Cancer clinical trials Flashcards
What is the definition of a clinical trial?
Any study where the investigator intentionally controls one or more factors relating to the health of the participant in order to study the effects of this
What are the interventions that may be used in clinical trials?
Use of a new procedure such as a drug, device, vaccine, surgical or other technique
Use of an established procedure for new purpose
Withholding or altered administration of a procedure
Change in the method of care delivery
Diagnostic, prophylactic or therapeutic
What are the phases in clinical trials?
Phase 1 clinical trials which are for safety and pharmacology investigation
Phase 2 clinical trials which test pilot efficacy, expanded safety and feasibility
Phase 3 clinical trials which are for a complete assessment of safety and efficacy
Phase 4 clinical studies
These are often observational and test the effects of the intervention in ‘field conditions’
What is the worth of clinical trials?
Provide objective results that establish the safety and efficacy of new interventions
Evaluation of the safety and efficacy of established interventions
Clinical research structure can improve the pattern of care and quality of services
Developing skills of practitioners in critical thinking, innovation and evidence-based practice
Economic savings from health gains and economic growth from innovation
What was the first clinical trial?
In 1747 James Lind used control groups in his experiments to prove that fruit could prevent scurvy
What phases of development have clinical trials gone through to reach the point where they are at today?
Control groups added in 1747
Placebos used from 1863
1923 randomized concept introduced
1948 there was a randomized control trial involving use of streptomycin to treat pulmonary tuberculosis
What are the general ethical considerations that are important in clinical trials?
Respect for persons Maori and ethical considerations Justice Beneficence and nonmaleficence Integrity Diversity
How must respect for persons be taken into consideration in clinical trials?
There must be respect for autonomy and a capacity for self-determination
Protection of persons with impaired or diminished autonomy which requires those that are dependent or vulnerable are given security against harm
What Maori and ethical considerations must be taken into account for clinical trials?
The special relationship between the crown and Maori under the treaty of Waitangi
Investigators must respect this and where applicable this should be reflected in design and conduct of studies
Issues relating to maori cultural and ethical values should be discussed with maori
Comprehensive maori health research needed
How must justice be taken into account in clinical trials?
This requires that within a population, there is a fair distribution of the benefits and burdens of participation in a study
Avoid imposing unfair burden on particular groups eg the vulnerable
Design fair exclusion and inclusion study
Not to discriminate on grounds of race, age, gender, disability or religious beliefs (except where this is essential to the purpose of the study)
How must beneficence and nonmaleficence be taken into account in clinical trials?
The risks of the study should be reasonable in light of the benefits
Early engagement of the community
How must integrity be taken into account of clinical trials?
This means the investigator has a duty to: conduct honest and thoughtful enquiry
Undertake rigorous analysis
Be accountable for his or her activities
How must diversity be taken into account in clinical trials?
Investigators should have an understanding and respect for the diversity of patients and their communities
How is good trial design and good ethics complementary?
The study question must be important and must not have already been answered
The study design must minimize the risk of harm, be the most appropriate to answer the question and meet ethical standards
How does equipoise result in ethics u research design?
This is the state of evidence, informed by applicable values that is equally poised regarding the comparative overall risk-benefit of two or more options
What is the protocol of ethics in research design?
All studies should be conducted according to written protocols with the details of the protocol being proportional to the risk the study poses
The protocol should be registered with an approved clinical trials register
How can conflicts of interest in clinical trials be addressed?
Investigators should declare any perceived, potential or actual personal conflicts of interest
Declare other conflicts of interest eg patient payments/inducements
Minimize any conflicts of interest
Manage actual, potential or perceived conflicts
Who are typically the participants in clinical trials?
Primary participants are usually individuals however some may be communities
What are the study groups in clinical trials?
These enable the comparison of outcomes for participants, with most studies having a control group or intervention group
How does participant selection occur in clinical trials?
This needs to reflect the population that will ultimately potentially benefit from the intervention and cannot exploit nor exclude vulnerable individuals
How does randomisation occur in clinical trials?
There is assignment of participants to groups which may be randomised, quasi-randomised or not
This is a powerful means by which to eliminate bias
What is allocation concealment in clinical trials?
This prevents those assessing participants from knowing which group they will be entered into and prevents selection bias
What is blinding in clinical trials?
This prevents people involved in study from knowing which group the participant has been allocated to
These studies may be single or double blind
How do placebos play a role in clinical trial?
This is when inactive or dummy interventions are used to assist in comparison of an active intervention which assists in blinding, placebos useful when active therapy is insufficiently active to be a control
What is the difference between an investigatory, principal investigator and sponsor in clinical trials?
An investigator is a qualified individual who conducts all or part of an investigation
A principal investigator has a primary responsibility for the design and conduct of the investigation
A sponsor is an individual, company, institution or organisation which is responsible for the initiation, management and/or financing of a trial
What occurred in the Nazi medical experiments?
During World War II german physicians conducted experiments on concentration camp prisoners without their consent these experiments can be grouped into three categories
Those undertaken by the german air force and german experimental institute for aviation which used freezing experiments to find a treatment for hypothermia
Testing pf pharmaceuticals and treatment methods for field injuries and illnesses
Experimentation to advance racial and ideological views such as the ability of different races to withstand various contagious diseases
What were the Nuremburg trials?
This was when the Drs running the Nazi experiments were put under trial where 16 were found guilty and 7 were executed
This also resulted in the formation of the Nuremburg code which was 10 points defining legitimate research and although this had no legal force it did shape ethics statements for the next 50 years
What was the Tuskegee syphilis experiment?
In 1932 399 african American men with syphallis enrolled on a US public health service study designed to discover how the disease affected them
Free care was offered to monitor bad blood and they were given bismuth, neoarsphenamine and mercury
In the 1940s, penicillin or the cure from syphilis was kept from patients
What was the result of the Tuskegee syphilis experiment?
Of the 399 subjects 28 died of syphilis and 100 of related complications, 40 wives were infected and 19 children were born with congenital syphilis
The PHS was initially unrepentant
What was the thalidomide disaster?
This studied a drug developed by a german company which was intended to help pregnant women rest and reduce morning sickness however the drug caused birth defects when taken during pregnancy
What are the roles of ethics committees in clinical trials?
To protect the rights and well being of participants
Prevent studies that pose an unacceptable risk of harm to participants
Ensure the participants are aware of what their participation involves and have given informed consent
Review of the trial documents such as protocol and informed consent documents provide ethical opinion and give approval or rejection for trial to commence
What is the role of regulatory approval in clinical trials?
Any clinical investigation of an unregistered medicine (or a new application of a registered one) requires regulatory approval
Preclincal data and the trial protocol are submitted for review
In NZ the applications are assessed by and advisory committee of the ministry of health known as SCOTT
How does data monitoring occur in clinical trials?
All clinical trials need a data safety monitoring plan
Most trials require a data safety monitoring board which is responsible for monitoring the performance of trial, safety of participants, and efficacy of treatment
They consider data from interim analysis and can recommend the trial be stopped early if this indicates the intervention is harmful or beneficial
What is ICH good clinical practice?
This was international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use of good clinical practice
Producing a unified standard to conduct clinical trials
Has differing legal status around the world with some variations to local GCP guidelines
However investigators are expected to be familiar and trained in GCP
What is the purpose of ICH good clinical practice?
To protect the rights, well being and confidentiality of trial subjects
To ensure integrity and credibility of clinical trial data
Mutual acceptance of clinical trial data by regulators in the 3 jurisdicitions
