FORMERLY HEPP Report
September 2005 Vol. 8, Issue 9

ABOUT IDCR
IDCR, a forum for
correctional problem solving, targets
correctional physicians, nurses,
administrators, outreach workers, and
case managers. Published monthly
and distributed by email and fax,
IDCR provides up-to-the moment
information on HIV/AIDS,
hepatitis, and other infectious
diseases, as well as efficient ways
to administer treatment in the
correctional environment. Continuing
Medical Education credits are
provided by the Brown University
Office of Continuing Medical
Education. IDCR is
distributed to all members of the
Society of Correctional Physicians
(SCP) within the SCP publication,
CorrDocs (www.corrdocs.org).

CO-CHIEF EDITORS
Anne S. De Groot, MD
Director, TB/HIV Research Lab,
Brown Medical School
David Thomas, MD, JD
Professor and Chairman,
Department of Surgery,
Division of Correctional Medicine
NSU-COM

DEPUTY EDITORS
Joseph Bick, MD
Chief Medical Officer,
California Medical Facility, California
Department of Corrections
Renee Ridzon, MD
Senior Program Officer,
HIV, TB, Reproductive Health,
Bill & Melinda Gates Foundation

Bethany Weaver, DO, MPH
Acting Instructor, Univ. of Washington,
Center for AIDS and STD Research

SUPPORTERS

IDCR is grateful for
the support of the following
companies through unrestricted
educational grants:
Major Support: Abbott Laboratories
and Roche Pharmaceuticals.
Sustaining: Pfizer Inc., Gilead
Sciences, Inc., GlaxoSmithKline, Merck
& Co., and Schering-Plough.

Brown Medical School

RESEARCH

IN

CORRECTIONS

By David Paar*, MD, David Thomas**, MD,
Jacqueline Thomas**, DO, Danielle Thomas**,
MS-IV, and Courtney Colton**, IDCR
DISCLOSURES: *Consultant: Gilead, Abbott,
Boehringer Ingelheim, Speaker's Bureau:
Gilead, Bristol Myers Squibb, GlaxoSmithKline,
Abbott, Boehringer Ingelheim, **Nothing to disclose
Whether or not the inclusion of incarcerated
individuals in clinical research studies is justified
has generated heated debate over the later part
of the past century. Some have advocated that
no research study can ethically include prisoners living in an inherently coercive environment,
while others counter that incarceration does not
strip an individual of his or her ability to make an
informed decision regarding participation as a
research subject.
Much of this debate is fueled by the competing
concerns of protecting inmates as a vulnerable
population while respecting their individual
autonomy. This conflict is waged against the
backdrop of a historical legacy of unethical
treatment of incarcerated, institutionalized and
other vulnerable groups during clinical research
studies.
HISTORY OF RESEARCH IN PRISONS IN
THE TWENTIETH CENTURY
Research involving prisoners has had a troubled past. During the early part of the twentieth
century, there were well-documented instances
of investigators in the United States, and elsewhere, using prison inmates to study the pathogenesis, prevention, and treatment of a variety
of illnesses including cholera, beriberi, pellagra,
and tuberculosis. Notorious experiments, such
as the transplantation or injection of human or
animal testicular material into senile men, were
conducted, and, although rare, reflected the
belief at the time that inmates were a population
that could be subjected to experimentation that
could not be performed on the general population. The unique vulnerabilities of inmates in
these studies were often exploited. For example, many of the participants were death row
inmates, some of whom died following injection
of cholera toxins or similarly dangerous procedures. "Volunteers" were recruited by promising
them clemency if they survived the experiment -

Providence, RI 02912

401.453.2068

an incentive that today would be considered
highly coercive - while other participants
received special privileges or compensation
such as cigars or cigarettes. Many inmates who
participated in studies during this period did not
give truly informed consent. Few understood
the risks and benefits, if any, of the research
protocols, and some may not have even been
asked to participate.1,2,3
The Second World War had a significant impact
on the inclusion of prisoners in research investigations. On the one hand, with the onset of the
war, investigators appealed to inmates to make
a patriotic contribution to the war effort by participating in medical research that would assist
the military. The research included injections of
blood from cattle to investigate alternate
sources of blood products, studies of atropine
as an antidote, as well as experiments in which
subjects were infected with sleeping sickness,
dengue fever, gonorrhea, malaria, and agents of
gas gangrene.1,2,3
However, at the conclusion of World War II, the
discovery of human experimentation conducted
by the Nazis on those they had imprisoned led
to a wide scale re-evaluation of the ethics of
research of human subjects and the study of the
incarcerated in particular. The Nuremberg War
Crime Tribunal was convened to investigate and
punish war time crimes perpetrated by the
Nazis, including hideous trials performed by the
Germans in concentration camps. In 1947, the
tribunal produced the Nuremberg Code, a set of
10 basic tenets, which was drafted as the standard by which to judge physicians and scientists
during their trial at Nuremberg. It became an
ethical standard for research for decades.
The first of these tenets, that "the voluntary consent of the human subject is absolutely essential . . . . [and] should be so situated as to be
Continued on page 2

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September 2005
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CORRECTIONS...

(continued from page 1)
able to exercise free power of choice without . . . the intervention of any element of
force, fraud, deceit, duress . . . or coercion
. . . ." has been widely interpreted as
excluding prisoners from research since
incarceration is a necessarily coercive condition. However, in the U.S., the prevalent
opinion in the medical community,
endorsed by the American Medical
Association, was that the Nuremberg Code
pertained to Nazi atrocities, but not to the
increasingly prevalent medical experiments
being conducted using inmates in state and
federal jurisdictions. In fact, the post-war
flourishing of medical experimentation within the U.S. penal system was being driven
by increased federal funding to investigate
medical illness, the formation of academicpharmaceutical alliances, and the need to
test various products in human subjects to
meet U.S. Food and Drug Administration
regulations.1,2,3,4
Prisoners were enlisted in a broad range of
clinical studies and the inclusion of inmates
in investigation became routine. In
Holmesburg Prison, a county facility in
Philadelphia, in the late 1960’s inmates
were recruited to participate in studies that
explored everything from simple detergents
and diet drinks to retinoic acid, dioxin, and
chemical warfare agents. The list of sponsors of these investigations included not
only pharmaceutical companies and other
corporations such as Dow Chemical, but
also the U.S. Army. However, in the early
1970's the public conscious shifted and
began to look unfavorably upon research
conducted in prisons. This change was
influenced by well-publicized revelations of
the serious side effects associated with
medications, such as birth defects caused
by the tranquilizer thalidomide and the
Tuskeegee syphilis experiments, which
were not conducted using inmates, but did
involve another vulnerable population:
black men in the U.S. rural south. By the
late 1970’s, legislation had been passed
preventing federal inmates from participating in clinical trials and very few state jurisdictions continued their clinical research
programs using inmates.
THE BELMONT REPORT AND
45 CFR 46
In response to the growing public concern
regarding abuses during clinical research,
the National Research Act was signed into
law on July 12, 1974. This federal law created the National Commission for the
Protection of Human Subjects of
Biomedical and Behavioral Research,
hereafter referred to as "The Commission".
One of The Commission's charges was to
identify the basic ethical principles that
should underlie the conduct of biomedical

visit IDCR online at www.IDCRonline.org
and behavioral research involving human
subjects and to develop guidelines, which
should be followed to assure that such
research is conducted in accordance with
those principles. The Belmont Report
resulted from an intensive four-day period
of discussions held at the Smithsonian
Institution's Belmont Conference Center
supplemented by monthly deliberations of
The Commission held over a four-year period. It was published in The Code of Federal
Regulations (CFR), commonly called the
federal register or common rule, on April
18, 1979 as a statement of the Department
of Health, Education, and Welfare's policy
of ethical principles and guidelines for the
protection of human subjects of research.
Later this department evolved into the
Department of Health and Human Services
(DHHS) which remains responsible for the
protection of human subjects involved in
biomedical research through the Office of
Human Research Protection (OHRP). The
three basic principles that were detailed in
this report were respect for persons, beneficence, and justice. Respect for persons
has two important components: individuals
should be treated as autonomous agents
and those with diminished autonomy are
entitled to protection. The report itself
directly addresses the issue of prisoner
participation in research:
"[R]espect for persons demands that subjects enter into the research voluntarily and
with adequate information… In some situations, however, application of the principle
is not obvious. The involvement of prisoners as subjects of research provides an
instructive example. On the one hand, it
would seem that the principle of respect for
persons requires that prisoners not be
deprived of the opportunity to volunteer for
research. On the other hand, under prison
conditions they may be subtly coerced or
unduly influenced to engage in research
activities, for which they would not otherwise volunteer…. Respect for persons
would then dictate that prisoners be protected. Whether to allow prisoners to "volunteer" or to "protect" them presents a
dilemma."
These passages accurately state the
equipoise that persists to this day regarding
prisoners as research subjects. How to
best balance between not "depriving" the
inmate of an opportunity to participate and
protecting the inmate from coercion
remains the enduring challenge of this
issue with vocal advocates of each position
weighing in.
The federal legislation, published in the
Code of Federal Regulations, that deals
with the protection of human research subjects is called Title 45 CFR Part 46 and is
commonly referred to as 45 CFR 46. It

2

became law in 1978, was revised in 2001
and provides some guidance regarding the
inclusion of prisoners in research. 45 CFR
46 applies to all research involving human
subjects that is conducted, supported by, or
otherwise subject to regulation by any federal department or agency. It provides
direction on how agencies and institutions
can file letters of assurance that they will
comply with these regulations, direction on
the composition and duties of institutional
review boards (IRBs) that oversee federally funded research, requirements for
informed consent, and documentation of
informed consent. Subpart B of this law
lists additional protections for pregnant
women, human fetuses, and neonates, and
Subpart C lists additional DHHS protections pertaining to biomedical and behavioral research involving prisoners as subjects (6 45 CFR 46).
The additional protections of Subpart C
provide for prisoners that participate in biomedical research including: 1. Inclusion of
a prisoner or a prisoner representative on
the IRB reviewing the research; 2.
Assigning additional duties to the reviewing
IRB to be sure that the research is permissible, free of undue influence, safe, accessible and fair to all inmates, presented in
understandable language, and does not
have any effect on parole. Permissible
research involving prisoners includes: "(A)
study of the possible causes, effects, and
processes of incarceration, and of criminal
behavior, provided that the study presents
no more than minimal risk and no more
than inconvenience to the subjects; (B)
study of prisons as institutional structures
or of prisoners as incarcerated persons,
provided that the study presents no more
than minimal risk and no more than inconvenience to the subjects; (C) research on
conditions particularly affecting prisoners
as a class (for example, vaccine trials and
other research on hepatitis which is much
more prevalent in prisons than elsewhere;
and research on social and psychological
problems such as alcoholism, drug addiction, and sexual assaults) provided that the
study may proceed only after the Secretary
[of the Department of Health and Human
Services] has consulted with appropriate
experts including experts in penology, medicine, and ethics, and published notice, in
the Federal Register, of his intent to
approve such research; or (D) research on
practices, both innovative and accepted,
which have the intent and reasonable probability of improving the health or well-being
of the subject. In cases in which those
studies require the assignment of prisoners
in a manner consistent with protocols
approved by the IRB to control groups
which may not benefit from the research,
Continued on page 3

September 2005
RESEARCH

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Vol. 8, Issue 9

CORRECTIONS...

(continued from page 2)
the study may proceed only after the
Secretary has consulted with appropriate
experts, including experts in penology,
medicine, and ethics, and published notice
in the Federal Register, of the intent to
approve such research."6
According to 45 CFR 46, permissible
research includes not only social, behavioral, and psychological research, but also
therapeutic trials using pharmaceutical
agents for medical conditions that particularly affect inmates (though the use of
placebos in this situation requires additional safeguards.) The example given in the
law specifically mentions hepatitis, but the
health condition that came to the forefront
as a condition particularly affecting prisoners was HIV infection and AIDS. Under
pressure from patients and patient advocacy groups, HIV clinical research moved
from the strictly academic setting to a variety of other patient sites including non-university affiliated hospitals, private physician
offices, and community consortiums. In the
1990s, when effective HIV treatment therapies were under investigation in multiple
clinical trials, HIV clinical trials at some academic sites re-entered the prison setting.
In this case, inclusion of prisoners was
often justified as a means to provide access
to cutting-edge therapies to persons living
with HIV who were incarcerated. At several major medical centers, HIV research was
extended into correctional facilities. For
example, clinical trials being conducted at
The University of Texas Medical Branch in
Galveston and the University of Miami in
Florida were offered to inmates in the Texas
Department of Criminal Justice and the
Florida Department of Corrections, respectively. Additionally, behavioral research
regarding AIDS in the incarcerated population were being conducted by Yale and
Brown Universities in their respective state
jurisdictions. Not all of these studies fell
under the purview of 45 CFR 46, as these
regulations apply to federally funded studies and some of these investigations were
funded by pharmaceutical industry support.
Allowing prisoners to participate seemed

visit IDCR online at www.IDCRonline.org
appropriate since life-saving treatment, not
available outside of clinical trials, became
available to incarcerated patients with
AIDS.
In 1998, one of the pharmaceutical manufacturers of HIV medications implemented
a non-comparative trial of a combination of
three nucleosides for the treatment of HIV
in prisoners only. Many prisoner advocates
became concerned that prisoners were
being exploited in the name of medical
research since all of the pharmaceutical
agents in this trial were available outside of
clinical trials and there was already some
question in 1998 if three nucleosides alone
were adequate therapy for HIV infection.7
Today we know that triple nucleoside therapy is inferior to either protease inhibitorbased or non-nucleoside reverse transcriptase inhibitor-based potent combination
therapy and is not recommended as first
line therapy for HIV infection. Subjecting
prisoners to the choice of receiving what
might be inferior treatment seemed to
exceed the limit of minimal risk that 45 CFR
46 had set as a standard. The scientific
research community was again faced with
the difficult question of how best to protect
prisoners.
As a result, a group of concerned correctional clinicians organized a conference,
"Clinical Trials in Corrections." Over 100
like-minded individuals and representatives
from the Office of Human Research
Protections attended this meeting, and proceeds were published in 2001 in AIDS
Reader.13 What happened next had a chilling effect on pharmaceutical medical
research using prisoners as subjects. The
IRBs at the University of Texas Medical
Branch, the University of Miami, Brown
University, and Yale University were
reviewed by the OHRP and received "letters of determination"8 that the composition
of the IRBs and their procedures to ensure
the protection of prisoners were inadequate. Enrollment in clinic trials was suspended at the University of Texas Medical
Branch at Galveston9 and the University of
Miami.10 Although each of the Universities
cited above eventually received permission

References:
1. Richardson T. Acres of Skin: human experiments at Holmesburg Prison,
a true story of abuse and exploitation in the name of medical science.
Canadian Journal of History. 2001; 36(1):184-6.
2. Caelleigh As. Prisoners. Academic Medicine. 2000; 75(10):999.
3. Hornblum Am. They were cheap and available: prisoners as research
subjects in twentieth century America. British Medical Journal. 1997;
315(7120):1437-41.
4. The Nuremberg Code. Last accessed August 30, 2005 from
http://ohsr.od.nih/gov/guidelines/nuremberg.html
5. The Belmont Report. Last accessed August 30, 2005 from
http://ohsr.od.nih.gov/guidelines/belmont.html
6. 45 CFR 46. Last accessed August 30, 2005 from
http://ohsr.od.nih.gov/guidelines/45cfr46.html
7. Department of Health and Human Services. Guidelines for the use of
antiretroviral agents in HIV-1-infected adults and adolescents. Last
accessed August 30, 2005 from

3

to resume research with prisoners, virtually
no clinical trials using pharmaceutical
agents are being conducted in the state
prison systems today. Behavioral, social,
and psychological research continues to be
pursued by many institutions using prisoners as subjects.
COMMENT
It has now been over 30 years since 45
CFR 46 Subpart C has been enacted.
Whether an inmate can ever act
autonomously and what the standard of
minimal risk for an inmate remains
unclear.11 Three issues are at the crux of
this question. First, are prisoners and the
general population well served by not having federal funding for clinical research
using pharmaceutical therapies in the
incarcerated population; second, does the
law serve its goal to protect a vulnerable
population; and third, does the federal law
impact
upon
non-federally
funded
research? Secretary Tommy Thompson of
the DHHS has speculated that it is past
time that Subpart C be evaluated again
(personal communication). To this end, the
DHHS has asked the Institute of Medicine
of the National Academy of Sciences to
investigate the impact of Subpart C, and to
determine if there should be any change in
the current law. The Committee of Ethical
Considerations for Revisions to the DHHS'
Regulations for Protection of Prisoners
Involved in Research was impaneled and
will examine whether the conclusions
reached by the National Commission for
the Protection of Human Subjects of
Biomedical and Behavioral Research in the
1970’s remain appropriate today.12 The
committee will hold five public meetings at
which they will collect data from invited
panelists who work or perform research in
the correctional setting and will also hold
two workshops to further inform the
process. Three of the public meetings have
been held: March 16, 2005, National
Academies of Science, Washington, D.C.,
May 4, 2005, The National Academies of
Science, Washington, D.C., and July 18,
the Gladstone Institute, San Francisco, CA.
The committee's final report is expected in
March, 2006.

http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=50
8. Department of Health and Human Services. OHRP determination letters.
Last accessed August 30, 2005 from
http://www.hhs.gov/ohrp/compliance/letters/index.html
9. Department of Health and Human Services. Letter of determination for
the University of Texas Medical Branch at Galveston. Last accessed
August 30, 2005 from http://www.hhs.gov/ohrp/detrm_letrs/jul00c.pdf
10. Department of Health and Human Services. Letter of determination for
the University of Miami. Last accessed August 30, 2005 from
http://www.hhs.gov/ohrp/detrm_letrs/jul00l.pdf
11. Stone TH. Discerning minimal risk in research involving prisoners as
human subjects. Journal of Law, Medicine & Ethics. 2004; 32(3):535-7.
12. Institute of Medicine. Ethical considerations for revisions to the DHHS
regulations for protection of prisoners involved in research. Last accessed
August 30, 2005 from http://iom.edu/project.asp?id=24594
13. DeGroot AS, et al. HIV in clinical trials: right or retrogressions? AIDS
Reader. 2001; 11(1):34-40.

September 2005

LETTER

visit IDCR online at www.IDCRonline.org

Vol. 8, Issue 9

FROM THE

4
Faculty Disclosure

EDITOR

Dear Colleagues,
This issue is dedicated to clinical trials in corrections. Prior to 2000, several correctional practitioners and facilities were involved in clinical trials in order to permit the incarcerated population to
gain the benefits of investigational drugs and other therapies that could only be obtained through
trials. In 2000, the Office of Protection from Research Risks (currently named Office for Human
Research Protections) investigated every clinical trial from every major university, correctional system, and quality Institutional Review Board involved in prisoner research. That investigation
caused most of the aforementioned programs to stop enrolling new patients and taper their existing efforts.
Many of us involved in correctional healthcare felt that both society and our patients were
inadequately served by this act. Although mostly minor violations were documented, the tone created by the investigation lead to irreparable damage to clinical trials in corrections. Universities
decided it was not worth the effort and correctional administrators wanted no part of any potential
controversy.
The advantages of clinical trials in correctional populations, both for the inmates and society, and
the advocacy for them, are phenomenal. There was a pervasive feeling that affording this benefit
to our patients was going to be impossible, even though many of us continually brought the issue
of clinical trials in corrections to the highest levels of authority.
In the last year of his position as Agency Head of the Department of Health and Human Services
(DHHS), Secretary Tommy Thompson personally determined that there might be real value to
inmates and society if the question of clinical trials within clinical settings were evaluated again. To
that end, the DHHS asked the Institute of Medicine of the National Academy of Sciences to reevaluate the pertinent parts of Federal law pertaining to prisoner inclusion in research.
It should be our job to advocate for our patients in this area and to remind the committee of two
specific items: first - the effect of Federal law is far more reaching than the words of the statute
themselves and, second - the current situation discriminates against legitimate scientific inquiry
and encourages unregulated research which may be performed solely for remuneration.
After reading this issue, readers should be familiar with the history of research involving prisoners,
45 CFR 46, the Belmont Report and the requirements for conducting research involving prisoners.
Readers should also be able to identify when research requires approval by an Institutional Review
Board.
Very truly yours,

In accordance with the Accreditation Council for
Continuing Medical Education Standards for
Commercial Support, the faculty for this activity have
been asked to complete Conflict of Interest
Disclosure forms. Disclosures are listed at the end of
articles. All of the individual medications discussed
in this newsletter are approved for treatment of HIV
and hepatitis unless otherwise indicated. For the
treatment of HIV and hepatitis infection, many physicians opt to use combination antiretroviral therapy
which is not addressed by the FDA.
Associate Editors
Rick Altice, MD
Director of Clinical Research,
Director, HIV in Prisons Program,
Director, Community Health Care Van,
Associate Professor of Medicine
Yale University AIDS Program
David Paar, MD
Associate Professor of Medicine,
University of Texas, Medical Branch
Karl Brown, MD, FACP
Infectious Disease Supervisor
PHS-Rikers Island
Ralf Jürgens
Consultant,
HIV/AIDS, Human Rights, Drug Policy and
Prisons
Joseph Paris, PhD, MD, FSCP, CCHP
Medical Director,
Georgia Dept. of Corrections
Lester Wright, MD, MPH
Chief Medical Officer,
New York State Dept. of Correctional Services
Dean Rieger, MD
Medical Director,
Indiana Dept. of Corrections
Neil Fisher, MD
Medical Director, Chief Health Officer,
Martin Correctional Institute
William Cassidy, MD
Associate Professor of Medicine,
Louisiana State University Health Sciences
Center

David Thomas*, MD

Editorial Board
Louis Tripoli, MD, FACFE
Correctional Medical Institute,
Correctional Medical Services

*Nothing to Disclose

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September 2005

Vol. 8, Issue 9

visit IDCR online at www.IDCRonline.org

5

IDCR-O-GRAM: Is the Research I want to Conduct Subject to IRB Approval?
Are the specimens/data obtained from living individuals?

YES, individuals ARE living

NO, individuals are NOT living

Are the specimens/data:
Unidentifiable specimens/data obtained from a commercial provider
OR
Unidentifiable specimens/data obtained from a provider that is prohibited from
releasing identifiers by established regulations/policies

NOT Human Subjects Research

NO

YES

Were/will the specimens/data be collected specifically for the proposed
research through an interaction or intervention with living individuals?

Human Subjects Research

NO

YES

Can the recipient link the specimens/data directly
to identifiable living individuals?

Human Subjects Research

NO

YES

Can the provider link the specimens/data, directly or
indirectly, to identifiable living individuals?

Human Subjects Research

NO

YES

NOT Human Subjects Research

Does the provider meet the definition of an "investigator" in the
recipient's research

NO

YES

NO, provider is "solely providing”

YES, provider is collaborating in recipient's research

Are the specimens/data provided with a code linking them to identifiable living individuals?

Human Subjects Research*

NO

YES

NOT Human Subjects Research

Can the recipient readily ascertain the identities of the individuals
studies research to whom the specimens/data pertain?**

NO

YES

NOT Human Subjects Research

Human Subjects Research*

IDCR-o-gram continued on page 6

September 2005

Vol. 8, Issue 9

visit IDCR online at www.IDCRonline.org

6

STATE LAWS 101*
State
California*

Florida**

Georgia***
Kentucky^
Maryland^^,
North Carolina^^^
Wisconsin,
Pennsylvania, Texas,
Ohio, Virginia
o
New York

Legislation
Specific legislation including criminal penalties for failure to comply; requirement that all clinical investigators - no matter the source of funding - present to all human subjects a document known as the
"Experimental Subjects Bill of Rights," and comply with other parts of its extensive statue
Florida has its own Review Council for Humans Subjects, but this only applies to research performed in
Department of Health or Department of Children and Family facilities (or by contract with those agencies).
The correctional systems have no similar protective agency.
Georgia has specific restrictions on cancer and THC research and surgical procedures under investigation.
Kentucky has a Cabinet for Health Services, which has specific requirements for research funded through
the state.
Maryland and North Carolina have adopted the Federal statute for all state participants in research.
Wisconsin, Pennsylvania, Texas, Ohio, and Virginia have all adopted the basic precepts of the Federal
statute, but have made modifications by their legislatures. For instance, Ohio requires fully informed consent even for proposals that have minimal risk.
New York has the most complex of the statutes, adopting both the Federal 45 CFR 46 and overlaying certain state requirements. Prisoner research requires the specific approval of the Commissioner of the
Department of Health. The New York statute directly attempts to limit single practitioners or small groups
from conducting clinical research by specifically requiring "All individuals seeking to conduct research must
affiliate themselves with an agency or institution that has…a human research review committee."

Of the state laws, only New York has specific requirements for prisoner research. States lacking specific requirements for prisoner
research must adhere to state provisions on research. Almost all states permit a researcher to opt out of the state statute if the
researcher is performing their research under a Federal-wide assurance and agrees to follow 45 CFR 46.
*CA Health & Saf. Code # 24171-24179.5 (2003) et. seq.
**Fl Stat. 381.85(2003) & 743.07 (2003).
***GA O.C.G.A. 33-24-59.1 (2002); & 39-1-1 (2003) & 360-121-01-05 (2003).
^KY 900 KAR 1:060 stat. 4(1)(a) (2003) & 920 KAR 1:060 ("Protection of Human Subjects") (2003).
^^MD Health Code Ann. Stat. 13-2001 and 2002 (2003).
^^^NC Gen. Stat. 58-3-255 (2004).
o
NY Public Health Law 2444(3) (2004).

IDCR-o-gram... (continued from page 5)
Footnotes
*All human subjects research must obtain institutional review
board (IRB) approval. Exceptions include when there is no effort
to contribute to the general body of knowledge and the information will be used only for risk management or internal modifications of ones' own system or facility.
All DHHS-supported human subjects research involving prisoners
as subjects must comply with all regulations set forth in 45 CFR
46 Subpart C. When prisoners are involved as subjects in
research, composition of the IRB must satisfy the following
requirements:
- A majority of the IRB (exclusive of prisoner members) shall
have no association with the prison(s) involved, apart from their
membership on the IRB.
- At least one member of the IRB must be a prisoner, or a prisoner representative with appropriate background and experience to
serve in that capacity, except that where a particular research
project is reviewed by more than one IRB, only one IRB need
satisfy this requirement.
Research involving prisoners (or other vulnerable populations)
cannot receive expedited IRB approval.

** Examples of situations in which the recipient cannot link the
specimens/data to living individuals include:
- The key to deciper the code is destroyed before the research
begins
- The investigators and the holder of the key to the code enter
into an agreement preventing the release of the key to investigators under any circumstances
- There are IRB-approved written policies in place preventing
release of the key under any circumstances
- There are other legal requirements prohibiting the release of the
key under any circumstances
Endnotes
Adapted from Office of Extramural Research. Research involving
private information or biological specimens. (n.d.). Accessed
August 17, 2005 from
http://grants.nih.gov/grants/policy/hs/index.htm and
NIH. Office of Human Research Protections. Guidance on the
involvement of prisoners as research. (n.d.). Accessed August
17, 2005 from http://www.hhs.gov/ohrp/humansubjects/guidance/prisoner.htm

September 2005

Vol. 8, Issue 9

visit IDCR online at www.IDCRonline.org

7

Research 101: Types of Clinical Trials
Type of Trial
Treatment Trials
Prevention Trials

Diagnostic Trials
Screening Trials
Quality of Life Trials

Purpose
Test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy
Look for better ways to prevent disease in people who have never had the disease or to prevent
a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes.
Conducted to find better tests or procedures for diagnosing a particular disease or condition.
Test the best way to detect certain diseases or health conditions.
Explore ways to improve comfort and the quality of life for individuals with a chronic illness.

Clinical Trial Phases*
Phase I
Initial studies

Phase II
Controlled clinical
studies

Phase III
Expanded controlled and uncontrolled trials
after preliminary evidence of the drug has
been obtained

Phase IV
Post-marketing
studies

Purpose

Assess the safety,
tolerability, metabolism, and pharmacologic actions
of the therapy in
humans and the
side effects associated with
increasing doses

Evaluate clinical
efficacy of the
therapy for a particular indication
or indications in
patients with the
disease/condition
under study;
determine the
common shortterm side effects
and risks

Gather additional information to evaluate the
overall benefit-risk relationship of the drug and
provide adequate basis for physician labeling;
definitively assesses efficacy of the new therapy, especially in comparison with currently
available alternatives

Detect any rare or
long-term adverse
effects over a
much larger
patient population
and timescale
than was possible
during the initial
clinical trials;
delineate additional information,
including drugs'
risks, benefits,
and optimal use

Number
of People
Given Drug

20-80

100-300

1,000-3,000

Varies

Additional
Information

Conducted in
inpatient clinic,
where subject can
be observed by
full-time medical
staff; not blinded;
often no placebo
control

The development
process for a new
therapy often fails
at this phase due
to the discovery of
poor efficacy or
toxic effects

Double-blind randomized controlled trials;
most expensive, time-consuming phase to
design and run; once a therapy has proven
satisfactory over Phase III trials, the trial
results are usually combined into a large document containing a comprehensive description
of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life. This collection of
information is then submitted to the FDA for
approval of the therapy.

Phase IV studies
may be mandated
by regulatory
authorities or may
be undertaken by
the sponsoring
company for competitive or other
reasons; adverse
effects detected
by Phase IV trials
may result in the
withdrawal or
restriction of a
therapy

Description

*All clinical trials are conducted in phases.
Tables adapted from: National Institutes of Health. Clinical Trials information. (n.d.). Accessed August 3, 2005 from
http://www.clinicaltrials.gov/ct/info/whatis

September 2005

Vol. 8, Issue 9

SAVE THE
DATES
United States Conference on
AIDS
September 28-October 2, 2005
Houston, Texas
Visit: www.nmac.org
IDSA Conference
October 6-9, 2005
San Francisco, CA
Visit: www.idsociety.org
National Conference on
Correctional Health Care
(NCCHC)
October 8-12, 2005
Denver, Colorado
Visit: www.ncchc.org
IDCR Pre-Conference Seminar
at NCCHC
"Infectious Diseases in
Corrections: An Integrated
Approach"
October 8, 2005
Denver, Colorado
Visit: www.ncchc.org
Society of Correctional
Physicians Annual Meeting
October 9, 2005
Denver, Colorado
Visit: www.corrdocs.org
"Drug-drug Interactions and
Metabolic Complications of
HIV"
Satellite Broadcast
October 26, 2005
12:30-2:30pm EST
Visit:
www.amc.edu/patient/hiv/hivconf/
index.htm
APHA Meeting and Exposition
November 5-9, 2005
New Orleans, LA
Visit: www.apha.org
American Association for the
Study of Liver Diseases
Meeting
November 11-15, 2005
San Francisco, CA
Visit: www.aasld.org
National Viral Hepatitis
Prevention Conference
December 5-9
Washington, DC
Visit: www.cdc.gov/ncidod/
diseases/hepatitis.conference.htm
XVI International AIDS
Conference
August 13-18, 2006
Toronto, Canada
Visit: www.aids2006.org

NEWS

visit IDCR online at www.IDCRonline.org

AND

8

LITERATURE REVIEWS

24 vs 48 Weeks Pegasys/RBV for Co-infection: Which is Better?
In a randomized, controlled trial, 128 patients coinfected with HIV and HCV genotype 2 or 3
received 180 mcg Pegasys sq once weekly in
combination with 10.6-13.0 mg/kg/day ribavirin
(RBV.) All patients with undetectable HCV RNA
at 24 weeks after initiation of therapy were randomized at 28 weeks to either stop treatment or
continue treatment for 20 weeks, for a total of 48
weeks of treatment. A significantly lower relapse
rate was found in the patient group receiving 48
weeks of treatment compared to those receiving
24 weeks of treatment (11% vs 40%.) Study
authors concluded that the optimal duration of
treatment in HCV genotype 2- and 3-infected
patients co-infected with HIV is at least 48 weeks.
Zanini, Puoti, et al.
Poster abstract
MoPpLB0103. International AIDS Conference.
Rio de Janeiro. July 25, 2005.
Texas Mandates HIV Testing for All Inmates
Texas Governor Rick Perry signed legislation on
June 21 implementing mandatory HIV testing for
inmates pending release from Texas' prisons.
The policy will be adopted in the Texas
Department of Criminal Justice by September 1,
with the hope of preventing the spread of the
virus both within and outside of the Texas prison
system and to inform inmates of their HIV status.
The University of Texas Medical Brach at
Galveston, which administers healthcare to the
majority of Texas' correctional facilities, recently
reported that HIV prevalence within the Texas
prison system is 2.1%.
West M. Daily Texan. Accessed June 21, 2005
from www.dailytexanonline.com/
media/paper410/news/2005/06/21/University/In
mates.To.Take.Hiv.Test.Before.Release958334.shtml.
Updates to the Guidelines for Use of ARVs in
HIV-1-Infected Adults/Adolescents
The Panel on Clinical Practices for the Treatment
of HIV Infection has issued the following supplemental recommendations, effective immediately,
for the use of antiretroviral agents (ARVs) in HIV1-infected adults and adolescents: (1) a regimen
containing "tenofovir + didanosine + NNRTI"

should not be used as an initial regimen in ARV
treatment-naïve patients and (2) lopinavir/ritonavir can be dosed as one single daily dose (6
capsules or 10mL - equivalent to 800mg
lopinavir/200mg ritonavir) in treatment-naïve
patients. Once-daily dosing is not recommended
in treatment-experienced patients or in patients
receiving concomitant efavirenz, nevirapine,
amprenavir, fosamprenavir or nelfinavir.
NIH. Antiretroviral treatment guidelines. (n.d.).
Accessed
August
15,
2005
from
http://aidsinfo.nih.gov/guidelines/default_db2.asp
?id=50
Pancreatitis in HIV-Infected Adults
In a cross-protocol analysis of 20 Adult AIDS
Clinical Trials Group (AACTG) study sites, rates
of clinical and clinical/laboratory pancreatitis were
relatively low. Seventeen of the 20 studies considered two definitions of pancreatitis: clinical
pancreatitis and a combined definition of clinical
and/or laboratory pancreatitis, defined as grade 3
or 4 amylase and/or lipase elevation. The remaining three studies defined pancreatitis as elevated
serum amylase and a compatible clinical syndrome of nausea, vomiting and/or abdominal
pain. Pancreatitis incident rates were calculated
based on a Poisson distribution. Analysis of 17
studies reflecting 4 arms yielded a relatively low
overall clinical pancreatitis rate of 0.61 per 100
person-years (PYs) and a higher clinical/laboratory pancreatitis rate of 2.23 per 100 PYs. Thus,
the clinical/laboratory pancreatitis definition yielded a rate nearly four-fold higher than the clinical
pancreatitis definition. Rates of pancreatitis in
didanosine (ddI) arms seemed to be dose dependent. Pancreatitis rates for ddI/stavudine (d4T)
trials were high at 4.16 per 100 PYs clinical and
6.25 per 100 PYs clinical/laboratory. The highest
rates were seen with the combination
indinavir/ddI/d4T. Study authors concluded that
the combination of nucleoside reverse transcriptase inhibitors (NRTIs) and definition of pancreatitis has an impact on the incidence of pancreatitis. Further evaluation is needed to determine
how much of this pancreatitis is directly caused
by antiretroviral drugs and how much is attributable to preexisting comorbidities.
Reisler R, et al. JAIDS. 2005; 39(2):159-66.

RESOURCES
NIH Clinical Trials Website
http://www.clinicaltrials.gov/ct/info/whatis
NIH Office of Extramural Research Human Subjects Website
http://grants.nih.gov/grants/policy/hs/index.htm
DHHS Office for Human Research Protections (OHRP)
http://www.hhs.gov/ohrp/
DHHS OHRP Guidance on the Involvement of Prisoners in Research
http://www.hhs.gov/ohrp/humansubjects/guidance/prisoner.htm
The Belmont Report. Full report available at:
http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm
OHRP Human Subject Assurance Online Training
http://ohrp-ed.od.nih.gov/CBTs/Assurance/login.asp

September 2005

Vol. 8, Issue 9

visit IDCR online at www.IDCRonline.org

SELF-ASSESSMENT TEST

FOR

9

CONTINUING MEDICAL EDUCATION CREDIT

Brown Medical School designates this educational activity for one hour in category one credit toward the AMA Physician’s Recognition
Award. To be eligible for CME credit, answer the questions below by circling the letter next to the correct answer to each of the questions.
A minimum of 70% of the questions must be answered correctly. This activity is eligible for CME credit through February 28, 2006.
The estimated time for completion of this activity is one hour and there is no fee for participation.

1. The following research examples are subject to IRB approval:
A. DHHS-supported research involving prisoners.
B. Research involving prisoners in which the information is
used solely for internal modifications of one's own
system/facility.
C. Research that involves prisoners, in which data may
indirectly be linked to identifiable participants of the study.
D. A and B
E. A and C
2. The following statement(s) regarding clinical trial phases
is/are false:
A. Phase II clinical trials are conducted to determine the
short- and long-term side effects and risks of a new
therapy/drug.
B. Phase III clinical trials typically involve 300-3,000
participants.
C. Phase I clinical trials assess the metabolism and safety of
a therapy/drug and are blinded, controlled studies.
D. None of the above statements are false.
E. All of the above statements are false.

5. Research involving prisoners cannot received expedited IRB
approval. True or false?
A. True
B. False

IDCR EVALUATION
5 Excellent

4 Very Good

3 Fair

2 Poor

1 Very Poor

1. Please evaluate the following sections with respect to:
Main Article

educational value
5 4 3 2 1

clarity
5 4 3 2 1

In the News

5 4 3 2 1

5 4 3 2 1

Save the
Dates

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2. Do you feel that IDCR helps you in your work?
Why or why not?

3. A prisoner or prisoner representative should be included on
the IRB reviewing research involving prisoners, but is not necessary if a therapy/drug is not being given to prisoners during the
study. True or false?
A. True
B. False
4. According to 45 CFR 46, permissible research involving prisoners includes the following:
A. The study of prisons as institutional entities, providing that
the research does not present a high risk to the subjects.
B. The study or prisoners as incarcerated persons, providing
that the research does not present a high risk to the
subjects.
C. Research which has the intent of improving the health of
the subject.
D. None of the above research is permissible under
45 CFR 46.
E. All of the above research is permissible under 45 CFR 46.

3. What future topics should IDCR address?

4. How can IDCR be made more useful to you?

5. Do you have specific comments on this issue?

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