The Basics of Clinical Trials

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The Basics of Clinical Trials

• Dorothy M K Keefe MD FRACP
• Chairman
• Cancer Research Advisory Committee
• Cancer Council South Australia

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What is a Clinical trial?

• A test of a new intervention or treatment on
  people

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Why are Clinical Trials conducted in Cancer?

• To allow medical professionals and patients to
  gain information about the benefits, side effects
  and possible uses of new drugs as well as new
  ways to use existing drugs
• To translate results of basic scientific research
  into better ways to prevent, diagnose, or treat
  cancer

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Why do we need them?

• 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!
• Especially in Oncology, people are always looking
  for the miracle cure-and it is easy to get
  dragged into the idea
• Scientific, medical, evidence-based paradigm

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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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Types of clinical trial

• It can be a phase I, II or III trial
• It can be randomized or not
• It can be blinded or not
• It can involve a placebo or not
• And it can be a pilot study or not

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Phase I

• 15-30 people
• Determines
• what dose is safe
• How the treatment should given
• How the treatment affects the body
• safety

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Phase II

• Less than 100 people
• Determines
• Whether the treatment does what it is supposed to
• How the treatment affects the body
• If the drug or intervention has an effect on the
  cancer
• Does not compare with other treatments

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Phase III

• From 100 to thousands of people
• Equal chance to be assigned to one of two or more
  groups
• Determines
• How the new treatment compares with the current
  standard
• Or how it compares with placebo

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Phase IV

• From hundreds to thousands of people
• Usually takes place after drug is approved to
  provide additional information on the drugs
  risks, benefits and optimal use

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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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Randomisation
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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

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Pilot Study

• A small study that helps develop a bigger study
• A first foray into a particular area
• Used to iron out possible difficulties, and help
  with design of the bigger, more pivotal study.

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Treatment Trials

• Involve people who have cancer
• Test new treatments, new combinations of drugs or
  new approaches to surgery or radiotherapy
• Determine the most effective treatment for people
  who have cancer
• Test safety and effectiveness of new agents or
  interventions in people with cancer

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Prevention Trials

• Evaluate the effectiveness of ways to reduce the
  risk of cancer or prevent the recurrence of
  cancer
• Enroll healthy people at high risk for developing
  cancer
• Assess new means of detecting cancer earlier in
  healthy people

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Early detection/screening/diagnosis

• Early-detection trials/screening trials
• Test the best way to detect early cancer,
• Pap smears, Mammograms
• Blood tests, X-rays
• Detect disease at an earlier stage, resulting in
  improved outcomes
• Diagnostic trials
• Develop better tools for classifying types and
  phases of cancer and managing patient care
• Usually include people who have signs or symptoms

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• Quality-of-life/supportive care studies
• Aim to improve comfort and quality of life for
  patients and their families
• Genetic trials
• Determine how ones genetic makeup can influence
  detection, diagnosis, prognosis, and treatment
• Broaden understanding of causes of cancer
• Develop targeted treatments based on the genetics
  of a tumor

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What happens in a clinical trial?

• Clinical research team check the health of the
  participant at the beginning of the trial, give
  specific instructions for participating in the
  trial, monitor the participant carefully during
  the trial, and stay in touch after the trial is
  completed.
• Tests
• Doctors visits
• Frequent follow up

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Who can participate in clinical trials?

• All clinical trials have guidelines about who can
  participate. Exclusion / inclusion criteria help
  produce reliable results
• Criteria based on factors such as
• Age / Gender
• Type and stage of disease
• Previous treatment
• Medical conditions

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Do Many People Participate in Cancer Clinical
Trials?

• Less than 5 of Adults with cancer participate in
  clinical trials

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Barriers to Participation in Clinical Trials

• Physicians and other health professionals may
• Be unaware of appropriate trials
• Be unwilling to lose control of patients care
• Believe that standard therapy is best
• Believe that clinical trials are more work
• Have concerns about the patients care or how the
  person will react to suggestion of clinical trial
  participation

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Barriers to Participation in Clinical Trials

• Patients may
• Be unaware of clinical trials
• Lack access to trials
• Fear, distrust, or be suspicious of research
• Have practical or personal obstacles
• Be unwilling to go against their physicians
  wishes

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Benefits of Participation in Clinical Trials

• At a minimum, the best standard treatment
• Early access to new treatments. If the new
  treatment or intervention is proven to work,
  patients may be among the first to benefit
• Participation in advancing medical knowledge.
  Patients have a chance to help others and improve
  cancer care
• Active role in own health care
• The medical team conducting the trial will
  carefully and regularly monitor the patients
  progress

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Risks of Participation in Clinical Trials

• New treatments or interventions under study are
  not always better than, or even as good as,
  standard care
• Even if a new treatment has benefits, it may not
  work for every patient
• Unpleasant, serious or even life threatening side
  effects
• May require more time and attention than a
  non-protocol treatment

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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

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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 they 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!
• Dr James will discuss

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Are they safe?

• Yes (usually)
• There are stringent guidelines in place
• Safety and toxicity are closely monitored
• Trials have built-in stopping rules
• Subjects are indemnified

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How can we tell they are done properly?

• The Declaration of Helsinki
• GCP guidelines
• Transparency and good communication
• Use of Institutional Ethics committees

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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 that
• Work out where funding will come from

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RAH Cancer Centre Clinical Trials

• A wide variety of clinical trials are performed.
  These include phase I/II and III studies of new
  drugs, and ongoing program in supportive care and
  psychosocial research

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The Protocol

• A study plan on which all clinical trials are
  base (recipe or blueprint)
• Provides background about the trial
• Describes trials design and organisation
• Ensures that trial procedures are consistently
  carried out
• Each study enrolls people who are alike in key
  ways

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The Sponsor

• Sponsor can be
• Pharmaceutical company
• Co-operative group (NHMRC, TROG, NSABP)
• Another Investigator
• Foundation
• Responsibilities of the sponsor
• update available data
• liaise with the appropriate regulatory bodies
• communication between trial centre and sponsor
• monitoring trial at the site
• ensuring all data collected

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The Investigator

• Profile
• Adequate qualifications to conduct research in a
  given area
• Necessary resources
• Sound knowledge of the investigational drug and
  protocol
• Sound knowledge of GCP
• Responsibilities
• training of staff
• ethics submission
• facilities and equipment
• resources for data collection
• informed consent
• reporting of serious adverse events

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The Clinical Trials Nurse

• Patient education
• Emotional support
• Management of side effects
• Source documentation
• Vital signs
• Adverse events - CTC
• Protocol deviations
• ECOG Performance status

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The Clinical Trial Coordinator or Data Manager

• Responsible for the collection, handling,
  manipulation, tracking and quality of the data.
• Ensure
• clinicians adhere to the protocol,
• trial patients receive the therapy dictated by
  the protocol,
• provide support to the patients
• All in accordance with Good Clinical Practice
  (GCP)

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What should you consider before joining a
clinical trial

• What is the purpose of the study?
• Why do researchers believe the new treatment
  being tested may be effective?
• What kinds of tests and treatments are involved?
• How do the possible risks, side effects, and
  benefits in the study compare with my current
  treatment?
• How long will the trial last?
• Who will pay for the treatment?
• How will I know that the treatment is working?
• Can I leave the study after it has begun?

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How do you find out about Clinical Trials?

• Oncologist
• NCI Web site www.cancer.gov
• NHMRC Web site www.ctc.usyd.edu.au
• National Breast Cancer Centre www.nbcc.org.au
• RAH Cancer Centre www.rah.sa.gov.au/cancer/medical
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