Possible project: Design and Implementation of Clinical Trials

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Possible project Design and Implementation of
Clinical Trials

• Stefano Iacobelli, Dept. of Oncology, University
• of Chieti
• Massimo Crespi, National Cancer Institute
• Regina Elena, Roma

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Cancer Clinical Trials
In-Depth Information
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The Drug Development and Approval Process

• 1. Early research and preclinical testing
• 2. IND application filed with FDA
• 3. Clinical trials (phases 1, 2, and 3)
• 4. NDA filed with FDA
• 5. FDA validates claim and approves drug

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Phases of Clinical Trials

• Phase 1 15-30 people
• What dosage is safe?
• How should treatment be given?
• How does treatment affect the body?
• Phase 2 Less than 100 people
• Does treatment do what it is supposed to?
• How does treatment affect the body?

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Phases of Clinical Trials

• Phase 3 From 100 to thousands of people
• Compare new treatment with current standard
• Phase 4 From hundreds to thousands of people
• Usually takes place after drug is approved
• Used to further evaluate long-term safety and
  effectiveness of new treatment

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Types of Clinical Trials

• Treatment
• Prevention
• Screening and early detection
• Diagnostic
• Genetics
• Quality-of-life / supportive care

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Treatment Trials

• Test safety and effectiveness of new agents or
  interventions in people with cancer
• Possible benefit
• Early access to new treatments
• Possible risk
• Occurrence of unknown side effects

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Prevention Trials

• For people at risk of developing cancer
• Action studies vs. agent studies
• Possible benefit
• Early access to new interventions
• Possible risk
• Unknown side effects and effectiveness

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Screening and Early-Detection Trials

• Assess new means of detecting cancer earlier in
  healthy people
• Possible benefit
• Detecting disease at an earlier stage, resulting
  in improved outcomes
• Possible risks
• Discomfort and inconvenience
• If imaging technique is studied, exposure to
  x-rays or radioactive substances

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Diagnostic Trials

• Develop better tools for classifying types and
  phases of cancer and managing patient care
• Possible benefits
• New technology may be better and less invasive
• Earlier detection of recurrences
• Possible risk
• May require people to take multiple tests

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Genetics Trials

• These trials seek to
• 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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Quality-of-Life / Supportive Care Trials

• Aim to improve quality of life for patients and
  their families
• Possible benefit
• Early access to new treatment
• Possible risk
• May not benefit from participation

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Clinical Trial Protocol

• A written, detailed action plan that
• Provides background about the trial
• Specifies trial objectives
• Describes trials design and organization
• Ensures that trial procedures are consistently
  carried out

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Investigational Drug UseOutside of a Clinical
Trial

• Group C drugs
• Treatment Investigational New Drug application
• Compassionate use program

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Clinical Trial Design

• Eligibility criteria Can range from general
  (age, sex, type of cancer) to specific (prior
  treatment, tumor characteristics, blood cell
  counts, organ function) eligibility criteria
  also vary with trial phase
• Varies with protocol and phases
• Endpoint Measurable outcome that indicates an
  interventions effectiveness

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Clinical Trial Design

• Randomization A method used to prevent bias in
  research a computer or a table of random numbers
  generates treatment assignments, and participants
  have an equal chance to be assigned to one of two
  or more groups (e.g., the control group or the
  investigational group)

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Randomization
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Clinical Trial Design

• Stratification Categorizing subjects into
  subgroups by specific characteristics
• Enables researchers to look into separate
  subgroups to see whether differences exist

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Stratification
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The Final Step FDA Approval

• Review of New Drug Application (NDA) or Biologics
  License Application (BLA)
• Labeling
• Continued monitoring
• Feedback

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Releasing the Results of Clinical Trials

• Peer-reviewed journals
• Public announcements
• Results not made public until end of trial

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Improving Cancer Prevention, Detection, and
Treatment

• Once proven safe and effective in a clinical
  trial, an intervention may become the new
  standard of care

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Advancing Cancer Care

• Gleevec for chronic myelogenous leukemia
• Cervical cancer improved survival rates
• Breast cancer less extensive surgery
• Intron-A for melanoma
• Biological therapy
• Monoclonal antibodies
• Cancer vaccines

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Evolution of Participant Protection

• Nuremberg
• Tuskegee Syphilis Study
• National Commission for the Protection of Human
  Subjects of Biomedical and Behavioral Research
• Belmont Report
• National Research Act

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Government Oversight of Safeguards for
Participants

• Office for Human Research Protections (OHRP)
• The Common Rule
• FDA Regulations

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Protecting Participants Before a Trial

• Scientific review by sponsoring organization
• Institutional review board approval
• Informed consent

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Protecting Participants During a Clinical Trial

• Institutional review boards (IRBs)
• Data and safety monitoring boards (DSMBs)
• Minimize risks
• Ensure integrity of data
• Can stop study if necessary

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Barriers to, Benefits of, and Risks of
Participation in Clinical Trials
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Barriers to Adult 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
• Harbor concerns about the patients care or how
  the person will react to suggestion of clinical
  trial participation

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Barriers to Adult 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
• Face insurance or cost problems
• Be unwilling to go against their physicians
  wishes

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Benefits of Participating in Clinical Trials

• Early access to new treatments
• Active role in own health care
• Participation in advancing medical knowledge

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Risks of Participating in Clinical Trials

• New treatments are not always better than
  standard care
• Unexpected side effects
• May not work for everyone
• Additional cost

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Referring Patients to Clinical Trials

• Health care professionals should know
• Trial objectives
• Eligibility criteria
• Treatment and prevention options