Outline Of Clinical Research

Short description: Overview of and topical guide to 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
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

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