Foundations of Clinical Research: Key Concepts and Frameworks

What is clinical research?

A structured, systematic process of investigating facts and theories to improve individual and public health.

What are the three types of research described by the NIH?

Patient-oriented research, epidemiologic/behavioral research, and outcomes/health services research.

What is the philosophy behind quantitative research?

Logical positivism — reality is measurable and controlled.

What is the philosophy behind qualitative research?

Social constructivism — reality is experienced and contextual.

What type of data is used in quantitative research?

Numerical, standardized instruments.

What is the goal of qualitative research?

Describe/explore lived experience and generate theory.

What are the five steps of the research process?

1. Identify the research question; 2. Design the study; 3. Implement the study; 4. Analyze the data; 5. Disseminate findings.

What is efficacy in research?

The benefit of an intervention under tightly controlled, ideal conditions.

What is effectiveness in research?

The benefit of an intervention under real-world conditions.

What does ICF stand for?

International Classification of Functioning, Disability and Health.

What is the translation gap?

The delay or failure between generating research evidence and its actual application in clinical practice.

What is an independent variable (IV)?

The variable manipulated or the presumed cause in an experiment.

What is a dependent variable (DV)?

The outcome measured, the presumed effect in an experiment.

What is a good research question characterized by?

Specific, feasible, novel/relevant, and ethical.

What is a research hypothesis?

A testable prediction about the relationship between IV and DV.

What is the definition of theory in research?

A set of interrelated concepts/propositions that explain or predict phenomena.

What is the EBP process?

1. Ask; 2. Acquire; 3. Appraise; 4. Apply; 5. Assess.

What does PICO stand for?

Population, Intervention, Comparison, Outcome.

What is Level I evidence?

Systematic reviews/meta-analyses of RCTs; generalizable, high-quality qualitative synthesis.

What is Level II evidence?

Individual RCTs (2A = well-designed RCT; 2B = lesser-quality RCT or other experimental).

What is Level III evidence?

Non-randomized/quasi-experimental or well-designed cohort & case-control studies; descriptive studies.

What is Level IV evidence?

Case series, poor cohort/case-control studies.

What is Level V evidence?

Expert opinion, case reports, editorials, non-systematic reviews.

What are bibliographic databases?

Organized collections of citations/abstracts used to locate literature.

What is MeSH?

Medical Subject Headings — a controlled vocabulary used to index and search MEDLINE/PubMed articles.

What are Boolean operators used for?

To refine or expand searches in literature.

What is the purpose of truncation in literature searches?

To capture word variants.

What are examples of bibliographic databases?

MEDLINE/PubMed, CINAHL, PsycINFO, Cochrane Library, Embase.

What is the goal of implementation studies?

To examine how to get proven interventions actually adopted into routine practice.

What are the core ethical principles established in the Belmont Report?

Respect for persons, beneficence, and justice.

What does the principle of respect for persons entail?

Individuals are autonomous agents; those with diminished autonomy get extra protection.

What is beneficence in the context of clinical research?

Maximize benefits and minimize harm, ensuring a favorable risk-benefit ratio.

What does the principle of justice refer to in research?

Fair distribution of the burdens and benefits of research.

What type of research must be approved by the IRB before it is conducted?

Human subjects research (research involving living individuals).

What is informed consent?

The outcome of an ongoing information-sharing process between investigator and subject.

What training must investigators complete before conducting research at most academic institutions?

CITI training (Collaborative Institutional Training Initiative).

What are the three levels of IRB review based on risk?

Exempt, expedited, and full board review.

What does the exempt level of IRB review apply to?

Minimal risk research meeting specific federal categories.

What type of studies require full board IRB review?

Studies with greater than minimal risk or involving vulnerable populations.

What is the primary purpose of the Institutional Review Board (IRB)?

To protect the rights and welfare of human subjects.

What is reliability in measurement?

The consistency/reproducibility of a measurement.

What does test-retest reliability assess?

Consistency of scores across repeated administrations over time by the same rater.

What is the definition of validity in measurement?

The degree to which an instrument measures what it purports to measure.

What is face validity?

The measure superficially appears to measure the construct (weakest form).

What is content validity?

The measure comprehensively samples the domain/construct of interest.

What is criterion validity?

The measure correlates with a gold-standard measure taken at the same time.

What is the difference between concurrent and predictive criterion validity?

Concurrent correlates with a measure taken at the same time; predictive correlates with a future outcome.

Can a measure be reliable but not valid?

Yes, reliability does not guarantee you're measuring the right construct.

Can a measure be valid but not reliable?

No, reliability is a prerequisite for validity.

What are summative scales?

Scales that sum multiple item scores to produce a total score.

What is a Visual Analog Scale (VAS)?

A continuous line subjects mark to indicate magnitude (e.g., pain intensity).

What are closed-ended questions?

Questions with fixed response options, easier to analyze.

What are open-ended questions?

Questions allowing free-text responses, richer but harder to quantify.

What is random assignment in clinical trials?

Allocating subjects to groups by chance to balance known/unknown confounders.

What is the purpose of a control group in clinical trials?

To receive no treatment, placebo, standard care, or a different treatment for comparison.

What is blinding in clinical trials?

Concealing group assignment from subjects or assessors to reduce bias.

What are the types of nonprobability sampling?

Convenience, purposive, quota, snowball sampling.

What are the types of probability sampling?

Simple random, stratified random, systematic, cluster sampling.

What is the significance of the Belmont Report?

It established guiding ethical principles for human subjects research.

What populations require extra IRB protections?

Children, pregnant women, prisoners, cognitively impaired individuals, and economically disadvantaged persons.

What is the role of CITI Training?

It provides standard online human-subjects-protection/research-ethics training.

What are pragmatic trials?

Trials that test effectiveness under real-world conditions.

What is a superiority trial?

A trial that tests whether a new treatment is better than a comparator.

What is a non-inferiority trial?

A trial that tests whether a new treatment is not unacceptably worse than a comparator.

What is the purpose of Phase I clinical trials?

To assess safety, dosage, and pharmacokinetics in a small sample.

What is the purpose of Phase II clinical trials?

To evaluate preliminary efficacy and side effects in a larger sample.

What is the purpose of Phase III clinical trials?

To conduct large-scale randomized controlled trials to compare efficacy against standard treatment and monitor adverse reactions.

What is the purpose of Phase IV clinical trials?

To perform post-marketing surveillance in the general population.

What is the difference between a superiority trial and a non-inferiority trial?

Superiority trials test if a new treatment is better; non-inferiority trials test if it's not unacceptably worse.

What is a pretest-posttest control group design?

A gold-standard RCT structure that measures baseline and outcome in both randomized groups.

What is a posttest-only control group design?

A design that avoids pretest sensitization but cannot confirm baseline equivalence.

What are factorial designs?

Designs that examine two or more independent variables simultaneously, including their interaction effects.

What are repeated measures designs?

Designs where the same subjects are measured multiple times, increasing power but risking carryover effects.

What is internal validity?

The degree to which the intervention, not confounders, caused the change in the dependent variable.

What is external validity?

The extent to which findings generalize to other people, settings, and times.

What are common threats to internal validity?

History, maturation, testing effects, instrumentation, regression to the mean, selection bias, attrition.

What is a time series design?

A design that involves repeated measurements before and after an intervention on the same group over time.

What is a cohort study?

A study where groups are defined by exposure status and followed forward to observe outcomes.

What is a case-control study?

A study where groups are defined by outcome status and look backward for prior exposure.

What is developmental research?

Research that studies change over time or age.

What are normative studies?

Studies that establish reference values or norms for a population.

What is qualitative research focused on?

The 'why' and lived experience, not just the 'what'.

What is a Type I error?

Rejecting a true null hypothesis, concluding there's a difference when there isn't.

What is a Type II error?

Failing to reject a false null hypothesis, missing a real difference.

What increases statistical power?

Larger sample size, larger effect size, reduced variability, and a higher alpha level.

What is a confidence interval (CI)?

A range of values likely to contain the true population parameter.

What is the null hypothesis (H₀)?

The hypothesis that states there is no difference or relationship between groups.

What is the alternative hypothesis (H₁)?

The hypothesis that states there is a difference or relationship between groups.

What is the purpose of parametric tests?

To analyze data that meets certain assumptions regarding the dependent variable.

What does an independent (unpaired) t-test compare?

Means between two different/independent groups of subjects.

What does a paired (dependent) t-test compare?

Means from the same subjects measured twice (or matched pairs).

What test compares means across three or more independent groups?

One-way ANOVA.

What does a repeated measures ANOVA compare?

Means across three or more measurements on the same subjects.

What does a two-way / factorial ANOVA examine?

Effects of two or more independent variables and their interaction.

What does Pearson's product-moment correlation (r) measure?

Strength and direction of a linear relationship between two continuous variables.

What is homogeneity of variance?

Assumption that variances are approximately equal across the groups being compared.

What tests assess homogeneity of variance?

Levene's test and Bartlett's test.

What happens if homogeneity of variance is not met?

The parametric assumption is violated; switch to a nonparametric test or a corrected parametric test.

What test measures the linear relationship between two continuous variables?

Pearson's correlation coefficient (r).

What test compares means between two independent groups of subjects?

The unpaired (independent-samples) t-test.