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

See also

• Glossary of clinical research
• List of biotechnology articles