臨床試驗與個人化醫療研究Clinical Trials and Personalized Medicine Research

90 Pages·2015·4.21 MB·English

臨床試驗與個人化醫療研究
Clinical Trials and
Personalized Medicine Research
陳 珍 信
中央研究院統計科學研究所
台灣大學公共衛生學院流行病學與預防醫學研究所

2015.9.9
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Historical Development of Clinical Trials
• The 1st controlled trial in history (James Lind, 1747)
– Treatment of scurvy (壞血病): Lemons and oranges were
the most effective treatment out of six alternatives.
• The 1st randomized controlled trial (RCT) in history
(pharmacists of Nuremberg, Germany, 1835)
– Experiment to tell whether a homeopathic “remedy”
(ordinary salt in a homeopathic C30-dilution of distilled
snow water) could be distinguished from a placebo
(distilled snow water)
• The first modern RCT in medicine (Austin Bradford Hill,
1948)
– The newly discovered antibiotic streptomycin (鏈黴素)
was effective against pulmonary tuberculosis (肺結核病 ).
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The Pioneer of Randomized
Clinical Trials
Control Trials presented fundamental
concepts in the early 1950’s:
★ Concurrent controls
★ Random allocation
★ Definition of eligible patients
★ Definition of treatment schedule
★ Objective evaluation
★ Statistical analysis
Streptomycin in Treatment of Pulmonary
Tuberculosis (MRC, 1948, British Med. J.)
★ The first properly randomized
controlled trial
? Why to randomize??
Sir Austin Bradford Hill
Doll, R. & Hill, A. B. (1950). Smoking and
(1897-1991)
Carcinoma of the Lung, British Med. J.
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Contributions to the Ascendance of RCTs
• One of the discoverers, Selman A. Waksman, of
streptomycin won the Nobel Prize in 1952.
• Tuberculosis, one of the greatest scourges of the
19th and early 20th centuries, suddenly became
a manageable disease.
• RCTs came into great demand, as the success of
“wonder drugs” (特效藥) like penicillin and vancomycin
made the development of new pharmaceuticals into a
highly lucrative business.
• The Food, Drug, and Cosmetic Act, passed in 1938,
required drug manufacturers to provide evidence of
safety to the Food and Drug Administration (FDA).
• The RCT was one of the greatest inventions in medical
history.
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Clinical Trials: Interdisciplinary Research
Contemporary Clinical Trials (2005 - )
(formerly, Controlled Clinical Trials, 1995-2004)
Contemporary Clinical Trials is an international peer reviewed journal that
publishes manuscripts pertaining to all aspects of clinical trials, including,
but not limited to, design, conduct, analysis, regulation and ethics.
Manuscripts submitted should appeal to a readership drawn from disciplines
including medicine, biostatistics, epidemiology, computer science,
management science, behavioural science, pharmaceutical science, and
bioethics.
Clinical Trials (2004 - ) Applied Clinical Trials (1992 - )
Journal of the Society for Peer-Reviewed Guide To Global
Clinical Trials Clinical Trials Management
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CONSORT (Consolidated Standards of Reporting Trials)
http://www.consort-statement.org/
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Clinical Study
• A clinical study involves research using human
volunteers (also called participants) that is
intended to add to medical knowledge.
• There are two main types of clinical studies:
– clinical trials (also called interventional studies),
and
– observational studies.
(Source: ClinicalTrials.gov )
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5 Phases of the Clinical Trial Defined by FDA
• Phase 0: Exploratory study involving very limited human exposure to the drug,
with no therapeutic or diagnostic goals (for example, screening studies, microdose
studies)
• Phase 1: Studies that are usually conducted with healthy volunteers and that
emphasize safety. The goal is to find out what the drug's most frequent and
serious adverse events are and, often, how the drug is metabolized and excreted.
• Phase 2: Studies that gather preliminary data on effectiveness (whether the drug
works in people who have a certain disease or condition). For example, participants
receiving the drug may be compared with similar participants receiving a different
treatment, usually an inactive substance (called a placebo) or a different drug.
Safety continues to be evaluated, and short-term adverse events are studied.
• Phase 3: Studies that gather more information about safety and effectiveness by
studying different populations and different dosages and by using the drug in
combination with other drugs.
• Phase 4: Studies occurring after FDA has approved a drug for marketing. These
including postmarket requirement and commitment studies that are required of
or agreed to by the sponsor. These studies gather additional information about a
drug's safety, efficacy, or optimal use.
(Source: ClinicalTrials.gov) 10