Clinical research pillar · 24 definitions
Clinical research & evidence-based medicine
Clear, citable definitions of the methodology of clinical research — clinical trials and their phases, randomised controlled trials, placebo and blinding, the PICO question framework, PRISMA reporting, the evidence hierarchy and the biostatistics behind it all. A research-methods reference, accurate and strictly non-clinical.
Designing trustworthy trials
The clinical trial is the engine of clinical research. Designs minimise bias through randomisation, blinding and placebo controls, and analyses such as intention-to-treat preserve those protections. Trials run in phases under ethics and quality standards including Good Clinical Practice.
Weighing the evidence
Evidence-based medicine provides the framework for using research in practice. It structures questions with PICO, ranks designs by the levels of evidence, and relies on transparent reporting standards — most prominently PRISMA for systematic reviews. CASRAI\'s wider systematic-review guidance complements these pages.
The biostatistics of clinical research
Interpreting trials means understanding their measures: the hazard ratio and Kaplan–Meier curve from survival analysis, the number needed to treat, and the ROC curve for diagnostic accuracy. The definitions below cover the designs, the EBM frameworks and these statistics together.
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Clinical research definitions
Clinical trial
What is a clinical trial?
A clinical trial is a prospective research study that evaluates a health intervention in human volunteers under a pre-specified protocol. It is the principal method for testing whether a treatment, device or procedure is effective and safe.
Read →Clinical research
What is clinical research?
Clinical research is the branch of medical science that studies health and disease directly in people. It spans interventional trials and observational studies, and is conducted by sponsors, investigators and research organisations under defined ethical and regulatory standards.
Read →Trial phases
What are the phases of a clinical trial?
Clinical trial phases are the staged sequence — Phase 0 through Phase 4 — through which a new drug is evaluated. Each phase asks a narrower question, enrols more participants, and gates progression to the next, concentrating early risk in small, closely monitored studies.
Read →RCT
What is a randomized controlled trial?
A randomized controlled trial is a study design in which participants are allocated to groups by chance to compare an intervention against a control. Random allocation balances known and unknown differences between groups, making the RCT the strongest single study design for causal inference.
Read →Placebo
What is a placebo?
A placebo is an inert or sham intervention, with no specific therapeutic action, used as a comparator in clinical trials. By giving the control group something indistinguishable from the real intervention, researchers can separate the effect of the intervention from expectation and the natural course of a condition.
Read →Placebo effect
What is the placebo effect?
The placebo effect is an improvement in symptoms that follows an inert intervention and is attributable to expectation and context rather than to active treatment. Understanding it explains why clinical trials need a placebo control to measure an intervention’s genuine effect.
Read →Double-blind
What is a double-blind study?
A double-blind study is a trial in which neither the participants nor the investigators delivering or assessing the intervention know who is in which group. Concealing the allocation in this way reduces performance and detection bias, strengthening confidence in the results.
Read →PICO
What is the PICO framework?
PICO is a framework for structuring an answerable clinical question into four parts — Population, Intervention, Comparison and Outcome. It helps researchers and clinicians frame focused questions and build precise literature searches in evidence-based practice.
Read →PRISMA
What is PRISMA?
PRISMA — Preferred Reporting Items for Systematic Reviews and Meta-Analyses — is a reporting standard that specifies what authors should disclose when publishing a systematic review. PRISMA 2020 provides a checklist and a flow diagram to make reviews transparent and reproducible.
Read →Evidence-based medicine
What is evidence-based medicine?
Evidence-based medicine is an approach that integrates the best available research evidence with clinical expertise and patient values to inform decisions. Defined by David Sackett and colleagues, it provides a framework — often summarised as the five As — for using evidence systematically.
Read →Levels of evidence
What are the levels of evidence?
Levels of evidence are a hierarchy that ranks study designs by how well they support causal conclusions, from systematic reviews and randomized controlled trials at the top to expert opinion at the base. The hierarchy guides which evidence to weight most heavily.
Read →Intention-to-treat
What is intention-to-treat analysis?
Intention-to-treat analysis is a principle for analysing a trial in which participants are kept in the group to which they were randomly assigned, regardless of whether they adhered to it. This preserves the benefit of randomisation and gives a realistic estimate of effectiveness.
Read →Number needed to treat
What is the number needed to treat?
The number needed to treat is a measure of an intervention’s effect, defined as the number of people who would need to receive it for one additional person to benefit. It is the reciprocal of the absolute risk reduction and helps express effect sizes intuitively.
Read →Hazard ratio
What is a hazard ratio?
A hazard ratio is a measure from survival analysis that compares how often an event occurs over time in one group relative to another. A hazard ratio of one means no difference; values above or below one indicate a higher or lower rate in the comparison group.
Read →Kaplan–Meier curve
What is a Kaplan–Meier curve?
A Kaplan–Meier curve is a step-shaped graph that estimates the probability of surviving — or remaining event-free — over time from time-to-event data. It accounts for censored observations and is a foundational tool of survival analysis.
Read →ROC / AUC
What is the ROC curve and AUC?
A receiver operating characteristic (ROC) curve plots a test’s sensitivity against one minus its specificity across thresholds, and the area under the curve (AUC) summarises how well the test discriminates between two states. AUC ranges from 0.5 (chance) to 1 (perfect).
Read →Crossover trial
What is a crossover trial?
A crossover trial is a study design in which each participant receives two or more interventions in sequence, acting as their own control. Comparing treatments within the same person removes between-person variability, making the design efficient for stable, chronic conditions.
Read →Non-inferiority trial
What is a non-inferiority trial?
A non-inferiority trial is designed to show that a new treatment is not unacceptably worse than an established comparator, by a pre-specified margin. Unlike a superiority trial, it does not aim to prove the new treatment is better — only that it is not meaningfully worse.
Read →Per-protocol analysis
What is per-protocol analysis?
Per-protocol analysis evaluates only the participants who completed a trial in accordance with the protocol, excluding those who deviated. It estimates the effect under ideal adherence, but by breaking the randomised comparison it risks bias, so it is usually reported alongside intention-to-treat.
Read →Forest plot
What is a forest plot?
A forest plot is a graph that displays the effect estimate and confidence interval from each study in a meta-analysis, alongside the pooled result. Each study is a square with a horizontal line; the combined estimate is the diamond at the foot of the plot.
Read →GRADE
What is the GRADE approach?
GRADE — Grading of Recommendations, Assessment, Development and Evaluations — is a system for rating the certainty of a body of evidence and the strength of recommendations in evidence-based medicine. It separates how sure we are of the evidence from how strongly something is recommended.
Read →Surrogate endpoint
What is a surrogate endpoint?
A surrogate endpoint is a substitute outcome — often a biomarker such as blood pressure or a laboratory value — measured in place of a clinical endpoint that matters directly to patients. Surrogates can speed up research, but they are only reliable when validated against the true outcome.
Read →Composite endpoint
What is a composite endpoint?
A composite endpoint is a single outcome that combines several individual events — counting a participant as having met it if any of the component events occurs. Composites increase the number of events and statistical power, but they must be interpreted with care when the components differ in importance.
Read →Clinical equipoise
What is clinical equipoise?
Clinical equipoise is genuine, honest uncertainty within the expert medical community about which arm of a trial is better. It is widely regarded as the ethical justification for randomisation: it is only fair to assign participants by chance when no one knows which treatment is superior.
Read →Common questions
Clinical research FAQ
What is a clinical trial?+
A clinical trial is a research study that tests an intervention in human volunteers under a predefined protocol to evaluate its effects. Trials are conducted in phases, follow ethical and quality standards such as Good Clinical Practice, and are designed to answer specific research questions.
What is evidence-based medicine?+
Evidence-based medicine is the conscientious integration of the best available research evidence with clinical expertise and patient values. As a research framework it ranks study designs by the strength of evidence they provide and uses tools such as the PICO framework to structure questions.
What is a randomised controlled trial?+
A randomised controlled trial allocates participants to intervention or control groups by chance. Randomisation minimises systematic differences between groups, which is why the RCT is regarded as the strongest design for establishing whether an intervention causes an effect.
Is this a clinical or treatment resource?+
No. These pages define the study designs, reporting standards and statistical concepts used in clinical research. They are not medical advice and do not cover diagnosis, treatment choices, dosing or interpreting individual results.
How does this relate to CASRAI standards?+
CASRAI is a research-standards body. Clinical research depends on transparent reporting standards such as CONSORT and PRISMA, ethical frameworks such as Good Clinical Practice, and rigorous design — the standards layer that makes evidence trustworthy and reproducible.
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