Evidence-based medicine (EBM) is "the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients." The aim of EBM is to integrate the experience of the clinician, the values of the patient, and the best available scientific information to guide decision-making about clinical management. The term was originally used to describe an approach to teaching the practice of medicine and improving decisions by individual physicians about individual patients.
A randomized controlled trial is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical techniques, medical devices, diagnostic procedures or other medical treatments.
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted.
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, it is not possible to blind a patient to their treatment in a physical therapy intervention. A good clinical protocol ensures that blinding is as effective as possible within ethical and practical constraints.
Personalized medicine, also referred to as precision medicine, is a medical model that separates people into different groups—with medical decisions, practices, interventions and/or products being tailored to the individual patient based on their predicted response or risk of disease. The terms personalized medicine, precision medicine, stratified medicine and P4 medicine are used interchangeably to describe this concept though some authors and organisations use these expressions separately to indicate particular nuances.
Clinical study design is the formulation of trials and experiments, as well as observational studies in medical, clinical and other types of research involving human beings. The goal of a clinical study is to assess the safety, efficacy, and / or the mechanism of action of an investigational medicinal product (IMP) or procedure, or new drug or device that is in development, but potentially not yet approved by a health authority. It can also be to investigate a drug, device or procedure that has already been approved but is still in need of further investigation, typically with respect to long-term effects or cost-effectiveness.
In causal inference, a confounder is a variable that influences both the dependent variable and independent variable, causing a spurious association. Confounding is a causal concept, and as such, cannot be described in terms of correlations or associations. The existence of confounders is an important quantitative explanation why correlation does not imply causation. Some notations are explicitly designed to identify the existence, possible existence, or non-existence of confounders in causal relationships between elements of a system.
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 and the endpoints measured 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). 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 an intention-to-treat (ITT) analysis of the results of a randomized controlled trial is based on the initial treatment assignment and not on the treatment eventually received. ITT analysis is intended to avoid various misleading artifacts that can arise in intervention research such as non-random attrition of participants from the study or crossover. ITT is also simpler than other forms of study design and analysis, because it does not require observation of compliance status for units assigned to different treatments or incorporation of compliance into the analysis. Although ITT analysis is widely employed in published clinical trials, it can be incorrectly described and there are some issues with its application. Furthermore, there is no consensus on how to carry out an ITT analysis in the presence of missing outcome data.
Zelen's design is an experimental design for randomized clinical trials proposed by Harvard School of Public Health statistician Marvin Zelen (1927-2014). In this design, patients are randomized to either the treatment or control group before giving informed consent. Because the group to which a given patient is assigned is known, consent can be sought conditionally.
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.
Nicholas James Gonzalez was a New York–based physician known for developing the Gonzalez regimen, an alternative cancer treatment. Gonzalez's treatments are based on the belief that pancreatic enzymes are the body's main defense against cancer and can be used as a cancer treatment. His methods have been generally rejected by the medical community. and he has been characterized as a quack and fraud by other doctors and health fraud watchdog groups. In 1994 Gonzalez was reprimanded and placed on two years' probation by the New York state medical board for "departing from accepted practice".
In medical research, a dynamic treatment regime (DTR), adaptive intervention, or adaptive treatment strategy is a set of rules for choosing effective treatments for individual patients. Historically, medical research and the practice of medicine tended to rely on an acute care model for the treatment of all medical problems, including chronic illness. Treatment choices made for a particular patient under a dynamic regime are based on that individual's characteristics and history, with the goal of optimizing his or her long-term clinical outcome. A dynamic treatment regime is analogous to a policy in the field of reinforcement learning, and analogous to a controller in control theory. While most work on dynamic treatment regimes has been done in the context of medicine, the same ideas apply to time-varying policies in other fields, such as education, marketing, and economics.
The experience sampling method (ESM), also referred to as a daily diary method, or ecological momentary assessment (EMA), is an intensive longitudinal research methodology that involves asking participants to report on their thoughts, feelings, behaviors, and/or environment on multiple occasions over time. Participants report on their thoughts, feelings, behaviors, and/or environment in the moment or shortly thereafter. Participants can be given a journal with many identical pages. Each page can have a psychometric scale, open-ended questions, or anything else used to assess their condition in that place and time. ESM studies can also operate fully automatized on portable electronic devices or via the internet. The experience sampling method was developed by Suzanne Prescott during doctoral work at University of Chicago's Committee on Human Development with assistance from her dissertation advisor Mihaly Csikszentmihalyi. Early studies that used ESM were coauthored by fellow students Reed W. Larson and Ronald Graef, whose dissertations both used the method.
The Jadad scale, sometimes known as Jadad scoring or the Oxford quality scoring system, is a procedure to assess the methodological quality of a clinical trial by objective criteria. It is named after Canadian-Colombian physician Alex Jadad who in 1996 described a system for allocating such trials a score of between zero and five (rigorous). It is the most widely used such assessment in the world, and as of 2022, its seminal paper has been cited in over 23,000 scientific works.
Placebo-controlled studies are a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed to have no real effect. Placebos are most commonly used in blinded trials, where subjects do not know whether they are receiving real or placebo treatment. Often, there is also a further "natural history" group that does not receive any treatment at all.
Patient participation is a trend that arose in answer to medical paternalism. Informed consent is a process where patients make decisions informed by the advice of medical professionals.
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for drug safety in a few human subjects, then expand to many study participants to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays.
In an adaptive design of a clinical trial, the parameters and conduct of the trial for a candidate drug or vaccine may be changed based on an interim analysis. Adaptive design typically involves advanced statistics to interpret a clinical trial endpoint. This is in contrast to traditional single-arm clinical trials or randomized clinical trials (RCTs) that are static in their protocol and do not modify any parameters until the trial is completed. The adaptation process takes place at certain points in the trial, prescribed in the trial protocol. Importantly, this trial protocol is set before the trial begins with the adaptation schedule and processes specified. Adaptions may include modifications to: dosage, sample size, drug undergoing trial, patient selection criteria and/or "cocktail" mix. The PANDA provides not only a summary of different adaptive designs, but also comprehensive information on adaptive design planning, conduct, analysis and reporting.
Psychoplastogens are a group of small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single administration. Several existing psychoplastogens have been identified and their therapeutic effects demonstrated; several are presently at various stages of development as medications including Ketamine, MDMA, Scopolamine, and the serotonergic psychedelics, including LSD, psilocin, DMT, and 5-MeO-DMT. Compounds of this sort are being explored as therapeutics for a variety of brain disorders including depression, addiction, and PTSD. The ability to rapidly promote neuronal changes via mechanisms of neuroplasticity was recently discovered as the common therapeutic activity and mechanism of action.
