Clinical research is the aspect of biomedical research that addresses the assessment of new pharmaceutical and biological drugs, medical devices and vaccines in humans.

Contents 1 General topics 2 Drug terminology 3 Types of study design 4 Study participant confidentiality and safety 5 Clinical study management 5.1 Clinical research documents 5.2 Clinical research personnel 5.3 Contract research organizations 6 Data collection and management 6.1 Medical term coding dictionaries 6.2 Clinical Data Interchange Standards Consortium 7 Data analysis 8 Results reporting 9 Notable clinical studies 10 Legislation, regulations and guidances 10.1 European Union 10.2 United States 10.3 Other 11 Government agencies 11.1 U.S. Food and Drug Administration 11.1.1 Departments 11.1.2 Review and approval programs

[edit] 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)
• 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

[edit] 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
• Investigational product–a drug that is undergoing preclinical or clinical testing
• 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

[edit] Types of 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

[edit] Study participant confidentiality and safety

• 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

[edit] Clinical study management

• Clinical monitoring
• Clinical site
• Clinical Trial Management System
• Good clinical practice

[edit] Clinical research documents

• Clinical trial protocol
• Informed consent
• Investigator's brochure
• Source document
• Standing operating procedure

[edit] Clinical research personnel

• Clinical investigator
• Clinical research associate
• Clinical research coordinator

[edit] Contract research organizations

• Covance
• Parexel
• Quintiles
• Westat

[edit] Data collection and management

• Case report form
• Clinical data management system
• Data clarification form
• Electronic data capture
• Good Clinical Data Management Practice
• Patient diary
• Patient-reported outcome
• Remote Data Entry

[edit] Medical term coding dictionaries

• Uppsala Monitoring Centre
• COSTART
• MedDRA
• Systematized Nomenclature of Medicine (SNOMED)
• WHOART

[edit] Clinical Data Interchange Standards Consortium

• Study Data Tabulation Model (SDTM)
• Standard for Exchange of Non-clinical Data (SEND)
• JANUS clinical trial data repository

[edit] Data analysis

• 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
• Per-protocol analysis
• Post-hoc analysis
• Relative risk
• Risk-benefit analysis
• Sensitivity and specificity
• Subgroup analysis
• Substantial equivalence
• Surrogate endpoint
• Systematic review
• Therapeutic effect

[edit] Results reporting

• Clinical trials publication
• Common Technical Document
• Consolidated Standards of Reporting Trials (CONSORT)
• Electronic Common Technical Document
• Strengthening the reporting of observational studies in epidemiology (STROBE)

[edit] 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.

[edit] 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 Comprehensive Drug Abuse Prevention and Control Act of 1970 Controlled Substances Act Prescription Drug Marketing Act Drug Price Competition and Patent Term Restoration Act Hatch-Waxman exemption Government agencies United States Department of Health and Human Services Food and Drug Administration Drug Enforcement Administration Center for Drug Evaluation and Research Process Drug discovery Drug design Drug development New drug application Investigational new drug Clinical trial (Phase I, II, III, IV) Randomized controlled trial Pharmacovigilance Abbreviated New Drug Application Fast track approval Off-label use International coordination International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Uppsala Monitoring Centre World Health Organization Council for International Organizations of Medical Sciences Single Convention on Narcotic Drugs Non-governmental organizations. Institute of Medicine Research on Adverse Drug events And Reports

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• Regulatory requirements

[edit] 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

[edit] 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.

[edit] 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)

[edit] Government agencies

• Australian Drug Evaluation Committee
• European Medicines Agency
• 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)

[edit] U.S. Food and Drug Administration

[edit] Departments

• FDA commissioner—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

[edit] 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

v • d • e Biomedical research: Study designs / Design of experiments Overview Clinical trial · Clinical trial protocol · Clinical trial management · Academic clinical trials · Study design Controlled study (EBM I to II-1; A to B) Randomized controlled trial (Blind experiment, Open-label trial) Observational study (EBM II-2 to II-3; B to C) Cross-sectional study vs. Longitudinal study Cohort study (Retrospective cohort study, Prospective cohort study) Case-control study (Nested case-control study) Case series · Case study/Case report Epidemiology/ methods occurrence: Incidence (Cumulative incidence) · Prevalence (Point prevalence, Period prevalence) association: absolute (Absolute risk reduction, Attributable risk, Attributable risk percent) · relative (Relative risk, Odds ratio, Hazard ratio) other: Virulence · Infectivity · Mortality rate · Morbidity · Case fatality · Specificity and sensitivity · Likelihood-ratio test Trial/test types In vitro/In vivo · Animal testing · Animal testing on non-human primates · First-in-man study · Multicenter trial · Seeding trial · Vaccine trial Analysis of clinical trials Risk-benefit analysis Interpretation of results Selection bias · Correlation does not imply causation · Null result Category • Glossary • List of topics

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