cancer clinical trials: in-depth information. 2 the drug development and approval process 1. early...

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 one’s 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 trial’s 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 intervention’s 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

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 patient’s care

• Believe that standard therapy is best

• Believe that clinical trials are more work

• Harbor concerns about the patient’s 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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NCI-Sponsored Clinical Trial Programs

• Clinical Trials Cooperative Group Program• Clinical Trials Support Unit (CTSU)• Community Clinical Oncology Program (CCOP)• Minority-Based Community Clinical Oncology

Program• Cancer Centers Program• Clinical Grants Program

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Referring Patients to Clinical Trials

Health care professionals should know:

• Trial objectives

• Eligibility criteria

• Treatment and prevention options

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Locating NCI Clinical Trials in the Community

NCI clinical trial registry:

• Nation’s most comprehensive resource on cancer clinical trials

• www.cancer.gov• 1-800-4-CANCER (1-800-422-6237)