Lecture 2 Monday afternoon From Disaster to Regulation
The first time a trial was written down was in the old testament. The case group was killed
because the investigator wanted to be right.
James Lind, came to the discovery that sailors/pirates got scurvies. The did a trial with citrus
fruit and came to the conclusion that when they ate citrus fruit they would heal better and
faster.
In the 1800s the first placebo trial was conducted.
1863 – The first comparative placebo controlled trial
1891 – First rule for regulation on clinical trials
1906 – The pure food & drug act – first real legislation in the US
1923 – First Randomized experiments
1937 – Sulphanilamide using diethylene glycol, which is poisonous. The US governments
could not get it of the market because there was no law. Eventually they got it off-
market because of mislabelling. This lead to the Food, Drug & Cosmetic act which
states that products have to be researched
1940 – 1945 Research was done without informed consent. Particularly on twins
1946 – 1947 Nuremberg – The Doctors Trial – American military tribunal -> outcome;
informed consent is necessary. The code of Nuremberg; remained an ethical
code rather than a law
1948 Frist proper double-blind controlled randomized trial was conducted
1964 – Thalidomide; Dr. Francis Kelsey; She stated ‘I do not have enough data’ to allow
market authorization in America. While in Europe the product was widely used. She
kept the US from drama.
1964 – Declaration of Helsinki; ethical standards set up by physicians for physicians. They
made the code of Nuremberg obsolete. They advise for others who work in clinical
trials to live up to these rules
2000s – Declaration of Helsinki came into trouble, use of language was not okey, for
regulatory authority. Ethically they wanted to give the best available treatment which
ruled out placebos. A feasibility study had to be done to prove that this was not
possible
2001 – Declaration of 1996 is currently still lived up to. The EU wrote a new law in 2014, the
declaration of Helsinki 2008 will be followed up to if this law is accepted
1
, 1932 – 1974 Syphilis study, the natural progression of syphilis. They did not tell patient
they had syphilis, there was no cure at the time. In the 50s there became a
cure available, while still not telling the subjects which disease they had they
did not give them this new treatment either. This was a scandal and lead to
the Belmont report
1979 – Belmont report for the protection of Human Services of biomedical and Behavioural
research.
1981 – First GCP guideline was incorporated in the US law
1986 – The UK followed
1987 – France followed
1989 – Japan followed
1990 – ICH, International Counsil for Harmonization was poineerd by the European
Committee. They write regulatory requirements. These were written by the US, EMA
and Japan. Not by physicians but by regulatory people
1996 – First ICH – GCP guideline was put into practice on 17 – 1 – 96. This guideline is still
valid. 2017 the first update since 1996. Revision 1 was never put in practice because
it was revised before this. Therefor we always worked with revision 2.
1999 – WMO, wet medisch-wetenschappelijk onderzoek met mensen in the NL
2001 – EU clinical trial directive, legal framework around ICH-GCP you need to be ethical,
level of legislation is incorporated in the laws of EU countries, new one is written in
2014
2005 – The good clinical practice EU directive adding to the 2001 with detailed guidelines for
GCP also big parts of GMP (Good Medical Practice)
2012 – Update WMO for example age 18 -> 16 for consent
2014 – New legislation, clnical trial regulation. Hugely delayed still not into practice.
www.clinicaltrials.gov Trials are registered when data used for research in America.
In this update that should also become the case for the EU. New database, all data
from clnical trials and the reports have to be built current expectation is that it is
going online in june 2019
2015 – ICH became a legal entity, based in Switzerland and added Switzerland and Canada to
the official regions.
2015 – Revision 2, currently updating the ICH-GCP. Also known as the addendum because it
just adds things to the existing GCP
2
The first time a trial was written down was in the old testament. The case group was killed
because the investigator wanted to be right.
James Lind, came to the discovery that sailors/pirates got scurvies. The did a trial with citrus
fruit and came to the conclusion that when they ate citrus fruit they would heal better and
faster.
In the 1800s the first placebo trial was conducted.
1863 – The first comparative placebo controlled trial
1891 – First rule for regulation on clinical trials
1906 – The pure food & drug act – first real legislation in the US
1923 – First Randomized experiments
1937 – Sulphanilamide using diethylene glycol, which is poisonous. The US governments
could not get it of the market because there was no law. Eventually they got it off-
market because of mislabelling. This lead to the Food, Drug & Cosmetic act which
states that products have to be researched
1940 – 1945 Research was done without informed consent. Particularly on twins
1946 – 1947 Nuremberg – The Doctors Trial – American military tribunal -> outcome;
informed consent is necessary. The code of Nuremberg; remained an ethical
code rather than a law
1948 Frist proper double-blind controlled randomized trial was conducted
1964 – Thalidomide; Dr. Francis Kelsey; She stated ‘I do not have enough data’ to allow
market authorization in America. While in Europe the product was widely used. She
kept the US from drama.
1964 – Declaration of Helsinki; ethical standards set up by physicians for physicians. They
made the code of Nuremberg obsolete. They advise for others who work in clinical
trials to live up to these rules
2000s – Declaration of Helsinki came into trouble, use of language was not okey, for
regulatory authority. Ethically they wanted to give the best available treatment which
ruled out placebos. A feasibility study had to be done to prove that this was not
possible
2001 – Declaration of 1996 is currently still lived up to. The EU wrote a new law in 2014, the
declaration of Helsinki 2008 will be followed up to if this law is accepted
1
, 1932 – 1974 Syphilis study, the natural progression of syphilis. They did not tell patient
they had syphilis, there was no cure at the time. In the 50s there became a
cure available, while still not telling the subjects which disease they had they
did not give them this new treatment either. This was a scandal and lead to
the Belmont report
1979 – Belmont report for the protection of Human Services of biomedical and Behavioural
research.
1981 – First GCP guideline was incorporated in the US law
1986 – The UK followed
1987 – France followed
1989 – Japan followed
1990 – ICH, International Counsil for Harmonization was poineerd by the European
Committee. They write regulatory requirements. These were written by the US, EMA
and Japan. Not by physicians but by regulatory people
1996 – First ICH – GCP guideline was put into practice on 17 – 1 – 96. This guideline is still
valid. 2017 the first update since 1996. Revision 1 was never put in practice because
it was revised before this. Therefor we always worked with revision 2.
1999 – WMO, wet medisch-wetenschappelijk onderzoek met mensen in the NL
2001 – EU clinical trial directive, legal framework around ICH-GCP you need to be ethical,
level of legislation is incorporated in the laws of EU countries, new one is written in
2014
2005 – The good clinical practice EU directive adding to the 2001 with detailed guidelines for
GCP also big parts of GMP (Good Medical Practice)
2012 – Update WMO for example age 18 -> 16 for consent
2014 – New legislation, clnical trial regulation. Hugely delayed still not into practice.
www.clinicaltrials.gov Trials are registered when data used for research in America.
In this update that should also become the case for the EU. New database, all data
from clnical trials and the reports have to be built current expectation is that it is
going online in june 2019
2015 – ICH became a legal entity, based in Switzerland and added Switzerland and Canada to
the official regions.
2015 – Revision 2, currently updating the ICH-GCP. Also known as the addendum because it
just adds things to the existing GCP
2
