1 - Clinical Trials Flashcards

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1
Q

What is the gold standard for clinical trials?

A

Blind randomised controlled trial as blinding reduces bias, random minimises confoundiing and comparison with a control enables additional therapeutic benefit

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2
Q

What is the definition and purpose of a clinical trial?

A
  • Form of planned experiment which involves patients and is used to decide the most appropriate method of treatment for future patients
  • Used to collect evidence of the efficacy and safety of the treatment in testing
  • After results you then look at 95% CI to see if statistically significant and if p>0.05 due to 1 in CI then can reject null
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3
Q

What does efficacy and safety mean when testing a treatment in a clinical trial?

A

Efficacy: ability of the intervention to improve health

Safety: ability of the intervention to do no harm

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4
Q

In order to be a fair comparison of efficacy and safety what three conditions must a clinical trial satisfy?

A

RANDOMISED CONTROL TRIAL

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5
Q

What are the different phases of drug development?

A

- Research: look at lots of compounds and animal testing may be implemented. Screening of different compounds through HTS

- I: small no of healthy volunteers

- II: small no of patients with disease

- III: large no of patients with disease and first control

- IV: long term safety after approval

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6
Q

What are the disadvantages of non-randomised clinical trials and the use of historical controls in a clinical trial?

A

- Non-random: allocation bias and confounding

- Historical controls: selection less defined, old group may be treated differently (e.g different hospital protocols decades ago), less information about confounders, unable to control confounders

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7
Q

What are the steps involved in a RCT?

A

1. Define the factors: disese of interest, treatments being compared, outcomes being measured, possible confounders, eligible patients

2. Conduct the trial: identify a source of patients and invite/consent eligible patients to the trial. Allocate the patients in a random way to stop allocation bias and confounding, e.g random number generator. Follow up patients and minimise loss

3. Comparison of Outcomes: is there an observed difference, is it statistically significant, is it clinicall important or a big enough difference, was the study design good

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8
Q

What is the p value?

A

p<0.05 as the null hypothesis is out of the CI so cannot reject the null

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9
Q

Why must outcomes be defined before a clinical trial?

A
  • Prevent data dredging and repeated analysis
  • Created a protocol for data collection and agreed criteria for measurement of outcomes
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10
Q

What are the different type of outcomes measured in a clinical trial?

A

- Primary outcome: main outcome and preferably the only one

- Secondary outcome: any other outcomes of interest e.g side effects

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11
Q

What are some features of an ideal outcome to investigate?

A
  • Relevant
  • Valid
  • Sensitive
  • Specific
  • Cheap

Best outcomes should be followed up for a long time but often too expensive

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12
Q

When in a clinical trial should you measure outcomes?

A

- Baseline at beginning to look for differences in groups

- During the trial to see if patients are being harmed or disadvantaged

- Final measurement at the end

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13
Q

What are the advantages of random allocation?

A
  • Random allocation allocates participants to treatments fairly, e.g equal number of smokers in each group
  • Better with larger studies and historicals that use random allocation can be used
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14
Q

Why may the clinician or the patient knowing the treatment allocation cause bias in the results?

A
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15
Q

What is blinding and the purpose of it in a clincial trial?

A
  • Used to minimise measurement bias, allocation bias and stop patients altering their behaviour
  • Difficult to do if treatment is surgical, if two treatments give different side effects or alternative medicine
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16
Q

What is an example of blinding used in a previous clinical trial?

A
  • Make treatments appear identical e.g appearance, tast, dosage regime, warnings
  • Get pharmacies to put different codes on the bottles so we can tell which treatment is which
17
Q

What is a placebo and what is the placebo effect?

A

Placebo: inert substance made to appear identical to the active formaltion to cancel out placebo effect. Used to see if difference between treatment and non-treatment is due to new treatment or coincidence/behaviour

Placebo effect: patient’s attitude to their illness/their illness itself may be imporved if they feel something is being done about it

18
Q

What are the ethical issues with the use of placebos?

A
  • Form of deception so must inform patients they may recieve a placebo
  • Placebo should only be used when no standard treatment is available
19
Q

What are the two different types of loss to follow up in a clinical trial?

A

- Appropriate: patient’s clinical condition may worsen so need to be removed from the trial

- Unfortunate: loss to withdrawal

20
Q

How can you minimise loss to follow up?

A
  • Be honest at the start about commit required for trial
  • Make follow up convenient and practical
  • Maintain contact with participants
  • Avoid coercion and inducements
21
Q

Apart from loss to follow up, patients in a clinical trial may non-comply with their treatment. How can we avoid this?

A
  • May not comply as may have misunderstood intructions, may not like taking treatment, may not think treatment is working, can’t be bothered
  • Simplify instructions and ask patients about side effects. Can also monitor compliance with tablet count and urine samples
  • Never possible to guarantee 100% compliance and follow up so note this in analysis
22
Q

What is an explanatory trial?

A
  • Trials that only analyse those who completed follow up and fully complied. This is As-treated analysis
  • Compares physiological effects of treatment better but loses randomisation
23
Q

What is a pragmatic trial?

A

Analysis is done according to allocation regardless of follow up/compliance. This is Intention-To-Treat analysis

  • Preserves randomisation, minimises selection bias and confounding. Gives more realistic sizes of effects
24
Q

What analysis is used in a clinical trial?

A

Intention-to-Treat

25
Q

What are two ways that we can interpret whether a new treatment is better than the old one?

A
  • Is the physiological action better?
  • Is the new treatment better in routine clinical practice, e.g will more patients comply for example?
26
Q

What are the collective and individual ethics of using humans in medical research, and why do RCTs still run even though they do not satisfy these ethics?

A

- Declaration of Helsinki: the health of my patient will be my first consideration

27
Q

What are some issues the Research Ethics Committee may have when deeming whether a clinical trial is ethical?

A
28
Q

What is clinical equipoise?

A
  • When there is reasonable uncertainty or genuine ignorance about the better treatment or intervention
  • Need to have this to launch a RCT
  • Cannot withold a well established treatment
29
Q

When is an RCT scientifically robust?

A
  • When it addresses a relevant or important issue
  • When it has an appropriate study design and protocol and has the potential to reach sound conclusions. Also has provisions for monitoring safety of participants and arrangements for reporting and publication
30
Q

What are some issues that can arise with ethical recruitment?

A

- Inappropriate inclusion: e.g participants not likely to benefit (AIDs), participants with high risk of harm (pregnancy), participants likely to be excluded from analysis (small sub-group of ethnic group)

- Inappropriate exclusion: e.g people who differ from ideal homogenous group, people who are difficult to get valid consent from (mentally ill, immigrants)

31
Q

How is valid consent gained for a RCT?

A
32
Q

What does voluntariness mean in the ethical criteria of a RCT?

A
  • Participants decision to take part in the trial should be free from coercion or manipulation
  • If the participant is under influence so that they act uncharacteristically this is unethical and consent is not valid
33
Q

What is the role of the Research Ethics Committee?

A

Make sure the dignity, rights, safety and well being of participants is the primary consideration of any research study

34
Q

What are they key points for interpreting a clinical trial?

A
35
Q

Why would you use intention to treat analysis?

A
  • Preserves randomisation
  • More like real life as contains non-compliers
36
Q

Why are randomised controlled trials top of the scientific evidence hierarchy triangle?

A
  • Can randomise properly so confounding minimised and can infer causality. Check an RCTs baseline characteristics at the start
  • If RCT would be unethical, e.g make 500 smoke and 500 ecig, use a cohort study