Contents

Outline of 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
• Covance
• 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

Regulation of therapeutic goods in the United States
Prescription drugs Over-the-counter drugs
Law Federal Food, Drug, and Cosmetic Act CDAPCA Controlled Substances Act Prescription Drug Marketing Act Hatch-Waxman Act exemptions Marihuana Tax Act of 1937
Government agencies Department of Health and Human Services Food and Drug Administration Department of Justice DEA
Process Drug discovery Drug design Drug development New Drug Application Investigational New Drug Clinical trial phases Randomized controlled trial Pharmacovigilance Abbreviated New Drug Application Fast track approval Off-label use
International coordination ICH Uppsala Monitoring Centre WHO CIOMS Single Convention on Narcotic Drugs
Non-governmental organizations National Academy of Medicine RADAR NORML
v t e

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