6. Clinical trials Flashcards
what are clinical trials?
a type of research that studies new tests and treatments and evaluates their effects on human health outcomes
what things can we do a clinical trial for?
- drugs
- vaccines
- life style changes
- cell based treatments
- surgeries
- radiology things
- clinical devices
who did the first organised clinical trials?
Josef Mengele and the Nazi twin experiments
what was the result of Josef Mengele’s experiments?
the declaration of helsinki and the Nuremberg code was made as a result of the Nuremberg trials
what is the Nuremberg code?
a set of rules on what could and couldn’t be done on humans
what is the declaration of Helsinki?
- it overs rides any national laws
- guides all clinical trials
- has 2 fundamental points: respect for the individual and the right to make an informed choice
- everyone running clinical trials undergoes training every 3 years
what are the 5 steps of drug development?
- Discovery and development
- preclinical research
- clinical research
- licencing review
- post-market drug safety monitoring
Process of drug development: discovery and development
Normally a university will get a new insight into disease/disease process
then they used a library of compounds to find potential future drugs and test them in the lab
OR
Use something normally and find out it has side effects that can be useful and it’ll become a new treatment
(like viagra is a an angina drug)
Process of drug development: preclinical research
before you get near a human you need to know if the drug is safe - testing toxicity
1. in lab = in vitro
2. primates/mammal research = in vivo
- controversial but important
- a minimum amount of work is needed to show the drug is safe
- the lab and experiments have to comply to regulations
Process of drug development: Clinical Research
to give the drug to humans
requires loads of paperwork like lorry loads
what is the investigational new drug (IND) process?
- happens before clincal research
- have to tell them it is coming and acts as a prevetting stage
- aims to protect the people you will be testing on
- either approval for trial or held for improvement
what is included in the IND process?
- animal study data and toxicity
- Manufacturing information
- clinical trial protocol
- data from any human research
- info about the investigators and trials team
why might a drug be prevented from entering clinical trials?
- its not safe
- misleading information in IND
- not happy with the trial leaders like not having enough experience
- too expensive
what do you need to consider when designing a clinical trial?
- who?
- how many people?
- how long for the trial?
- control group? address bias?
- how will the drug be given? at what dose?
- end points?
- agreed safety and efficacy endpoints
what is the protocol for ethical approval?
- all trials are published online
- a pre defined protocol that is submitted for ethical approval
clinical trials: phase 1
- first trial in humans
- 20-100 healthy volunteers or those with the condition
- main aim is to find the safety and dosage for the phase 2 trials and to know it is safe
- often several months long
how are safe doses found in phase 1 trials?
- give a low dose to a few participants and observe side effects
- go to another level of doses and see the side effects
- keep going until we see too many side effects and then back off
- we want to go through the low doses fast as they are the least dangerous
Clincial trials: phase 2
- hundreds of people with the disease condition
- to see the evidence of benefit to the patient
- often several months long but follow up could last longer
Clinical trials: phase 3
- hundreds to thousands of people with the disease condition
- compare against the best current treatment
- randomly allocated groups - double blind is the best so both the doctors and patients don’t know who has which treatment
- years long
what happens after a phase 3 trial?
regulatory drug review
what is a regulatory drug review?
- take the drug back to the regulatory body to get the drug licenced
- New drug application with lots of paperwork
- every single bit of paper from lab work to clinical trial
- drug bottles
- labelling
- sterile process
- patient information - yes or no and what we can use it for
4.UK and USA mirror approval
why might a drug be approved but not funded by the NHS?
due to value for money and the NHS often negotiates drug for cheaper
a threshold of amount of QALIs need to be met before funding
except for rare condition with not frequent treatment
what is a QALI?
a quality adjusted life year
Clinical trials: phase 4
- the drug is approved but often needs thousand of patients to get an idea of overall safety
- doctors/pharmacists constantly inform the authorities about adverse events they see
- once more people take it more side effects are seen like interactions with other drugs
what is the success rate of clinical trials?
very low around 10%
improved slightly due to biomarkers and genetics
what are the costs of conducting trials?
phase 1: 3/4 million
phase 2: 10ish million
phase 3: 30-50 million
what is the cost of bringing drugs to market?
around $1.1-1.5 billion (including failed trials)
cancer drugs cost the most
periods of exclusivity help companies earn back money and make profit
what are the challenges of trials?
- Equipoise - needing to have a balanced view and knowing not everyone who wants the new drug will get it
- time
- demanding on the patients - extra tests/scans and travel, hate the randomisation of the trials
why did the covid vaccine enter the market so quickly?
- BioNTech was already looking at similar viruses and developing vaccines
- regulatory processes were fast tracked and everything else was side lined
