Biostat Test 1

Question 1

Define Alpha Error?

Answer 1

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).

Question 2

Define A Priori?

Answer 2

Literally for “from what comes before”

Question 3

Define A Priori Comparison?

Answer 3

A comparison that a researcher decides to make before (prior to) performing an experiment or gathering data.

Question 4

Define Beta Error?

Answer 4

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.

Question 5

Define Bias?

Answer 5

Anything that produces systematic error in a research finding.

Question 6

Define Blind or Blinded?

Answer 6

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.

Question 7

Defined Case-Control study?

Case-Referent or Case Comparison

Answer 7

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.

Question 8

Define Case Series?

Answer 8

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.

Question 9

COHORT

Answer 9

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).

Question 10

COHORT STUDY

Answer 10

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

Question 11

CONFIDENCE INTERVAL:

Answer 11

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%

Question 12

CONFOUNDER, COFOUNDING VARIABLE

Answer 12

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

Question 13

CONSECUTIVE SAMPLE

Answer 13

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

Question 14

COST–BENEFIT ANALYSIS

Answer 14

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.

Question 15

CRITERION STANDARD.

Answer 15

. 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

Question 16

CROSSOVER TRIAL

Answer 16

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.

Question 17

DATA-SET

Answer 17

Raw data gathered by investigators.

Question 18

DICHOTOMOUS VARIABLE

Answer 18

A categorical variable that can place subjects into only two groups, such as male/female, dead/alive or pass/fail

Question 19

DOUBLE-BLIND or DOUBLE MASK.

Answer 19

(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.

Question 20

ECONOMIC EVALUATION

Answer 20

Comparative analysis of alternative courses of action in terms of both their costs and consequences.

Question 21

END POINT

Answer 21

OUTCOMES

Question 22

EQUIVOCAL

Answer 22

1. Open to two or more interpretations and often intended to mislead; ambiguous. 2. Of uncertain significance. 3. Of a doubtful or uncertain nature.

Question 23

EXPERIMENTAL GROUP

Answer 23

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).

Question 24

EXTERNAL VALIDITY

Answer 24

The extent to which findings of a study are relevant to subjects and settings beyond those in the study. Another term for generalizability

Question 25

EXTRANEOUS

Answer 25

1. 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.

Question 26

GENERALIZABILITY

Answer 26

The extent to which you can come to conclusions about a population based on information about a study population.

Question 27

GOLD STANDARD

Answer 27

See CRITERION STANDARD

Question 28

HETEROGENEOUS

Answer 28

generally, Mixed or diverse. Used to describe samples and populations with high variability.

Question 29

HOMOGENEOUS

Answer 29

Generally, the same or similar. Used to refer to populations and samples that have low variability

Question 30

HYPOTHESIS

Answer 30

A statement of (or conjecture about) the relationships among variables that a researcher intends to study

Question 31

INCEPTION COHORT

Answer 31

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).

Question 32

INTERNAL VALIDITY

Answer 32

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

Question 33

JOHN HENERY EFFECT

Answer 33

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

Question 34

LIFE TABLE

Answer 34

A table showing life expectancy at various dates and/or for different groups.

Question 35

LIKELIHOOD RATIO

Answer 35

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.

Question 36

MASKED

Answer 36

See BLIND

Question 37

MATCHING

Answer 37

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).

Question 38

n

Answer 38

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.

Question 39

N

Answer 39

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

Question 40

NONRANDOMIZED CONTROL TRIAL

Answer 40

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.

Question 41

NULL HYPOTHESIS

Answer 41

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

Question 42

OUTCOMES

Answer 42

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.

Question 43

OUTLIER

Answer 43

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.

Question 44

P VALUE

Answer 44

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%.

Question 45

PLACEBO EFFECT

Answer 45

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.

Question 46

PLAUSIBLE

Answer 46

1. 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.

Question 47

RANDOM

Answer 47

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

Question 48

RANDOM SAMPLE

Answer 48

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).

Question 49

RANDOMIZATION, RANDOM ALLOCATION

Answer 49

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.

Question 50

RANDOM TRIAL.

RANDOMIZED CONTROLED TRIAL, RANDOMIZED CLINICAL TRIAL, RCT

Answer 50

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

Question 51

REFERRED CARE

Answer 51

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

Question 52

SENSITIVITY

Answer 52

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.

Question 53

SPECIFICITY

Answer 53

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

Question 54

SURVEY

Answer 54

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.

Question 55

TERTIARY CARE CENTER

Answer 55

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.

Question 56

TWO-TAILED TEST

Answer 56

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

Question 57

TYPE I ERROR

Answer 57

See alpha error

Question 58

TYPE II ERROR

Answer 58

See beta error

Question 59

Primary Bias?

Answer 59

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

Question 60

Preclinical Trials

Answer 60

(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.

Question 61

Phase I Clinical Trials

Answer 61

(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

Question 62

Phase II Clinical Trials

Answer 62

(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

Question 63

Phase III Clinical Trials

Answer 63

(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.

Question 64

Phase IV Clinical Trials:

Answer 64

(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)

Question 65

Case Control Studies (SLIDES)

Answer 65

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)

Question 66

Prospective Cohort Study

Answer 66

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

Question 67

Disadvantages of Case Control and Cohort Studies

Answer 67

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

Question 68

Case Report(s)

Answer 68

Anecdotal or spontaneous reporting

Can’t replace clinical trial data

Useful in situations where the condition being studied is rare.

Question 69

Title

Answer 69

Brief description of the research conducted

Question 70

Abstract

Answer 70

Overview of the research conducted

Question 71

Introduction

Answer 71

Background information for the trial including results of prior research

Question 72

Methods

Answer 72

Description of drug research design

Inclusion/exclusion criteria, number needed, dosing information, measures of efficacy and safety

Question 73

Results & Data Analysis

Answer 73

Analysis of research findings, including discussion of dropouts, discontinuation of drug therapy

Question 74

Discussion & Conclusions

Answer 74

Interpretation of results, comparison to current standard drug treatment, discussion of future implication of research

Question 75

References

Answer 75

Evidence that prior research has been considered in designing and interpreting the trials.

Question 76

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!

Answer 76

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

Question 77

What procedures does the journal use to ensure that quality articles are published?

Peer Review

Answer 77

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

Question 78

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

Answer 78

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

Question 79

Redundant articles

Answer 79

same information in more than one journal.

Question 80

Repetitive articles

Answer 80

same material in more than one type of publication. (Book chapters, journal articles, abstracts or review articles).

Question 81

Divided articles

Answer 81

splitting of findings of a single project into a string of publications.

Question 82

retracted articles

Answer 82

Articles may be retracted because of research errors, fraudulent data or ideas.

Question 83

Does the literature review provide adequate background information?

Answer 83

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

Question 84

Citation errors

Answer 84

certain facts about a referenced article are incorrectly listed.

Authors name, article title, journal source

Question 85

Quotation errors

Answer 85

the original intent of the clinical trial is inadequately reflected in the literature review.

Examine the original references

Question 86

Are the “objectives” or “purpose” of the clinical trial clear, unbiased, specific, consistent and important?

Answer 86

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

Question 87

Were the patients selected by appropriate means?

Answer 87

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