Biostat Test 1 Flashcards
Define Alpha Error?
An error by rejecting a true null hypothesis (such claiming a relationship exist it does not). False positive.
A Type I error occurs when we believe a falsehood.[4] In terms of folk tales, an investigator may be “crying wolf” without a wolf in sight (raising a false alarm) (H0: no wolf).
Define A Priori?
Literally for “from what comes before”
Define A Priori Comparison?
A comparison that a researcher decides to make before (prior to) performing an experiment or gathering data.
Define Beta Error?
An error made by accepting or retaining a false null hypothesis, more precisely, by failing a false null hypothesis. This might involve, for example, claiming that relationship does not exist when it in fact does. TYPE II error.
Define Bias?
Anything that produces systematic error in a research finding.
Define Blind or Blinded?
Masked. Unaware.
The term may be modified according to the purpose of the blinding.
Example, Clinician or patients can be blind to the treatment that patients are receiving and observers can be blind to each other’s assessments, making their uninfluenced by one another.
To avoid confusion, the term MASKED is preferred in studies in which vision is an outcome of interest.
Defined Case-Control study?
Case-Referent or Case Comparison
Study generally used to test possible causes of disease or disorder, in which individuals who have a designated disorder are compared with individuals who do not have the disorder with respect to previous or current exposure to a putative casual order.
For example, person with hepatic cancer (cases) are compared with persons without hepatic cancer (controls) and history of hepatitis B is determined for the two groups.
A Case-Control study is often referred and a RESTROPECTIVE STUDY (even if patients are recruited prospective) because the logic of the design leads from from effect to cause.
Define Case Series?
A series of patients with a defined disorder. The term is usually used to describe a study reporting on a consecutive collection of patients treated in similar manner, and outcomes for 100 consecutive patients with cerebral ischemia who received a revascularation procedure.
COHORT
A group of persons with a common characteristic or set of characteristics. Typically, the group is followed for a specific period to determine the incidence of a disorder or complications of an established disorder (that is, prognosis) as in COHORT STUDY (prospective study).
COHORT STUDY
Prospective investigation of the factors that might cause a disorder in which a cohort of individuals who do not have evidence of an outcome of interest but who are exposed to the putative cause are compared with a concurrent cohort, who are also free of the outcomes but not exposed to the putative cause. Both cohorts are then followed to compare the incidence of the outcome of interest
CONFIDENCE INTERVAL:
A range of values of a sample statistic that is likely to contain a population parameter. The interval that will include the population parameter a certain percentage of the time. The desired level of confidence is usually 95%
CONFOUNDER, COFOUNDING VARIABLE
A factor that distorts the true relationship of the study variables of central interest by virtue of being related to the outcome of interest but extraneous to the study question and unequally distributed among the groups being compared. For example, age might confound a study of the effect of a toxin on longevity if individuals exposed to the toxin were older than those not exposed
CONSECUTIVE SAMPLE
Sample in which the units are chosen on a strict “first come, first chosen” basis. All individuals who are eligible should be included as they are seen
COST–BENEFIT ANALYSIS
An economic assessment, usually from society ‘s perspective, in which the costs of medical care are compared with the economic benefits of the care, with both cost and benefits expressed in units of currency. The benefits typically include reductions in future health care costs and increased earnings due to the improved health of those receiving the care.
CRITERION STANDARD.
. Preferred term to “gold standard”. A method having established or widely accepted accuracy for determining a diagnosis, providing a standard to which a new screening or diagnostic test can be compared. The method need not be a single or simple procedure but could include follow-up of patients to observe the evolution of their conditions or the consensus of an expert panel of clinicians. CRITERION STANDARD can also be used in studies of the quality of care to indicate a level of performance, agreed to by expert or peers, to which the performance of individual practitioners or institutions can be compared
CROSSOVER TRIAL
A method of comparing two or more treatments or interventions in which subjects or patients, on completion of the course of one treatment, are switched to another. Typically, allocation to the first treatment is by random process. Participants’ performance in one period is used to judge their performance in others, usually reducing variability.
DATA-SET
Raw data gathered by investigators.
DICHOTOMOUS VARIABLE
A categorical variable that can place subjects into only two groups, such as male/female, dead/alive or pass/fail
DOUBLE-BLIND or DOUBLE MASK.
(1) Neither the subject nor the study staff (those responsible for patient treatment and data collection) are aware of the group or intervention to which the subject has been assigned. (2) Any condition in which two different groups of persons are purposely denied access to information in order to keep the information from influencing some measurement, observation, or process.
ECONOMIC EVALUATION
Comparative analysis of alternative courses of action in terms of both their costs and consequences.
END POINT
OUTCOMES
EQUIVOCAL
- Open to two or more interpretations and often intended to mislead; ambiguous. 2. Of uncertain significance. 3. Of a doubtful or uncertain nature.
EXPERIMENTAL GROUP
A group receiving some treatment in an experiment. Data collected about people in the experimental group are compared with data about people in a control group (who received no treatment) and/or another experimental group (who received a different treatment).
EXTERNAL VALIDITY
The extent to which findings of a study are relevant to subjects and settings beyond those in the study. Another term for generalizability
EXTRANEOUS
- Not constituting a vital element or part. 2. Inessential or unrelated to the topic or matter at hand; irrelevant. 3. Coming from the outside: extraneous interference.
GENERALIZABILITY
The extent to which you can come to conclusions about a population based on information about a study population.
GOLD STANDARD
See CRITERION STANDARD
HETEROGENEOUS
generally, Mixed or diverse. Used to describe samples and populations with high variability.
HOMOGENEOUS
Generally, the same or similar. Used to refer to populations and samples that have low variability
HYPOTHESIS
A statement of (or conjecture about) the relationships among variables that a researcher intends to study
INCEPTION COHORT
A designated group of persons, assembled at a common time early in the development of a specific clinical disorder (for example, at the time of first exposure to the putative cause or at the time of initial diagnosis) who are followed thereafter (see COHORT).
INTERNAL VALIDITY
The extent to which the results of a study can be attributed to the treatments rather than to flaws in the research design; in other words, the degree to which one can draw valid conclusions about the causal effects of one variable on another
JOHN HENERY EFFECT
A tendency of persons in a control group to take the experimental situation as a challenge and exert more effort than they otherwise would; they try to beat those in the experimental group. This, of course, negates the whole purpose for having a control group
LIFE TABLE
A table showing life expectancy at various dates and/or for different groups.
LIKELIHOOD RATIO
For a screening or diagnostic test (including clinical signs or symptoms), expresses the relative odds that a given test result would be expected in a patient with (as opposed to one without) a disorder of interest.
MASKED
See BLIND
MATCHING
The deliberate process of making a study group and a comparison group comparable with respect to factors that are extraneous to the purpose of the investigation but that might interfere with the interpretation of the study’s finding (for example, in case-control studies, individual cases might be matched or paired with a specific control on the basis of comparable age, gender, clinical features, or a combination).
n
Number. Usage varies; among the most common meanings of lowercase n are the number of patients in a sample or the number of cases in a subgroup.
N
Number. Usage varies; among the most common meanings of uppercase N are the total number of subjects in a particular study, the number of individuals in a population or the number of variables in a study
NONRANDOMIZED CONTROL TRIAL
Experiment in which assignment of patients to the intervention groups is at the convenience of the investigator or according to a preset plan that does not conform to the definition of RANDOM. See also RANDOMIZED CONTROL TRIAL.
NULL HYPOTHESIS
The hypothesis that two or more variables or that two or more statistics (means for two different groups) are the same. In accumulating evidence that the null hypothesis is false, the researcher indirectly demonstrates that the statistics are different. The null hypothesis is the core idea in hypothesis testing
OUTCOMES
All possible changes in health status that may occur in following subjects or that may stem from exposure to a causal factor or from preventive or therapeutic interventions. The narrower term END POINTS refers to health events that lead to completion or termination of follow-up of an individual in a trial or cohort study, for example, death or major morbidity, particularly related to the study question.
OUTLIER
A subject or other unit of analysis that has extreme values on a variables. Outliers are important because they can distort the interpretation of data or make misleading a statistic that summarizes values, such as the mean.
P VALUE
Probability value. Usually found in an expression such as p < 0.05. The probability that this result could have been produced by chance (random error) is less than 5%.
PLACEBO EFFECT
Improvement in the condition of sick persons that cannot be attributed to the physiological effect of treatment that was used but is due, rather, to their (mistaken) belief that they received an effective treatment.
PLAUSIBLE
- Seemingly or apparently valid, likely, or acceptable; credible: a plausible excuse. 2. Giving a deceptive impression of truth, acceptability, or reliability; specious: the plausible talk of a crafty salesperson.
RANDOM
Governed by a formal chance process in which the occurrence of previous events is of no value in predicting future events. The probability of assignment of, for example, a given subject to a specified treatment group is fixed and constant (typically 0.50) but the subject’s actual assignment cannot be known until it occurs
RANDOM SAMPLE
A sample derived by selecting sampling units (for example, individual patients,) such that each unit has an independent and fixed (generally equal) chance of selection. Whether a given unit is selected is determined by chance for example, by a table of randomly ordered numbers).
RANDOMIZATION, RANDOM ALLOCATION
Allocation of individuals to groups by chance, usually done with the aid of a table of random numbers. Not to be confused with systematic allocation (for example, on even and odd days of the month) or allocation at the convenience or discretion of the investigator.
RANDOM TRIAL.
RANDOMIZED CONTROLED TRIAL, RANDOMIZED CLINICAL TRIAL, RCT
Experiment in which individuals are randomly allocated to receive or not receive an experimental preventive, therapeutic, or diagnostic procedure and then followed to determine the effect of the intervention
REFERRED CARE
Medical care provided to a patient when referred by one health professional to another with more specialized qualifications or interests. There are two levels of referred care: secondary and tertiary. Secondary care is usually provided by a broadly skilled specialist such as a general surgeon, general internist, or obstetrician. Tertiary care is provided on referral of a patient to a sub-specialist, such as an orthopedic surgeon, neurologist, or neonatologist. See also TERTIARY CARE CENTER
SENSITIVITY
The sensitivity of a diagnostic or screening test is the proportion of people who truly have a designated disorder who are so identified by the test. The test may consist of or include clinical observations.
SPECIFICITY
The specificity of a diagnostic or screening test is the proportion of people who are truly free of a designated disorder who are so identified by the test. The test may consist of or include clinical observations
SURVEY
Observational or descriptive, non-experimental study in which individuals are systematically examined for the absence or presence (or degree of presence) of characteristics of interest.
TERTIARY CARE CENTER
A tertiary care center is a medical facility that receives referrals from both primary and secondary care levels and usually offers tests, treatments and procedures that are not available elsewhere. Most tertiary care centers offer a mixture of primary, secondary, and tertiary care services so that it is the specific level of service rendered rather than the facility that determines the designation of care in a given study. See also REFERRED CARE.
TWO-TAILED TEST
A statistical test in which the critical region (region of rejection of the null hypothesis) is divided into two areas or tails of the sampling distribution
TYPE I ERROR
See alpha error
TYPE II ERROR
See beta error
Primary Bias?
primary bias is the tendency to report only “positive” results
examples: Pressure to publish: Exaggerated claims Fragmented results Incomplete descriptions of methods and/or results Scientific fraud
Preclinical Trials
(average duration 3.5 years)
Conducted at the beginning of the drug development process and involve:
Initial synthesis of the drug (1 to 3 years)
Long-term animal and in vitro testing (2-10 years)
Main purpose is to assess initial drug effects:
biological activity
pharmacokinetic profile
toxicological profile
Many preclinical trials are performed on specific animal species and extrapolation to humans is difficult.
Phase I Clinical Trials
(average duration 1 year) First use of a new drug in humans Studies involve various drug doses and schedules in order to focus on drug safety and pharmacokinetics. Primary focus: Define which organs are adversely affected by the new drug. Preferred route of administration Safe dosage range Trial design: Escalating single doses Short-term, multiple doses
Phase II Clinical Trials
(Average duration 2 to 5 years)
Introduction of the new drug into the population for which it is intended.
Primary purpose:
Demonstrate the new drugs effectiveness (Should company further develop the drug?)
Learn more about drug safety (Define the importance of certain side effects)
Research is usually controlled studies on a limited number of patients (100 to 500) completed in a relatively short period of time
Phase III Clinical Trials
(Average duration 2 to 4 years)
Expansion of the trials to a larger number of patients (1000 to 3000) for longer periods of time (3 to 12 months).
The most rigorous and extensive evaluation of the new drug, usually involves:
Large scale
Well-controlled
Multi-center clinical trials
The new drug is usually compared to placebo or currently accepted standard therapy.
Primary purpose :
Demonstrate safety over longer periods of time. (Accumulation)
Continued drug effectiveness without the development of tolerance.
Phase IV Clinical Trials:
(Indefinite duration) Post-marketing surveillance, includes research sponsored by: Manufacturers Government Institutions
Some Phase IV trials are required by the FDA before the drug gets final approval.
Principle purpose:
Obtain better appreciation of the full benefits and hazards of the drug once it is in the general population.
Typical information gathered:
Proper dosing in specific populations
elderly
patients with renal or hepatic impairment
existence or frequency of less frequent, but important, side effects
Phase IV studies include:
Anecdotal reports of adverse effects (published case reports)
Long-term epidemiological trials (retrospective or prospective)
Case Control Studies (SLIDES)
Retrospective*
Usually evaluating side effects
Patients that have a specific disease or symptoms are examined to determine if they were exposed to the research medication.
APAP and ESRD Case Control
STEPS:
Select a population with the disease state in question. (Present)
Select a population “at risk” without the disease state. (Present)
Measure the predictor variables. (Past)
Prospective Cohort Study
Begin with patients taking the research drug.
Patients followed for an extended period of time.
Patients monitored to see if they develop a specific side effect (or condition).
Example: Effects of Fluoxetine in pregnancy.
STEPS:
Select a sample
Measure predictor variables (risk factors)
Follow the cohort
Measure the outcome (disease or no disease develops
Disadvantages of Case Control and Cohort Studies
Good to assess hazards of drug therapy but…
–Causal relationships are difficult to establish
Inability to determine the timing of drug exposure relative to ADR
Failure to control the influence of other possible causative factors
Case Report(s)
Anecdotal or spontaneous reporting
Can’t replace clinical trial data
Useful in situations where the condition being studied is rare.
Title
Brief description of the research conducted
Abstract
Overview of the research conducted
Introduction
Background information for the trial including results of prior research
Methods
Description of drug research design
Inclusion/exclusion criteria, number needed, dosing information, measures of efficacy and safety
Results & Data Analysis
Analysis of research findings, including discussion of dropouts, discontinuation of drug therapy
Discussion & Conclusions
Interpretation of results, comparison to current standard drug treatment, discussion of future implication of research
References
Evidence that prior research has been considered in designing and interpreting the trials.
Does the abstract concisely discuss all major aspects of the clinical drug trial?
concise summary of the article and are usually restricted to 200 to 400 words focused on reporting the results of the data analysis
Abstracts can be misleading because the research methodology and results sometimes cannot be sufficiently explained in the limited space allocated.
Some times skewed by the author’s tendency to describe the trial in the best possible manner.
Don’t base your decision on the abstract alone!
Objective
The exact question addressed by the article
Design
The basic clinical drug trial design, including duration of follow-up
Setting
The location and the type of care provided
Patients/Participants
Number of patients who entered and completed the trial, including how they were selected
Interventions
The essential features of the intervention, including the method of administration and duration of therapy
Measurements/Results
Important methods of assessing patients and key results reported
Conclusions
Important, clinically relevant conclusions
What procedures does the journal use to ensure that quality articles are published?
Peer Review
Peer Review
Assessment by experts of the material submitted for publication in scientific and technical journals.
One to three experts review a manuscript
Anonymous
Decision: Accept, revise or reject
Journal editor has the final decision
Is there any information present which suggests bias in the publication of the article?
While most research is presented fairly, investigators may feel pressured to
Compromise methodological standards
Report only positive results
Exaggerate their findings to ensure additional funding
BIAS
Publication bias: preference to publish significant or positive results.
Learn about the authors
Examine the funding source Government Drug companies Professional organizations Publish or perish
Redundant articles
same information in more than one journal.
Repetitive articles
same material in more than one type of publication. (Book chapters, journal articles, abstracts or review articles).
Divided articles
splitting of findings of a single project into a string of publications.
retracted articles
Articles may be retracted because of research errors, fraudulent data or ideas.
Does the literature review provide adequate background information?
Provides an overview of earlier research and describes the rational for performing the study.
Investigators may be selective regarding the references they site.
Redundant articles
Repetitive articles
Divided articles
Retracted articles
Citation errors
certain facts about a referenced article are incorrectly listed.
Authors name, article title, journal source
Quotation errors
the original intent of the clinical trial is inadequately reflected in the literature review.
Examine the original references
Are the “objectives” or “purpose” of the clinical trial clear, unbiased, specific, consistent and important?
Primary questions the investigator is most interested in answering.
Usually provided at the end of the introduction.
Clear objectives indicate a clear research plan.
Type of patient studied
Research setting
Drugs involved
Drug effect to be measured
Were the patients selected by appropriate means?
Enrollment Process
Selection Criteria
Broad Selection Criteria:
Ensures a large sample size
Narrow Selection Criteria:
Increases the likelihood of achieving statistically significant results.
Inclusion Criteria
Exclusion Criteria
Quality of the Patient Enrollment Process
Enrollment Process:
Patient or physician perceives a need for drug treatment.
Patients are enrolled if they meet inclusion criteria.
Patient formally consents to enter the trial (informed consent)
Once enrolled the patient is assigned to a treatment group.
Random Choice (random enrollment) In random enrollment each member of the trial population has an equal chance of being selected. Randomly selected patients are more likely to be representative of the target population because there is less chance of bias. Trials patients are rarely randomly chosen
Convenience Sample
The more common approach is to select eligible patients that either arrive consecutively or are referred by a participating physician.
This is referred to as a Convenience sample and is dependent on the bias of the individual selecting patients.
Reporting of patients who were excluded:
Rarely this information is reported in the clinical article.
The results of poor enrollment may leave the investigators with an overrepresentation of certain types of patients
Reporting of patients who were excluded:
Rarely this information is reported in the clinical article.
The results of poor enrollment may leave the investigators with an overrepresentation of certain types of patients
Poor Extrapolation of Data
Patients can differ:
Age,Gender,Race,Concurrent diseases,Organ function
