Literature Reviews: Types of Clinical Study Designs

Bias - Any deviation of results or inferences from the truth, or processes leading to such deviation. Bias can result from several sources: one-sided or systematic variations in measurement from the true value (systematic error); flaws in study design; deviation of inferences, interpretations, or analyses based on flawed data or data collection; etc. There is no sense of prejudice or subjectivity implied in the assessment of bias under these conditions.

Case Control Studies - Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.

Causality - The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors.

Control Groups - Groups that serve as a standard for comparison in experimental studies. They are similar in relevant characteristics to the experimental group but do not receive the experimental intervention.

Controlled Clinical Trials - Clinical trials involving one or more test treatments, at least one control treatment, specified outcome measures for evaluating the studied intervention, and a bias-free method for assigning patients to the test treatment. The treatment may be drugs, devices, or procedures studied for diagnostic, therapeutic, or prophylactic effectiveness. Control measures include placebos, active medicines, no-treatment, dosage forms and regimens, historical comparisons, etc. When randomization using mathematical techniques, such as the use of a random numbers table, is employed to assign patients to test or control treatments, the trials are characterized as Randomized Controlled Trials.

Cost-Benefit Analysis - A method of comparing the cost of a program with its expected benefits in dollars (or other currency). The benefit-to-cost ratio is a measure of total return expected per unit of money spent. This analysis generally excludes consideration of factors that are not measured ultimately in economic terms. Cost effectiveness compares alternative ways to achieve a specific set of results.

Cross-Over Studies - Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given.

Cross-Sectional Studies - Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.

Double-Blind Method - A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.

Empirical Research - The study, based on direct observation, use of statistical records, interviews, or experimental methods, of actual practices or the actual impact of practices or policies.

Evaluation Studies - Works consisting of studies determining the effectiveness or utility of processes, personnel, and equipment.

Genome-Wide Association Study - An analysis comparing the allele frequencies of all available (or a whole genome representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.

Intention to Treat Analysis - Strategy for the analysis of Randomized Controlled Trial that compares patients in the groups to which they were originally randomly assigned.

Logistic Models - Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor.

Longitudinal Studies - Studies in which variables relating to an individual or group of individuals are assessed over a period of time.

Lost to Follow-Up - Study subjects in cohort studies whose outcomes are unknown e.g., because they could not or did not wish to attend follow-up visits.

Matched-Pair Analysis - A type of analysis in which subjects in a study group and a comparison group are made comparable with respect to extraneous factors by individually pairing study subjects with the comparison group subjects (e.g., age-matched controls).

Meta-Analysis - Works consisting of studies using a quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc. It is often an overview of clinical trials. It is usually called a meta-analysis by the author or sponsoring body and should be differentiated from reviews of literature.

Numbers Needed To Treat - Number of patients who need to be treated in order to prevent one additional bad outcome. It is the inverse of Absolute Risk Reduction.

Odds Ratio - The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases.

Patient Selection - Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols.

Predictive Value of Tests - In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.

Prospective Studies - Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.

Qualitative Studies - Research that derives data from observation, interviews, or verbal interactions and focuses on the meanings and interpretations of the participants.

Quantitative Studies - Quantitative research is research that uses numerical analysis.

Random Allocation - A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.

Randomized Controlled Trial - Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table.

Reproducibility of Results - The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.

Retrospective Studies - Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.