What is clinical trial and how does it work? Flashcards
What are 4 phases of clinical trials?
pre clinical phase 1 phase 2 phase 3 phase 4
What are controlled clinical trials?
MHRA- medical and healthcare regulatory agents
FDA- food and drug administration of USA
Phase 1
-safety of drug
20-30 healthy volunteers
=>months
phase 2
-safety study
-identify side effects
-measure effectiveness
-100-300 patients
=> 6 months to 2years
Early phase: 20-200 patients with disease:
-therapeutic benefits
Late phase 50-500
-double blind
-compared with placebo or standard drug
Outcomes :
- assess efficacy against a defined therapeutic endpoint
- establishes a dose
Phase 3
- measure effectiveness
Method:
-multicentric : ensures geographic and ethnic variations
-Randomised allocation of test drug/placebo/standard drug
-Double blinded:
-vigilant recording of all adverse drug reactions
-rigorous stastical evaluation of all clinical data - monitor side effect
-1000 -3000 ppl
=>years to decade
phase 4
- long term side effects monitored
-post marketing surveillance
-helps to detect:
rare ADRs, Drug interactions, new uses of drugs.
=> ongoing
Which parties participate in clinical trial?
- patient/health volunteer
- clinical pharmacologist , clinical investigator
- institution where trials are held
- research ethics committee (REC) or institutional ethical committee
=>supervise and onitor every step
=>safeguard the welfare and rights of participants - Sponsor
=>pays all expenses
=>appoints competent investigators
=>ship all drugs for trial
=>files all papers to legal - regulatory authorities
=>legal authority
MHRA, HPA
What is the structure of clinical trial protocol?
- Title and abstract
- Introduction
- general statements of purpose
- complete preclinical results on animal study
- clinical data available - Goals: primary and secondary objectives
- Study design:
- type of study
- recruitment criteria : exclusion and inclusion criteria
- randomisation criteria and sample size
- duration of study - Data analysis
- case reports forms , statistical analysis
Types of observational studies
cohort studies
- group of subjects followed over time
- purpose: defining the incidence and ivestigatiing potential ccauses of a condition.
- can be prospective
- can be retrospective
Experimental/intervention studies
- these studies evaluate the effects of an intervention types of intervention: -Behaviour modification -drug -device strength : can demonstrate causality
What is parallel design?
-simple treatment versus placebo
What is crossover designs?
-comparison of treatment and placebo made in each subject
What are advantages of crossover?
- allows each subject to be a control such that treatments can be assessed in each subject
- smaller study sample required for power
What are disadvantage of crossover?
- period effects, carry over effects , sequence effects all need to be considered
- longer duration and more complex stats
what are steps in running a trial?
- recruitment
- screening
- informed consent after patient information sheet
- Randomisation/double blinded
- protocol visits step by step procedures
- reports of adverse events
- store investigatory product
- subject compensation
- electronic data collection
- study closure
What should informed consent be?
- voluntary
- explained in simple nontechnical language
- comprehensive information regarding the trials
- all possible adverse reactions
- freedom to withdraw from the trial
Ethical considerations
- treated with respect
- not harmed in any way
- fully informed about what is being done
Syphilis study
- originally designed to make treatment available to african -American men with syphilis
issues:
1. Men were recruited without their consent
2. Misinformation about procedures, ie. 6 month duration and free health care
3. After penicillin was proven an effective treatment, men were denied antibiotics and prevented treatment from military and local physician.
Nuremberg (1947)
- rials of Nazi doctors and scientist from WWII
- Did NOT follow these guidelines:
1. need for informed consent
2. Research should be based on prior animal work
3. Risks should be justified
4. only qualified scientists must conduct research
5. physical and mental suffering must be avoided
6. no research where death/serious injury is expected.
What are good clinical practices?
- kown GCPs
- Misnomer- they are rules/regulations for the conduct of research
- standard for design, conduct, performance, monitoring, analyses and reporting of research
- even though established for drug studies, they dictate appropriate conduct for all research
What are key principles of good clinical practice?
- anonymity
- confidentiality
- Data protection
- consent
