Randomized controlled trial in the context of Placebo

In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws inferences from a sample to a population where the independent variable is not under the control of the researcher because of ethical concerns or logistical constraints. One common observational study is about the possible effect of a treatment on subjects, where the assignment of subjects into a treated group versus a control group is outside the control of the investigator. This is in contrast with experiments, such as randomized controlled trials, where each subject is randomly assigned to a treated group or a control group. Observational studies, for lacking an assignment mechanism, naturally present difficulties for inferential analysis.

Scholarly peer review or academic peer review (also known as refereeing) is the process of having a draft version of a researcher's methods and findings reviewed (usually anonymously) by experts (or "peers") in the same field. Peer review is widely used for helping the academic publisher (that is, the editor-in-chief, the editorial board or the program committee) decide whether the work should be accepted, considered acceptable with revisions, or rejected for official publication in an academic journal, a monograph or in the proceedings of an academic conference. If the identities of authors are not revealed to each other, the procedure is called dual-anonymous peer review.

Academic peer review requires a community of experts in a given (and often narrowly defined) academic field, who are qualified and able to perform reasonably impartial review. Impartial review, especially of work in less narrowly defined or inter-disciplinary fields, may be difficult to accomplish, and the significance (good or bad) of an idea may never be widely appreciated among its contemporaries. Peer review is generally considered necessary to academic quality and is used in most major scholarly journals. However, peer review does not prevent publication of invalid research, and as experimentally controlled studies of this process are difficult to arrange, direct evidence that peer review improves the quality of published papers is scarce. One recent analysis of randomized controlled trial abstracts found that editorial and peer review processes led to substantive improvements between submission and publication.

Randomness has multiple uses in science, art, statistics, cryptography, gaming, gambling, and other fields. For example, random assignment in randomized controlled trials helps scientists to test hypotheses, and random numbers or pseudorandom numbers help video games such as video poker.

These uses have different levels of requirements, which leads to the use of different methods. Mathematically, there are distinctions between randomization, pseudorandomization, and quasirandomization, as well as between random number generators and pseudorandom number generators. For example, applications in cryptography usually have strict requirements, whereas other uses (such as generating a "quote of the day") can use a looser standard of pseudorandomness.

In metaphysics and statistics, a causal model (also called a structural causal model) is a conceptual model that represents the causal mechanisms of a system. Causal models often employ formal causal notation, such as structural equation modeling or causal directed acyclic graphs (DAGs), to describe relationships among variables and to guide inference.

By clarifying which variables should be included, excluded, or controlled for, causal models can improve the design of empirical studies and the interpretation of results. They can also enable researchers to answer some causal questions using observational data, reducing the need for interventional studies such as randomized controlled trials.

Random assignment or random placement is an experimental technique for assigning human participants or animal subjects to different groups in an experiment (e.g., a treatment group versus a control group) using randomization, such as by a chance procedure (e.g., flipping a coin) or a random number generator. This ensures that each participant or subject has an equal chance of being placed in any group. Random assignment of participants helps to ensure that any differences between and within the groups are not systematic at the outset of the experiment. Thus, any differences between groups recorded at the end of the experiment can be more confidently attributed to the experimental procedures or treatment.

Random assignment, blinding, and controlling are key aspects of the design of experiments because they help ensure that the results are not spurious or deceptive via confounding. This is why randomized controlled trials are vital in clinical research, especially ones that can be double-blinded and placebo-controlled.

A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on the topic (in the scientific literature), then analyzes, describes, critically appraises and summarizes interpretations into a refined evidence-based conclusion. For example, a systematic review of randomized controlled trials is a way of summarizing and implementing evidence-based medicine. Systematic reviews, sometimes along with meta-analyses, are generally considered the highest level of evidence in medical research.

While a systematic review may be applied in the biomedical or health care context, it may also be used where an assessment of a precisely defined subject can advance understanding in a field of research. A systematic review may examine clinical tests, public health interventions, environmental interventions, social interventions, adverse effects, qualitative evidence syntheses, methodological reviews, policy reviews, and economic evaluations.

A quasi-experiment is a research design used to estimate the causal impact of an intervention. Quasi-experiments share similarities with experiments and randomized controlled trials, but specifically lack random assignment to treatment or control. Instead, quasi-experimental designs typically allow assignment to treatment condition to proceed how it would in the absence of an experiment.

Quasi-experiments are subject to concerns regarding internal validity, because the treatment and control groups may not be comparable at baseline. In other words, it may not be possible to convincingly demonstrate a causal link between the treatment condition and observed outcomes. This is particularly true if there are confounding variables that cannot be controlled or accounted for.

Vaccine efficacy or vaccine effectiveness is the percentage reduction of disease cases in a vaccinated group of people compared to an unvaccinated group. For example, a vaccine efficacy or effectiveness of 80% indicates an 80% decrease in the number of disease cases among a group of vaccinated people compared to a group in which nobody was vaccinated. When a study is carried out using the most favorable, ideal or perfectly controlled conditions, such as those in a clinical trial, the term vaccine efficacy is used. On the other hand, when a study is carried out to show how well a vaccine works when they are used in a bigger, typical population under less-than-perfectly controlled conditions, the term vaccine effectiveness is used.

Vaccine efficacy was designed and calculated by Greenwood and Yule in 1915 for the cholera and typhoid vaccines. It is best measured using double-blind, randomized, clinical controlled trials, such that it is studied under "best case scenarios."

A hierarchy of evidence, comprising levels of evidence (LOEs), that is, evidence levels (ELs), is a heuristic used to rank the relative strength of results obtained from experimental research, especially medical research. There is broad agreement on the relative strength of large-scale, epidemiological studies. More than 80 different hierarchies have been proposed for assessing medical evidence. The design of the study (such as a case report for an individual patient or a blinded randomized controlled trial) and the endpoints measured (such as survival or quality of life) affect the strength of the evidence. In clinical research, the best evidence for treatment efficacy is mainly from meta-analyses of randomized controlled trials (RCTs) and the least relevant evidence is expert opinion, including consensus of such. Systematic reviews of completed, high-quality randomized controlled trials – such as those published by the Cochrane Collaboration – rank the same as systematic review of completed high-quality observational studies in regard to the study of side effects. Evidence hierarchies are often applied in evidence-based practices and are integral to evidence-based medicine (EBM).

In medicine (oncology and other fields), performance status is an attempt to quantify cancer patients' general well-being and activities of daily life. This measure is used to determine whether they can receive chemotherapy, whether dose adjustment is necessary, and as a measure for the required intensity of palliative care. It is also used in oncological randomized controlled trials as a measure of quality of life.

In causal inference, a confounder is a variable that affects both the dependent variable and the independent variable, creating a spurious relationship.

Confounding is a causal concept rather than a purely statistical one, and therefore cannot be fully described by correlations or associations alone. The presence of confounders helps explain why correlation does not imply causation, and why careful study design and analytical methods (such as randomization, statistical adjustment, or causal diagrams) are required to distinguish causal effects from spurious associations.

Consolidated Standards of Reporting Trials (CONSORT) encompasses various initiatives developed by the CONSORT Group to alleviate the problems arising from inadequate reporting of randomized controlled trials. It is part of the larger EQUATOR Network initiative to enhance the transparency and accuracy of reporting in research.