1. Informed Consent in Clinical Trials
Clinical Trials Seminar Series
Centre for Clinical Trials and Epidemiological Research
Faculty of Medicine, The Chinese University of Hong Kong
Grace Lau PhD
Associate Director, Medical Affairs
Merck Sharp & Dohme (Asia) Ltd.
13 September 2001

2. Today’s agenda Informed Consent - cornerstone of ethics
Historical Background
Current international requirements
Elements of Informed Consent - the ideal Informed Consent form
Process of obtaining Informed Consent
Patient’s rights
Responsibilities of the Tripartite in ethical clinical research
Whom does the IC protect?
Patients
Investigators
Sponsors
Non-therapeutic trials - Phase I
Ethics of clinical trials - IC is only one part of it. Protocol, need of the study,
scientific value, ongoing monitoring, standard of performance, facilities, …etc
Central - voluntary basis on patient’s part

3. Historical Background
1947 Nuremberg Code
1964 Declaration of Helsinki
1978 US-FDA Code of Federal Regulations
1980s France, UK, Nordic, Japan
1991 Australia
1993 WHO
1997 ICH GCP guidelines
2000 Latest update of DoH

4. Declaration of Helsinki Nov 2000
“ In any research on human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential riks of the study and the discomfort it may entail
The subject should be informed of the right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal ………..”
Embedded in Declaration of Helsinki:
Patients’ rights:
Right to receive clear and understandable information
Right to refuse to participate without negative consequences
Right to know which choices are available
Right to privacy
Right to give written permission
Right to know what medical treatment is available in case of complication
Right to be compensated in case of injury
Right to be free from pressure, duress and coercion while making decision
Righ to know the risks and benefits of the treatment
Right to withdraw from the clinical investigation at any time

5. International Conference on Harmonisation
E6 - Good Clinical Practice
Informed Consent:
“A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is documented by means of a written, signed and dated informed consent form.”

6. Basic principles
Comply with applicable regulatory requirements and adhere to GCP
Ethics Committee approval
Continuous update
Documentation of communication
Local language!!
Non-technical, practical and easily understood by lay person
Language - no waiving of legal rights of subjects
Subject + legally acceptable representative
No coercion, undue influence on subjects

7. Elements of Informed Consent Form
The trial involves research
Purpose of the trial
The trial treatment(s) and probability of random assignment
Trial procedures
The subject’s responsibilities
Explain experimental aspects
Reasonably foreseeable risks
Reasonably expected benefits
Alternative treatment

8. Elements of Informed Consent Form
Compensation in event of trial-related injury
Anticipated payment
Voluntary participation. Can withdraw anytime without penalty of loss of benefit
Access to medical records but maintain confidentiality
New information
Contact persons
Termination of trial
Duration of trial
Total no. of subjects

9. Example
You are invited to be in a research study. You need to decide whether you want to participate or not. Please take your time to make your decision. Carefully read the following and ask the study doctor any questions which you may have. (The study is being conducted for XXX company., the Sponsor.)
Why is the study being done?
The purpose of this study is to test the safety of the research study drug, [insert name of drug]. Another purpose is to see if [insert name of drug] has any effect on your [insert “disease” or “condition”].
Who should not be in the study?
[Insert exclusion criteria that the patient can assess in simple language].

10. Example What will I be asked to do? What are my requirements?
The study doctor or staff will ask you about your medical history and will examine you. You will be assigned to either receive [insert name of drug] or a pill that looks the same as [insert name of drug] that has no active ingredient (or you may receive [insert name of active comparator, if any]). You have a ______ in ___ chance of receiving the active study drug. You and your study doctor will not know whether you are receiving the real drug or the inactive look-alike pill. You will be required to visit the study doctor about [insert number of times]. At each visit the study doctor or staff may do any or all of the following [insert a summary of study procedures in simple language (e.g., a bulleted list, a simplified table, a checklist of procedures)].

11. Example How long will I be in the study?
You will be in the study about [insert number of weeks, months, or years].
How many other people will be participating in the study?
About [insert number of participants at all sites] people will be participating in the study.
Will I be paid? [Include section only if applicable.]
You will be paid as follows: [insert payment information]

12. Example
Can I refuse to be in the study and can I be asked to leave the study?
Your participation in this study is voluntary. You can choose not to take part in the study, or you can quit at any time. You will not lose any benefits to which you are otherwise entitled. If you quit the study, you can receive the standard treatment for this condition. You will not be prevented from participating in future studies.
You may be asked to leave the study by the study doctor or the Spnsor, without your consent if you need other treatment, if you do not follow the study plan, if you have a study-related injury or for any other reason. If you leave the study, the doctor may ask to examine you and do some final tests.
You will receive a signed copy of this consent form.

13. Process of Obtaining IC
Investigator or a person designated by the investigator to fully inform subject
Impartial witness / legal representative should be present when appropriate
Provide ample time and opportunity for questions
All questions should be answered to the subject’s satisfaction
Written IC form should be signed and personally dated by the subject, and by the person conducting the IC discussion
Copy of signed IC form and other patient information to be provided to subject

14. Process of Obtaining IC
The IC process should be conducted prior to ANY protocol related procedures and any procedures that would otherwise not be performed on the subject
Any future amendment of IC form, subject should be informed and amended IC form signed again
Non-therapeutic trials usually should only be conducted in subjects who can personally give consent
Other exceptions: to be described in protocol and approved by IRB/IEC
The process should be documented

15. Other Considerations Illiterate subjects / paediatric patients
Relationship of the ‘impartial witness’
More than one person conducting the IC process
Patient information material
Registered product information - patient leaflet
Information of unregistered products / placebos
Disclosure of allocation of treatment group at the end of trial
DNA sampling, genotyping experiments, video/audio taping of patient interviews, chart review studies….
Source data verification and auditing
USFDA audit findings on informed consent.
Fail to explain in technical / scientific language
Fail to state all purposes of the research
Date of consent after protocol specific procedures are carried out

16. QUESTIONS?