Exam 1 (First Two Handouts) Flashcards
The degree of confidence a researcher has that the changes observed in the dependent variable (clinical outcome) are because of the independent variable (treatment)
Internal Validity
The extent to which the results of a study can be generalized to other settings
External Validity
The outcome is a result of the treatment
Causality
Cause occurs before the outcome
Temporality
Plausibility of causation increases with the strength of the relationship
Strength
A linear relationship like a dose-response is observed
Biological Gradient
One-to-one relationship between cause and effect
Specificity
There should be a reasonable biological explanation/mechanism for the effect
Plausibility
The relationship should be explained by existing knowledge
Coherence
The effect is similar to those accepted phenomena as observed in preclinical trials
Analogy
It is the strongest evidence when the cause is controlled by the researcher and the effect is observed in randomly assigned subjects as in RCTs
Experiment
To describe a phenomenon
Descriptive
Provide casual interpretation of an existing phenomenon
Analytical
What are the five important elements (5 W’s) pertaining to a new disease or event:
-Who
-What
-Why
-When
-Where
-So What (later added as a 6th element)
Analytical studies typically involve this word (hint)
Causal
Prospective Studies
-data are collected after the study as individuals are followed
-researchers get to determine the variables and collect relevant data
-they are resource (time and cost) intensive
Retrospective Studies
-researchers go backward in time to determine the relationship between cause and outcome that has already occurred
-analyze existing data so they relatively require minimal resources
-researchers have no control over the variables needed and how they are defined and collected
What three things play an important role in choosing an appropriate research design?
-objective of research
-topic of research
-practical considerations
Experimental designs to test their research hypotheses are common in what type of research?
Basic
We see both experimental and observational designs in what type of research?
Clinical Research
What is the most commonly used experimental design?
RCTs
What are the commonly used observational designs are..
-cohort
-case-control
-cross-sectional
-case series
-case reports
What is the gold standard in evaluating the safety and efficacy of an intervention?
Randomized Controlled Trials
What are the TWO essential elements of RCTS?
-randomization
-prospective
However the elements of RCTs that increase the internal validity of study results also contribute towards restricting…
their external validity (generalizability)
The key element in observational studies is..
non-randomization of the independent variable of interest
Primary data technique examples
-interviews
-surveys
Secondary data technique examples
-medical charts
-medical claims
Involve a study of a single case of a new disease or manifestation
Case Report
Exposure and outcome are measured at the same point in time
Cross-sectional
Involve comparison of exposure status among individuals with the disease or outcome of interest (cases) and those without the disease or outcome (controls)
Case-control
Cases and controls are both identified from the same..
source population
Follow exposed and unexposed over a period until the development of outcome
Cohort
Cohort studies determine the incidence of the outcome among exposed and unexposed groups and therefore provide a measure of..
relative risk
There is no randomization involved in Cohort studies which makes it vulnerable to..
selection bias
Cohort studies can be divided into two types:
retrospective and prospective
Involve numerical or countable information to study research phenomenon
Quantitative Data
Involve words or textual information
Qualitative Data
The consistency and reproducibility of results
Reliability
Consistent when the same measurement instrument is used by multiple investigators
Reproducibility
Measures what is it intended
Validity
Participant is aware that he/she is being observed
Obtrusive Observation
Participant is unaware of the observer who may be either hidden or under disguise
Unobtrusive Observation
Strongest type of primary study design and most common type of trial
RCTs
RCTs are required by the FDA as part of a…
New Drug Application (NDA)
Phase 3 studies are also referred to as..
“pivotal trials”
The degree to which the findings represent the truth
Validity
How can you strengthen internal validity?
include a control group
What is the most effective way to reduce selection bias?
Randomization
Subjects modify their behavior because of the fact that they are being studied or observed
Hawthorne Effect
The external events that occur during the course of the study
History Bias
Normal changes in study participants over time
Maturation Bias
Refers to differential dropout of patients from the treatment or control groups
Attrition Bias
The mean refers to cases where initial measurements of a variable are extremely different from the population mean, but then subsequent measurements are closer to the average
Regression (or reversion)
Systematic differences between groups in how outcomes are determined
Detection Bias
Random Number Generator
Simple Randomization
To ensure that treatment groups have an equal number of patients
Block Randomization
Ensuring certain baseline characteristics are equal between the groups of a study
Stratified Randomization
A specific group of subjects are selected for randomization such as those enrolled in a clinic or hospital
Cluster (Group) Randomization
Those involved in the trial are unaware of what treatment the patients are receiving
Blinding (masking)
-Least object type of design
-All individuals in the study are aware of what treatment the patients are receiving
-Restricted to early pharmacokinetic studies or phase 1 trials
Open Label
Only one set of individuals is unaware
Single Blind
Two sets of individuals are unaware
Double Blind
All individuals involved in the study are unaware of what the patients were receiving (including investigators)
Triple Blind
More than one placebo is used
Double Dummy
Measures the capacity to detect a difference in the study groups if a true difference exists
Power
Standardized document that provides instructions to the investigators on all aspects of carrying out the study
Clinical Research Protocol
Specific characteristics that the investigator is most interested in studying
Inclusion Criteria
Factors that would confound or impair the ability not interpret the study results or eliminate patients that should not be receiving the intervention or an active control
Exclusion Criteria
Each subject is only randomized to either to a treatment group or a control group
Parallel Study Design
Receives all of the interventions based on a specified sequence of events
Crossover
Each subject receives all of the interventions based on a specified sequence of events
Crossover
What is the most common type of RCT and what is its purpose?
-Superiority trial
-Which aims to determine whether or not one treatment is better than another
Aims to determine whether or not two interventions are equivalent or nearly equivalent based on a set of acceptance criteria
Noninferiority Trial
Systematic study to gain knowledge or understanding necessary to determine the means by which a recognized and specific need may be met
Applied Research
Refers to the collection of information based on human experience. All aspects of science should be observed and measured to be considered as scientific evidence
Empiricism
Means that there is no subjectivity or bias in any aspect of research including definition, measurement, design, and analysis
Objectivity
Provides an understanding or explanation of a natural phenomenon. In pharmaceutical research, theories are often based on pathophysiology of a disease and pharmacology of a medication to investigate medication effects
Theory
Provide the moral societal standards for responsible research conduct
Ethics
What is the framework often used to develop a good clinical question?
PICOTS
What does PICOT stand for
P- Population to be studied
I- Intervention to be applied
C- Comparator to be used
O- Outcomes to be evaluated
T- Timeline to evaluate the outcomes and healthcare
S- Setting of interest
Specifies an expected relationship between intervention and outcome, or two or more variables.
Hypothesis
involve testing a drug in humans with the intent of establishing the initial toxicity profile of the substance (“tolerability”)
Phase 1 Trials
Are designed to provide preliminary evidence of efficacy and safety
Phase 2 Trials
-Generate efficacy and safety data to allow evaluation of the overall risk to benefit relationship of the drug
-Are usually set up as a Randomized Controlled Trial (RCT) often involving blinding and placebo controls.
Phase 3 Trials
Studies may be required by FDA to generate longerterm safety/toxicity data.
Phase 4 Trials or Post-Marketing
Is intended to allow patients to obtain investigational medications outside of clinical trials or current expanded access programs
Right-To-Try Act
-Individuals should be treated as autonomous agents
-Persons with diminished autonomy are entitled to protection
-The informed consent process ensures the respect to person
Respect for Persons
-Maximizing possible benefits.
-Minimizing possible harm.
-Never knowingly cause (permanent) injury
Beneficence
-Sense of fairness in distributing the burdens and benefits of research.
-Researchers are obligated to ensure that no group inappropriately bears the burdens of research for others’ benefit.
Justice
What are the three basic principles of the Belmont Report?
-Respect for persons
-Beneficence
-Justice
National Commission for Protection of Human Subjects of Biomedical and Behavioral Research, which was set up by the National Research Act, published Ethical Principles and Guidelines for the Protection of Human Subjects of Research known as the
Belmont Report
There are three types of IRB review:
-Exemption
*Surveys/interviews, use of existing data, or specimens without identifiers
-Expedited review by the chair or designee
*minimal risk protocols that do not meet one of the exemptions
-Full review by the whole board
*all protocols involving greater than minimal risk
Charged with protecting the rights and welfare of human subjects of research and ensuring that research is conducted in accordance with accepted ethical standards.
Institutional Review Board
Used to estimate the effect of an exposure on a disease outcome (measures of effect such as causal RRs and causal rate ratios, respectively).
Risk ratios (RRs) and rate ratios
The most basic form of medical evidence that often provides the first suspicion that an issue exists
Case Report
Case reports only serve to provide a description of a situation and is not…
intended to lead to a conclusion or answer a hypothesis
The removal of most medications from the market due to adverse reactions are due to…
case report evidence
Report adverse drug reactions to…
MedWatch
Why are adverse drug reactions in special populations not frequently identified?
these patients are often excluded from research
Due to case reports describing novel occurrences, it has a high _______
sensitivity; however it has a chance of reporting false results and therefore a lower level of specificity
How are sensitivity and specificity related?
Inversely
Case Series
Descriptive
