The following

outline Outline or outlining may refer to: * Outline (list), a document summary, in hierarchical list format * Code folding, a method of hiding or collapsing code or text to see content in outline form * Outline drawing, a sketch depicting the outer edge ...

is provided as an overview of and topical guide to clinical research: Clinical research is the aspect of

biomedical research Medical research (or biomedical research), also known as experimental medicine, encompasses a wide array of research, extending from "basic research" (also called ''bench science'' or ''bench research''), – involving fundamental scientif ...

that addresses the assessment of new pharmaceutical and

biological Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary in ...

drugs, medical devices and vaccines in humans.

General topics

Clinical significance In medicine and psychology, clinical significance is the practical importance of a treatment effect—whether it has a real genuine, palpable, noticeable effect on daily life. Types of significance Statistical significance Statistical significance ...

– a conclusion that an intervention has an effect that is of practical meaning to patients *

Drug discovery In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by ...

– the identification of candidates, synthesis, characterization, screening, and assays for therapeutic efficacy * Drug development – the process of taking a new chemical through the stages necessary to allow testing in clinical trials * Biotechnology – the technological application that uses biological systems, living organisms to make or modify products or processes for specific use ** Biopharmaceutical – a drug produced using biotechnology * Clinical trial – an experiment with human subjects to assess safety and efficacy of drugs **

Academic clinical trials An academic clinical trial is a clinical trial not funded by pharmaceutical or biotechnology company for commercial ends but by public-good agencies (usually universities or medical trusts) to advance medicine. These trials are a valuable compon ...

– clinical trials run at academic centers (e.g., medical schools, academic hospitals, and universities) **

Clinical trials unit Clinical trials units (CTU) are specialised biomedical research units which design, centrally coordinate and analyse clinical trials and other studies. Some CTUs specialise in different methodologies, such as randomised controlled trials, cluste ...

– biomedical research units dedicated to conducting clinical trials * Epidemiology – the study of factors affecting the health and illness of populations **

Epidemiological methods The science of epidemiology has matured significantly from the times of Hippocrates, Semmelweis and John Snow. The techniques for gathering and analyzing epidemiological data vary depending on the type of disease being monitored but each study wi ...

– statistical techniques used in epidemiology *

Evidence-based medicine 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 t ...

– the assessment of the quality of evidence relevant to the risks and benefits of medical treatments *

Pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

– the study of the interactions that occur between a living organism and drugs that alter normal biochemical function **

Biopharmacology A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesis, semisynthesized from biology, biological sources. Different from total synthesis, ...

– the pharmacology of biopharmaceuticals ** Clinical pharmacology – the scientific discipline focused on rational drug development and utilization in therapeutics **

Pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

– the study of the fate of drugs administered to the body *** Bioequivalence – the biological equivalence of two preparations of a drug ** Pharmacodynamics – the study of the biochemical and physiological effects of drugs on the body **

Pharmacometrics Pharmacometrics is a field of study of the methodology and application of models for disease and pharmacological measurement. It uses mathematical models of biology, pharmacology, disease, and physiology to describe and quantify interactions between ...

– the science of interpreting and describing pharmacology in a quantitative fashion * Pharmacovigilance – the detection, assessment, understanding and prevention of adverse effects of medicines

Drug terminology

* Active ingredient – the substance in a drug that is pharmaceutically active *

Approved drug An approved drug is a medicinal preparation that has been validated for a therapeutic use by a ruling authority of a government. This process is usually specific by country, unless specified otherwise. Process by country United States In the ...

– a drug that has been approved for marketing by a regulatory body such as the U.S. Food and Drug Administration or the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

* Excipient – an inactive substance used as a carrier for the active ingredients of a drug * Medicinal product – any substance or combination of substances used for treating or preventing disease in humans * Off-label use – the practice of prescribing a drug for an indication for which the drug has not been approved *

Orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

– a drug used to treat a rare medical condition, or orphan disease * Placebo – a sham treatment given to a control group in a clinical study *

Prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...

– a licensed medicine that can only be obtained by prescription from a doctor *

Standard treatment The standard treatment, also known as the standard of care, is the medical treatment that is normally provided to people with a given condition. In many scientific studies, the control group receives the standard treatment rather than a placebo wh ...

– a currently available drug used in an active control clinical study

Types of study design

Clinical study design Clinical study design is the formulation of trials and experiments, as well as observational studies in medical, clinical and other types of research (e.g., epidemiological) involving human beings. The goal of a clinical study is to assess the saf ...

* Blind experiment *

Case report In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrence ...

* Case series * Case study * Case-control study *

Clinical control group In the design of experiments, hypotheses are applied to experimental units in a treatment group. In comparative experiments, members of a control group receive a standard treatment, a placebo, or no treatment at all. There may be more than one tr ...

* Cohort study * Cross-sectional study * Crossover study *

First-in-man study 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 ...

* Longitudinal study * Minimisation *

Multicenter trial A multicenter research trial is a clinical trial conducted at more than one medical center or clinic. Most large clinical trials, particularly Clinical trial#Phase III, Phase III trials, are conducted at several clinical research centers. Benefit ...

Nested case-control study ''Nested'' is the seventh studio album by Bronx-born singer, songwriter and pianist Laura Nyro, released in 1978 on Columbia Records. Following on from her extensive tour to promote 1976's ''Smile'', which resulted in the 1977 live album ''Season ...

* Observational study *

Open-label trial An open-label trial, or open trial, is a type of clinical trial in which information is not withheld from trial participants. In particular, both the researchers and participants know which treatment is being administered. This contrasts with a do ...

* Placebo-controlled studies * Prospective cohort study * Randomized controlled trial * Retrospective cohort study *

Run-in period Run-in period is a period between the recruitment and randomization phases of a clinical trial, when all participants receive the same treatment, which may be active treatment, a placebo or no treatment at all. The clinical data from this stage of ...

Seeding trial A seeding trial or marketing trial is a form of marketing, conducted in the name of research, designed to target product sampling towards selected consumers. In the marketing research field, seeding is the process of allocating marketing to specific ...

* Vaccine trial

Study participant confidentiality and safety

Human subject research * Adverse drug reaction * Adverse event * Council for International Organizations of Medical Sciences * Data confidentiality in clinical trials * Data monitoring committees *

Ethics Committee (European Union) The ethics committee, according to Directive 2001/20/EC, is an independent body in a member state of the European Union, consisting of healthcare professionals and non-medical members, whose responsibility is to protect the rights, safety and well b ...

* EudraVigilance *

Exclusion criteria In a clinical trial, the investigators must specify inclusion and exclusion criteria for participation in the study. Inclusion and exclusion criteria define the characteristics that prospective subjects must have if they are to be included in a st ...

* Great ape research ban * Inclusion criteria * Institutional review board * MedWatch *

Safety monitoring Clinical monitoring is the oversight and administrative efforts that monitor a participant's health and efficacy of the treatment during a clinical trial. Both independent and government-run grant-funding agencies, such as the National Institutes o ...

* Serious adverse event * Suspected Adverse Reaction Surveillance Scheme

Clinical study management

* Clinical monitoring * Clinical Trial Management System * Good clinical practice

Clinical research documents

Clinical trial protocol In natural and social science research, a protocol is most commonly a predefined procedural method in the design and implementation of an experiment. Protocols are written whenever it is desirable to standardize a laboratory method to ensure succe ...

Informed consent Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...

* Investigator's brochure * Source document * Standing operating procedure

Clinical research personnel

Clinical investigator A clinical investigator involved in a clinical trial is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safe ...

Clinical research associate A clinical research associate (CRA), also called a clinical monitor or trial monitor, is a health-care professional who performs many activities related to medical research, particularly clinical trials. Clinical research associates work in vario ...

* Clinical research coordinator

Contract research organizations

Contract research organization In the life sciences, a contract research organization (CRO) is a company that provides support to the pharmaceutical, biotechnology, and medical device industries in the form of research services outsourced on a contract basis. A CRO may provid ...

* PPD * Covance * Parexel *

Quintiles IQVIA, formerly Quintiles and IMS Health, Inc., is an American multinational company serving the combined industries of health information technology and clinical research. IQVIA is a provider of biopharmaceutical development and commercial outs ...

Westat Westat is an employee-owned professional services corporation located in Rockville, Maryland, USA. It provides research services to agencies of the U.S. Government, as well as businesses, foundations, and state and local governments. The corpo ...

Data collection and management

Clinical data acquisition * Case report form *

Clinical data management system A clinical data management system or CDMS is a tool used in clinical research to manage the data of a clinical trial. The clinical trial data gathered at the investigator site in the case report form are stored in the CDMS. To reduce the possibili ...

Clinical data repository A Clinical Data Repository (CDR) or Clinical Data Warehouse (CDW) is a real time database that consolidates data from a variety of clinical sources to present a unified view of a single patient. It is optimized to allow clinicians to retrieve data f ...

* Data clarification form * Electronic data capture *

Good clinical data management practice Good clinical data management practice (GCDMP) is the current industry standards for clinical data management that consist of best business practice and acceptable regulatory standards. In all phases of clinical trials, clinical and laboratory inf ...

Patient diary A patient diary is a tool used during a clinical trial or a disease treatment to assess the patient's condition (e.g. symptom severity, quality of life) or to measure treatment compliance. An electronic patient diary registers the data in a storage ...

Patient-reported outcome A patient-reported outcome (PRO) is a health outcome directly reported by the patient who experienced it. It stands in contrast to an outcome reported by someone else, such as a physician-reported outcome, a nurse-reported outcome, and so on. PRO m ...

Remote data entry {{Unreferenced, date=December 2009 A remote data entry (RDE) system is a computerized system designed for the collection of data in electronic format. The term is most commonly applied to a class of software used in the life sciences industry for c ...

Medical term coding dictionaries

Medical classification * Uppsala Monitoring Centre * COSTART * MedDRA *

Systematized Nomenclature of Medicine The Systematized Nomenclature of Medicine (SNOMED) is a systematic, computer-processable collection of medical terms, in human and veterinary medicine, to provide codes, terms, synonyms and definitions which cover anatomy, diseases, findings, pro ...

(SNOMED) * WHOART * Common Terminology Criteria for Adverse Events

Clinical Data Interchange Standards Consortium

Clinical Data Interchange Standards Consortium * Study Data Tabulation Model ( SDTM) * Standard for Exchange of Non-clinical Data (SEND) * JANUS clinical trial data repository

Data analysis

Analysis of clinical trials Clinical trials are medical research studies conducted on human subjects. The human subjects are assigned to one or more interventions, and the investigators evaluate the effects of those interventions. The progress and results of clinical trials ...

Censoring (clinical trials) In statistics, censoring is a condition in which the value of a measurement or observation is only partially known. For example, suppose a study is conducted to measure the impact of a drug on mortality rate. In such a study, it may be known ...

* Effect size *

End point of clinical trials Clinical endpoints or clinical outcomes are Outcome measure, outcome measures referring to occurrence of disease, symptom, Medical sign, sign or laboratory abnormality constituting a target outcome in clinical trial, clinical research trials. The t ...

* Hazard ratio * Meta-analysis * Number needed to harm * Number needed to treat * Odds ratio *

Intention to treat analysis 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 artifac ...

Post-hoc analysis In a scientific study, post hoc analysis (from Latin '' post hoc'', "after this") consists of statistical analyses that were specified after the data were seen. They are usually used to uncover specific differences between three or more group mea ...

Relative risk The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Together with risk difference and odds ratio, relative risk measures the association bet ...

* Risk–benefit analysis * Sensitivity and specificity *

Subgroup analysis Subgroup analysis refers to repeating the analysis of a study within subgroups of subjects defined by a subgrouping variable (e.g. smoking status defining two subgroups: smokers and non-smokers). Aim The aim of subgroup analysis is usually to ass ...

* Substantial equivalence *

Surrogate endpoint In clinical trials, a surrogate endpoint (or surrogate marker) is a measure of effect of a specific treatment that may correlate with a ''real'' clinical endpoint but does not necessarily have a guaranteed relationship. The National Institutes of He ...

Systematic review A systematic review is a Literature review, 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 publ ...

* Therapeutic effect

Results reporting

* Medical writing *

Clinical trials publication Clinical trials publication is having research published in a peer reviewed journal following clinical trials. Most investigators will want to have such a publication but the nature of clinical trials may create special considerations and obstacle ...

* Common Technical Document * Consolidated Standards of Reporting Trials (CONSORT) *

Electronic Common Technical Document The electronic common technical document (eCTD) is an interface and international specification for the pharmaceutical industry to agency transfer of regulatory information. The specification is based on the Common Technical Document (CTD) format a ...

* Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) *

Strengthening the reporting of observational studies in epidemiology The STROBE ''(STrengthening the Reporting of OBservational studies in Epidemiology)'' Statement is a reporting guideline including a checklist of 22 items that are considered essential for good reporting of observational studies. It was published si ...

(STROBE) * Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URM)

Notable clinical studies

* British Doctors Study – in 1956 provided convincing statistical proof that tobacco smoking increased the risk of lung cancer. * Framingham Heart Study – a cardiovascular study based in Framingham, Massachusetts, which began in 1948 with 5,209, and is now on its third generation of participants. *

Heart Protection Study The Heart Protection Study was a randomized controlled trial run by the Clinical Trial Service Unit, and funded by the Medical Research Council (UK), Medical Research Council (MRC) and the British Heart Foundation (BHF) in the United Kingdom. It st ...

– the largest study to investigate the use of statins in the prevention of cardiovascular disease. * International Studies of Infarct Survival – four randomized controlled trials of several drugs for treating suspected acute myocardial infarction. * Intersalt study – a landmark observational study that showed a strong association between dietary salt and risk of cardiovascular disease. *

JUPITER trial The JUPITER trial (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial) was a clinical trial aimed at evaluating whether statins reduce heart attacks and strokes in people with normal chole ...

– the first clinical trial to demonstrate that statin therapy may provide benefit to patients with low-to-normal LDL levels and no known cardiovascular disease. * Multicenter AIDS Cohort Study – a study of over 6,000 men infected with HIV that has been ongoing for over 25 years * Stateville Penitentiary Malaria Study – a controlled study of the effects of malaria on the inmates of Stateville Penitentiary near Joliet, Illinois. * Tuskegee Study of Untreated Syphilis in the Negro Male – a clinical study, conducted between 1932 and 1972 in Tuskegee, Alabama studied the natural progression of the disease if left untreated.

Legislation, regulations and guidances

European Union

* Directive 2001/20/EC * Directive 2001/83/EC *

Directive 2005/28/EC {{Use dmy dates, date=July 2018 The Good Clinical Practice Directive (Directive 2005/28/EC of 8 April 2005 of the European Parliament and of the Council) lays down principles and detailed guidelines for good clinical practice as regards conducting ...

* Directive 65/65/EEC *

Directive 93/41/EEC Council of the European Communities Directive 93/41/EEC of 14 June 1993 repealed Directive 87/22/EEC on the approximation of national measures relating to the marketing of high-technology medicinal products, as this directive had been superseded by ...

* Directive 95/46/EC on the protection of personal data

United States

Federal Food, Drug, and Cosmetic Act The United States Federal Food, Drug, and Cosmetic Act (abbreviated as FFDCA, FDCA, or FD&C) is a set of laws passed by the United States Congress in 1938 giving authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of f ...

(FD&C) – gives authority to the Food and Drug Administration (FDA) to oversee the safety of food, drugs, and cosmetics. ** Kefauver Harris Amendment – requires drug manufacturers to provide proof of the effectiveness and safety of drugs before approval. *

Prescription Drug User Fee Act The ''Prescription Drug User Fee Act'' (PDUFA) was a law passed by the United States Congress in 1992 which allowed the Food and Drug Administration (FDA) to collect fees from Pharmaceutical company, drug manufacturers to fund the new medication, ...

– allows the Food and Drug Administration (FDA) to collect fees from drug manufacturers to fund the new drug approval process. * Title 21 of the Code of Federal Regulations – the section of Federal regulations that interprets and enforces FD&C. * Title 21 CFR Part 11 – defines the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and equivalent to paper records. *

Health Insurance Portability and Accountability Act The Health Insurance Portability and Accountability Act of 1996 (HIPAA or the Kennedy– Kassebaum Act) is a United States Act of Congress enacted by the 104th United States Congress and signed into law by President Bill Clinton on August 21, 1 ...

(HIPAA) – Title II of HIPAA addresses the security and privacy of health data, including data collected from subjects in clinical research.

Other

* Declaration of Helsinki (United Nations) * Food and Drugs Act (Canada) *

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an initiative that brings together regulatory authorities and pharmaceutical industry to discuss scientific and technical aspects of pha ...

(European Union, Japan, and United States)

Government agencies

* Australian Drug Evaluation Committee *

** Committee for Medicinal Products for Human Use *

Federal Agency for Medicines and Health Products The Federal Agency for Medicines and Health Products (FAMHP) of Belgium is responsible for the approval and registration of new medication in Belgium and for pharmacovigilance. Xavier De Cuyper is General Administrator of the agency. The Dutch nam ...

(Belgium) *

Medicines and Healthcare products Regulatory Agency The Medicines and Healthcare products Regulatory Agency (MHRA) is an executive agency of the Department of Health and Social Care in the United Kingdom which is responsible for ensuring that medicines and medical devices work and are acceptably ...

(United Kingdom) *

Ministry of Health, Labour and Welfare (Japan) The is a cabinet level ministry of the Japanese government. It is commonly known as in Japan. The ministry provides services on health, labour and welfare. It was formed with the merger of the former Ministry of Health and Welfare or and the ...

* Norwegian Medicines Agency *

State Food and Drug Administration The National Medical Products Administration (NMPA, , formerly the China Food and Drug Administration, or CFDA) was founded on the basis of the former State Food and Drug Administration (SFDA). In March 2013, the former regulatory body was rebra ...

(China) *

Swedish Medical Products Agency The Medical Products Agency (MPA; sv, Läkemedelsverket) is the government agency in Sweden responsible for regulation and surveillance of the development, manufacturing and sale of medicinal drugs, medical devices and cosmetics. Its task is als ...

* Therapeutic Products Directorate (Canada) * Therapeutic Goods Administration (Australia)

United States Food and Drug Administration

Food and Drug Administration

Departments

* Commissioner of Food and Drugs – as head of the Food and Drug Administration, the commissioner reports to the Secretary of the Department of Health and Human Services * Center for Biologics Evaluation and Research – responsible for review and approval of biologic products, including vaccines, blood products, gene therapy and human cloning *

Center for Devices and Radiological Health The Center for Devices and Radiological Health (CDRH) is the branch of the United States Food and Drug Administration (FDA) responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance and safe ...

– responsible for review and approval of medical devices and safety of non-medical equipment that emit certain types of radiation * Center for Drug Evaluation and Research – responsible for review and approval of all drugs * Office of Regulatory Affairs – enforces FDA laws and regulations

Review and approval programs

* Investigational Device Exemption – allows an investigational device to be used in a clinical study in order to collect safety and effectiveness data * Investigational New Drug – allows an investigational drug to be used in a clinical study in order to collect safety and effectiveness data * New Drug Application – a submission to the FDA by a pharmaceutical company for review and approval of a new drug **

Abbreviated New Drug Application An Abbreviated New Drug Application (ANDA) is an application for a U.S. generic drug approval for an existing licensed medication or approved drug. The ANDA is submitted to Food and Drug Administration, FDA's Center for Drug Evaluation and Resea ...

– a submission to the FDA review and approval of a

generic drug A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

** FDA Fast Track Development Program – a designation given to an NDA by the FDA that accelerates review and approval of new drugs