Clinical Research: An Overview

Dr. Bruce L. Pihlstrom, DDS, MS

Define clinical research and provide an overview of the objectives and outcomes of various types of clinical research.

Course Details:

1. Define clinical research

  • Patient-oriented research
  • Epidemiologic and behavioral studies
  • Health services and outcomes research

2. Describe and outline methods, differences, and outcomes of observational research

  • Case reports and case series – may generate research ideas
  • Prevalence surveys and cross-sectional studies
  • Case control studies
  • Longitudinal cohort studies

3. Describe and outline methods, differences, and clinically meaningful outcomes of interventional research

  • Clinical trials types:
  • Efficacy trials
  • Effectiveness (pragmatic) trials
  • Superiority, non-inferiority & equivalence trials
  • Phase I. II, III, IV trials
  • Clinically meaningful outcomes

4. Describe and contrast internal vs. external validity of clinical research

  • Scientific rigor (internal validity) of well-controlled clinical trial
  • Generalizability (external validity) to everyday clinical practice

Glossary – Definitions of Key Terms

  • Association
  • Benefit
    • A benefit is a positive or valued outcome of an action or event. A potential benefit is a positive but uncertain outcome, for example, the desired result of an experimental intervention. Typically associated with cost-benefit or risk-benefit.
    • http://www.ncbi.nlm.nih.gov/books/NBK25555/
  • Bias
    • Deviation of results or inferences from the truth, or processes leading to such systematic deviation. Any trend in the collection, analysis, interpretation, publication, or review of data that can lead to conclusions that are systematically different from the truth. Bias is the average (expected) difference between the measurement or estimator and the truth. Sometimes referred to as systematic error.
    • http://www.cdc.gov/reproductivehealth/data_stats/glossary.html
  • Blinding (Or Masking)
    • A clinical trial design strategy in which one or more parties involved in the trial, such as the investigator or participants, do not know which participants have been assigned which interventions. Types of Masking include Open Label, Single Blind Masking, and Double Blind Masking. This is a process of keeping the study group assignment hidden after distribution in order to reduce the risk of bias. NOTE: the word “masking” is now more often used than “blinding” because of issues surrounding patients in trials that relate to eyesight.
    • https://clinicaltrials.gov/ct2/about-studies/glossary#B
  • Clinical Research
    • Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, or (d) development of new technologies.
    • Epidemiologic and behavioral studies.
    • Outcomes research and health.
    • https://www.nia.nih.gov/research/dgcg/clinical-research-study-investigators-toolbox/nia-glossary-clinical-research-terms
  • Clinical Trial
    • The NIH defines a clinical trial as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, nutritional supplements, surgical intervention, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective. Behavioral clinical trials involving an intervention to modify behavior (diet, physical activity, cognitive therapy, etc.) fit this definition of a clinical trial.
    • https://www.nia.nih.gov/research/dgcg/clinical-research-study-investigators-toolbox/nia-glossary-clinical-research-terms
  • Cross-Sectional Study
    • A cross-sectional study collects data on relevant variables one time only from a variety of people, subjects, or phenomena. The data are collected all at the same time (or within a short time frame). A cross-sectional design provides a snapshot of the variables included in the study, at one particular point in time. It may reveal how those variables are represented in a cross-section of a population. Cross-sectional designs generally use survey techniques to gather data, for example, the U.S. Census.
    • http://web.csulb.edu/~msaintg/ppa696/696preex.htm#Cross-Sectional%20Design
  • Cohort
    • A well-defined group of people who have had a common experience or exposure, who are then followed up for the incidence of new diseases or events, as in a cohort or prospective study. A group of people born during a particular period or year is called a birth cohort.
    • http://www.cdc.gov/reproductivehealth/data_stats/glossary.html#B
  • Confounding Variable
    • Confounding variables or confounders are often defined as the variables correlate (positively or negatively) with both the dependent variable and the independent variable. A Confounder is an extraneous variable whose presence affects the variables being studied so that the results do not reflect the actual relationship between the variables under study.
    • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017459/
  • Endpoint
    • An event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.
    • http://www.cancer.gov/publications/dictionaries/cancer-terms?expand=E
  • Epidemiology
    • Epidemiology is the study (scientific, systematic, data-driven) of the distribution (frequency, pattern) and determinants (causes, risk factors) of health-related states and events (not just diseases) in specified populations (patient is community, individuals viewed collectively), and the application of (since epidemiology is a discipline within public health) this study to the control of health problems.
    • http://www.cdc.gov/ophss/csels/dsepd/ss1978/lesson1/section1.html
  • Equipoise
    • A state in which an investigator is uncertain about which arm of a clinical trial would be therapeutically superior for a patient. NOTE: An investigator who has a treatment preference or finds out that one arm of a comparative trial offers a clinically therapeutic advantage should disclose this information to subjects participating in the trial.
  • External Validity
    • The extent to which a study’s results (regardless of whether the study is descriptive or experimental) can be generalized/applied to other people or settings reflects its external validity. Typically, group research employing randomization will initially possess higher external validity than will studies (e.g., case studies and single-subject experimental research) that do not use random selection/assignment.
    • http://www.edpsycinteractive.org/topics/intro/valdgn.html
  • Generalizability
    • The extent to which the findings of a clinical research study can be reliably extrapolated from the subjects who participated in the trial to a broader patient population and a broader range of clinical settings.
  • Incidence
  • Institutional Review Board (IRB)
    • An independent body constituted of medical, scientific, and non-scientific members, whose responsibility it is to ensure the protection of the rights, safety, and well-being of human subjects involved in a trial or study by, among other things, reviewing, approving, and providing continuing review of trial/study protocol and of the methods and materials to be used in obtaining and documenting informed consent of the trial/study subjects. Synonyms: independent review board, independent ethics committee, committee for the protection of human subjects.
  • Internal Validity
    • One of the keys to understanding internal validity (IV) is the recognition that when it is associated with experimental research it refers both to how well the study was run (research design, operational definitions used, how variables were measured, what was/wasn’t measured, etc.), and how confidently one can conclude that the change in the dependent variable was produced solely by the independent variable and not extraneous ones.
    • http://www.edpsycinteractive.org/topics/intro/valdgn.html
  • Longitudinal Study
    • A longitudinal study is an observational research method in which data is gathered for the same subjects repeatedly over a period of time. Longitudinal research projects can extend over years or even decades. In a longitudinal cohort study, the same individuals are observed over the study period.
    • http://whatis.techtarget.com/definition/longitudinal-study
  • Odds Ratio (Or)
    • An odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions).
    • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938757/
  • Placebo
  • Prevalence
  • Prospective Study
    • A prospective study watches for outcomes, such as the development of a disease, during the study period and relates this to other factors such as suspected risk or protection factor(s). The study usually involves taking a cohort of subjects and watching them over a long period. All efforts should be made to avoid sources of bias such as the loss of individuals to follow up during the study. Prospective studies usually have fewer potential sources of bias and confounding than retrospective studies.
    • http://www.statsdirect.com/help/content/basics/prospective.htm
  • Randomization
  • Retrospective Study
    • A retrospective study looks backwards and examines exposures to suspected risk or protection factors in relation to an outcome that is established at the start of the study. Most sources of error due to confounding and bias are more common in retrospective studies than in prospective studies. In retrospective studies the odds ratio provides an estimate of relative risk. One should take special care to avoid sources of bias and confounding in retrospective studies.
    • http://www.statsdirect.com/help/content/basics/prospective.htm
  • Risk
  • Risk Factor
  • Sample
  • Surrogate Endpoint
    • In clinical trials, an indicator or sign used in place of another to tell if a treatment works. Surrogate endpoints include a shrinking tumor or lower biomarker levels. They may be used instead of stronger indicators, such as longer survival or improved quality of life, because the results of the trial can be measured sooner. The use of surrogate endpoints in clinical trials may allow earlier approval of new drugs to treat serious or life-threatening diseases, such as cancer. Surrogate endpoints are not always true indicators or signs of how well a treatment works.
    • https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=729831
  • Variable
    • An element or factor that the research is designed to study, either as an experimental intervention or a possible outcome (or factor affecting the outcome) of that intervention.
  • Validity