Ethics of Clinical Trials

1
Ethics of Clinical Trials

• Janet Leung
• Sophomore, Course 9
• 5.22 Biotechnology and Engineering
• Professors Essigmann and Langer
• May 1, 2003

2
Overview

• What are clinical trials?
• Development of ethical code
• What makes trials ethical?
• Further research
• Questions

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What Are Clinical Trials?

• Occurs after extensive laboratory testing in the
  treatment development process
• Determines whether new treatments are safe,
  better than the current ones
• Is the fastest way to find treatments that work

http//www.nlm.nih.gov/medlineplus/tutorials/clini
caltrials/hc019101.html
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What Are Clinical Trials? (cont)

• Study is carefully designed to answer the
  research questions posed and protect participants
• Regulatory agencies and ethics committees
• Institutional Review Boards
• Benefits and risks of being in a clinical trial

http//www.nlm.nih.gov/medlineplus/tutorials/clini
caltrials/hc019101.html
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Phases of Clinical Trials
Phase Participants Participants Research questions
Phase Number Characteristics Research questions
I 20-80 Usually young, healthy, male volunteers Tolerability Pharmacokinetics Pharmacodynamics
II 100-300 Patients rather than volunteers Effectiveness Dosage, Safety
III 1,000 -3,000 Approximate real-life patient population Compare to placebo, current treatments Effects of compound on targets, side-effects
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Phases of Clinical Trials (cont.)
Phase Research questions
IIIb Marketing cost/value Compares with market leader Further data on safety and efficacy
IV New formulations Identify best patients Safety assessment
Hall, John. The Drug Development Process.
http//clinicaltrials.gov/ct/gui/info/whatisjse
ssionid FBB62CC45DC724E2251E4920F86084CCphases
Guidant
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Development of Ethical Guidelines
1803 Percivals Medical Ethics
1900 The Directive on Human Experimentation
1947 Nuremberg Code
1964, 1975, 1983, 1989, 1996, 2000 Declaration of Helsinki
1979 Belmont Report
1982, 1993, 2002 International Ethical Guidelines for Biomedical Research Involving Human Subjects
http//www.patientcenters.com/trials/news/ethics_o
f.html Emanuel, Ezekiel, et al. What Makes
Clinical Research Ethical? Talbot, David and
Joan Perou. Ethical Issues
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What Makes Clinical Trials Ethical?

• Social or scientific value
• Scientific validity independent review
• Favorable risk-benefit ratio
• Fair subject selection
• Informed consent
• Respect for potential and enrolled subjects

Looking at Sirolimus- and Paclitaxel-eluting
stents
Emanuel, Ezekiel, et. al. What Makes Clinical
Research Ethical?
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Social or Scientific Value

• Finite resources, especially funding and
  volunteers
• Experiments that do
• Generalizable results
• Strong hypotheses
• Unique

Emanuel, Ezekiel, et. al. What Makes Clinical
Research Ethical? Sung, Nancy, et. al. Central
Challenges Facing the National
Clinical Research Enterprise.
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Scientific Validity Independent Review

• Methodical, rigorous
• Investigators have multiple, sometimes competing
  interests
• Adverse Event Reports to sponsors and IRB (IEC)
• Data monitoring committees
• Series of sirolimus and paclitaxel clinical
  trials in peer-reviewed journals, regardless of
  results
• Sirolimus and paclitaxel after negative results

Callahan, Timothy. Research Ethics. Emanuel,
Ezekiel, et. al. What Makes Clinical Research
Ethical? Virmani, Renu. Mechanism of Late
In-Stent Restenosis . . .
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Regarding Subjects

• Favorable risk-benefit ratio
• To subject
• To society
• Fair subject selection
• Consider scientific objectives, not just
  convenience
• Exclude those who are at higher risk of being
  harmed
• Investigators agreed on not using critical cases

Schwartz, Robert, et. al. Drug-Eluting Stents in
Preclinical Sudies Emanuel, Ezekiel, et. al.
What Makes Clinical Research Ethical?
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Informed consent

• The most important ethical consideration?
• Components
• Volunteer
• Understanding
• Disclosure
• Signed agreements
• Patients especially tend to be well-informed
  explain terminology, pamphlets

Callahan, Timothy. Research Ethics. Emanuel,
Ezekiel, et. al. What Makes Clinical Research
Ethical?
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Respect for potential and enrolled subjects

• Even if they refuse
• Confidentiality
• Allow them to withdrawal from program
• Keep them informed of developments, carefully
  monitor

Callahan, Timothy. Research Ethics. Emanuel,
Ezekiel, et. al. What Makes Clinical Research
Ethical?
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Conclusions

• Clinical trials are necessary but need to be
  carefully monitored
• In general, nowadays clinical trials in the
  United States are ethical
• There needs to be a single, legally-binding
  ethical guideline
• Sirolimus and paclitaxel need to be tracked
  longer

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Further Research
i.e. the next forty minutes of the presentation
Joking

• Possibly animal testing
• More info on drug-eluting stent clinical trials

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Sources

• Callahan, Timothy. Research Ethics. University
  of Washington School of
• Medicine Ethics in Medicine. 31 March 2003.
  lthttp//eduserv.hscer.washington.edu/bioethics/to
  pics/resrch.htmlgt
• Clinical Trial Ethics. Cancer Clinical Trials
  Center. 17 March 2003
• lthttp//www.patientcenters.com/trials/news/ethic
  s_of.htmlgt.
• Guidant
• Emanuel, Ezekiel, David Wendler, and Christine
  Grady. What Makes Clinical Research Ethical?
  Journal of the American Medical Association, 283
• 2701-2711.
• Hall, John. The Drug Development Process. The
  Institute of Clinical Research
• Principles of Clinical Research. Ed. Ignazio Di
  Giovanna and Gareth
• Hayes. Petersfield Wrightson Biomedical
  Publishing Ltd, 2001. 1-16.
• National Library of Medicine. Clinical Trials.
  3 March 2003.
• lthttp//www.nlm.nih.gov/medlineplus/tutorials/cl
  inicaltrials/
• hc019101.html.gt.

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Sources (cont.)

• National Library of Medicine. An Introduction to
  Clinical Trials.
• ClinicalTrials.gov. 10 March 2003.
  lthttp//clinicaltrials.gov/ct/gui/
• info/whatisjsessionidFBB62CC45DC724E2251E4920F
  86084CC
• phases
• Sung, Nancy, et. al. Central Challenges Facing
  the National Clinical Research
• Enterprise. Journal of the American Medical
  Association, 289
• 1278-1287.
• Schwartz, Robert, et. al. Drug-Eluting Stents in
  Preclinical Studies. Circulation,
• 106 1867.
• Talbot, David and Joan Perou. Ethical Issues.
  The Institute of Clinical Research Principles of
  Clinical Research. Ed. Ignazio Di Giovanna and
  Gareth Hayes. Petersfield Wrightson Biomedical
  Publishing Ltd, 2001. 63-83.
• Virmani, Reny, et. al. Mechanism of Late
  In-Stent Restenosis after Implantation
• of a Paclitaxel Derivate-Eluting Polymer Stent
  System in Humans. Circulation, 106 2649.

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Questions?
Im paying attention, I swear zzz