Unit 4- Clinical Trials Flashcards
What is a clinical Trial?
A rigorously controlled experimental technique for assessing the effectiveness of a medical intervention
Discuss the two types of clinical trial study designs
Observational – case report, retrospective case-study (looking at factors effecting incidence/outcome, prospective cohort (those who don’t have the disease yet – incidence like HRT therapy causing breast cancer)
Experimental – randomized control trial with a group of patients randomly allocated to different arms
What could be the purpose of a trial?
To investigate:
- A treatment
- A preventive strategy – vaccine/lifestyle
- Screening/diagnosis tests
- Quality of life
Describe a phase 0 trial
Looks at pharmacokinetic parameters (ADME) – given at 1/100th of pharmacological dose which is crude. A week
Describe a phase 1 trial.
Looks at dose escalation with ADME, toxicity and MTD – usually involved a small group of healthy volunteers or terminal patients. A few months
What factors were responsible for issues associated with TGN1412 trial.
- Short time span between initial 2 patients and remaining 6- this was not enough time to monitor toxicity
- Preformed at a private site rather than hospital to delay response time
- Ignorance of significance in vivo observation – low level cytokine release in animal models
- Extrapolation of in vitro data to human – CD28 receptor structure differences in primates and humans
Describe a phase 2 trial
To assess; effectiveness of treatment, appropriate dosing regime and safety in randomized arms (usually with placebo). Several months to years
Describe a phase 3 trial.
To assess
a. Safety and effectiveness
b. Confirm dose regime
c. Identify possible side effects and contraindications
d. Allow assessment of benefit vs risk
e. Compare results against existing treatment
I. Use large number of patients – 100s-1000s in multiple countries
II. Lasts for several years
III. If passes this phase, a pharmaceutical company can seek regulatory approval for marketing
What information is required by the FDA/MHRA/EMA for regulatory approval
- Methods and results of human/animal studies
- Manufacturing procedures – GMP – consistent high-quality production
- Formulation
- Shelf-life
What is a phase IV trial
Looks at the long-term or rare adverse effects over a much larger patient population – which may also reveal new possible drug interactions. Troglitazone – hepatitis (liver failure)
What is the difference between blind and double-blind trials??
Blind – the patient does not know which arm of the trial they are in (placebo vs drug) but the conductors of the trial do.
Double-blind – neither the patient or those conducting the trials know which arm the patients are in
What is an open-label trial?
Where the researcher and the participants know which treatment is being administered
What factors make up good-clinical practice?
- Scientific rationale
- Objectives of the study
- Design of the study
- Methodology of the study
- Statistical consideration
- Protect the rights, safety and well-being of study participants
What do staff members of clinical trials have to ensure?
- They do not coerce patients into trials
- Have to manage patient expectation
- Communication risks and benefits
- Explain randomization
- Have to be neutral to prevent bias
Describe the Nuremberg code
- Those involved must give voluntary and informed consent
- These must be scientific rigor and design of the research
- Autonomy of decision making – patients are not pressured into taking part
- Avoidance of harm to the patient
- The right to withdrawal at any time without repercussions
