SHOULD I PARTICIPATE IN A CLINICAL TRIAL?

GARY C. PIEN, MD/PhDAllergist/Immunologist

SMG Research Director

June 5, 2013

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

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

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

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

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

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

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

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

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

PROTECTION OF RESEARCH PATIENTS

http://www.mastercontrol.com/newsletter/good-clinical-practices-review-application.html

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/

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

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-2http://www.wma.net/en/30publications/10policies/b3/

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

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

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.htmhttp://ori.dhhs.gov/education/products/RCRintro/c03/0%20c3.html

MEMBERS OF THE RESEARCH TEAM

PATIENT

ClinicalResearch

Coordinator

Principal Investigator

Sub-investigator

Privatephysicia

n

Clinical research associate

Study monitor

Contractresearch

organization

Study sponsor

IRB

FDA

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

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

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

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.

ADDITIONAL RESOURCES

http://clinicalresearchtrials.nih.gov

http://www.researchmatch.org

http://www.clinicaltrials.gov

RESEARCH AT SMG

CURRENT• Breast cancer• Breast implants• Colorectal cancer• Dust mite allergies• Osteoporosis• Overactive bladder

PAST• Diabetes• Prostate cancer• Rheumatoid arthritis• Tinnitus

THANK YOU!

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