Cancer clinical trials

Question 1

What is the definition of a clinical trial?

Answer 1

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

Question 2

What are the interventions that may be used in clinical trials?

Answer 2

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

Question 3

What are the phases in clinical trials?

Answer 3

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’

Question 4

What is the worth of clinical trials?

Answer 4

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

Question 5

What was the first clinical trial?

Answer 5

In 1747 James Lind used control groups in his experiments to prove that fruit could prevent scurvy

Question 6

What phases of development have clinical trials gone through to reach the point where they are at today?

Answer 6

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

Question 7

What are the general ethical considerations that are important in clinical trials?

Answer 7

Respect for persons
Maori and ethical considerations
Justice
Beneficence and nonmaleficence
Integrity
Diversity

Question 8

How must respect for persons be taken into consideration in clinical trials?

Answer 8

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

Question 9

What Maori and ethical considerations must be taken into account for clinical trials?

Answer 9

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

Question 10

How must justice be taken into account in clinical trials?

Answer 10

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)

Question 11

How must beneficence and nonmaleficence be taken into account in clinical trials?

Answer 11

The risks of the study should be reasonable in light of the benefits
Early engagement of the community

Question 12

How must integrity be taken into account of clinical trials?

Answer 12

This means the investigator has a duty to: conduct honest and thoughtful enquiry
Undertake rigorous analysis
Be accountable for his or her activities

Question 13

How must diversity be taken into account in clinical trials?

Answer 13

Investigators should have an understanding and respect for the diversity of patients and their communities

Question 14

How is good trial design and good ethics complementary?

Answer 14

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

Question 15

How does equipoise result in ethics u research design?

Answer 15

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

Question 16

What is the protocol of ethics in research design?

Answer 16

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

Question 17

How can conflicts of interest in clinical trials be addressed?

Answer 17

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

Question 18

Who are typically the participants in clinical trials?

Answer 18

Primary participants are usually individuals however some may be communities

Question 19

What are the study groups in clinical trials?

Answer 19

These enable the comparison of outcomes for participants, with most studies having a control group or intervention group

Question 20

How does participant selection occur in clinical trials?

Answer 20

This needs to reflect the population that will ultimately potentially benefit from the intervention and cannot exploit nor exclude vulnerable individuals

Question 21

How does randomisation occur in clinical trials?

Answer 21

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

Question 22

What is allocation concealment in clinical trials?

Answer 22

This prevents those assessing participants from knowing which group they will be entered into and prevents selection bias

Question 23

What is blinding in clinical trials?

Answer 23

This prevents people involved in study from knowing which group the participant has been allocated to
These studies may be single or double blind

Question 24

How do placebos play a role in clinical trial?

Answer 24

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

Question 25

What is the difference between an investigatory, principal investigator and sponsor in clinical trials?

Answer 25

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

Question 26

What occurred in the Nazi medical experiments?

Answer 26

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

Question 27

What were the Nuremburg trials?

Answer 27

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

Question 28

What was the Tuskegee syphilis experiment?

Answer 28

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

Question 29

What was the result of the Tuskegee syphilis experiment?

Answer 29

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

Question 30

What was the thalidomide disaster?

Answer 30

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

Question 31

What are the roles of ethics committees in clinical trials?

Answer 31

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

Question 32

What is the role of regulatory approval in clinical trials?

Answer 32

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

Question 33

How does data monitoring occur in clinical trials?

Answer 33

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

Question 34

What is ICH good clinical practice?

Answer 34

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

Question 35

What is the purpose of ICH good clinical practice?

Answer 35

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