1. clinical trials Flashcards
Definition of a Clinical Trial
Any form of planned experiment which involves patients and is designed to elucidate the most appropriate method of treatment for future patients with a given medical condition
Purpose of a Clinical Trial
To provide reliable evidence of treatment efficacy
and safety
define efficacy
the ability of a health care intervention to improve the health of a defined group under specific conditions
define safety
the ability of a health care intervention not to harm a defined group under specific conditions
what are the 5 Stages in Drug Development & Monitoring, who are the stages tested on and how many people?
Pre-Clinical Phase - Laboratory studies
• Pharmacology, Animal toxicology
• Cell cultures, Animals
Phase I- Volunteer studies
• Pharmacodynamics, Pharmacokinetics, Major side-effects
• <100 healthy volunteers
Phase II - Treatment studies
• Effects and dosages, Common side-effects
• <1,000 patients
Phase III- Clinical trials
• Comparison with standard treatments
• <10,000 patients
Phase IV- Post-marketing surveillance
• Monitoring for adverse reactions, Potential new uses
• Whole population
what needs to be considered in clinical trials?
- Inclusion criteria
* Exclusion criteria
Reasons for Pre-Defining Outcomes
Need to define what, when and how outcomes are to be measured before start of the clinical trial:
– prevent ‘data dredging’, ‘repeated analyses’
– have a clear protocol for data collection
– agreed criteria for measurement and assessment of
outcomes
Primary outcome
– preferably only one primary outcome
– used in the sample size calculation
Secondary outcomes
– other outcomes of interest
– often includes occurrence of side-effects
Types of Outcomes
- Patho-physiological
- Clinically defined
- Patient-focused
examples of Patho-physiological outcomes
– tumour size
– thyroxine level
– other biomarkers
examples of Clinically defined outcomes
– death (mortality)
– disease (morbidity)
– disability
examples of Patient-focused outcomes
. – quality of life
– psychological well-being
– social well-being
– satisfaction
Features of an Ideal Outcome
• Appropriate and Relevant – to patient, clinician, society, etc.
• Valid and Attributable – any observed effect can be
reasonably linked to the treatments being compared
• Sensitive and Specific – chosen method of measurement can detect changes accurately
• Reliable and Robust – outcome measurable by different people in various settings → similar result
• Simple and Sustainable – method of measurement is easily carried out repeatedly
• Cheap and Timely – not excessively expensive to measure nor has a long lag time
How do we show comparability between groups?
• We need to try to ensure groups compared are
as equivalent as possible.
• One way of demonstrating ‘comparability’ between groups is by collecting baseline data on characteristics that we think may relate to both the condition and the outcomes we are investigating
Suggested baseline data
- Age
* Gender
What are the most important ethical considerations
for any trial to go ahead
- Trials of new drugs may do harm
- So…you should only conduct a trial if you are genuinely in ‘clinical equipoise’ and don’t know what is best treatment for patients.
- Patients/participants must understand what participation involves (including known and unknown risks)
In order to be able to give a fair comparison of effect
and safety, a clinical trial needs to be?
- Reproducible – in experimental conditions
- Controlled – comparison of interventions
- Fair – unbiased without confounding
Explain the disadvantages of non-randomised
clinical trials
• Non-randomised clinical trials involve the allocation
of patients receiving a new treatment to compare with a group of patients receiving the standard treatment
BUT
• Allocation bias – by patient, clinician or investigator
• Confounding – known and unknown
Non-Random Allocation
Allocation of participants to treatments by a person, historical basis, geographical location, convenience, numerical order, etc. leads to the potential for allocation [aka. selection] bias and confounding factors to unwittingly cause unidentified differences between the treatment groups being compared
Comparison with Historical Controls?
Comparison with historical controls involves the comparison of a group of patients who had the standard treatment with a group of patients receiving a new treatment