This talk will review the importance of ongoing medical research and how it helps advance medical knowledge and promote the development of new treatments. We will discuss the research process, the protection of study participants, and how individuals may find and choose research studies to volunteer in at SMG or elsewhere.

1. SHOULD I PARTICIPATE IN A
CLINICAL TRIAL?
GARY C. PIEN, MD/PhD
Allergist/Immunologist
SMG Research Director
June 5, 2013

2. OBJECTIVES
• Understand what is a clinical trial
• Examine the role of medical research and clinical trials in
developing new therapies
• Review the drug development process
• Discuss ethical and scientific safeguards to protect research
participants
• Highlight ways to participate in medical research

3. WHAT IS A CLINICAL TRIAL?
• medical research
• novel methods to diagnose, prevent, or treat diseases
 new drugs
 new combinations of drugs
 new indications of an existing drug
 new surgical techniques or medical devices
 new test for diagnosing disease or risk of disease
 establishing new guidelines or recommendations
• goal is to determine if new intervention is safe and effective
http://www.nih.gov/health/clinicaltrials/basics.htm

4. TYPES OF CLINICAL TRIALS
NATURAL HISTORY
• how does a disease change, progress, or develop over time?
PREVENTION
• how to prevent a disease from developing or recurring?
SCREENING OR DIAGNOSTIC
• how to detect a medical condition or diagnose a particular disease
QUALITY OF LIFE
• measure ways to improve comfort and quality of life with a chronic illness
TREATMENT
• testing a new medication, procedure, or device
http://www.nih.gov/health/clinicaltrials/basics.htm

5. CLINICAL TRIAL “PHASES”
PHASE I
• healthy human volunteers (20-80)
• establish safety and side effects
• evaluate drug absorption, metabolism, clearance
PHASE II
• first use in patients with disease/medical condition (100-300)
• limited duration, narrow patient criteria
• establish efficacy, short-term safety
http://www.nih.gov/health/clinicaltrials/basics.htm

6. CLINICAL TRIAL “PHASES”
PHASE III
• confirmation of therapeutic benefit under “real-life” conditions
• 1000-3000 patients
• wider patient criteria
• often multi-center, multi-national, comparative
• longer-term safety, drug interactions, contraindications
PHASE IV
• after-market trials
• long-term safety data
• identify rare side effects
http://www.nih.gov/health/clinicaltrials/basics.htm

7. HOW A DRUG COMES TO BE
DiMasi et al, 2003, Journal of Health Economics 22: 151–185.
Preclinical
1 - 6 yrs
1 in 8 move on
Drug discovery
and
development

8. HOW A DRUG COMES TO BE
DiMasi et al, 2003, Journal of Health Economics 22: 151–185.
Preclinical
1 - 6 yrs
1 in 8 move on
Drug discovery
and
development
http://sydney.edu.au/bmri/research/brain-drug-discovery/index.php

9. HOW A DRUG COMES TO BE
DiMasi et al, 2003, Journal of Health Economics 22: 151–185.
Clinical
Phase I
• safety
• $15 million
• 22 months
Phase II
• safety,
dosing,
efficacy
• $23 million
• 26 months
Phase III
• safety,
efficacy, side
effects
• $87 million
• 31 months
Investigational
new drug
application
6 - 11 yrs
30% 14% 9%40%
Preclinical
1 - 6 yrs
1 in 8 move on
Drug discovery
and
development

10. HOW A DRUG COMES TO BE
DiMasi et al, 2003, Journal of Health Economics 22: 151–185.
Clinical
Phase I
• safety
• $15 million
• 22 months
Phase II
• safety,
dosing,
efficacy
• $23 million
• 26 months
Phase III
• safety,
efficacy, side
effects
• $87 million
• 31 months
Investigational
new drug
application
6 - 11 yrs
30% 14% 9%40%
Approval
1-2 yrs
8%
New drug
application
Market
11-14 yrs
Phase IV
also post-
market
surveillance
Preclinical
1 - 6 yrs
1 in 8 move on
Drug discovery
and
development

11. PROTECTION OF RESEARCH PATIENTS
http://www.mastercontrol.com/newsletter/good-clinical-practices-review-application.html

12. PROTECTION OF RESEARCH PATIENTS
DECLARATION OF HELSINKI - 1975
• protect health, dignity, integrity, privacy of volunteers
• study must conform to accepted scientific principles
• research protocol must be established and followed
• protocol must be approved by independent ethics committee
• benefits must outweigh risks
• participation must be voluntary, without duress
• informed consent must be obtained
• privacy and confidentiality must be protected
http://www.wma.net/en/30publications/10policies/b3/

13. PROTECTION OF RESEARCH PATIENTS
BELMONT REPORT - 1979
• Smithsonian Institute
• respect for persons – autonomy of patients
• beneficence – protection from harm, ensure well-being of patients
• justice – results should benefit all (not just those who can afford it, etc)
COMMON RULE - 1981
• US federal policy derived from Declaration of Helsinki
• enforces compliance by research bodies
• safeguards informed consent
• provides for IRB regulations
• establishes protections for vulnerable populations (prisoners, children,
pregnant women)
http://www.mastercontrol.com/newsletter/good-clinical-practices-review-application.html

14. PROTECTION OF RESEARCH PATIENTS
ICH
• International Conference on Harmonisation
• brings together regulatory bodies of Japan, Europe and US
• develop standards for ethical and scientific research
• quality, safety, efficacy, regulatory issues
• reduce duplicate testing
GCP
• Good Clinical Practices
• human subject protection – patient rights, integrity, confidentiality
• standards for design, conduct, performing, monitoring, recording data
http://ichgcp.net/2-the-principles-of-ich-gcp-2
http://www.wma.net/en/30publications/10policies/b3/

15. PROTECTION OF RESEARCH PATIENTS
IRB
• institutional review board
• doctors, scientists, lay people
• scientific, ethical, and regulatory oversight
• ensure that rights and welfare of participants are protected
• appropriate recruitment population?
• how are patients recruited?
• adequate disclosure and informed consent?
• are risks too great?
http://www.fda.gov/forconsumers/consumerupdates/ucm134723.htm

16. PROTECTION OF RESEARCH PATIENTS
FDA
• Food and Drug Administration
• has authority over clinical trials
• inspects and audit research sites
• ensures rights and welfare of participants
• reviews data quality and integrity
http://www.fda.gov/forconsumers/consumerupdates/ucm134723.htm

17. PROTECTION OF RESEARCH PATIENTS
INFORMED CONSENT
• disclose purpose and protocol for study
• adequate information for potential volunteers to decide
whether to enroll
• Q&A opportunity for investigator and patient
• no obligation to join a study
• consent must be written
• consent may be withdrawn at any time
http://www.fda.gov/forconsumers/consumerupdates/ucm134723.htm
http://ori.dhhs.gov/education/products/RCRintro/c03/0%20c3.html

18. MEMBERS OF THE RESEARCH TEAM
PATIENT
Clinical
Research Coordinator
Principal Investigator
Sub-investigator
Private
physician
Clinical research associate
Study monitor
Contract
research organization
Study sponsorIRB FDA

19. CONSIDERATIONS BEFORE ENROLLING
RISKS
• potential side effects from treatment (may be minor to life-threatening)
• may be assigned to a placebo control group
• impact on daily activities (time commitment, etc)
BENEFITS
• access to new treatments before they are widely available
• regular and careful medical follow-up with research team during trial
• help contribute to medical science
• play more active role in one’s medical care
• results of the study may benefit other people and future generations
http://www.nih.gov/health/clinicaltrials/basics.htm

20. QUESTIONS TO ASK
THE STUDY
• what is the purpose of the trial?
• why do we think this new treatment will work or help?
PARTICIPATION
• what tests or procedures are required during the study?
• how do these tests/procedures differ from standard treatment?
• who will be in charge of my care?
RISKS AND BENEFITS
• benefits to me?
• what are the chances of side effects?
• how serious are those potential side effects?
• are there other options to treat my condition?
http://www.nih.gov/health/clinicaltrials/basics.htm

21. QUESTIONS TO ASK
QUALITY OF LIFE
• how will this trial impact my daily living?
• how long will the study last?
• what are my responsibilities?
• can I take other medications during the trial?
COST
• will I have to pay for any part of the trial?
• will my health insurance cover any part of the costs?
• are there any travel expenses?
• is there compensation for my participation?
http://www.nih.gov/health/clinicaltrials/basics.htm

22. REASONS FOR ENROLLING (OR NOT)
ENROLL
• a trusted physician
recommended study
• additional attention and care
through trial participation
• encouraged by friends/family
• altruism
• (desire to live)
DECLINE
• anxiety about randomization
• worry not best treatment
• logistical difficulties
• concerned about side effects
• friends/family against study
Albrecht et al, 2003, Journal of Cancer Educ 18: 210–214.

23. ADDITIONAL RESOURCES
http://clinicalresearchtrials.nih.gov
http://www.researchmatch.org
http://www.clinicaltrials.gov

24. RESEARCH AT SMG
CURRENT
• Breast cancer
• Breast implants
• Colorectal cancer
• Dust mite allergies
• Osteoporosis
• Overactive bladder
PAST
• Diabetes
• Prostate cancer
• Rheumatoid arthritis
• Tinnitus

25. THANK YOU!

26. ETHICAL ATROCITIES
WORLD WAR II
• Nazi experimentation on human prisoners
 freezing, poison, chemical warfare, etc
 tried at Nuremberg
• Imperial Japanese Army experimented on coerced humans
 biological warfare agents
 offered immunity by General MacArthur for exclusive access to data
TUSKEGEE SYPHILIS
• compared effects of treating vs no treatment for syphilis
• involved impoverished African-American men
• not given informed consent
• not informed of diagnosis, placebo treatment, or risks