Major clinical studies & trial types
To browse other articles on a range of HSL topics, see the A-Z index.
Clinical trials are biomedical studies that follow pre-defined protocols. Whether interventional or observation-based, clinical trials are regarded as an important way to make advances in healthcare. (Interventional studies are those where research subjects are assigned to treatments and outcomes are measured. Observational studies are those where individuals are observed and their outcomes measured by investigators.) Databases such as MEDLINE, CINAHL and Embase (even Google scholar) are used to search for information that is evidence-based. Locating evidence in the journal literature is facilitated by publication types in MEDLINE and filters (ie. hedges) that limit searches to articles reporting research conducted using specific methodologies. For example, PubMed has filters set up in clinical queries, and clinical queries is now seen in both EMBASE and CINAHL.
Case Control Studies
Case control studies examine patients who have a specific condition compared with people who do not. Case studies are less reliable than randomized trials and cohort studies because showing a statistical relationship does not mean that one factor caused the other. Case studies include retrospective studies, used to test hypotheses where inferences about an exposure to causal factors are derived from data related to people under study or to events or experiences in their past. Their essential feature is that some people have the disease or outcome of interest and their characteristics are compared with those who do not. (See MeSH Case Control Studies)
Case Series and Case Reports
Case series and case reports are collections of reports of treatments of individual patients or reports on single patients. Because case reports use no control groups to compare outcomes, they do not have statistical validity. (See MeSH Case series and case reports)
A clinical trial is any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. Clinical trials may also be referred to as interventional trials. Interventions include but are not limited to drugs, cells and other biological agents, surgical procedures, radiologic procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc. This definition includes Phase I to Phase IV trials.
A cohort study follows patients with specific conditions or receiving particular treatments over time. This data is compared with a second group unaffected by conditions/treatments under review. Cohort studies are not as reliable as RCTs because the two groups differ in ways other than the variables under study. By comparing incidence of disease in different groups, researchers can make quantitative evaluations about the strength of association between risk factors and diseases. (Note: used for studies related to prognosis, harm/etiology or prevention). Cohort studies include longitudinal perspectives where variables of individuals or groups are assessed over time. (See MeSH Cohort studies)
Crossover design refers to 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.(See MeSH Crossover Design)
Double-blinding is a method of studying drugs or interventions where both subjects and investigators (i.e. physicians, health care workers) do not know who is getting the placebo and who is on the treatment arm of the study. (See MeSH Double-blind method)
See also Systematic narrative review methods
Meta-analysis is a quantitative method of combining results of independent studies (usually from the published literature) and synthesized summaries and conclusions for the purpose of evaluating therapeutic effectiveness, planning new studies, etc. As an overview of clinical trials, a meta-analysis looks for consensus within published data, culled during the systematic review searching phase of the study. The MeSH definition of meta-analysis: 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., with application chiefly in the areas of research and medicine. (See MeSH Meta-Analysis)
Multicentre studies are clinical trials conducted at multiple medical centres or clinics. Most large clinical trials, particularly Phase III trials, are conducted at several clinical research centres. The benefits of multicentre trials include a large number of participants, different geographic locations, the possibility of inclusion of a wider range of population groups, and the ability to compare results across centres - all of which increase the generalizability of the study to the broader population. (See MeSH Multicentre studies)
Narrative reviews critically appraise and summarize literature but do not state explicit criteria for selecting articles. A narrative review draws together major arguments in the discourse and provides an historical review of important concepts. Narrative reviews are about topics that do not lend themselves to systematic reviews ie. examination of mechanisms underlying phenomena; most medical journals now have rules about excluding narrative reviews for intervention, diagnosis and prognosis topics. (Use MeSH [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=mesh&Cmd=DetailsSearch& Term=%22review%22%5BMeSH+Terms%5D+OR+review%5BText+Word%5D Reviews]).
Predictive Value of Tests
The predictive value of tests is related to sensitivity and specificity of screening and diagnostic tests. For example, the probability that a patient with a positive test is a true positive (i.e., has the disease) is referred to as the predictive value of a positive test. Conversely, the probability that a patient with a negative test does not have the disease in question is referred to as the predictive value of a negative test. (See MeSH Predictive Value of Tests)
Prospective cohort study
A prospective cohort study is a cohort study that follows a group of similar individuals (cohorts) over time who may differ with respect to certain factors under study. The goal is to determine how these factors affect rates of certain outcomes. The prospective study is important for research into the etiology of diseases and disorders because patients cannot be deliberately exposed to health risks in controlled experiments. Prospective cohort studies are typically ranked higher in the hierarchy of evidence than retrospective cohort studies. (See Prospective studies)
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. (See MeSH Random allocation).
Randomized Controlled Clinical Trial/Controlled Clinical Trial
Randomized controlled clinical trials are carefully planned projects undertaken to evaluate the clinical effects of interventions on real patients. They include methodologies that reduce the potential for bias (randomization and blinding) and those that allow for comparison between intervention groups and control groups. When randomization using mathematical techniques, such as the use of a random numbers table, is employed to assign patients to test or control groups, the trial is characterized as a randomized controlled trial. Trials using non-validated allocation methods are designated as controlled clinical trials. (Note: used for studies related to therapy or diagnosis.) According to the CIHR, "...a randomized controlled trial (RCT) is an experiment in which investigators randomly assign eligible human research participants or other units of study (e.g., classrooms, clinics, playgrounds) into groups to receive or not receive one or more interventions that are being compared. The results are analyzed by comparing outcomes in the groups."
(See MeSH Randomized Controlled Trial)
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. (See MeSH Reproducibility of Results)
Reviews/ Systematic Reviews
See also Systematic reviews
Reviews are articles published after the cumulation of published material on a specific subject and the material is synthesized in some way. Reviews can focus on clinical materials as well as experimental research or case reports. State-of-the-art reviews tend to address more current topics. The notion of systematic reviews centres on one clinical topic and answers a specific question, and involves an extensive review of medical evidence. SRs include a methodology for identifying studies. (Use MeSH Reviews).
A sample is the number of units (persons, animals, patients, specified circumstances, etc.) in a population to be studied. The sample size should be big enough to have a high likelihood of detecting a true difference between two groups. (See MeSH Sample size)
Sensitivity and Specificity
Sensitivity and specificity - like precision and recall in information retrieval - refers to measurements for assessing the reliability of diagnostic and screening tests. Sensitivity represents the true positive ratio, that is, the proportion of patients with the disease that are identified by the test. It is a measure of the probability of correctly diagnosing a condition. Specificity is the proportion of subjects without the disease that are so identified by the screening test, that is, test negative. It is a measure of the probability of correctly identifying a nondiseased person. (See MeSH Sensitivity and Specificity)
Single-blinding is a method where either observers or clinical trial participants are not aware of who is getting the placebo and who is actually receiving the intervention. (See MeSH Single blind method)
Systematic reviews (SRs) are described as 'papers that summarize other papers'. Systematic review(s) may also be defined as "overviews of primary studies that have used explicit and reproducible methods". Typically, SRs synthesize findings from key, high-powered trials and reports of therapies and interventions using explicit inclusion and exclusion criteria, and may or may not include a meta-analysis. (Search for Systematic Reviews in PubMed).
See also Systematic narrative review methods