Basics of drug development and clinical trials

Question 1

why must a drug be thoroughly tested before it is used in patients?

Answer 1

To ensure that it is relatively well tolerated

any risks or SEs do not outweigh the relative benefits

Question 2

Clinical trials are designed to answer what question(s)?

Answer 2

• Does the new treatment work in humans?

- Does the new treatment have an acceptable safety profile?

Question 3

How many phases exist in clinical trials ?

Answer 3

4

Phase I - IV

Question 4

what occurs during pre clinical studies?

Answer 4

basic info about a drug’s safety profile

drug is tested in vitro (in isolated biological systems e.g. cancer cells cultured in labs) OR in vivo ( in non human living organisms)

once preclinical testing is done, researchers will determine if a drug is suitable for testing in humans in phase I safety and tolerability trial.

Question 5

Phase I

Answer 5

Healthy volunteers are recruited for the majority of phase I CTs

however cancer pts are recruited for phase I trials of oncology drugs

• what is the right dose?
• what is the dose response?
• what is the safety and toxicity profile?

Question 6

Phase II

Answer 6

Involves for pts

researchers gather more safety data & begin to investigate the efficacy of a drug in specific tumour types or identify the optimal dose

• is it effective?

Question 7

Phase III

Answer 7

To demonstrate whether a product offers a treatment benefit to a patient population compared with a control

number of patients: 100s - several 1000s

depending on the sample size required to demonstrate a statistically significant improvement in outcomes

• how effective?
• what is the safety and toxicity profile?

Question 8

Phase IV

Answer 8

Carried out post approval of a drug and often involve observing several 1000 pts with the disease who have been prescribed the drug as part of routine treatment.

aim to investigate the benefits and risks associated with longer term use in patients outside of a CT setting.

thus more representative of real life clinical practice

Question 9

what are the key endpoints for oncology CTs?

Answer 9

• Overall survival (OS) GOLD STANDARD
• Time to tumour progression and progression free survival
• Overall response rate
• time to treatment failure
• patient reported outcomes

Question 10

Overall Survival (OS)

Answer 10

time from randomisation to death

widely acceptable endpoint

Question 11

Time to tumour progression

progression free survival

Answer 11

TTP: time from randomisation to time of progressive disease

PFS: time from randomisation to objective tumour progression or death

PFS may be preferred over TTP from a regulatory standpoint, as it includes death and may correlate better with OS

Question 12

Overall response rate

Answer 12

The sum of complete and partial responses

direct measure of anti- tumour activity

Question 13

Time to treatment failure

Answer 13

time from randomisation to treatment discontinuation for any reason

generally not accepted as a valid endpoint from a regulatory perspective

Question 14

Patient reported outcomes

Answer 14

Symptomatic and QOL improvement

Gaining importance with both clinicians and regulators as pt views are further taken into account

Question 15

as per good clinical practice guidelines, what info must be reported in CT protocol and study reported intended for submission to regulatory authorities ?

Answer 15

• the number of subjects enrolled
• a description of the statistical methods
• the level of significance to be tested

Question 16

what are statistical concepts used for/

Answer 16

to assess a drug’s performance

Question 17

what is a clinical study?

Answer 17

A research study using human subjects to evaluate biomedical or health related outcomes

Question 18

what is a clinical Trial?

Answer 18

AKA “interventional study”

finds out whether a treatment works

pts are assigned to specific interventions such as medical treatment(s).

Question 19

observational study?

Answer 19

Gathers information

pts are observed, usually in a RW clinical setting, but not assigned to specific treatments

Question 20

what are the types of observational studies?

Answer 20

Cross sectional studies

case control studies

cohort studies

case series & case reports

Question 21

cross sectional studies:

Answer 21

observe a specific population at a point in time

search for associations between risk factors and disease.

Question 22

case control studies:

Answer 22

compare pts with a condition to matched pts without the condition

usually retrospective (evaluate pts’ histories)

search for associations between risk factors and disease

Question 23

cohort studies:

Answer 23

follow 1 or more groups for pts over time

groups are often matched for age, gender, race/ethnicity and other relevant characteristics

usually prospective

evaluate factors associated with differences in outcomes

Question 24

case series & case reports

Answer 24

observe a single patient, a few patients or a series of patients

describe outcomes associated with treatment