Lecture 15: General Methodological Concepts Of Research

Question 1

List the major stages of research evidence period (in order of increasing evidence)

Answer 1

1. Bench Research
2. Animal Research (These first two don’t involve humans)
3. Ecological
4. Cross-Sectional
5. Case Control
6. Cohort
7. Interventional Studies & Pragmatic Studies

Question 2

So what is the most useful and appropriate study design?

Answer 2

IT DEPENDS on the QUESTION being asked and the desired perspective.

Question 3

What are the two types study design and methodology?

Answer 3

• Quantitative: Numbers are used to represent data
• Qualitative: Words are used to represent data

Breaking All studies into two groups: this would be it.

Note: Surveys such as “Highly Agree, Disagree” are quantitive since they’re taking number rankings between 1 through 5 or whatever. Quantitative seems more common.
Qualitative Research: If you were giving an essay response and keywords and consistencies are reported are interpreted as qualitative. Seems much less common.

Question 4

What are the two types of quantitative study designs?

Answer 4

• Interventional - Forced Allocation to study groups
• Researcher is more strict and controlling. Conditions are forced into certain situations and scenarios.
• Observational: No forced allocation to study groups
• Researchers don’t get as involved and allow results to form naturally. Don’t know of an example yet. However, should be obvious when it’s interventional.

Question 5

Give an overview of Study Designs

Answer 5

• Various types of study designs & methodologies used by researchers
• Each design represents its own, unique way of harvesting information to answer a research question
• Every design has its STRENGTHS and WEAKNESSES.

Question 6

Describe the selection-based approach for study designs

Answer 6

• Study design selection based on:
• Perspective of research question (Hypothesis)
• Ability/Desire of researcher to force group allocation (randomization)
• Ethics of methodology
• Efficiency & Practicality (time/resource commitment)
• Costs
• Validity of acquired information (Internal Validity)
• Applicability of acquired information to non-study patients (External Validity; Generalizability)
• See Slide 8

Question 7

What is what he calls the “Research Question”?

Answer 7

Research Question: (‘I wonder if….’ statement)

- Helps frame study intent and can direct researcher to more effective study design to answer question

Question 8

Describe Null Hypothesis

Answer 8

• Null Hypothesis (H0): Researchers either ACCEPT or REJECT this perspective, based on results (data analysis)
• A research perspective which states there will be no (true) difference between the groups being compared
• Most conservative and commonly utilized
• Various statistical-perspectives can be taken by the researcher:
• Superiority
• Noninferiority
• Equivalency

3 potential comparisons to placebo/other drug:

1. Better
2. Equal
3. Worse.

(Not actually represented by the bullet list)

For Noninferiority: When using placebos are unethical, researchers often go with “Not Worse”.
So those bullets represent goals. If it’s Not Superior, then it’s either equal or worse. So…Noninferiority seems to be the most uncertain one. Compared against something that’s proven to work.
Null hypothesis is always “No Effect”.
This is done this way to prevent falling into the habit of looking for something that’s not there.
Classic FDA strategy too. Hence the use of placebos.

Question 9

Describe Alternative Hypothesis

Answer 9

Alternative Hypothesis (H1) 
- A research perspective which states there will be a (true) difference between the groups being compared

Question 10

What are the two types of errors in inaccurately accepting or rejecting null hypothesis.

Answer 10

Type I Error (Alpha Error) = False positive; Such as a male patient being told he’s pregnant.

Type II Error (Beta Error) = False Negative; Such as a female pregnant women being told she’s not pregnant.

See Slide 12

Question 11

What are some of the Main differences between Interventional and Observational Study Designs?

Answer 11

• Interventional study designs considered “experimental”
• Investigator-selects interventions (exposure)
• **There IS researcher-forced group allocation
• Randomization processes commonly utilized to accomplish this step
• Observational study designs considered “natural”
• Researchers “observe” subject-elements occurring naturally or selected by individual (naturally or freely)
• Useful for unethical study designs using forced interventions
• Most observational study designs not able to prove Causation
• ** There is NO researcher-forced group allocation

Question 12

In human studies, what are the two subcategories of study subjects used?

Answer 12

• Whole Populations
• All individuals making up a common group; from which a sample (smaller set) can be obtained, if desired
• Not to be confused with the “study population”, which is simply the final group of individuals selected for a study
• Samples:
• A subset or portion of the full, complete population (“representatives”)
• Useful when studying the complete population is not feasible
• Random processes commonly utilized to draw sample

Question 13

In human studies, what is the population selection based on?

Answer 13

• Research Hypothesis/Question
• Population of Interest
• Group of individuals most useful and applicable to answer the research question
• INCLUSION & EXCLUSION selection criteria (Interventional studies) & Case & Control group OR Exposed & Non-Exposed group selection criteria (Observational studies)
• Desired vs. Logical vs. Plausible selection criteria
• These ABSOLUTELY impact generalizability!
• • External Validity

Question 14

In human studies, what Ethical requirements are needed for a study population selection?

Answer 14

• Principles of Bioethics MUST be met…
• Some don’t agree with use of placebo if a treatment is available
• Recall Null Hypothesis perspectives…:
• Superiority
• Noninferiority
• Equivalency

Question 15

Define EQUIPOISE

(Very NTK)

Answer 15

** Genuine confidence that an intervention may be worthwhile (risk vs. benefit) in order to use it in humans

Note: Definition is definite test question. Preferably reworded.
States that the study you’re doing holds the potential for more benefits and a higher risk/reward ratio.
Controversy states that using placebos violates equipoise principles.

Question 16

What are the 4 key principles of bioethics

Answer 16

• Autonomy
• Self-rule/Self-determination. Participants must…
• Decide for ones-self, without outside influences
• No coercion, reprisal, financial manipulation
• Have full & complete understanding of the risks and benefits
• No misinformation, incomplete information, or ineffectively-conveyed information (language or education level)
• Beneficence
• To benefit, or do good for, the patient (not society)
• Justice
• Equal & Fair treatment regardless of patient characteristics
• Nonmaleficence
• Do no harm. Researchers must not…
• Withhold information
• Provide false information
• Exhibit professional incompetence

Question 17

What is The Belmont Report?

• NTK

Answer 17

• 1978; issued by National Commission for Protection of Human Subjects of Biomedical and Behavioral Research

Question 18

What are the 3 guiding principles of the Belmont Report

Answer 18

• Respect for persons:
• research should be voluntary, subjects autonomous
• Beneficence:
• research risks are justified by potential benefits
• Justice:
• risks and benefits of the research are equally distributed

Question 19

What are the 2 factors in an agreement to participate in an interventional study?

Answer 19

• Consent
• Agreement to participate, based on being fully and completely informed [given by mentally-capable individuals of legal consenting age (i.e., adults; age 18 in most states)]
• Assent
• Agreement to participate, based on being fully and completely informed, given by mentally-capable individuals NOT able to give legal consent (i.e., children and adolescents)
• Children or adults not capable of giving consent requires the consent of the parent or legal guardian and the assent of the potential study subject

Question 20

Who Determines The Ethical Conduct of Research?

Answer 20

• Ethical (& safe; protections in place) determination performed by INSTITUTIONAL REVIEW BOARD (IRB)
• Sometimes referred to internationally as the “ETHICS COMMITTEE”
• IRB’s role is to PROTECT HUMAN SUBJECTS from undue risk (research not complying with principles of bioethics)
• ** ALL human subject studies MUST be reviewed by an IRB PRIOR TO study initiation
• Observational and Interventional studies (all use humans)

Question 21

Who normally regulates the IRB?

Answer 21

• IRBs are regulated by Federal statutes (laws & regulations) developed by the Department of Health and Human Services (DHHS)
• Rules are referred to by CFR (Common Federal Rules)
• Applies to all studies funded by federal government; standards also usually apply to studies reviewed by an IRB
• The OFFICE OF HUMAN RESEARCH PROTECTIONS (OHRP) IS AGENCY THAT ADMINISTERS AND ENFORCES THE REGULATIONS.

Question 22

What are the levels of IRB review?

(Ranked From Heaviest Amount of Review to the Least

Answer 22

• FULL BOARD – used for ALL interventional trials with more than minimal risk to patients
• EXPEDITED – minimal risk and/or no patient identifiers
• EXEMPT – no patient identifiers, low/no risk, de-identified dataset analysis, environmental studies, use of existing data/specimens (de-identified)
• Main differences between 3 levels of Review:
• Number of Members & Time for Committee Review/Approval
• Level of detail to Documentation needed for Review

Question 23

Who Decides The Levels of IRB Review?

Answer 23

It’s still the IRB that gets to choose what level is necessary. So it’s their say. Not yours.

Question 24

What is the DSMB?

Answer 24

• Data Safety & Monitoring Board (DSMB)
• Semi-Independent committee not involved with the conduct of the study but charged with reviewing study data AS STUDY PROGRESSES to assess for undue Risk/Benefit between groups
• Pre-determined review periods (interim analyses)
• Can stop study early, for either overly-positive or overly-negative findings in one or more groups (compared to the others)

Question 25

Describe the 2 Principles of the Methodology of Studying?

Answer 25

* OUTCOMES: - Patient-oriented (vs. Disease-oriented) outcomes are most important & useful - Individual vs. Combined Outcomes - INTERNAL VALIDITY (METHODS OF 'INSIDE' STUDY): - Assessments (Measurements) - Scientifically-rigorous and standardized - Objective better than Subjective assessments - Accurate and reproducible and scientifically

Question 26

List the 3 Strength-of-recommendation grades

Answer 26

Grade A: Consistent, good quality, patient-oriented evidence Grade B: Inconsistent, or limited quality patient oriented evidence. Grade C: Consensus, disease oriented-evidence, usual practice, expert opinion, or case series for studies of diagnosis, treatment, prevention, or screening. - See Slides 30, 31, and 32