Good Clinical Practice GCP - Uppsala University

UCRUppsala kliniskaforskningscentrum

Good Clinical PracticeGCP

Susanne HellerClinical Trial Manager

UCR, Uppsala Clinical Research center


What is Good Clinical Practice?

International ethical and scientific standardto produce research with Quality and Safety

Guidelines and rules how to conduct researchinvolving humans


The main aims are:

to protect the subjects/patients rights,integrity and well-being

produce reliable, reproducable results


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


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


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


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


The Nürnberg code 5,

No trials should beperformed if there is arisk of death ordisabiling…

…only might be possibleif the subject is theresearcher himself…..


After 1947,

good clinical trials with goodresearch and respect tosubjects well-being, integrityand safety??

Answer is NO!


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”


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


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


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


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


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)


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.


Adaption of GCP for clinicaltrials in Europe…

EU-directive 2001/20/EC


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)


ICH-GCP

EU-directive 2001/20/EC

LVFS 2003:6(LVFS 2005:3, LVFS 2006:1)

LVFS: Läkemedelverkets författningssamling

Declaration ofHelsinki


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


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?


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•……


but…

Rules, regulations and guidelines can not guarantee Quality and Safety

They are working tools constituted ofcriteria and standard accepted over the world


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


Documents

Good Clinical Practice GCP - Uppsala University