Trials Flashcards
What is Blinding?
In a single blind study – patients do not know which study group they are in and whether they are taking part in an experimental or a placebo. In a double blind test- not the patient nor the researcher know . Triple blind test- the patnet,clinician and the people carrying out the statistical analysis do not know which treatment had what.
What are the phases of a clinical trial?
- 1 First administration and safety evaluation- using healthy volunteers- exploratory. - 2 Early exploratory and dose establishing studies in diseased vilunteers –
exploratory and confirmatory - 3 Large scale studies in diseased volunteers – confirmatory
- 4 Post marketing safety monitoring – post market surveillance.
Explain what phase 1 of a clinical trial Is?
The aim is to find preliminary information about the effects of a drug when introduced to a human- safety,tolerability,bioavailabilty.pharmacokinetics and pharmacodynamics – established in a healthy human volunteer.- healthy as part of the inclusion and exclusion criteria – will just mean someone without the disease,representation of the population as a whole. It is randomised- with a double blind test – blind placebo to compare the drug against. LIMITATION = most volunteers are men – only post menopausal women can take part due to fetility – foetal effects.Genetic polymorphism can affect pharmacokinetic factors and the target population acnt alsos be representative of the whole.
What are 1a, 1b?
A) 4-8 cohorts each cohort 6-8 ppl, take the drug for 6M escalating the dose from one cohort to the next – max tolerated does is recorded – pharmaceutical and pharmacodynamics effects and parameters are established.Cmax – peak conce,tmax- max time takn to reach cmax, Auc- bioavailibilty,total exposure,Half life- rate of eliminating half. Vd- volume distribution, MRT – mean residence time.
RCT
RCT – randomised control trials – there may be a specific
group of pts being treated by a drug – and a control group is taking a placebo – for a set period of time. For trials where conditions have serios side effects a placebo wouldn’t be given as that is unethical – instead best current treatment is used and a comparison is made with the new drug. The outcome of the trial should relate to the overall benefit of the therapy.
What are absolute and relative risks?
The actual risk of an event occurring- relative risk ARTis the risk of of an event occurring in one group compared to the other group.
Absolute risk
Absolute risk is the actual risk of an event occurring; relative risk is the risk of an event occurring in one group compared to another group(s).
Absolute risk reduction (ARR) is the absolute risk of the treated group (ART) subtracted from absolute risk of control group (ARC):
“ARR = ARC – ART”
Relative risk reduction (RRR) is a ratio absolute risk of the treated group (ART) subtracted from absolute risk of control group (ARC):
“RRR = “ “ARC – ART” /”ARC”
What does intention to treat mean?
ITT – an asessmnet of the people taking part in a trial based on the group they wer initially and randomly allocated to .This is regardless of whether or not they are dropped out, fully adhered to the treatment or switch to something that is an alternative.- ITT nanalyses are often used to acess the clinical effectiveness because they mirror the actual practice. When not everone adheres to the medication.and treatment may be changed according to how their condition responds to it.- studies of drug treatments = often use a modified ITT analysis – which includes onlt the people who have taken at least one dose of the drug.
What does numbers needed to treat mean?
This is the number of patients who would have to receive treatment for 1 of them to benefit.
“NNT = “ “1” /”ARR”
What is statistical analysis?
Null hypothesis is sessntial in testing a hypothesis, it essentially is the opposite of what you are looking for– or aiming to prove -
What is the analysis of clinical trials?
Clinical appraisal is the process of carefully and systematically assessing the outcome of scientific reaserch- evidence.to judge if it is worth the amount and value.The validity of the study can be assessed for bias here and the method used and significance of the results should be determined.
What exactly is CASP
critical – appraisal skills program
Critical appraisal is the process of carefully and systematically assessing the outcome of scientific research (evidence) to judge its trustworthiness, value and relevance in a particular context. The validity of a study should be assessed for bias & methods used, and significance of the results should be determined.
What are the appraisal tools, list the 11 present and explain them
Did the trial
address a clearly focused issue?the population studie,the intervention given,the outcomes given,
- Was the assignment of patienst to treatment randomised?(was allocation
concealed from researcher?)
- Were paiteints health workers and study personelle blinded
- Aside from experimental interventions was anything else administered to the
patients?
- Were all patienst who entered the trial properly accounted for?
- How large was the treatment effect
- How precise was the estimate of the treatment
- Can results be applied in the context of the populations
- Were all clinically important outcomes considered?
- Are the benefits worth the harm and costs.
Phase II
The aim is to ensure safety & efficacy, and indicate the dose required for therapeutic effects in a larger group of diseased volunteers.
Phase 2a
The dose and regimen are based on the findings in Phase I. It is randomised, with a double-blind placebo control given to compare the drug against. This stage takes 9 months – 2 years.
Phase 2b
This part of phase II trials is confirmatory – the dose selection supports previous trial findings. Patients with one or more indications are trialled at different doses. It is randomised, with a double-blind placebo control given to compare the drug against. This stage takes 2-3 years.
Phase III
This stage sees a big increase in number of participants, providing confirmatory efficacy and safety data to support registration. The aim is to find statistically rigorous results that clearly demonstrate efficacy and safety and may include pharmacoeconomic data, as an indicator to compare against any drugs existing on the market (if applicable). A power calculation should be performed to ensure all findings are valid.
Patients are chosen if they meet the criteria of the target indication and different sub-groups should be included – age, ethnicity etc. It is randomised, with a double-blind placebo control given to compare the drug against. As a minimum, this stage takes 2 years.
Drugs may fail at this stage due to:
* Insufficient biological activity
* Unacceptable toxicity
* Design flaws (end-point, patient selection, duration, sample size)
* Execution failures (randomisation of patients, analysis of data)
