L37 Clinical Trials LA

Question 1

What does the “protocol” contain

Answer 1

backround on:

• Pathology of the disease
• Rationale for development of the compound
• Rationale for the study
• Information on the past and current developments.

Protocol design uses simple writing tyles and flow diagrams as visual aids.

Question 2

What are the protocol objectives?

Answer 2

Derived from the hypothesis being tested -> e.g is A more effective than B?

Study endpoints need to be clearly stated -> e.g asthma frequency reduction

needs to be SMART:
Specific, Measurable, Achievable, Releastic, Timely

Question 3

What is a blinding trial?

Answer 3

Identity of treatment is known by 1 or more parties.

single blind trial is when only one party is aware.

double blind is when two parties are unaware. More commonly used.

Blinding trial is beneficial as it avoids bias in the interpretation of data.

BUT increase blindness means increasedd study complexity and costs

Question 4

How many parties are there in clinical trials

Answer 4

Sponsor, Investigator, Patient

Question 5

What is a randomised trial?

Answer 5

Subjects will be assigned to a treatment group be chance.

Normally involves two similar treatment arms: Drug vs Placebo

The purpose is to reduce bias with data interpretation.

Randomisation can be stratified via various factors:

• age + gender
• smoking status
• alcohol intake
• disease stage
• genetic profile

Question 6

What is a control

Answer 6

used as a comparison benchmark. Determines the efficacy of the drug being tested.

choice of control depends on study objective and phase of development

Question 7

State the different types of controls. and what they’re for

Answer 7

Reference Standards -> for PK studies in phase 0 and 1

Placebo -> for phase 1 and 2a studies

Activr comparator -> phase 2a and 3

Question 8

what are placebos when to use placebos?

Answer 8

Placebos are inert medicines.

• used to remove physcological factor -> so only account for the pharmacodynamic factors.
• Used in early phase studies to determine whether investment is worthwhile.
• Used in later phase studies if no standard treatments are available,
• Reduces bias so avoid incorrect conclusions
• Exception: Unethical to replace current treatment with a placebo.

Question 9

what is a pilot exploratory study

Answer 9

phase 0 and 1

Question 10

phase 2 and 3 studies are

Answer 10

pivotal! They confirm safety and efficacy.

Question 11

what study type is generally unused and why

Answer 11

open label study

Question 12

Outline a parallel design

Answer 12

Taking subject randomly and allocating to a treatment group.

The subject numbers aer increased to achieve statistical power

There are no periods to enable carry over. Only Treatment.

Ideally a stable disease condition is requried.

Question 13

Outline a crossover design

Answer 13

• mainly used in early phase drug development
• Fewer subjects required -> still able to achieve statisitcal power
• All subjects will be given both placebo and active treatments in random orders
• Between each treatment -> sufficient washout period required.
• Subjects act as their own controls -> but compromised by dropouts

Question 14

What is an integrated protocol

Answer 14

a form of an adaptive trial:

Mainly used early in development.
Flexible and adaptive, progressing the study in a safe and appropriate manner.

Combines various studies and forms a single protocol.

Question 15

What is an Adaptive Trial Design

Answer 15

Uses emerging data to modify aspects of the study

Enhances study efficiency + does not undermine validity and integrity of the trial

permits the use of interim analysis of critical data