ethical and legal issues in clinical trials Flashcards
(34 cards)
What is the Nuremburg Code?
A set of 10 guidelines aiming to regulate ethical principles of carrying out experiments on human subjects, e.g. voluntary consent. These principles were set out after the inhuman and unethical Nuremburg Trials.
What is the Declaration of Helsinki?
These are a set of principles released as guidelines for human medical research. Although not legally binding, it is morally binding for physicians. It is revised regularly and includes principles such as: informed consent, right to make own decision, study must be ethically reviewed, etc.
Name the principles of the Declaration of Helsinki.
DOH is revised regularly and includes principles such as:
- informed consent
- right to make own decision
- study must be ethically reviewed
- Must have scientific background knowledge before trial commences
- Approved protocols must be followed and only trained personnel should be involved 6. Investigator must primarily ensure the safety of patient.
What is Good Clinical Practice?
A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurances that the data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial subjects are protected.
What are the 11 components of the International Council of Harmonisation GCP guidelines?
- The rights, safety, and well-being of the trial subjects should take priority over interests of science and society.
- Each individual involved in conducting a trial shall be qualified by education, training and
experience to perform their tasks. - Clinical trials shall be scientifically sound and guided by ethical principles in all their aspects.
- The necessary procedures to secure the quality of every aspect of the trial shall be
complied with. - The available non-clinical and clinical information on an investigational medicinal product shall be adequate to support the proposed clinical trial.
- Clinical trials shall be conducted in accordance with the principles of the Declaration of
Helsinki. - The protocol shall provide for the definition of inclusion and exclusion of subjects
participating in a clinical trial, monitoring and publication policy. - The investigator and sponsor shall consider all relevant guidance with respect to commencing and conducting a clinical trial.
- All clinical information shall be recorded, handled and stored in such a way that it can be accurately reported, interpreted and verified, while the confidentiality of records of the trial subjects remains protected.
- Before the trial is initiated, foreseeable risks and inconveniences have been weighed against the anticipated benefit for the individual trial subject and other present and future
patients. A trial should be initiated and continued only if the anticipated benefits justify the risks. - A trial shall be initiated only if an ethics committee and the licensing authority comes to the conclusion that the anticipated therapeutic and public health benefits justify the risks and
may be continued only if compliance with this requirement is permanently monitored. - The rights of each subject to physical and mental integrity, to privacy and to the
protection of the data concerning him in accordance with the Data Protection Act 1998 are
safeguarded. - Provision has been made for insurance or indemnity to cover the liability of the
investigator and sponsor that may arise in relation to the clinical trial.
Why do we need Good Clinical Practice?
Before the implementation of ICH GCP guidelines, there were various disastrous events which occurred due to the lack of ethical and legal regulations preventing physicians from doing patient harm. For example, the ‘Tuskegee Syphilis Study’ in 1932 involved researchers aiming to assess the progression of untreated syphilis in black men. However no informed consent was received, they did not receive the treatment that they needed, and participants were bribed to take part, being told they could have free medical exams and free meals. The trial went on for 40 years. Furthermore, the Pfizer antibiotic trial in Nigeria occurred in 1996. 100 Nigerian children were treated with Trovan to determine its effectiveness, but 11 children died, others suffered brain damage, paralysis or deafness. Pfizer had not gained Nigerian government approval therefore involuntary experimentation had occurred.
What is research governance and what is its purpose?
Research governance is defined as a range of regulations and principles which exist to improve standards and quality of research across all aspects of health and social care. The purpose is to safeguard research participants, protect researchers and enhance the ethical and scientific quality of the research. As a result, risk should be minimised and good practice is promoted. Also ensures patient confidentiality and data protection.
Name some examples of research regulations and legislations.
EU Clinical Trials Directive, Human Tissue Act, Mental Capacity Act, DOH Research Governance Framework.
What is the role of the Health Research Authority (HRA)
HRA oversees research ethics committee’s in the UK. Appropriate NHS REC approval is required for any research involving patients and/or access to organs, or other bodily material of NHS patients, or if NHS facilities are to be used.
What is NHS Permission
This is permission required for the conduct of research within NHS facilities, even if REC approval is acquired. Often called NHS R&D Approval
List the steps required for approval of a typical clinical trial involving patients.
As the project is classified as research, will firstly need approval from HRA. Then you would need NHS R&D Approval and REC approval (via an IRAS Form). Would also need Clinical Trial Authorisation (CTA).
What is a sponsor?
An organisation or group that accepts responsibility for ensuring that there are proper arrangements to initiate, manage, monitor and finance a study. Organisations include: universities, NHS trust, the pharmaceutical company developing the drug, etc.
What are the responsibilities of the sponsor?
Primarily, the responsibility is to safeguard the rights, safety, dignity, and well-being of research participants. In doing this, the sponsor takes responsibility for securing the necessary arrangements to conduct the research,
ensuring the required authorisations have been obtained before commencing the research and monitoring to ensure the research is conducted in accordance with legislation and guidance.
What is the role of the Chief Investigator?
The chief investigator acts as the person who takes overall responsibility of the design, conduct, and reporting of the study. For multi-centre studies there is a Chief Investigator at the main sites, and other Principal Investigators at the other sites with delegated responsibilities. The Chief Investigator must ensure that all staff have the correct permission to work on the trial.
What is the role of the Principal Investigator?
The Principal Investigator is an authorised healthcare professional who takes responsibility for running the study at their trial site. PI may also be the CI in single-centre trials.
Name examples of Research Sites.
You can have sites for various activities of the clinical trial, e.g. patient recruitment, informed consent. These may not occur in the same place as the research activities, e.g. these may occur in a University setting, but research activities may occur in the Toxicology Unit of the Newcastle RVI.
What is peer-review in the research authorisation of clinical trials?
Peer review refers to the scrutiny of a clinical trial protocol by independent experts to ensure only high quality research is carried out. Either the funder or the sponsor must acquire this.
Name the risk assessments that are required for studies.
Patient Safety Assessment, Financial Risk Assessment, Organisation Risk Assessment (sponsorship, insurance and indemnity, Investigator/Research Staff Risk Assessment, Scientific Risk Assessment (scientific quality of the research via good design, etc.)
What is insurance and indemnity and why is it required?
For a clinical trial, insurance and indemnity must be set up by the Sponsor to ensure there is compensation available for patients if any harm is to be suffer after involvement of the research trial.
What is a Research Passport
A research passport is the mechanism for non-NHS staff to obtain an honorary research contract to conduct research in the NHS. It provides a set of checks on the researcher and allows a faster study start up.
What is the Institutional Review Boards and what are their roles?
Institutional Review Boards are the ethics committees in the USA which receive ethical applications for the conduct of clinical trials. IRB must approve or reject applications for ethical approval, as well as monitor and audit whether trials in place are abiding by the ethical and legal regulations to protect patients from physiological and psychological harm.
When evaluating research proposals, what do IRBs look at?
These ethics committees will evaluate the proposal of research and how patients may be affected, the emergency use of consent methodology, the investigator qualifications, subject compensation plans, the study consent materials (consent forms, recruitment forms, study outline forms, etc.) They also ensure that once the study is underway, there are no deviations (if so, these must be approved). They must also ensure that documents are kept for at least 5 years after trial close-out.
What is informed consent?
This is the ethical and legal obligation to obtain voluntary consent from a patient, after all aspects of the trial have been explained, and the patient has had time to contemplate their participation.
Why is informed consent important?
All persons are entitled to their own right make their own decisions about whether they wish to receive treatment or not, even if it could be life-saving. Patients also have the right to withdraw the consent at any time. Failure to achieve this is a serious criminal offence, and in the past has led to trials which have had debilitating consequences to the patient. It is ultimately the principal investigators responsibility to obtain informed consent from the patient.
