Clinical trials

Question 1

Who conducts clinical trials?

Answer 1

In Canada, they are sponsored by the company developing the drug and are legally responsible for the experiment

Each trial has a principal investigator who supervises the trial (medical doctor)

Question 2

Where are clinical trials conducted?

Answer 2

• Universities and hospital research institutes (30%)
• private clinical research organizations (70%)

Question 3

How can someone participate in a clinical trial?

Answer 3

• contact family doctor (refer to the site investigator)
• Call site directly

Question 4

What is the goal of a telephone interview?

Answer 4

see whether you are eligible to participate according to the trial entry criteria

Question 5

What happens after a telephone interview?

Answer 5

screening visit

Question 6

What happens during a screening visit?

Answer 6

• asked if you want to enter the trial
• receive an info package (with an informed consent form)
• run tests (questionnaire/ physical)

Question 7

How does someone decide whether to participate in a clinical trial?

Answer 7

• discuss trial with doctor, friends, family
• contact previous trial participants
• consider all factors (time, risks, benefits)

Question 8

In Canada, how does someone find out about clinical trials?

Answer 8

Government of Canada website

Question 9

How is a phase 1 trial designed?

Answer 9

dosing is guided by preclinical animals, multiped by a safety factor

Test doses in ascending order (rise over time)

Question 10

What is a single ascending dose study?

Answer 10

tests one dosage level of drug once

Question 11

What is a multiple ascending dose study?

Answer 11

tests one dosage level over many days

Question 12

Who’s in a phase 1 trial?

Answer 12

Healthy volunteers

exception: oncology

Question 13

Why are phase 1 cancer clinical trials tested on “not healthy” volunteers?

Answer 13

these drugs have a risk-benefit ratio that makes them too risky and ethically unacceptable for healthy volunteers

Question 14

How does someone start participation in a phase 1 clinical trial?

Answer 14

contact the place where the trial is being conducted
- the research organization
- or the hospital

Question 15

What are some questions that want to be answered in phase 1?

Answer 15

• what doses are tolerated?
• what doses are safe?
• how does the drug move in the body?

Question 16

How does someone tell if a drug is safe?

Answer 16

• Clinical signs (how does a person feel)
• biomarkers

Question 17

What is an adverse event?

Answer 17

any undesirable experience associated with the use of a medical product in a patient

Question 18

What is a serious adverse event?

Answer 18

a subset of adverse events
the event is serious and should be reported to FDA when the patient’s outcome is very serious

Question 19

How and why are the pharmacokinetics of a drug tested in phase 1?

Answer 19

frequent blood and urine tests to measure drug concentration in bodily fluids

gives an indication of where the drug is moving, how quickly it is being absorbed, and how quickly it is eliminated

Question 20

What happened during a phase 1 clinical trial in 2016?

Answer 20

a drug for treating anxiety
July 2015 - October 2015, single ascending dose (given one dose) for 64 volunteers (went from 0.25 to 100 mg)

November 2015, multiple ascending doses. The fifth group received 50 mg daily, which resulted in one person brain dead and 5 in the hospital

Question 21

Why did the accident in 2016 occur?

Answer 21

a likely gradual accumulation in the brain, which explains why the accident took place on the fifth day

Question 22

What went wrong with the selection of patients in the 2016 accident?

Answer 22

the dead man had previously suffered a head injury (the drug is aimed at the head)
and another patient has hypertension (high blood pressure)

Question 23

What is an inclusion criteria?

Answer 23

it ensures that relatively similar people take part in a trial, which allows for more reliable comparisons of the drug

Question 24

what is an exclusion criteria?

Answer 24

protects people who might be harmed by the study drug

Question 25

What are some qualities of a good biomarker?

Answer 25

Sensitivity: the fraction of person with disease characterized as sick by the test

Specificity: the fraction of person without the disease characterized as healthy by the test

Question 26

How do people know that a drug is effective is phase 2?

Answer 26

• based off biomarkers

Phase 2 trials are shorted (compared to phase 3) and biomarkers are well suited for that

Question 27

What are some biomarkers for HIV/AIDs drugs?

Answer 27

• Viral load (blood test)
  (high viral load = virus replication quickly in body)
• CD4 cell count (# of immune system cells that have CD4 receptors)
  (low of falling CD4 count can mean HIV is progressing)

Question 28

How does Lurasidone act in the brain?

Answer 28

• dopamine D2 receptors
• serotonin receptor

Question 29

What medical conditions has Lurasidone been approved for?

Answer 29

• schizophrenia
• Bipolar depression

Question 30

What were some inclusion criteria for lurasidone trials?

Answer 30

• not pregnant or nursing (no pregnancy within the trial)
• good health

Question 31

What were some exclusion criteria for lurasidone trials?

Answer 31

• risk of self-harm
• chronic organic disease of the CNS
• Hospitalization for a manic or mixed episode in the past 2 months
• Used investigational compound within the past 6 months
• clinically significant history of alcohol or substance abuse within past 3 months