Lectures 9&10 - Study design

Question 1

what is a clinical trial?

Answer 1

a planned experiment on humans, designed to measure the effectiveness of an intervention (usually a new drug but may be surgical procedure, vaccine or complementary therapy)

Question 2

what is the difference between an observational study and a clinical trial?

Answer 2

observational study: the investigator measures what happens but does not control it

clinical trial: investigator allocates one group to one procedure and another group to another and measures the outcome

Question 3

what are the necessary steps to conduct a clinical trial?

Answer 3

• define your intervention
• define your comparator: placebo, alternative treatment, standard of care
• define inclusion/exclusion criteria

Question 4

what are the features of a clinical trial?

Answer 4

• experimental study
• must have control group
• prospective
• patients treated and followed over same period of time
• randomisation
• blinding

Question 5

what are the 3 types of randomisation?

Answer 5

• block randomisation
• stratification
• minimisation

Question 6

what ethics and consent regulations must all clinical trials have?

Answer 6

• Registered
• Reviewed by an independent scientific committee
• Approved by a Research Ethics Committee
• Adhere to gov’t and international guidelines

participants must provide informed consent and be free to withdraw at any time without affecting their care

Question 7

at the end of a trial the results are analysed. what may results be presented in terms of?

Answer 7

• efficacy - the true biological effect of a treatment

- effectiveness - effect of a treatment when actually used in a ‘normal’ practice

Question 8

what are the trial outcomes?

Answer 8

• experimental event rate (EER) - incidence in the intervention arm
• control event rate (CER) - incidence in the control arm
  (relative risk = EER/CER)
• absolute risk reduction (ARR) - CER - EER
• number needed to treat (NNT) - 1/ARR

Question 9

what is involved in Phase 1 trials?

Answer 9

• safety of a new treatment is tested
• side effects looked at
• involves only a small number of people (usually healthy volunteers)

Question 10

what is involved in phase 2 trials?

Answer 10

• test the treatment in a larger group of people (usually few hundred) who have the disease relevant for the treatment so see whether the treatment is effective in the short term
• look at safety

Question 11

what is involved in phase 3 trials?

Answer 11

• test the treatment in a larger group of people (often several thousand)
• recruit people from multiple locations/different countries
• compare the new treatment with the treatment currently in use or a placebo
• look at how well the treatment works and any side effects

Question 12

what is involved in phase 4 trials?

Answer 12

• done after the drug/treatment has been marketed to gather information of the drug’s effect in various populations and assess any side effects associated with long-term use

Question 13

what did studies on circumcision conducted in Africa show?

Answer 13

lower levels of HIV infection in men - medical male circumcision can reduce the risk of sexually-acquired HIV infection by approximately 60%

Question 14

how may prevalence of HIV in African tribes be measured?

Answer 14

• blood or saliva testing (e.g. ELISA)

- self-report

Question 15

what issues do different methods of determining HIV prevalence present?

Answer 15

• participation bias - who’s data was not available on the day?
• self-reporting errors of HIV and circumcision
• sensitivity (positive/true positives) and specificity (negatives/true negatives of the HIV test)

Question 16

what is relative risk?

Answer 16

the incidence in the exposed group (e.g. non-circumcised) divided by the incidence in the non-exposed group (e.g. circumcised)

Question 17

what does relative risk show?

Answer 17

how many times higher/lower the risk of acquiring a disease is when an individual is exposed to a factor

Question 18

use the factors that evaluate statistical association to suggest why the risk of HIV infection in non-circumcised men is more than 8 times higher than circumcised men in Africa

Answer 18

CHANCE - possibility of study findings being due to chance because of small study
BIAS - selection bias as men who visit prostitutes were the only ones sampled
CONFOUNDING FACTORS - tribal differences in sexual behaviours, condom use etc.
CAUSAL EFFECT - If all else is ruled out then circumcision may be causally related to HIV

Question 19

what are the arguments for use of circumcision in reducing HIV?

Answer 19

could dramatically reduce HIV infection rates in men and women and could prevent the epidemic from progressing as fast, until a vaccine or other preventative strategy is identified

Question 20

what are the arguments against use of circumcision in reducing HIV?

Answer 20

circumcised men are still vulnerable as they can still become infected so circumcision should be used as part of a wider strategy to reduce infection rates (e.g. condom use, HIV testing and counselling, treatment for STIs)

Question 21

what are the WHO/UNAIDS recommendations for male circumcision?

Answer 21

it should be considered an effective intervention for HIV prevention in countries with heterosexual epidemics, high HIV and low male circumcision prevalence