clinical trials Flashcards
describe controlled clinical trials
series of test scientists need to conduct when they come up with new ideas for new drugs, medical procedures or medical devices.
describe phase I objectives
- assess safe and tolerated dose
- see if pharmokinetics differ much from animal to man
- detect any predictable toxicity
requirements:
- healthy volunteers
exception:
women of child bearing age, children
phase I
First in Man : Small number of healthy volunteers
First in a small group of 20 to 25
Start with a dose of about 1/10 to 1/5 tolerated animal dose
Slowly increase the dose to find a safe tolerated dose
If safe in a larger group of up to about 50 –75
No blinding
Performed by clinical pharmacologists
Performed in a single centre
Takes 3 – 6 months [ 70% success rate]
phase II
First in patient [ different from healthy volunteer]
Early phase [20 – 200 patients with relevant disease]
Therapeutic benefits & ADRs evaluated
Establish a dose range to be used in late phase
Single blind [Only patient knows] comparison with standard drug
Late phase [ 50 – 500]
Double blind
Compared with a placebo or standard drug
Outcomes
Assesses efficacy against a defined therapeutic endpoint
Detailed P.kinetic & P.dynamic data
Establishes a dose & a dosage form for future trials
Takes 6 months to 2 years [ 35% success rate]
phase III
- large scale, random, controlled trials
- 250-1000 patients target
- performed by clinicians in hospital
methods used: - multi centric = geographic and ethnic variations
- randomised allocation of test drug/placebo/standard drug
- double blinded
- vigilant recording of all adverse drug reactions
- rigorous statistical evaluation of all clinical data
takes up to 5 years = 25% success
phase IV or post marketing surveillance
no fixed duration/patient population starts immediately after marketing report all adverse reactions helps detect: - rare ADRs - drug interactions - also new uses for drugs
participating parties in clinical trial
- patient/healthy volunteer
- clinical pharmacologist, clinical investigator And team
- institution where trials are held
- research ethics committee or institutional ethical committee
- sponsor
- regulatory authorities
functions of parties 2
[4] Research Ethics Committee or Institutional Ethical Committee:
Supervises and monitors every step;
Safeguard the welfare and the rights of the participants
[5] Sponsor (responsible for trial)
Pays for all expenses;
Appoints competent investigators,
Ships all drugs for the trial,
Files all papers to legal / regulatory authorities,
[6] Regulatory Authorities:
Legal authority on the outcomes of the trial (e.g. MHRA, HPA ect)
clinical trial protocol
Title & Abstract Introduction General statement of purpose Complete Preclinical results on animal study Clinical data if available Goals: Primary & secondary objectives Study Design: Type of study Recruitment criteria : Exclusion & Inclusion criteria Randomisation criteria and Sample size Duration of study Data Analysis: Case report forms, Statistical Analysis, Bibliography
type of observational studies
cohort studies:
- group of subjects followed over time
- purpose: defining incidence and investigating potential causes of a condition
- can be prospective - investigator chooses a sample group and measures characteristics in each subject over a period of time that might predict outcomes
- can be retrospective = all data collection and follow up has happened in past, only possible if adequate data is available
experimental/intervention studies
these studies evaluate effects of an intervention
types of intervention:
- behaviour modification
- drug
- device (e.g. new investigational stent - subject to FDA regulations
strength: can demonstrate causality
describe parallel vs crossover designs
parallel = simple treatment versus placebo
crossover = comparison of treatment and placebo made in each subject
- allows each subject to be a control such that treatments can be assessed in each subject
- period effects, carry-over effects, sequence effects all need to be considered
- long duration and more complex
- smaller study sample required for power
running of clinical trial
1) recruitment (adverts)
2) Screening (inclusion/exclusion criteria)
3) Informed Consent after patient information sheet
4) Randomisation/blinding
5) Protocol visits step by step procedures (deviations have to be communicated to sponsor and ethics research committee)
6) Reports of adverse events
7) Store investigatory product
8) Subject compensation
9) Electronic data collection
10) Study closure
what is informed consent
- voluntary
- explained in simple non technical language
- translated in the native language of the subject
- comprehensive info regarding trials = benefit of new therapy over old, alternative treatment available
- all possible adverse reactions
- freedom to withdraw from the trial (any time, without reason)
ethical issues/rules
treated with respect
not harmed in any way
fully informed about what is being done
