- does not report original research
Research Process
topic -> research questions -> study design -> data collection -> analysis -> dissemination of findings
Institutional Review Board (IRB)
- systematic investigation designed to develop/contribute to generalizable knowledge
- protect human subjects
- based on 4 pillars of medical ethics: autonomy, beneficence, nonmaleficence, justice
Vulnerable Populations
prisoners, children, fetuses, economically/educationally disadvantaged
Categories of IRB Review
- exempt: does not qualify as research with human subjects
- expedited: poses no more than minimal risk
- full: poses more than minimal risk, vulnerable population
3 Areas of Ethical Concern for Research
- relationship between society and science; extent to which societal concerns and cultural values should direct course of research
- professional issues; research misconduct
- treatment of research participants
Accepted Professional Norms in Research
honesty, accuracy, efficiency, objectivity
Conflict of Interest
- conflict between private interests and official responsibilities of person in position of trust
- financial gains or promotions
- working for company that funds or directly conducts study
- statements demonstrate authors have considered potential for bias and have made attempts to minimize them
Genome Wide Association Studies
- case-control studies that look at people with disease (cases) and those without (controls) in conjunction with SNPs across genome to see if any more or less likely to be found in either group
- P-value <5*10-8 to reduce false positive rate
- significance of association not same as strength of association nor does it indicate clinical significance
- most variants identified account for only small fraction of known genetic variation
- success found in pharmacogenomic applications
T/F: Federally funded dried blood spot research (from NBS) is considered human subject research that requires parental consent
True
