Clinical Trials

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The Research Question: The best research question should specify a single measurable outcome, as well as all the conditions and important variables. The question contains the population, the maneuver or conditions affecting the study population, and the outcomes.

Randomization: Ideally, a process that ensures every member of a population has an equal chance to be included in the study's sample. This is often not possible. Cardiologist at MUSC can not select study patients from all patients with unstable angina, only those who are admitted to MUSC. More importantly, randomization means that study patients are assigned to treatment or placebo groups for the experiment, without regard to any patient characteristics or study personnel desires or biases.

Population: Every person who satisfies inclusion criteria for the study. Group of people with a defined characteristic (e.g. white females) or in a defined setting (e.g. people living in South Carolina). The denominator in the calculation of a rate.

Sample: The people who satisfied the study's inclusion criteria and who actually entered the study. A subset of the population.

Generalizability or applicability of results to your population: Given the validity of the results, the similarity of the study population to your patients or in particular, the patient in front of you.

Control group: The study patients that did NOT receive the experimental maneuver. Subjects who do not receive the drug, test, or intervention under study.

Maneuver: Any exposure or treatment that acts upon patients to produce a result (an outcome).

Outcome: The effect of a maneuver.

Randomized Controlled Trial (RCT): A true experiment, in which the researcher randomly assigns some patients to at least one maneuver (treatment) and other patients to a placebo, or usual treatment. Key features = the classic way to evaluate effectiveness of drugs (or exercise, diet, counseling). Patients are followed over time (Prospective). Properly done an RCT can be used to determine cause and effect.

Cohort Study: A longitudinal study that begins with the gathering of two groups of patients (the cohorts), one which received the exposure of interest, and one which did not, and then following this group over time (prospective) to measure the development of different outcomes (diseases). Key features -- the best way to determine risk relating to exposure to a harmful substance. Remember = the researcher may begin direct work on a cohort study after the cohort has been assembled by someone else for another purpose. Important: A cohort study starts with assembling a cohort. The researcher conducting the study may begin the study at any time, as long as all the baseline information about the patients was collected during a specific time period and exposure was determined before measuring outcomes.

Case-control study: This type of research begins by identifying patients with the outcome (disease) of interest and looks backward (retrospective) to see if they had the exposure of interest. Cases, people who have the outcome (disease) in question, are linked with controls, people from the same population without the outcome (disease). Controls are chosen to look identical to cases for baseline variables that are known to relate to the outcome. The effort is to find the maneuver(s), or the exposure(s), that occurs more frequently in the cases than the control(s). Key features = the classic study design for the initial investigation of cause-effect relationships. Given one outcome, or effect, this design can look for many causes. This is the reverse of a cohort study where, given one maneuver, a cohort study looks for many different outcomes. A case-control study cannot be used to prove cause-effect relationships and cannot be used to determine incidence of a disease.

A case-control study is generally easier to do than a cohort study. The case-control study is ideal for rare diseases, because a cohort study would require too many patients in the study group to be feasible. Similarly, the case-control study is ideal for a disease that takes many years to develop, because a cohort study would require too long to complete.

A logical sequence is: first, a case-control study to determine the most important maneuvers associated with the specific outcome. Then, a cohort study to profile the development over time of the outcome in a given population with differing amounts of exposure.

Cross-sectional study: Prevalence study. Survey of an entire population for the presence or absence of a disease and/or other variable in every member (or a representative sample) and the potential risk factors at a particular point in time or time interval. Exposure and outcome are determined simultaneously.

Community Trial: An entire community receives a treatment or preventative measure to determine if it works in the "real world".

Crossover Study Design: The administration of two or more experimental therapies one after the other to the same group of patients.

Case Series: A collection of anecdotes (patients with an outcome of interest). Some anecdotes have been quite instructive in the history of medicine but a busy practitioner should not waste her time trying to figure out the potential, future meaning of a case series. No control group is involved.

Case Report: An anecdote. To get into the medical literature, a case report typically must convey the message "man bites dog."

Double-Blind: Typically used in Randomized Controlled Trials (RCTs). An experimental method in which both the patients and the research staff do not know and cannot figure out which patients are receiving treatment and which placebo.

Internal Validity: Are the results of the study valid for the patient population studied?

External Validity: Are the results valid outside the patient population studied? Are results from studies done on males valid for females?

Intention-to-treat Analysis: In a randomized control trial patients can be randomly assigned to different treatments, for example the 5 year mortality of medical treatment for angina versus surgical - coronary artery bypass grafting (CABG). After randomization, patients who were assigned to medical therapy may decide to have surgery or patients assigned to the surgical arm may elect not to undergo surgery. In an intent-to-treat analysis patients would be analyzed for mortality according to the groups for which they were originally assigned. Why is this necessary? We know that patients who change groups are often "different" and allowing them to change groups may alter the randomization. To continue the example. After the randomization, patients in the medical treatment group with more severe angina (a group which should do worse no matter which arm they are assigned to) decided to have surgery and patients in the surgical treatment arm whose angina really was not so bad (a group who should do well) decided not to have surgery. If the study was analyzed according to the final treatment group the surgical arm would appear to do worse since all the patients with potential poor outcomes would have gravitated to the surgery group. In contrast, an intent-to-treat analysis might show that patients originally assigned to the surgical group actually did better at 5 years.

See Study Design