1 Introduction and History of Clinical Research

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Introduction to Clinical trial


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Introduction and history of CT

Over view of drug development

Brief introduction to clinical trial

Where to get more information


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Drug development summarized

Number of years:2-3 2-3 5-8 1-2

Molecules successful

5-10,000 250 5 1

Number of subjects: Ph I Ph II Ph III Ph IV


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History of clinical trials

1906 1916 1926 1936 1946 1956 1966 1976 1986 1996 2006

1020s

Avicennas the canon of

medicine- guide to

experimental process for

medical substances1947 Nuremburg

code- humanresearch ethics

principle

1964 Declaration of Helsinki- ethical principles. The

health of my patient will be my first consideration

1966 statement

of human

experimentation

1997 ICH-GCP

Good clinical

practice

1906

USA Food and Drug Act

20 may 1747

James Lind trial

of 6 treatments

for scurvy

1937Theoretic goods Legislation;

Medical Research Endowment Fund

Act 1937

1961

Dr William

McBride

thalidomide

Therapeutic Goods Act 1989,

Therapeutic Good Reg s 1990

1999

National

Statement

2007 National

Statement;

Code of

Research


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History Cont..

Research and the clinical trial is a fundamental toolof modern medicine.

In fact, the clinical trial is the medical invention thathas contributed to nearly all of the life savingmedicines we know today.

These medicines have:

Added 10 years to our life expectancy.

Made organ transplants possible.

Made diabetes a manageable condition.

Extended the life expectancy of AIDS patients.

Prolonged the lives of millions of cancer patients.


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History Cont.

Egypt 1550 BC

Medicines or formulas have been used to helpheal the sick for centuries. Ancient Egyptiansregularly documented their prescriptions, but

there was no proof they worked.600 BC

It wasnt until 600 BC in the Book ofDaniel the

Bible describes what might be the firstcomparative trial. Daniel tested two diets to seewhich was healthier, a vegetarian diet or a dietrich with meats and wine. After a 10-day test, thevegetarian diet was judged most healthy.


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History cont

1700's

In 1754, Surgeon James Lind discovered that citrus

fruit prevented scurvy by testing different foods

aboard the HMS Salisbury. He ultimately saved thelives of thousands of British sailors.

And in 1796, Edward Jenner conducted the

famous trial that proved inoculation could prevent

smallpox. Jenners trial was the first step toward

mass vaccinations that conquered epidemics such

as typhoid, yellow fever, polio and measles.


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First use of a placebo: 1863

First regulations against false therapeutic claims:1912 US product labeling laws enacted

F

irst use of randomization: 1923


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History cont

1900's The first modern clinical trial was conducted in

1946. British epidemiologist, Sir Austin Bradford

Hill put patients into experimental and control

groups at random. This eliminated any bias - onlythe test medicine would account for differences

seen in the health of the two groups.

With the establishment of guidelines for ethical

clinical trial conduct and regulations for drugdevelopment, more than 1019 novel drug

therapies have been approved by the Food and

Drug Administration thats virtually all the

medicines used today.


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First body to manage clinical trials: 1930 Therapeutic Trials Committee (UK)

First US regulation to require drug safety: 1938 USFood, Drug, and Cosmetic Act

First multicenter studies employing the sameprotocol: 1938 enabled pooling of data to increasestatistical power

First properly randomized clinical trial with control

groups and blind assessment: 1948 The BritishMedical Research Council (MRC) evaluated the use ofstreptomycin to treat pulmonary tuberculosis


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Thalidomide episode

The drug Thalidomide was mainly prescribed to

pregnant women for morning sickness in the late 50s

and early 60s.

Instead the drug caused severe deformities in babieswith missing limbs.

Some thalidomiders were also born with internal

deformities. Its estimated that over 3,500 babies

died before their first birthday.


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Thalidomide episode

Thalidomide was invented in 1954 at the Grnenthal

Labs in Germany by the inventors Dr. W. Kunz

(chemical synthesis) and Dr. H. Keller

pharmacological description of sedative properties At the time of the drug's development it was not

thought likely that any drug could pass from the

mother across the placental barrier and harm the

developing fetus


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Types of Clinical Trials

For :

Prevention

Screening

Diagnosis

Treatment

Quality of life

Can be:

Observational

Investigational

Drug/supplement

Device

Procedure

Technique


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Who runs clinical trials and where?

Performed under a supervision of doctor or

researchers

May be located at:

Hospitals

Private specialty

Research institutes

Academic institutions

Other health providers


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Study design

Design study documentation:

Protocol/CRFPatient information sheet

Notification to appropriate authority Investigator/ site selection

Ethics committee submission/ review

Approval letter

Commencement of investigator

meeting

Follow- up visits

Monitoring

Site initiation

Investigator

Data management Statistical review

Final report

Patient enrolment

End of trial


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Why participate in trial

Help future patients, advance medical knowledge

Entrance to new treatments earlier

Improved clinical access

To help self to get treated


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To find more about trials

www.clinicaltrials.gov (US)

www.anzctr.org.gov (Australia/NZ)

www.who.int/trialsearch/(International)


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1 Introduction and History of Clinical Research

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