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

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

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

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

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.”

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

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

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

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].

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)].

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]

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.

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

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

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

QUESTIONS?