Lecture 2 Flashcards
When did scientific trials begin?
in the 1930s
statistics were introduced into scientific clinical trials in 1937.
–> trials not monitored for ethical principles and safety of subjects
What incident in 1930s leads to pharmaceutical companies carrying out scientific trials?
In 1937, Sulphanilamide elixir (an antibiotic) was manufactured using diethylene glycol (a toxic medium)
–> 105 deaths
What act was introduced by the government in 1938 following the sandal of ‘sulphanilamide’?
The Food, Drug and Cosmetic Act
-new drug application report
-review tests
-demonstrate drug safety
-formula disclosing all ingredients
-directions for use and warnings about
misuse
What act relating to human experimentation was introduced in 1947 following the world war II?
The Nuremberg Code
It set the standard for medical experimentation on human Subjects
–> consent essential
–> benefit of research outweigh risks
Briefly explain the Thalimode disaster that occured in 1950s.
-launched as a sleeping tablet ‘Contergan’ by Chemie Grnenthal in 1957
-sold in over 40 countries under license
-US had not given licensing approval
-caused birth defects in 10,000 to 20,000 babies
-withdrawn from most markets in 1961
In what ways does the Nuremberg Code introduced in 1947 protect human subjects in scientific trials?
Introduced the requirements for obtaining informed consent
-Voluntary
-Right to withdraw
-Avoid unnecessary physical and mental suffering
State 2 incidents in the 20th century where the rights of clinical subjects were violated.
- World War II 1939-1945 nazi medical
experiments - Tuskegee sharecroppers USA (1932-
1972)
–> long-term study of untreated syphilis
–> 600 low-income African Americans
males, 400 infected with syphilis
What act did the US government introduced in 1962 following the thalidomide incident?
Kefauver-Harris Drug Amendments (1962)
State the contributions and outcomes of Decleration of Helsinki intorduced in 1964?
-Recognized as the gold standard for conducting research
-World Medical Association
-1st attempt of medical community to regulate itself
What is the contribution of Belmont report and when was it released?
in 1979
Three fundamental ethical principles
1. Respect for others
2. Beneficence
3. Justice
What are the 3 fundamental ethical principles of the Belmont Report?
- Respect for others
- Beneficence
- Justice
When were the ICH GCP Guidlines first introduced?
1996
ICH - internatioal council of humanisation
GCP - good clinical practice
When was ICH founded?
April 1990
Who were the initial ICH parties?
EU, US and Japan
Who were the initial ICH observrs?
WHO
European free trade association (EFTA)
Canada
When did ICH further expand and what countries were invited to join?
2007
Countries with a history of ICH guideline implementation and/or where major production and clinical research are done (Australia, Brazil, China, Chinese, Taipei, India, Republic of Korea, Russia and Singapore)
What are the 2 types of applications for marketing of pharmaceutical products?
New Drug Application (NDA)
Market Authorization Application (MAA)
What is INDs and what is it for?
Investigational New Drug Applications
–>for clinical trial authorization from FDA
–> safety and efficacy of drug examined
What kind of content does an IND application need?
-protocol
-Chemistry, Manufacturing and Control
Data
-Pharmacology and Toxicology Data
-previous human experience
What is the general sequence of events leading to clinical study approval?
- protocol finalization
- investigator selection
- IRB/IEC approval
- Regulatory approval
- import license (if applicable)
What is CTA?
clinical trial authoriation
-needed to run clinical trials in HK for new drugs
What is the sequence of events leading to getting CTA (clinical trial authorization) for new drugs in HK?
Receipt of clinical documents required. Translated.
Simultaneously,
–> submitted by PI to hospital IRB for
review
–> submitted by CRO to DoH for approval
Application by CRO for import license
*DoH only approve after green light from IRB
How long does the CTA process take in Hong Kong?
3-4 months
What is the content of NDA?
-chemistry
-nonclinical toxicology
-human PK and bioavailability
-clinical microbiology
-clinical data
-case reports
-patent info
What does MAA in HK need to include?
- GMP certificate
- free sale certificate from country of
origin - outer pack photo
- copy of relevant licenses (poison,
antibiotic etc)
What is Good Clinical Practice (GCP)
A standard for
1.design
2. conduct
3. performance
4. monitoring,
5. auditing
6. recording
7. analyses and
8. reporting
of clinical trials that provides assurance that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial subjects are protected
Why regulate clincal research?
- To ensure the rights, safety and well-being of human subjects
- To ensure scientific integrity
Why follow GCP?
- Subjects are properly protected in studies
- Studies are based on good science, are well designed and properly analysed
- Study procedures are properly undertaken and documented
What do the principles of ICH GCP include?
- ethics
- protocol and sciences
- responsibilties
- informed data quality/integrity
- QC/QA
What are the responsible parties regarding clinical paractice?
- study sponsor/ contract research
organisation (CRO) - Clinical investigators (CI)
- independent ethics committee (IEC)/
independent review board (IRB)
What is a sponsor?
An individual, company, institution, or organisation that takes responsibility for the initiation, management, and/or financing of a clinical trial
Who could be sponsor?
- commercial (pharmaceutical and
device) companies - government
- funding agencies
- private foundations
- individuals
GCP requires certain direct communications and interactions between the sponsor and the
regulatory authority.
True or false.
True
What is CRO (contract research organisation) and what are its duties?
A person or an organisation (commercial
academic, or other) contracted by the
sponsor to perform one or more of a
sponsor’s trial-related duties and functions.
–> responsible for the conduct of thes study
What is a monitor and what are his/her duties in a clinical trial?
Employee of the sponsor (or CRO) who oversees the progress of a clinical study through on-site visits and other means
–> to ensure conducted, recorded, and
reported in accordance with the protocol, SOPs, GCP and the applicable regulatory requirements(s).
What is a Medical Expert (medical monitor)?
Employee of the sponsor (or CRO) who is readily available to advise on trial-
related medical questions or problems
*If neccessary outside consultants may be appointed
What is DMC/DSMB?
Independent Data Monitoring Committee
What is the purpose of DMC/DSMB?
A committee established by, but acting
independent of, the sponsor to assess at
intervals the progress of a clinical trial, the
safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify or stop a trial
What are the key responsibilities of a sponsor?
- Obtain regulatory approval before
initiating a study - Manufacture and label investigational
products appropriately - Initiate, withhold, or discontinue studies
–> Includes protocol development,
often in consultation with one or
more clinical investigators
–> select investigators
–> select qualified persons to monitor
study
–> report adverse experiences and
maintain records
