Clinical trials

Question 1

What is the Investigational Medicinal Product?

Answer 1

Investigational medicinal product- pharmaceutical formulation -> active comparator and placebo. Marketed medicinal product used or assembled in a different way -> outside SPC-> Further info about product

Question 2

Who is an investigator?

Answer 2

An investigator is a health care professional (doctor, nurse, pharmacist, dentist) responsible for the conduct of the trial at the site

Question 3

Who is the chief investigator?

Answer 3

The chief investigator has the primary responsibility of the conduct of a trial

Question 4

Who is a qualified person?

Answer 4

A qualified person is a member of the institute of biology, RPS or other such bodies. It is responsible for the release of investigational medicinal products to be used in clinical trials.

Question 5

What does good clinical practice consist of?

Answer 5

Good clinical practice is an international ethical, and scientific standard for: designing, auditing, monitoring, peformance, analysing and reporting trials that include the participation of humans. Compliance of GCP provides the safety and well being of trial subjects are protected and that the results from the data obtained are relaible and credible.Any risk associated with the trial must be justified using an anticipated benefit. The rights and the well being of the patients should prevail over the interests of science and society. Furthermore, freely given informed consent should be given from all subjects.

Question 6

What is good manufacturing practice?

Answer 6

Practice that is apart of quality assurance which ensures that the medicinal products that are constantly produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorisation or product specification.

Question 7

Define a clinical trial

Answer 7

A clinical trial is a carefully and ethically designed experiment with the aim of answering some precisely framed questions.

Question 8

What is the protocol?

Answer 8

A formal document that describes all aspects of the trial. The design of the protocol is clinical to the outcome of the trial, as poorly designed trials can result in unsafe, unethical and unscientific conclusions, which could be harmful.

Question 9

What is the background?

Answer 9

The background is the: pathology of the disease, rationale for the development of the novel compound,( new drug or improving existing). The preclinical data should be available to date.

Question 10

What are protocol objectives?

Answer 10

These are derived from the hypothesis being testedThe end point of a trial should be stated, eg: stopping of seizures.

Question 11

What is a Pilot exploratory?

Answer 11

The first study conducted in humans (healthy volunteers). They aim to examine practical feasibility and is not statistically powered.

Question 12

What is a pivotal study?

Answer 12

A pivotal study is one which is critical in the submission dossier for a product licence. The pivotal study design defines crucial landmarks such as what the efficacious dose is and the confirmation of bioequivalence. This should be randomised and statistically powered design. The subject numbers must be a coefficient to enable the objectives to be met. This is the likely to be the subject if regulatory audits for a product licence application.

Question 13

What is an open label study?

Answer 13

A study where everyone apart of the trial is aware of the drug being taken, including the patients themselves. However, as everyone is aware of what drug is being taken, this can introduce bias with regards to prejudice or preference. This should be avoided unless it is on compassionate grounds, treatment investigational new drug application or phase 1 dose ranging in terminally ill patients.

Question 14

Define blinding

Answer 14

Blinding is where one or more parties is unaware of the identity of the treatment. The 3 parties consist of: an investigator, a subject and the sponsor. A single blind test is when one party such as the analyst is unaware. Double blind 2 parties eg: investigator and subject are blind. This aims to reduced bias in the data, but this increases both complexity and cost.

Question 15

Define randomisation

Answer 15

Subjects assigned a group by chance. Bias lowered in groups of people as the particular target group cannot be targetted. The randomisation can be stratified and balanced for treatments and subjects, taking into account factors such as: age and gender, smoking status, alcohol intake, stage of a particular disease and the genetic profile.

Question 16

What are controls?

Answer 16

Controls are used to confirm the validity of the study design as they are used as a benchmark when assessing new therapy. The choice of control depends on the phase of development and the specific objectives of the trial. There are two main types of controls. These are placebos and active comparators (used in phase 2 and 3 studies). Placebo has no pharmacological action. Reduces bias and background noise from when interpreting data. Important for distinguishing pharmaceutical and psychological effect and can help in identifying any incorrect conclusions.

Question 17

What are parallel designs?

Answer 17

Parallel designs involve taking subjects randomly and allocationg to a treatment group. The subject numbers increased in order to achieve statistical power. There are no treatments to enable carry over- only treatment, Ideally a stable disease condition is required. Note: high intra subject variability

Question 18

What are cross over designs?

Answer 18

Cross over designs - each treatment in a random order separated by an appropriate washout period. This reduces intra subject variability as all subjects have to take part in all treatments. The subjects are able to act as their own controls. Smaller numbers of people needed to get statistical power. A stable disease conditon is essential and the patients are subject t carry over and period effects (roughly 5.5 half lives). However there are several withdrawals and dropouts. TCross overs are ussually selected for early phase drug development.

Question 19

What are integrated protocols?

Answer 19

Single protocols that are very useful om early clinical development. They combine exploratory, flexible and adaptive in one study, which is usually divided into a small number of parts. Single protocols
These are tightly controlled investigation producing
reproducible serial homogenous data without
compromising safety or scientific validity.

Advantages:
• Allows a more focussed scientific investigation
of safety, exposure and activity
• Maximises information gathering under very
controlled conditions
• Where possible allows a go/no go decision
about compound progression to be made earlier
• Permits a more rationale dose selection for
later phase studies

Question 20

What are adaptive clinical trials?

Answer 20

•A clinical study design that uses accumulating data to
decide how to modify aspects of the study as it
continues, without undermining the validity and
integrity of the trial.’
• Any changes should not be ad hoc, but ‘by design.’
• Adaptive designs are not a solution for inadequate
planning, but are meant to enhance study efficiency
while maintaining validity and integrity
• When considering an adaptive design feasibility,
validity, integrity, efficiency, and flexibility should be
assessed.

Permits interim analyses of critical data (efficacy, safety)
– Allow the utilization of emerging data (patient
outcomes) to alter patient allocation or some other
aspect of the study design
– Appealing when credible responses can be
observed at an early stage
– Ensures the study design is still appropriate for long
running trials
– Allows improvement of patient outcomes without
compromising statistical validity in a timely manner
– Can improve safety
– Offers significant ethical and cost advantages over
standard fixed designs