Clinical Trials & Drug Discovery

What are clinical trials?

Medical research studies involving people

How were clinical trials recorded in the bible?

The king allowed people to eat vegetables and water for 10 days to see the outcome

What was the first clinical trial in the modern era?

James Lind’s scurvy trial

What was the first ever experimental vaccination?

Edward Jenner on an 8 year old boy using cow pox to prevent small pox

When were placebos first coined?

Early 1800s in Hoopers Medical Dictionary

When was the first double blind controlled trial?

1943 with Patulin (related to penecillin for common cold)

When was the first randomised curative trial?

1946 using Streptomycin to treat tuberculosis

Why are clinical trials so important?

Without trials people would be given medicines that do not work, waste resources or make things worse

Who is in control of the clinical trial process?

Doctors, nurses, patients, statisticians, trial managers and representatives from pharmaceutical companies to design the best possible trial

Who can give ethical approval?

A research ethics committee which is an independent group of people that includes doctors, nurses, other medical staff, members of the public and sometimes lawyers

What is a sponsor in context of NHS research?

Individual, company, institution or group of organisations that takes on responsibility for initiation, management and financing of the research.

What does sponsorship of involving medicines mean?

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.

What is phase 1 of clinical trials?

Generally small groups of healthy subjects but sometimes patients – Used to test how safe the treatment is are there any large side effects

What is phase 2 of clinical trials?

This will now be tested in a larger group of people to assess safety and side effects in greater detail

For the first time to see if the treatment has a positive effect in patients

What is phase 3 of clinical trials?

Moves up to hundreds if not 1000s of people often international groups of people

Compare the new drug to a standard treatment

How well drug works and how long the effects last for

Finds out more about any serious side effects and how long they last for.

What is phase 4 of clinical trials?

The drug is now licensed and being used as a treatment

Gets stats on how well the drug is working on a large population

Any long term risks and benefits

Rare side effects.

What are controlled trials?

• Designed to compare different treatments

• Usually two groups – trials group – given new treatment

• Control group given standard treatment –

• Where no standard treatment  - the control group may not be given any treatment or may be given a placebo

What are blind trials?

• Participants are not told which group they are in

• Some trials are double blinded – this means participants and teams treatment them do not  know which group they are in – takes away any bias toward of the team treating the patient in terms of hoping that its going to work.

• Really important for all groups not to know or guess which one they are in – treatments must look identical

What is randomisation?

• This is essential and is usually assigned by a computer

• Ensures their no biases and groups have a similar mix of ages, sec and state of health

• With random allocation – if one group does better than the other – it is likely that it is the treatment that is working

• If it were left to the doctor to assign, then they might be influenced by putting patients they think will respond into the treatment group – biasing the outcome

What is informed consent?

A doctor, nurse or other researcher should always ask your permission to enter you into a clinical trial

How does informed consent affect children?

The process involving children is again different and the has to be fully explained by the person recruiting to the trial

What happens during a trial?

• As well as test to assess whether the treatment is working the researchers will also assess

  • Any potential side effects

  • Any new symptoms

  • Wider effects of treatment such as quality of life, day to day activities

    • Your mental state is the treatment making you happy, sad, anxious or depressed?

  • Cost effectiveness of treatment – are you able to work, how often you need to visit the doctor

What happens at the end of a trial?

• All participants will have access to the results of the trial if they want them.

• They will also be published to help other researchers in the field and allow advancements to be taken up by everyone

• In some instances the treatment used as part of the trial may not be available on the NHS – at the end of the trial you will be given the standard treatment.

• In some cases you may be able to buy the new treatment

• All you information will be kept confidential : a key requirement of the trials process.

What happens if something goes wrong?

• Before the start of any trial arrangements need to be put in place in case something goes wrong an people are harmed

• Ethics committees can refuse permission if this is not in place

• Important for participants to know that insurance is in place before the trial starts.

What are the costs and success rates of clinical trials?

Very expensive due to failures

What is the Valley of Death?

his process of going from drug discovery to developing a new medicine

What is discovery in the drug discovery process?

Finding new drugs through tests, new insights, existing treatments and new tech

What is development in the drug discovery process?

Figuring out the best method of entering the body, the dosage, toxicity, interactions and comparisons with other drugs

What is in vitro testing?

often looking at how cells in a test tube are effected by the treatment

What is in vivo testing?

often involving small animals usually mice, but for some studies especially brain diseases, non-human primates may be used in the later stages

What is good laboratory practice?

Basic requirements for study conduct & facilities

Why do clinical studies fail?

Focusing on the wrong aspect of treatment, late interventions, need early biomarkers

Is the ADNI approach working?

Theoretically yes

What may clinical trials in future contain?

Using more targeted approaches to select more targeted patient populations

How can clinical trials be sped up?

Funding and infrastructure development