clinical trials 1 - history, trial process

Question 1

what is a clinical trial

Answer 1

medical research studies

reasons:

• prevent disease and reduce number of ill people
• treat illness
• improve quality of life
• disease and diagnosis
• for interventions to modify lifestyle/behaviour

Question 2

origins of clinical trials - bible

Answer 2

in the bible - book of Daniel

people ate meat or vegetables
vegetarians appeared better than meat eaters

Question 3

history of clinical trials - scurvy (1747)

Answer 3

treated sailors with different food supplements

oranges and lemons = quick recovery

first description of controlled trial and systematic review of previous literature on scurvy

Question 4

history of clinical trials - Jenner (1700s)

Answer 4

rural GP in England noticed milk maids didn’t get small pox as they had all previously had cow pox (milder and shorter lasting)

1976 = first experimental vaccination on 8 year old - infect with cow pox to prevent small pox

it worked, but this would be illegal today

led to modern day vaccination

when he presented findings, was rejected - so he collected a larger sample

still ridiculed - especially by religious groups

Question 5

history of clinical trials - vaccination in 1800s

Answer 5

major hospitals did clinical trials of vaccination following Jenner’s findings

basis of rigorous clinical trials

Question 6

history of clinical trials - placebo

Answer 6

first defined in early 1800s

first study with placebo = 1863, remedy for rheumatism - all reported positive effects even though there’s no active part of treatment

Question 7

history of clinical trials - double blind

Answer 7

1943 = first double blind controlled trials - for Patulin (related to penicillin for the common cold)

1000 subjects from offices and factories suffering from common cold

Dr’s and patients were blinded to treatment

BUT results failed to show an effect

Question 8

history of clinical trials - randomised curative trial

Answer 8

1946 = first trial - streptomycin to treat tuberculosis

systematic and randomised enrolment to treatment and control groups

Dr’s looking at x-rays were blind to patient groups

groundwork for clinical trials used today and frameworks/regulations

Question 9

why are clinical trials important

Answer 9

evidence for best way to compare approaches

without them, could prescribe medicines which don’t work, waste money/resources, medicine could make patients worse

Question 10

who is in control of clinical trial process

Answer 10

designed by doctors and specialist

but involves variety of people: doctors, nurses, patients, statisticians, trial managers, and pharma companies

to make best possible trial

for least risk to patient and maximum potential for testing of new treatment or intervention

begins with systematic review of previous trials in a similar area of disease with similar drugs

Question 11

gaining ethical approval for clinical trials (+ 5 focuses)

Answer 11

ethics committee = independent group of people including drs, nurses, medical staff, lawyers, members of public (maybe)

focus on:

• potential benefits, do they outweigh costs
• clear info given to participants
• approach participants appropriately
• compensation for if it goes wrong
• travel expenses

trial cannot begin until ethical approval

Question 12

clinical trial sponsor

Answer 12

specifically in the NHS

need funding by a sponsor: individual, company, institution

take on responsibility for initiation, management, and financing of research

all research under the remit of Secretary of State for Health must have a formal sponsor

sponsorship involving medicines:

It is a legal requirement for any clinical trial of an investigational medicinal product (CTIMP) to be sponsored. This includes provision for insurance in case things go wrong

Question 13

4 phases of clinical trials

Answer 13

0. preclinical
1. early stage
   small groups of healthy subjects (but sometimes patients)
   test how safe the treatment is
   is there any side effects
2. know a lot more about treatment
   test larger group
   assess safety and side effects in more detail
   first time to see if there is a positive effect of treatment
3. hundreds-thousands of people, often international
   compare new drug to standard treatment
   how well drug works
   how long effects last for
   serious side effects and how long they last
4. drug is licensed and used as treatment
   stats on how well drug is working on large population
   long term risks and benefits
   rare side effects

Question 14

define controlled trials

Answer 14

to compare different treatments

usually 2 groups (trial groups) given new treatment

control group given standard treatment

if there’s no standard treatment, control group may not be given and treatment or may be given placebo

Question 15

define blind trial

Answer 15

participants not told which group they are in

double blind = participant and person administering/assessing do not know which group they’re in

Question 16

define randomisation

Answer 16

usually by a computer

no biases and groups with similar mix of age/sex/health etc.

therefore if one group is better than another it is likely to be due to the treatment

otherwise outcome could be biased

Question 17

define informed consent

Answer 17

cannot do a trial without consent

different processes without consent for those with dementia or those being treated for head injuries

for these, a relative or legal representative will safeguard for them

Question 18

informed consent in children

Answer 18

participant or representative has to have the study fully explained by the recruiter:

• aim
• how you will be treated
• what you need to do
• risks and benefits

enough info is needed for full informed consent

questions are encouraged to make the decision - no pressure on family

Question 19

what is assessed in a trial other than the treatment effects

Answer 19

• side effects
• new symptoms
• quality of life, day to day
• mental state
• cost effectiveness
• ability to work

Question 20

what happens at the end of a trial

Answer 20

• participants have access to results
• published
• treatment used may not be on NHS so they may go back to standard treatment
• other times you can buy new treatment

all info MUST be kept confidential

Question 21

what happens if something goes wrong in a trial

Answer 21

arrangements are made before the trial starts

ethics committees can refuse it if they aren’t in place

participants know insurance is in place before trial starts

Question 22

Thalidomide case

Answer 22

drug marketed as sleeping pill safe for pregnant women in late 1950s

also said it helped morning sickness

but then babies were born with malformed limbs

because no animal testing was done on pregnant animals

it is still being used to treat leprosy

in USA, the FDA was pressured to approved but Frances Kelsey refused and saved many lives

Question 23

cost and success rate of clinical trials

Answer 23

they are expensive

average cost of a 5.5 year (non-pharmacological) clinical trial involving data across 20 centres in UK would cost £1 million to administer

highest cost = staff needed (managers, researchers, statisticians)

then also cost of ethical approval etc was 30%

UK cost of developing a drug to market is £1.1billion

only 1 in 10 drugs make it through stage 4 in clinical trials

partially explains why drugs are so expensive due to this high failure rate