# Outline of clinical research

The following outline is provided as an overview of and topical guide to clinical research:
Clinical research is the aspect of biomedical research that addresses the assessment of new pharmaceutical and biological drugs, medical devices and vaccines in humans.

## General topics

* Clinical significance – a conclusion that an intervention has an effect that is of practical meaning to patients
* Drug discovery – 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 – clinical trials run at academic centers (e.g., medical schools, academic hospitals, and universities)
** Clinical trials unit – biomedical research units dedicated to conducting clinical trials
* Epidemiology – the study of factors affecting the health and illness of populations
** Epidemiological methods – statistical techniques used in epidemiology
* Evidence-based medicine – the assessment of the quality of evidence relevant to the risks and benefits of medical treatments
* Pharmacology – the study of the interactions that occur between a living organism and drugs that alter normal biochemical function
** Biopharmacology – the pharmacology of biopharmaceuticals
** Clinical pharmacology – the scientific discipline focused on rational drug development and utilization in therapeutics
** Pharmacokinetics – 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 – 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 – 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
* 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 – 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 licensed medicine that can only be obtained by prescription from a doctor
* Standard treatment – a currently available drug used in an active control clinical study

## Types of study design

Clinical study design
* Blind experiment
* Case report
* Case series
* Case study
* Case-control study
* Clinical control group
* Cohort study
* Cross-sectional study
* Crossover study
* First-in-man study
* Longitudinal study
* Minimisation
* Multicenter trial
* Nested case-control study
* Observational study
* Open-label trial
* Placebo-controlled studies
* Prospective cohort study
* Randomized controlled trial
* Retrospective cohort study
* Run-in period
* Seeding trial
* 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)
* EudraVigilance
* Exclusion criteria
* Great ape research ban
* Inclusion criteria
* Institutional review board
* MedWatch
* Safety monitoring
* 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
* Informed consent
* Investigator's brochure
* Source document
* Standing operating procedure

### Clinical research personnel

* Clinical investigator
* Clinical research associate
* Clinical research coordinator

### Contract research organizations

Contract research organization
* PPD
* Fortrea
* Parexel
* Quintiles
* Westat

## Data collection and management

Clinical data acquisition
* Case report form
* Clinical data management system
* Clinical data repository
* Data clarification form
* Electronic data capture
* Good clinical data management practice
* Patient diary
* Patient-reported outcome
* Remote data entry

### Medical term coding dictionaries

Medical classification
* Uppsala Monitoring Centre
* COSTART
* MedDRA
* Systematized Nomenclature of Medicine (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
* Censoring (clinical trials)
* Effect size
* End point of clinical trials
* Hazard ratio
* Meta-analysis
* Number needed to harm
* Number needed to treat
* Odds ratio
* Intention to treat analysis
* Post-hoc analysis
* Relative risk
* Risk–benefit analysis
* Sensitivity and specificity
* Subgroup analysis
* Substantial equivalence
* Surrogate endpoint
* Systematic review
* Therapeutic effect

## Results reporting

* Medical writing
* Clinical trials publication
* Common Technical Document
* Consolidated Standards of Reporting Trials (CONSORT)
* Electronic Common Technical Document
* Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
* Strengthening the reporting of observational studies in epidemiology (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 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 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
* Directive 65/65/EEC
* Directive 93/41/EEC
* Directive 95/46/EC on the protection of personal data

### United States

* Federal Food, Drug, and Cosmetic Act (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 – 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 (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 (European Union, Japan, and United States)

## Government agencies

* Australian Drug Evaluation Committee
* European Medicines Agency
** Committee for Medicinal Products for Human Use
* Federal Agency for Medicines and Health Products (Belgium)
* Medicines and Healthcare products Regulatory Agency (United Kingdom)
* Ministry of Health, Labour and Welfare (Japan)
* Norwegian Medicines Agency
* State Food and Drug Administration (China)
* Swedish Medical Products Agency
* 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 – 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 – a submission to the FDA review and approval of a generic drug
** FDA Fast Track Development Program – a designation given to an NDA by the FDA that accelerates review and approval of new drugs