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Introduction to clinical trials

BENG495
Nathalia Peixoto
Spring 2014
Main references used here
http://www.clinicaltrials.gov/

Concise Guide to Clinical Trials
Author: Hackshaw, Allan K.
Publisher: BMJ Books
Original Publication Date: 04/2009

National Cancer Clinical Trials System for the 21st Century : Reinvigorating the NCI Cooperative Group Program
Author: Nass, Sharyl J. Institute of Medicine
Publisher: National Academies Press
Original Publication Date: 2010 .

Design, Execution, and Management of Medical Device Clinical Trials
Author: Abdel-aleem, Salah M.
Publisher: Wiley
Original Publication Date: 08/2009

Slides by Dr D.Keefe,
The Cancer Council of South Australia
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How did clinical trials start?
On a boat, 1747 James Lind

http://www.med.uc.edu/departme/cellbiol/ecm.htm
Dr Lind and scurvy
http://askabiologist.asu.edu/explore/sailors-called-limeys
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Scurvy results (eat more fruit)
showed:
Importance of comparison (several groups)
Importance of keeping the same
characteristics (sailors sitting on the same side
of the boat)

It did not use:
Randomization: only introduced in 1948.
Studies in health research
Observational and
experimental.
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Issues with observational studies
Confounding variables
http://sjccfthynet.blogspot.com/2012/02/thyroid-cancer-clinical-trials-what-you.html
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Objectives of a clinical trial:
Definition
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Why do we need clinical trials?
We need to know that any treatments we
recommend are both safe and effective in
humans.
Cell culture and animal work can only take us
so far!
People are always looking for the miracle cure-
and it is easy to get dragged into the idea.
Scientific, medical, evidence-based paradigm.
Types of Clinical Trials
Treatment trials
Prevention trials
Early-detection trials/screening trials
Diagnostic trials
Quality-of-life studies/supportive care studies
Genetic trials




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Why would you want a small clinical
trial?
Design is important
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Types of clinical trial
phase I, II or III
randomized or not
blinded or not
involve a placebo or not
pilot study or not


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Clinical trials, phase I, II, and III
# people Length Purpose
% Drugs
Successfully
Tested
Phase I
Approx 30 Several
months
Safety; initial
dosage
70%
Phase II
Up to
several
100
Several
months to
2 yrs.
Short term safety;
mainly
effectiveness
33%
Phase III
100s to
several
1000
1 to 4 yrs. Safety, dosage &
effectiveness
<25%
Concepts in clinical design
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Effective is not efficacious
Effective treatment provides positive results in a usual or routine care condition that
may or may not be controlled for research purposes but may be controlled in the
sense of specific activities are undertaken to increase the likelihood of positive
results.
Effectiveness studies use real-world clinicians and clients, and clients who have
multiple diagnoses or needs.

In contrast, efficacious treatment provides positive results in a controlled
experimental research trial.
A study that shows a treatment approach to be efficacious means that the study
produced good outcomes, which were identified in advance, in a controlled
experimental trial, often in highly constrained conditions.


Translating efficacious practices to routine practice settings to
produce effective results is one of the more challenging issues
of evidence-based practice.
http://www.amhd.org/cebp/concept3.html
Randomised Clinical Trials
Equal chance to be assigned to one of two or more groups
One gets the most widely accepted treatment
(standard treatment)
The other gets the new treatment being tested, which
researchers hope and have reason to believe will be
better than standard treatment
All groups are as alike as possible
Provides the best way to prove the effectiveness of a new
agent or intervention
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What is a blind experiment?

http://www.dcscience.net/?p=239
Open versus Blinded Clinical Trials
Open Label clinical trials
The doctor and patient know which drug or
vaccine is being administered

Blinded clinical trial
Single Blind: the patient doesnt know which
treatment he/she is getting

Double Blind: neither doctor nor patient knows
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Placebo control
The new treatment is tested against an
inactive (or dummy) treatment that looks the
same
Involve people who have a specific condition
Test new treatments, new combinations of drugs
or new approaches to surgery
Determine the most efficacious treatment for
people who have that condition
Test safety and efficacy of new agents or
interventions in people with condition

Treatment Trials
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Evaluate the effectiveness of ways to reduce the
risk of the disease or prevent its recurrence
Enroll healthy people at high risk for developing the
disease being prevented
Assess new means of detecting disease earlier in
healthy people

Prevention Trials
How are patients rights protected?
Ethical and legal codes that govern
medical practice also apply to clinical trials
Informed consent
Review boards
Scientific review
Institutional review boards (IRBs)
Data safety and monitoring boards
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Informed Consent
Informed consent is a document designed to inform the
patient of the purpose and design of a clinical study,
possible side effects and benefits and if there are any
other options. It should also include information on
Voluntary participation
Duration of trial
Insurance and compensation
Name and phone number of contact person
Procedures
Individual rights and confidentiality

http://paxbalkana.blogspot.com/2011_06_01_archive.html
Review boards
Scientific review
Panel of experts
Institutional review boards (IRBs)
Qualified people to evaluate new and ongoing trials
All institutions that conduct clinical trials must, by law, have a IRB
that approves the protocol
Data and safety monitoring boards:
Ensure that risks are minimized
Ensure data integrity
Stop a trial if safety concerns arise or objectives have been
met

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Are trials ethical?
Yes, in general they are.
We (the scientific community) strive to make them so.
There are unscrupulous people (and companies) in any
area
Guidelines make it easier for us to check up on ourselves!
Are trials safe?
Yes (usually)
There are stringent guidelines in place
Safety and toxicity are closely monitored
Trials have built-in stopping rules
Subjects are indemnified
Indemnified = compensated for loss or damage / reimbursed
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How can we tell they are done properly?
The Declaration of Helsinki*
GCP (good clinical practice) guidelines
Transparency and good communication
Use of institutional ethics committees

* World medical association publishes a 5 page statement of ethical
principles for medical research:
http://www.wma.net/en/30publications/10policies/b3/17c.pdf
So what do I personally do if I have an idea for a
trial?
Consider the question I want to answer
Write a draft protocol
Decide if it is a phase I, II, III or pilot study
Write the Ethics Committee application
Submit to IRB (complete CITI training first!)
Work out where funding will come from