Week 2 - Good Clinical Practice Flashcards
1
Q
What are clinical studies required for? Give a specific example of a type of study and its use
A
- Determine the safety and effectiveness of health and medical product
- Randomised controlled clinical trials address scientific and health care questions, which has assisted our knowledge concerning the safety and efficacy of specific products.
- Randomised controlled trials form the basis for evidence-based medicine.
2
Q
When can randomised controlled clinical trials be considered credible?
What is the term for this? Give an overview
A
- Only credible if it is conducted according to the fundamental principles known as “Good Clinical Research Practice” (GCP).
- GCP is an international set of ethical and quality standards that applies to clinical trials involving the participation of human subjects.
- GCP compliance provides the general public and the health authorities, with assurance of the integrity and the validity of the data produced in clinical trial experiments.
3
Q
What are the GCP standards intented for?
Give an exception
A
- Intended to produce data for marketing authorisation procedures, which can be for new pharmaceutical/ medicinal products or can be an extended form of research for marketed products already established.
- A general exception is academic research using established marketed products, with no intention to produce data for marketing authorisation purposes.
4
Q
Briefly outline the history of GCP
A
- In the late 1960s, the WHO created a Scientific Group on Principles for Clinical Evaluation of Drugs.
- The Scientific Group was responsible for assessing regulations for clinical evaluation of drug products, for both new and old marketed drugs, including considerations for new dosage forms, concerning marketed products.
- Another WHO Scientific Group formed in 1975, to address all aspects of the evaluation and testing of drugs and to create standard guidelines for clinical research
- These reports form the foundation for WHO’s ‘Guidelines for good clinical practice (GCP)’ concerning trials on pharmaceutical drugs, which was published in 1995. Following this, several international guidelines were convened.
5
Q
What does research conducted according to the GCP guidelines ensure?
A
- Research conducted in compliance with GCP helps ensure the integrity and welfare of the human research participants were upheld and the results produced from the research are valid and accurate.
6
Q
Define the following GCP terms:
Sponsor
Investigator
Monitoring
SOP
A
- Sponsor: A person, company, or institution, who are accountable for the management and/ or financing of a clinical trial
- Investigator: person who is accountable for the conduct of the clinical trial. Principal investigator is appointed if multiple investigators are involved at the trial site.
- Monitoring: The act of supervising a clinical trial to ensure that it is carried out in accordance to the study plan, standard operating procedures (SOPs), GCP and regulatory requirements.
- SOP: set of written detailed instructions to attain consistency in the performance, of a given task
7
Q
Define the GCP term “audit”
A
- An independent assessment of all trial associated documents and activities in order to identify if the trial was conducted, recorded, and evaluated according to the study plan, GCP regulations and SOPs. The audit procedure is independent of the monitoring procedure.
8
Q
Describe a Clinical Trial Protocol
A
- Clinical trials must be described in a succinct, detailed protocol.
- Often the sponsor and the clinical investigators design the study protocol.
- Factors that need to be considered when designing the protocl include: statistical methodology, confounding variables, risk factors, control groups, and study design.
- need to abide to any national regulations concerning the design and conduct of the clinical trial.
9
Q
Who, in a clinical trial, needs to adhere to SOPs?
A
- All people supervising clinical research such as the sponsors, contract research organisations, clinical investigators, Independent Ethics Committees (IECs) / institutional review Boards (IRBs), should adhere to SOPs
10
Q
Who should prepare SOPs for clinical trails and who should they prepare them for?
A
- Project sponsors should prepare SOPs for:
- Creating and adapting the protocol and other documentations such as case report forms (CRFs).
- Supplies, shipping, handling of the trial product.
- Regulating trial activities to ensure that the data is accurately generated.
- Ensuring that processes are routinely followed and that experimental activities are recorded.
- Auditing to establish whether processes are conducted effectively and the systems for quality control are functioning.
11
Q
With regards the regulation of clinical trials, what SOPs should be developed? What should it contain?
A
- Regulators of the clinical trial are recommended to develop standard procedures concerning the activities relating to the regulation of clinical research.
- This document may include safety reports, GCP inspections and sanctions specific to the individuals who defy the national regulations.
12
Q
Describe the support systems and tools for a clinical trail, what they are for & what they include.
A
- Suitable support systems and equipment assist the performance of the study and the collection of the experimental data.
- Support systems and tools include, checklists, specification sheets, drug accountability records and trial-related credentials.
13
Q
Who is responsible for managing the accessibility to support systems and tools? Give some examples
A
- The sponsor is accountable for managing the accessibility of support systems and tools. For example, the sponsor may consider acquiring:
- Diagnostic equipment
- Computer software
- Software validation systems
- Communication equipment
- Training equipment
14
Q
What are trial related credentials? What is their purpose and what may they include?
A
- Developing trial-related documentations serve to assist the progress of the study, including the collection and reporting of the experimental data and analysis of the results
- Trial-related documentation may include:
- Consent documents
- Checklists
- Documentation concerning the supplier of the investigational compound, the amount given to the participants, disposal instructions of any unused product
- CRFs
- Safety documents
- Expenses and funding documents
15
Q
Describe how personnel and trail sites are assigned to clinical trails
A
- Clinical trials require qualified and experienced investigators to conduct the study. Sponsors are required to allocate suitable clinical investigators who have the required expertise.
16
Q
Describe the ethics committee review of a clinical trail
A
- According to GCP, clinical studies must be appraised and be given approval from IEC/ IRB before recruiting participants.
- Usually, the investigator is accountable for obtaining IEC/ IRB approval of the study protocol, which is subsequently given to the sponsor.
17
Q
Describe how clinical trials are assessed by regulatory authorities
A
- According to GCP, clinical studies are obliged to undergo assessment by regulatory aunthorites for the experimental use of the investigational compound in human subjects and to ensure that the study has been effectively designed to address the main objectives of the study, with compliance to the national regulations.
- The sponsor is usually responsible for ensuring that the relevant regulatory authorities review and approve the design of the study.
18
Q
Describe the process of enrollment of participants into a clinical trial
A
- The clinical investigator is responsible for the recruitment of the participants for the study.
- They have the responsibility of ensuring that only eligible participants are enrolled in the study and obtaining relevant documentations e.g. the consent forms.
19
Q
Describe the “investigational product” with regards a clinical trial and who is responsible fr regulating access to the investigational compound
A
- Quality of the investigational compound is guaranteed by compliance with Good Manufacturing Practice (GMP) and by managing the product according to the manufacturing specifications and the study protocol.
- in accordance to GCP, sponsors regulate access permitted to the investigational compound.
- GCP also requires that the clinical investigators mange the receipt, administration and disposal of the investigational product.
20
Q
Describe “trial data attainment” with regards clinical trials
A
- Clinical research must be conducted in conferring to the approved protocol and regulatory obligations.
- Documenting each trial-related activity enables clinical verification that the study have been performed in compliance with the protocol.
21
Q
Describe “safety management” with regards clinical trials
A
- The clinical investigator is accountable for informing the sponsor and the IEC/IRB to contrary events, observed during the course of the study.
- The sponsor has the responsibility for reporting the safety of the study to regulatory authorities and other investigational organisations.
- In some circumstances, the Data and Safety Monitoring Board (DSMB) may be assigned by the sponsor to aid overall safety management.
22
Q
Describe the monitoring of a clinical trial
A
- In order to assure that a high quality trial experiments are being performed, sponsors may perform set monitoring tasks, which can be done directly or via a contract research organisation (CRO).
- Depending on the type of study conducted, the sponsor dictates the extent and type of monitoring needed.
23
Q
Describe how trial data is supervised
A
- Managing clinical trial data effectively ensures that the data sets are complete, reliable and processed in an appropriate manner, which ensures that the integrity and quality of the data is preserved.
- Sponsor is ensures that suitable data management systems are in place.
- Sponsor and the investigator are both accountable for implementing data management systems, thereby ensuring that the integrity of trial data is preserved.
24
Q
With regards supervising trial data, what should the data management system address?
A
- Should address the following:
- Data attainment
- Confidentiality
- Completion of CRFs
- Safety data reporting
- Data processing
- Electronic data storage
- Supervision of vendors
25
Describe the Quality Assurance (QA) aspect of clinical trials
* QA certifies that existing quality control systems are working effectively by using systematic and independent audits.
* Sponsors are also liable for developing quality systems and conducting quality assurance audits.
26
Describe how the results of a clinical trial are reported
* The results generated by each controlled experiment, using the investigational compound, are described in the clinical study report.
* The sponsor is also responsible for the preparation of clinical study reports.
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What should the clinical trial report include?
* These reports generally include:
* The rationale of the study
* Ethical aspects of the study
* Administrative structure of the study (e.g. the expertise of the investigators)
* Study design
* Protocol amendments
* Protocol violations
* Suitability of the human participants
* Safety evaluation
* A discussion
* References
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WHO Principles of GCP: Principle 1
What is Principle 1? Where did it originate from?
* Clinical trials involving human subjects must be scientifically comprehensive and performed in accordance with the fundamental ethical principles.
* These principles originated from the Worlds Medical Association’s Declaration of Helsinki.
* There are three main ethical principles of equal importance: “…respect for persons, beneficence and justice”.
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WHO Principles of GCP: Principle 1
How is it applied?
* Applied through:
* Design and authorisation of the protocol
* Consent
* Scientific and ethical review
* Risk assessment
* Selection of human participants
* Compliance with national and international regulation
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WHO Principles of GCP: Principle 1
What does "respect for persons" mean regarding GCP - What are the ethical components?
* According to the International Ethical Guidelines this term has two ethical components:
* (1) that the participants should be treated as impartial subjects
* (2) that participants with diminished autonomy are entitled to protection.
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WHO Principles of GCP: Principle 1
What does "respect for persons" mean regarding GCP -what does this term take into account and how should be treated as "intrinsically vulnerable"?
* Takes into account that the participants have a right to choose what will happen to them.
* All participants, irrespective of the health, should be regarded as “intrinsically vulnerable”.
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WHO Principles of GCP: Principle 1
What does "respect for persons" mean regarding GCP - when should additional safeguards be considered and what do these safeguards include?
How is "respect for persons" applied?
* Additional safeguards for participants are considered to be mentally, physically, economically, or educationally disadvantaged.
* Depending on the degree of vulnerability, these safeguarding’s may include: obtaining permission from a legal guardian, incorporating an impartial witness to be present and or additional monitoring in the clinical study.
* Applied through the process of informed consent.
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WHO Principles of GCP: Principle 1
What does the term beneficence mean in compliance to GCP?
What does the term "justice" mean in compliance to GCP?
* Refers to the ethical duty to obtain maximum benefit and to prevent non-maleficence (prevent harm).
* Beneficence is linked to the GCP requirement that clinical research is acceptable based on “favourable risk/benefit assessment”.
* According to GCP, the principle of “beneficence” is mainly applied through risk/benefit assessments during the study design.
* Jusrice refers to moral obligations, in terms of unbiased procedures and in the recruitment of participants
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WHO Principles of GCP: Principle 2
What is principle 2?
* Clinical research involving participation from human subject must be logically defensible and explained in a succinct protocol.
35
WHO Principles of GCP: Principle 2
What does principle 2 mean? How is it implemented? What does the protocol state?
* Implemented through the development of a protocol that is justifiable and ethically comprehensive.
* The protocol identifies the objective of the study, the experimental design, methodology, and usually described the rationale for the biomedical research.
* The clinical research must also be ethically justified by its capacity of generating scientifically reliable results.
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WHO Principles of GCP: Principle 2
How can experimental bias be minimised in a clinical study?
* Bias in a clinical trial can distort the credibility of the results.
* Impartiality/ bias can be minimised in clinical research designing well-controlled studies, implementing randonisation and using a "blinding/ masking procedure”.
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WHO Principles of GCP: Principle 2
Describe in *more* detail how principle 2 is implemented
* Sponsors are mainly responsible for designing the experiments and generating the protocol for the study. In some cases, investigators mat contribute to the design of the protocol.
* IECs/IRBs have a duty to carry out an ethical review of the study protocol. By comparison, regulators are responsible for permitting the clinical research to proceed with their protocol, in agreement with the national and international laws and regulations.
38
WHO Principles of GCP: principle 2
Explain how using "well-controlled studies”, randomisation and blinding/ masking procedures can minimise bias in a clinical study.
* This type of design ensures that comparisons between the experimental group and a suitable control group can be made which enables the investigator to distinguish the effect that the investigational compound may have on the experimental group and identify potential “placebo” effects.
* Where applicable, a randomised assignment of participants to treatment or control groups is the preferred method of selection in clinical studies. This is because randomisation serves to reduce partiality in the research.
* Blinding/ masking is a procedure, which aims to keep selected parties uninformed of the treatment groups. “single blinding” generally refers to the participants being unaware or it can be “double blinding”, which generally refers to the participants, investigators, and/ or the data analyst being unaware of the treatment groups.
39
WHO Principles of GCP: Principle 3
What does principle 2 state?
* States that before clinical research begins, anticipatable risks and benefits for the research must be acknowledged.
40
WHO Principles of GCP: Principle 3
According to the Declaration of Helsinki how are the purposes of clinical trials justified?
* Clinical experiments should be based on the results of non-clinical studies and the knowledge of the history of the investigational compound and the clinical conditions, will help justify the purpose of the experiment.
* Identifying the potential risks and benefits of the clinical study ensures that systematic and comprehensive information of the study is obtained before the experiments begin.
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WHO Principles of GCP: Principle 3
How is principle 3 implemented?
Implemented through:
* Thorough knowledge of the scientific literature concerning the investigational compound and procedures that will be used.
* Developing the study protocol.
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WHO Principles of GCP: Principle 3
What does the term "risk" mean in compliance with GCP?
* Refers to the likelihood that harm may occur.
* The expressions "small risk” and "high risk” are commonly used, which refer to the probability and severity of experiencing harm.
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WHO Principles of GCP: Principle 3
What does the term benefit mean in complaince to GCP?
* In the clinical research industry, this term refers to a positive result that may advance health or welfare.
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WHO Principles of GCP: Principle 3
How are the risks and benefits established prior to the clinical study?
* Establishing the risks and benefits is addressed in the scientific review that supplements protocol development. An important aspect of a scientific review is the evaluation of relevant published and unpublished data.
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WHO Principles of GCP: Principle 3
Who is responsible for implementing this principle?
* Sponsor
* IECs/ IRBs
* Investigators
* Regulators
46
WHO Principles of GCP: Principle 3
How is the sponsor responsible for implementing this principle?
* Responsible for conducting a literature review to ensure that adequate information is available to support the reasoning behind carrying out the clinical trial.
* There must be sufficient safety and efficacy data to support using human participants. This information can be summarised in the investigator's brochure.
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WHO Principles of GCP: Principle 3
How are IECs/ IRBs responsible for implementing this principle?
When they review the study protocol, investigator's brochure and other relevant documentation, it enables them to:
* (1) Identify whether the benefits outweigh the risks
* (2) Comprehend the strategy that will be used to minimise risks
* (3) Ensures that the consent documents clearly identify the potential risks and benefits of the study to the participants.
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WHO Principles of GCP: Principle 3
How are the investigators responsible for implementing this principle?
* Must be conversant of the study protocol, investigator's brochure, and other relevant documentation concerning the potential risks and benefits associated with the study.
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WHO Principles of GCP: Principle 3
How are the regulators responsible for implementing this principle?
* Responsible for authorising a protocol to proceed in accordance to national and international laws and regulations.
* Regulators also have to ensure that the risks and benefits are accurately identified and justifiable.
50
WHO Principles of GCP: Principle 4
What is principle 4?
* Clinical research should only be initiated providing that the benefits clearly outweighs the risks.
* Most important points to consider is that the rights, safety and welfare of the human subjects are upheld and to a lesser extent, the benefits of the results.
* This means that the welfare of the human subjects must take precedence over the interests of science and the general public. (Declaration of Helsinki).
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WHO Principles of GCP: Principle 4
How is principle 4 applied?
What should be carefully considered?
* A suitable study design and by reviewing the ethical, scientific and regulatory aspects of the study protocol, before starting the study.
* Consider whether using human subjects is completely necessary
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WHO Principles of GCP: Principle 4
Who's duty is it to implement principle 4 and how is it implemented?
* Sponsor, investigator(s), IECs/ IRBs, and the regulatory authorities each assess the risk/benefit profile of a study.
* The regulatory authorities may prevent a study from starting or may require modifications to the protocol based on an unacceptable risk/ benefit profile, in accordance to relevant laws and regulations.
* IEC/IRB issue recommendations of the study such as disapproval/ negative opinion; approval/favourable opinion; or requires adaptions prior to approval.
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WHO Principles of GCP: Principle 5
What is principle 5?
* Before starting a clinical trial, research involving human participants should IEC/IRB approval/favourable opinion.
54
WHO Principles of GCP: Principle 5
Who should the study be submitted to and why?
* According to the Declaration of Helsinki, the study protocol should be submitted for approval to IEC/IRB.
* Failure to submit a study protocol to the appropriate committee should be seen as an infringement of ethical guidelines.
* Applied through protocol review by an IEC/IRB, which are compliant to GCP and national/international laws and regulations.
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WHO Principles of GCP: Principle 5
What is the importance of receiving an IEC/IRB review of the study protocol?
* IEC/IRB are responsible for ensuring that the rights, safety, and welfare of the participants are protected and to assure the public of this protection for all approved clinical trial protocols.
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WHO Principles of GCP: Principle 5
What are the requirements for the IEC/IRB?
* IEC/IRB should have a satisfactory amount of members with the expertise to review and assess the science, medical and ethical aspects of the proposed clinical trial.
* Members of IEC/IRB must be independent of the investigator or the sponsor of the trial, to prevent favouritism, the committee insists on a declaration of possible conflicts of interest by all members.
* IEC/IRB approval/ favourable opinion must be issued before initiating a clinical trial.
* All opinions issued by the IEC/IRB should be communicated in writing to the specific applicant.
57
WHO Principles of GCP: Principle 5
What are the possible decisions issued by the IEC/IRB?
* Approval/favourable opinion
* Termination of any prior approval/ favourable opinion
* Modifications needed before its approval/favourable opinion
* Disapproval opinion
58
WHO Principles of GCP: Principle 5
Describe the IEC/IRB "Approval/favourable opinion"
* A satisfactory decision which is required before starting or changing the study protocol.
* The approval documentation sent to the applicant is accompanied with a statement of responsibilities that the applicant must abide to.
59
WHO Principles of GCP: Principle 5
Describe the IEC/IRB "Termination of any prior approval/ favourable opinion"
Describe the "Disapproval opinion"
* This refers to when the IEC/IRB terminate or suspend its first decision of approval/favourable opinion.
* Dissatisfactory decision, which may apply to a new protocol or a protocol that was modified.
* The disapproval documentation sent to the application must state the reasons for the rejection.
60
WHO Principles of GCP: Principle 5
Describe the IEC/IRB "Modifications needed before its approval/favourable opinion"
* Conditional decision that requires the applicant to make changes to the protocol.
* The study protocol cannot be initiated until the modifications are made and the IEC/IRB has issued an approval/favourable opinion based on these modifications.
61
WHO Principles of GCP: Principle 6
Describe principle 6
* All approved clinical studies must be compliant with the authorised protocol.
* Once the protocol have been granted an approval/ favourable decision, it is crucial that the trial is conducted in agreement with the protocol that was accepted by the IEC/IRB.
62
WHO Principles of GCP: Principle 6
What does protocol compliance mean?
* This refers to performing all experiments stated in the approved protocol. It is crucial that the activities related to the well-being of the participants are performed exactly as stated in the protocol.
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WHO Principles of GCP: Principle 6
What are some of the aspects included in the protocol?
* Informing the participants of the risk/benefits associated with the study, in their consent documentation, prior to their enrolment.
* Treating the participants with the investigational compound, as stated in the approved protocol.
* Accurately recording all safety and efficacy data.
* Reporting all “serious adverse events” (SAEs) to the sponsor promptly.
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WHO Principles of GCP: Principle 6
How is principle 6 implemented?
* The first step in implementing compliance with the study protocol is to ensure that a well-designed protocol is written.
* To ensure that the protocol is fully understood, the sponsor must obtain written agreement by the investigators, which will confirm their agreement with the protocol.
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WHO Principles of GCP: Principle 6
Who is responsible for ensuring compliance with the approved protocol?
* Since the investigator has direct contact with the participants, they have the main responsibility of ensuring compliance with the approved protocol, from all parties involved.
* However, the responsibility for applying this principle is shared by IECs/ IRB, sponsors, investigators and regulators.
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WHO Principles of GCP: Principle 7
What is principle 7?
* Prior to participation, the subjects, or their authorised representative, are required to give informed consent.
* Obtaining informed consent is a step that occurs when the initial contact is made between the investigator and the participants.
67
WHO Principles of GCP: Principle 7
What does "informed consent" mean?
* Refers to a decision to take part in the research study, given by a competent individual, who are well informed of all the necessary information before given consent.
* All information must be communicated in a comprehensive and understandable way to the participants
68
WHO Principles of GCP: Principle 7
What type of information should be given to patients in accordance with GCP?
* Title of the protocol
* Identities of the sponsor(s) and the clinical investigator(s)
* Source of funding
* Purpose of the clinical trial
* The trial treatments
* The responsibilities of the participants
* The potential risks associated with the study
* The possible reasons for removing the participant from the study
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WHO Principles of GCP: Principle 7
What is informed consent based on and how is it applied?
* Based on the concept that competent individuals are permitted to choose whether to take part in the research study. Informed consent serves to protect the participants' freedom of choice. This principle is therefore applied through informing and ensuring understanding by the participants about the research and obtaining their written consent
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WHO Principles of GCP: Principle 7
When is informed consent valid and who is responsible for supervising the informed consent process?
* Valid providing that it is given by voluntarily by the participants themselves and authorised bodies, free from external influences.
* The investigator should not provide the participants with unjustifiable assurances concerning the risks and benefits of the research.
* IECs/ IRBs, sponsors, clinical investigators, and regulatory authorities share the responsibility for applying and supervising the informed consent process.
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WHO Principles of GCP: Principle 8
What is principle 8?
* Clinical research should only continue if the benefit-risk assessment remains favourable
* It is the experimenter’s responsibility to prepare to terminate the experiment during the course of the experiment, if after careful judgment, that the continuation of study may result in serious harm.
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WHO Principles of GCP: Principle 8
What is the sponsors responsability of principle 8?
* Sponsors of clinical trials are recommended to create an evaluation process to assess safety information concerning the investigational compound to ensure that the potential safety issues are identified and addressed as early as possible
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WHO Principles of GCP: Principle 8
How is principle 8 implemented?
* Implemented through the development and implementation of processes for assessing risks and benefits of the research, during the course of the study.
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WHO Principles of GCP: Principle 8
What are the four key points covered by principle 8?
1. Investigators and sponsors are required to continuously monitor the safety of the study.
2. Reporting unexpected risks to the relevant personnel.
3. The IEC/ IRB are required to review unexpected risks associated with the study at regular intervals.
4. Amending the study protocol, investigator’s brochure, consent documentation and terminating studies if necessary.
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WHO Principles of GCP: Principle 8
What methods are used to identify unexpected risks during the course of the experiment?
* This can be achieved by regular reviews of all experimental data.
* Investigators and staff allocated to the trial experiments are typically the first to detect unforeseen risks to the participants during the course of a study.
* Sponsors should be immediately informed of all serious unexpected adverse events.
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WHO Principles of GCP: Principle 8
With regards risk, what is the sponsor responsible for?
* Reviewing the benefit-risk profile of the investigation compound, while the study is ongoing.
* Sponsors monitor the progress of clinical trials to must ensure that
* (1) the study is conducted in compliance to GCP, the approved protocol and regulatory requirements
* (2) all results, including risk assessments, are accurately recorded.
* Notify all safety concerns with the investigators and the regulatory authorities
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WHO Principles of GCP: Principle 8
What are the additional responsabilities of the sponsor regarding documentation?
What are the IEC/ IRB responsabilities?
* Sponsors amend the informed consent documentation if there are significant amendments to the experimental procedures or treatment conditions, which may affect their desire to continue the study
* IEC/ IRB tracks progress of clinical trials because risks that could adverse effects on the safety of the participants may alter the approval/ favourable opinion to continue with the study. A substantial safety issue may lead to the withdrawal of the approval/favourable opinion.
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WHO Principles of GCP: Principle 8
What are the responsabilities of the Drug Safety and Monitoring Board?
* protect the participants of the clinical trial from unanticipated adverse events
* reviewing the data on clinical efficacy and safety produced during the study, and assess reports on serious adverse event
* provides recommendations to the sponsor concerning whether the study protocol needs to be amended or whether the study should be terminated, based on the data presented by the sponsor
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WHO Principles of GCP: Principle 8
When are Drug Safety and Monitoring Boards required and when are they not needed?
* DSMBs are used for clinical trials conducted on a large scale, which have the intention of using the investigational compound to increase the life expectancy or minimise risks of major adverse health outcome
* Typically not required for experimental trials at early stages of product development.
80
When did GCP compliance become a legal requirement?
How is it enforced?
* Following the Clinical Trials Directive, GCP became a legal requirement for everyone in the European Union involved in the conduct of a clinical trial with a medicinal product
* Compliance with the requirements issued in the protocol will need to be certified. inspector may need to further clarify and discuss the relevance of the records which are present in terms of the clinical trial design, trial results and their level of completion.
81
What does the concept of risk based quality management in clinical research take into account ?
* Establishing the main priorities of the clinical trial i.e. the production of trial participants and achieving the scientific objectives of the study.
* Identifying the risks associated with the clinical trial.
* Establishing tolerance limits and the documentation of the processes for mitigation of risks linked with the main priorities of the study.
* Evaluating the results of the risks identified in the study and implementation of the actions need.
82
Describe the GCP Risk-Based Inspection Process
* Since 2009, takes into account a range of information including compliance reports provided by MHRA, internal inspection history, organisational adaptions and other compliance reports, to establish an organisation’s strategy for controlling risks.
* Pharmaceutical organisations assigned a risk rating based on the results from the risk assessment and GCP inspections will be prioritised to the organisations with the highest risk rating
83
What could result in a pharmaceutical company being rated as high risk regarding Risk-based complaince?
* Dponsors are not obliged to complete a Compliance Report. but failure to submit a completed Compliance Report may result in the organisation being assigned to a high-risk rating.
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WHO Principles of GCP: Principle 9
Outline principle 9
* Qualified medical professionals should have the responsibility of administering medical care to the human subjects and for medical decisions made in their best interest.
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WHO Principles of GCP: Principle 9
What is the signficance of principle 9 and how is the principle implemented?
* Clinical research involving human subjects is performed by staff members that have the required expertise and qualifications, under the supervision of a medical professional
* implemented through the sponsor’s recruitment of qualified clinical investigator
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WHO Principles of GCP: Principle 9
What is the investigator responsible for?
What qualities must the investigator have?
* Investigator is responsible for an array of duties, including the protection of the rights, safety and well-being of the human subjects during a clinical trial
* Must be knowledgeable of nature of the research, and in most cases, the investigator will be a medical professional e.g. a physician or a dentist.
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WHO Principles of GCP: Principle 9
What is the duty of the investigator?
What should the sponsor provide?
* Duty to ensure that the participants have access to medical aid that may be required as a result of the participation in the clinical trial
* It's not mandatory that the sponsor provides healthcare services, which are not related to the clinical research, it is commendable, services may refer to treatment for diseases gained during course of the study or to provide treatment for unrelated conditions to the study.
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WHO Principles of GCP: Principle 10
What is principle 10?
* All staff members involved in the clinical trial must have the desired expertise and must be qualified to perform their specific duties.
* (Unlike Principle 9, which was concerned with the investigator’s qualification, Principle 10 is concerned with the qualification of all staff members involved in the clinical trial)
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WHO Principles of GCP: Principle 10
What are the requirements placed on the clinical investigator?
* Not only requires that the clinical investigator to be appropriated qualified, but also requires that clinical investigator’s will have sufficient resources available, including competent staff, with the appropriate education needed to perform their tasks
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WHO Principles of GCP: Principle 10
How is principle 10 applied?
* Mainly applied through the investigator’s recruitment process of suitable staff to help conduct the clinical trial
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WHO Principles of GCP: Principle 10
What are the clinical investigators responsabilities?
ensure that all staff members are:
* Qualified
* Acquainted with the study protocol and investigational compound
* sufficient training to perform their respective duties
* provided with clear procedures for activities related to performing the experiments
* Allocated to the appropriate task
* Aware of their duty to ensure the rights, safety and well-being of the participants are protected
* Familiar with all relevant requirements enforced by regulatory authorities for GCP
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WHO Principles of GCP: Principle 10
Give an additional responsability of the clinical investigator regarding staff
* duty of supervising staff to ensure that they adequately perform they duties related to the trial.
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WHO Principles of GCP: Principle 11
What is principle 11?
* All documentation, associated with the clinical trial, needs to be records and stored in a satisfactory manner, which permits accurate interpretation of the results.
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WHO Principles of GCP: Principle 11
What does this principle emphasize and how is it implemented?
* Importance of maintaining data quality and data integrity, in addition to satisfactory procedures for data handling and data recording.
Principle 11 is implemented through:
* Comprehending and upholding data quality and integrity
* Commitment to following the study protocol
* Preparing documentation, for all stages of the clinical trial
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WHO Principles of GCP: Principle 11
What does the term "data quality" refer to?
What does "data integrity" refer to?
Data quality refers to data that is:
* Original
* Accurate
* Comprehensive
Data integrity refers to reliability of the data in its entirety, the data must be valid, consistent, and certifiable.
The data must be accurately transcribed, analysed, interpreted, reported and stored.
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WHO Principles of GCP: Principle 11
What constitutes as clinical trial information?
* All experimental data, materials, and documents - information that describes all factors (e.g. methods, conduct and results) that are related to the clinical trial.
* These documents provide evidence that the study has been GCP-compliant.
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WHO Principles of GCP: Principle 11
Give some examples of clinical trial information
* Source data
* Source documents
* Case report forms
* Study protocol
* Documentations
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WHO Principles of GCP: Principle 11
With regards clinical trial information, what does the term "handling" refer to?
* a sequence of events i.e. how data are “maintained, analysed, interpreted, shared, transmitter and reported…” to other interested parties.
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WHO Principles of GCP: Principle 11
With regards clinical trial information, what does the term "reporting" refer to?
Whos responsability is it to report clinical trial information?
* The act of providing information or data to another party. For instance, regulatory parties may request for unanticipated adverse events to be reported within a specified timeframe
* Responsibility for reporting clinical trial information is shared by the study monitor, sponsor, clinical investigator(s) and IEC/IRB
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WHO Principles of GCP: Principle 11
With regards reporting what is the clinical investigators responsability?
* Investigators have duty to preserve the accuracy of the results.
* ]According to the Declaration of Helsinki, clinical trial reports that do not abide with the principles set by this declaration, should be classified as unsuitable for publication.
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WHO Principles of GCP: Principle 12
What is principle 12?
How is it applied?
* The confidentiality of the clinical trial participants must be respected and protected in accordance to the applicable regulatory requirements.
* Applied through processes to ensure that the privacy of the participant is protected; relies heavily on the informed consent process, which involves explaining the confidentiality element of the contract.
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WHO Principles of GCP: Principle 12
What forms the basis of principle 12?
* The Declaration of Helsinki emphasises that precaution must be taken to ensure that the privacy of the participants are always respected and care must be taken to minimise how the study may influence the participants physical and mental integrity
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WHO Principles of GCP: Principle 12
What does the term "privacy mean" in this context?
* Privacy refers to the right of each participant to control personal and delicate information concerning them.
* Privacy indicates that sensitive/personal information, which may be noted in medical records, will be protected and not disclosed without permission of the specific individual.
* Thus, participants of the clinical trial study must be informed to what extent their personal information will be protected and the circumstances that this may be breached.
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WHO Principles of GCP: Principle 12
What does the term "confidentiality" mean in this context?
* Confidentiality embraces the philosophy that authorities who obtain personal information from patients and participant will protect the information and any records that contain such information from unauthorised disclosure.
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WHO Principles of GCP: Principle 12
Whos responsability is it to ensure that confidentiality of patients information is followed?
* Responsibility is shared by the study sponsor, monitor, IECs/IRBs, investigator, and regulators.
* This information includes the participants’ CRFs, source data, documents, and safety reports. According to the Declaration of Helsinki
“it is the duty of the physician in medical research to protect the life, health, privacy, dignity of the human subject”.
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WHO Principles of GCP: Principle 13
What is principle 13?
How is it implemented?
* Investigational compound must be manufactured, handled and stored in accordance with Good Manufacturing Practice (GMP)
Implemented through
* Characterisation of the investigational compound
* Compliance with GMP standards
* Categorical use of the investigation compound
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WHO Principles of GCP: Principle 14
What is principle 14 and how is it implemented?
* Developing procedures that assure the quality of every aspect of the clinical trial.
* Implemented through the development of procedures to regulate, assure, and enhance the quality of experimental data and activities relating to the clinical research.
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WHO Principles of GCP: Principle 14
What does the term "quality" refer to in this context?
* Serves as an indication of the capability of the product or process to satisfy the intentional use.
* In terms of clinical trial, it refers to the accuracy and/or the reliability of the results, processes, and GCP.
* In most cases, the quality of data is assured through the development of SOPs
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WHO Principles of GCP: Principle 14
What does the term "quality control" mean?
* Refers to the steps taken during the production of a product/compound or service, to assure product/service quality.
* This phrase refers to methods taken during the clinical trial to ensure that the trial follows the study protocol and is compliant with the applicable regulations
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WHO Principles of GCP: Principle 14
What does the term "quality assurance" refer to?
* The process of establishing whether the quality control system is effective and operational.
* In relation to clinical trials, quality assurance is applied by the study sponsor through independent auditing of quality regulatory activities, which can be carried out during or after the clinical trial.
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WHO Principles of GCP: Principle 14
What does the term "quality improvement" refer to?
* refers to the process of applying the knowledge gained through the quality assurance audits to implement changes in systems and activities in order to increase the ability to satisfy quality requirements of the study.
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WHO Principles of GCP: Principle 14
What does the term "monitoring" refer to?
* Quality control activity performed by the sponsor or delegated representative, to ensure that the study is conduced in accordance to the protocol, GCP and associated regulatory requirements.
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WHO Principles of GCP: Principle 14
What does the term "auditing" refer to?
* independent quality assurance activity performed by sponsors' to assess the effectiveness of a monitoring system.
* Unlike monitoring, which is performed while the study is occurring, auditing can occur at anytime during or after the study.
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WHO Principles of GCP: Principle 14
What does the term "inspection" refer to?
* Act by regulatory authorities of reviewing documentations, facilities, records and other resources that are associated with the clinical trial study.
* The purpose is to establish whether research was conducted in compliance with the study protocol, GCP and applicable enforced regulations.
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WHO Principles of GCP: Principle 14
Who's responsability is it to implement principle 14?
* Responsibility of implementing quality systems for the clinical trial are shared by the study sponsors, clinical investigators, IECs/IRBs and regulatory authorities.
