Good Clinical Practice GCP - Uppsala University
Transcript of Good Clinical Practice GCP - Uppsala University
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Good Clinical PracticeGCP
Susanne HellerClinical Trial Manager
UCR, Uppsala Clinical Research center
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What is Good Clinical Practice?
International ethical and scientific standardto produce research with Quality and Safety
Guidelines and rules how to conduct researchinvolving humans
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The main aims are:
to protect the subjects/patients rights,integrity and well-being
produce reliable, reproducable results
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The first controlled trial?
174712 sailors in the British Navy with scurvy (lack of vitamin C)
2 sailors got cider2 sailors got mixture of cinnamon, ginger and sulphuric acid2 sailors got vinegar2 sailors got sea water2 sailors got oranges and lemon2 sailors got mixture of garlic, mustard seed and radish
James Lind1716-1794
Outcome:”All ships in the navy should bring lemon juice”
British Navy 1795
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USA 1938
Incident:Sulfanilamide, new formulafor children by addingglycol – made it sweet
About 100 children died
Consequence: FDA demands security requirement and animal toxicological studies
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Nürnberg trials 1947
Incident:Experiments madeby Nazi doctors onhumans in theconcentration campsduring the secondworld war
Consecuence:Nürnberg code,The first official code for medical research
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The Nürnberg code establishedthat:
Inform consent is necessary
The research must have positive consequences forthe community
The risk for the research subjects must be minimized
The subject has the right to terminate participation atany time
The researcher must terminate the trial if it seemsprobable that the subject is being harmed
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The Nürnberg code 5,
No trials should beperformed if there is arisk of death ordisabiling…
…only might be possibleif the subject is theresearcher himself…..
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After 1947,
good clinical trials with goodresearch and respect tosubjects well-being, integrityand safety??
Answer is NO!
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Vipeholm trial (Sweden)1945-1955
Incident:Mental retarded people were givensweets and candy during a 10 yearperiod.
•No dental care was given•The participants did not know theywere involved in a trial
The aim was to studydevelopment of dental caries.
Outcome: “Lördagsgodis”
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1962 Talidomid (Neurosedyn)
Incident:Poor toxicological resultsGiven to employees without control ofside effects and safety
More than 5 000 deformed children
Consequence: Demands on safety and proved efficacy
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1964 Declaration of Helsinki
For biomedical research involving humans
WMA (World Medical Assembly)Last update 2008
The Declaration still serves as the fundamental document in regard to this type of research
More detailed than the Nurnberg code
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History
- 1947 Nürnberg code
- 1964 Declaration of Helsinki
- 1977 FDA implements GCP
- 1986 UK implements GCP
- 1989 The Nordic countries implements GCP
- 1996 ICH-GCP
-1 May 2004 EU demands that all clinical trials are
conducted according to GCP
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ICH-GCP
International Conference on Harmonisation –Good Clinical Practice
Cooperation between the pharmaceutical industry and theauthorities to improve the development and registration ofmedical products in Europe, USA and Japan.(Canada and Australia).
1996 ICH-GCP
For other countries: WHO-GCP
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13 principles of ICH-GCP
1. Clinical trials should be conducted inaccordance to Declaration of Helsinki, GCPand applicable regulatory requirements
2. Risk / benefit3. The subjects rights and safety should be
more important than interests of scienceand society
4. Adequate information on an investigationproduct
5. Clinical trial protocol (GCP template)
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6. Approval from IEC (independent ethics committee)
7. Medical responsibility – physician or dentist8. Qualified personnel9. Freely given inform consent10. Source data, handling, storage, filing11. Confidentiality12. Investigational product – GMP13. Quality control –quality assurance
13 principles of ICH-GCP cont.
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Adaption of GCP for clinicaltrials in Europe…
EU-directive 2001/20/EC
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Adaption to Swedenof 2001/20/EC
LVFS 1996:17 (MPA, Medical Products Agency)Trials approved before May 1, 2004
LVFS 2003:6, 2006:1Trials approved after May 1, 2004.Läkemedelsverkets författningssamling och allmänna råd omklinisk prövning av läkemedel för humant bruk.
LVFS 2005:3 (children)
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ICH-GCP
EU-directive 2001/20/EC
LVFS 2003:6(LVFS 2005:3, LVFS 2006:1)
LVFS: Läkemedelverkets författningssamling
Declaration ofHelsinki
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London, March 2006Incident:Phase I study conducted according to GCPhealthy young menImmnuological trial, antibodiesSix persons got severe side-effects
Concequence:Raised the demands on internal reviews of firstin man trials. New law regarding Phase I trialsImplemented 2007, EU
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Audit and inspections
According to ICH-GCP: “ A systematic and independent examination of trial-related activities”
•Audit – sponsor or sponsor representative•Inspection – Competent authorities, MPA, FDA
Aim:Quality assurance and prevent or reveal fraud
Poor research –subjects well-being and intregity, publications?
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Audits and Inspections – prevention of fraud
•Trials conducted against the rules and regulations•Poor understanding in how to conduct trials•Hide data•Add data •Copying data•……
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but…
Rules, regulations and guidelines can not guarantee Quality and Safety
They are working tools constituted ofcriteria and standard accepted over the world
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Useful links
MPA www.lakemedelsverket.se
Independent Etichs committee www.epn.se
The National Board of Health and Welfare www.socialstyrelsen.se
LIF (läkemedelsindustriföreningen) www.lif.se
EMEA (European Medicines Agency) www.emea.eu.int
ICH guidelines www.ich.org