Ethical, legal and regulatory aspects Flashcards
Why is the historical context, including the Nuremberg Code, critical for understanding modern clinical research ethics?
“many who conducted lethal experiments… argued that it was reasonable to sacrifice the interests of the few in order to benefit the majority”
WWII - between december 1939 and august 1941, about 50,000 to 60,000 Germans - children and adults - were secretly killed bvy lethal injections or in gassing installations designed to look like shower stalls
The Nuremberg Code (1947)
§ 10 principles to protect the rights of human research participants
1. Voluntary consent of a human subject is absolutely essential
Ensured that anyone particip[ating in a clinical trial is doing so out of their own free will - historically patients were forced to participate in trials and experiments without their consent - could be seen as torture
How does the Helsinki Declaration balance the well-being of individual participants with the advancement of medical knowledge?
The well-being of the individual research subject MUST take place over all other concerns
§ Allows patients the right to feel like they can drop out of a clinical trial if the side effects they are experiencing are too severe without being forced to remain in the trial
Places a positive duty on research physicians to safeguard the health of research subjects
What is the role of the ICH in harmonizing clinical trial standards globally?
The International Council for Harmonisation (ICH) held the inaugral Assembly meetings on 23 October 2015 establishing the ICH as an international association, a legal entity under Swiss ;law
ICH’s mission to achieve greater harmonisation worldwide to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner
The ICH develops guidelines and technical requirements for the development, approval and safety monitoring of medicines involving regulatory and industry experts
ICH guidance of good practice:
○ Good clinical practice
○ Good laboratory practice
○ Good manufacturing practice
How does the MHRA ensure compliance with GCP in the UK, and what are the key steps in obtaining clinical trial authorization?
Good clinical practice (GCP)
Internationally recognised ethical and scientific quality requirements that must be followed when designing, conducting, recording and reporting clinical trials that involve people
In the UK, the medicines products Regulatory Agency has the role of enforcing compliance with GCP through inspections and receiving reports
What responsibilities do investigators have under GCP to protect participants and ensure valid data?
Qualification and agreement (including appropriate delegation of study-related tasks)
Adequate resources - suitably qualified staff informed of the protocol
Medical care of study patients
Communication with the Ethics Committee
Compliance with the protocol
IMP - accountability, storage only used in accordance with the protocol
Randomisation and Un-blinding
Informed consent of study patients
Records and reports - data in the CRF need to be supported by source data
Progress reports - ethics committee and sponsor
Safety reporting AEs, SAEs
Premature termination or suspension of the study
Final report
What are the ethical and legal requirements for obtaining valid informed consent in clinical trials?
Consent must be a positive, voluntary action
1. Competent patient - Capacity 2. Sufficiently informed - Duty of care to explain any material risks, any reasonable alternatives or variant treatments 3. Not subject to coercion or undue influence (voluntariness) A) Coercion i) Agent of influence must INTEND to influence by presenting a severe threat; ii) There must be CREDIBLE threat iii) The threat must be IRRESISTABLE B) Influence - Strength of will of patient and relationship with the influencer 4. Reaches a clear decision
There a limits on what a person can consent to:
- Public good
- Evolving concept of dignity
How does the Mental Capacity Act (2005) guide assessments of a participant’s ability to consent, and what challenges might arise?
Competence is determined by the Mental Capacity Act (2005)
A person must be assumed to have capacity unless it is established that they lack capacity
A person is not to be treated as unable to make a decision unless all practicable steps to help him to do so have been taken without success
A person is not to be treated as unable to make a decision merely because he makes an unwise decision
An act done or decision made, under this act or on behalf of a person who lacks capacity must be done, or made, in his best interests
Before the act is done, or the decision is made, regard must be had to whether the purpose for which it is needed can be as effectively achieved in a way that is less restrictive of the person’s rights and freedom of action
What is the purpose of a capacity assessment
A capacity assessment can be performed to determine if an individual lacks capacity
A person lacks capacity in relation to a matter if at the material time he is unable to make a decision for himself in relation to the matter because of an impairment of, or a disturbance in the functioning of the mind or brain. “Diagnostic test”
This could cover a range of problems, such as psychiatric illness, learning disability, dementia, brain damage or even a toxic confusional state, as long as it has the necessary effects on the functioning of the mind or brain, causing the person to be unable to make the decision
What are the steps of a capacity assessment
A person is unable to make a decision if unable:
i) To understand the information relevant to the decision
ii) To retain that information
iii) To use or weigh that information as part of the process of making the decision, or
iv) To communicate his decision (whether by talking, using sign language or any other means)
What is informed consent and how is it obtained
Informed consent must be obtained by an investigator and must meet the following points:
- Investigator has been delegated that responsibility
- Give a full explanation of the trial including the risks and benefits both verbally and in writing
- Give the trial subject ample time to decide and not place the trial subject under any obligation to participate
- Must be taken before any study related procedure is carried out and document that informed consent was obtained in source notes
- Must be signed and personally dated by the investigator conducting the process and signed and personally dated by the subject. Time of consent also needs to be documented
- ORIGINAL CONSENT is to be filed in study officers file and made available for review throughout the study - this includes screen failures
- One copy of the participant information sheet and consent form is provided to the subject and one copy filed in the VMF
