FORMERLY HEPP Report

September 2005 Vol. 8, Issue 9

ABOUT IDCR ESEARCHINORRECTIONS IDCR, a forum for R C correctional problem solving, targets By David Paar*, MD, David Thomas**, MD, an incentive that today would be considered correctional physicians, nurses, Jacqueline Thomas**, DO, Danielle Thomas**, highly coercive - while other participants administrators, outreach workers, and MS-IV, and Courtney Colton**, IDCR received special privileges or compensation case managers. Published monthly DISCLOSURES:*Consultant: Gilead, Abbott, such as cigars or cigarettes. Many inmates who and distributed by email and fax, Boehringer Ingelheim, Speaker's Bureau: participated in studies during this period did not IDCR provides up-to-the moment Gilead, Bristol Myers Squibb, GlaxoSmithKline, give truly informed consent. Few understood information on HIV/AIDS, Abbott, Boehringer Ingelheim, **Nothing to dis- the risks and benefits, if any, of the research hepatitis, and other infectious close protocols, and some may not have even been diseases, as well as efficient ways asked to participate.1,2,3 to administer treatment in the Whether or not the inclusion of incarcerated correctional environment. Continuing individuals in clinical research studies is justifiedThe Second World War had a significant impact Medical Education credits are has generated heated debate over the later parton the inclusion of prisoners in research investi- provided by the Brown University of the past century. Some have advocated thatgations. On the one hand, with the onset of the Office of Continuing Medical no research study can ethically include prison-war, investigators appealed to inmates to make Education. IDCR is ers living in an inherently coercive environment,a patriotic contribution to the war effort by par- distributed to all members of the while others counter that incarceration does notticipating in medical research that would assist Society of Correctional Physicians strip an individual of his or her ability to make anthe military. The research included injections of (SCP) within the SCP publication, blood from cattle to investigate alternate CorrDocs (www.corrdocs.org). informed decision regarding participation as a research subject. sources of blood products, studies of atropine as an antidote, as well as experiments in which CO-CHIEF EDITORS Much of this debate is fueled by the competingsubjects were infected with sleeping sickness, Anne S. De Groot, MDconcerns of protecting inmates as a vulnerabledengue fever, gonorrhea, malaria, and agents of Director, TB/HIV Research Lab, population while respecting their individualgas gangrene.1,2,3 Brown Medical School autonomy. This conflict is waged against the David Thomas, MD, JDbackdrop of a historical legacy of unethicalHowever, at the conclusion of World War II, the Professor and Chairman, treatment of incarcerated, institutionalized anddiscovery of human experimentation conducted Department of Surgery, by the Nazis on those they had imprisoned led Division of Correctional Medicine other vulnerable groups during clinical research NSU-COM studies. to a wide scale re-evaluation of the ethics of research of human subjects and the study of the DEPUTY EDITORS HISTORY OF RESEARCH IN PRISONS IN incarcerated in particular. The Nuremberg War Joseph Bick, MD Chief Medical Officer, THE TWENTIETH CENTURY Crime Tribunal was convened to investigate and California Medical Facility, California Research involving prisoners has had a trou-punish war time crimes perpetrated by the Department of Corrections bled past. During the early part of the twentiethNazis, including hideous trials performed by the Renee Ridzon, MDcentury, there were well-documented instancesGermans in concentration camps. In 1947, the Senior Program Officer, of investigators in the United States, and else-tribunal produced the Nuremberg Code, a set of HIV, TB, Reproductive Health, where, using prison inmates to study the patho-10 basic tenets, which was drafted as the stan- Bill & Melinda Gates Foundation genesis, prevention, and treatment of a varietydard by which to judge physicians and scientists Bethany Weaver, DO, MPHof illnesses including cholera, beriberi, pellagra,during their trial at Nuremberg. It became an Acting Instructor, Univ. of Washington, and tuberculosis. Notorious experiments, suchethical standard for research for decades. Center for AIDS and STD Research as the transplantation or injection of human or animal testicular material into senile men, wereThe first of these tenets, that "the voluntary con- SUPPORTERS conducted, and, although rare, reflected thesent of the human subject is absolutely essen- IDCR is grateful for tial . . . . [and] should be so situated as to be the support of the following belief at the time that inmates were a population Continued on page 2 companies through unrestricted that could be subjected to experimentation that educational grants: could not be performed on the general popula- tion. The unique vulnerabilities of inmates in HATSNSIDE Major Support:Abbott Laboratories W ’I these studies were often exploited. For exam- IDCR-o-gram pg 5 and Roche Pharmaceuticals. ple, many of the participants were death row State Laws 101 pg 6 inmates, some of whom died following injection Sustaining:Pfizer Inc., Gilead IDCR 101 pg 7 of cholera toxins or similarly dangerous proce- Sciences, Inc., GlaxoSmithKline, Merck In The News pg 8 & Co., and Schering-Plough. dures. "Volunteers" were recruited by promising them clemency if they survived the experiment - Self-Assessment Test pg 9

Brown Medical School Providence, RI 02912 401.453.2068 fax: 401.863.6087 www.IDCRonline.org If you have any problems with this fax transmission please call 800.748.4336 or e-mail us at [email protected] September 2005 Vol. 8, Issue 9 visit IDCR online at www.IDCRonline.org 2

RESEARCHINCORRECTIONS... and behavioral research involving humanbecame law in 1978, was revised in 2001 (continued from page 1) subjects and to develop guidelines, whichand provides some guidance regarding the able to exercise free power of choice with-should be followed to assure that suchinclusion of prisoners in research. 45 CFR out . . . the intervention of any element ofresearch is conducted in accordance with46 applies to all research involving human force, fraud, deceit, duress . . . or coercionthose principles. The Belmont Reportsubjects that is conducted, supported by, or . . . ." has been widely interpreted asresulted from an intensive four-day periodotherwise subject to regulation by any fed- excluding prisoners from research sinceof discussions held at the Smithsonianeral department or agency. It provides incarceration is a necessarily coercive con-Institution's Belmont Conference Centerdirection on how agencies and institutions dition. However, in the U.S., the prevalentsupplemented by monthly deliberations ofcan file letters of assurance that they will opinion in the medical community,The Commission held over a four-year peri-comply with these regulations, direction on endorsed by the American Medicalod. It was published in The Code of Federalthe composition and duties of institutional Association, was that the Nuremberg CodeRegulations (CFR), commonly called thereview boards (IRBs) that oversee federal- pertained to Nazi atrocities, but not to thefederal register or common rule, on Aprilly funded research, requirements for increasingly prevalent medical experiments18, 1979 as a statement of the Departmentinformed consent, and documentation of being conducted using inmates in state andof Health, Education, and Welfare's policyinformed consent. Subpart B of this law federal jurisdictions. In fact, the post-warof ethical principles and guidelines for thelists additional protections for pregnant flourishing of medical experimentation with-protection of human subjects of research.women, human fetuses, and neonates, and in the U.S. penal system was being drivenLater this department evolved into theSubpart C lists additional DHHS protec- by increased federal funding to investigateDepartment of Health and Human Servicestions pertaining to biomedical and behav- medical illness, the formation of academic-(DHHS) which remains responsible for theioral research involving prisoners as sub- pharmaceutical alliances, and the need toprotection of human subjects involved injects (6 45 CFR 46). test various products in human subjects tobiomedical research through the Office of The additional protections of Subpart C meet U.S. Food and Drug AdministrationHuman Research Protection (OHRP). The provide for prisoners that participate in bio- regulations.1,2,3,4 three basic principles that were detailed in this report were respect for persons, benef-medical research including: 1. Inclusion of Prisoners were enlisted in a broad range oficence, and justice. Respect for personsa prisoner or a prisoner representative on clinical studies and the inclusion of inmateshas two important components: individualsthe IRB reviewing the research; 2. in investigation became routine. Inshould be treated as autonomous agentsAssigning additional duties to the reviewing Holmesburg Prison, a county facility inand those with diminished autonomy areIRB to be sure that the research is permis- Philadelphia, in the late 1960’s inmatesentitled to protection. The report itselfsible, free of undue influence, safe, acces- were recruited to participate in studies thatdirectly addresses the issue of prisonersible and fair to all inmates, presented in explored everything from simple detergentsparticipation in research: understandable language, and does not and diet drinks to retinoic acid, dioxin, and have any effect on parole. Permissible chemical warfare agents. The list of spon-"[R]espect for persons demands that sub-research involving prisoners includes: "(A) sors of these investigations included notjects enter into the research voluntarily andstudy of the possible causes, effects, and only pharmaceutical companies and otherwith adequate information… In some situa-processes of incarceration, and of criminal corporations such as Dow Chemical, buttions, however, application of the principlebehavior, provided that the study presents also the U.S. Army. However, in the earlyis not obvious. The involvement of prison-no more than minimal risk and no more 1970's the public conscious shifted anders as subjects of research provides anthan inconvenience to the subjects; (B) began to look unfavorably upon researchinstructive example. On the one hand, itstudy of prisons as institutional structures conducted in prisons. This change waswould seem that the principle of respect foror of prisoners as incarcerated persons, influenced by well-publicized revelations ofpersons requires that prisoners not beprovided that the study presents no more the serious side effects associated withdeprived of the opportunity to volunteer forthan minimal risk and no more than incon- medications, such as birth defects causedresearch. On the other hand, under prisonvenience to the subjects; (C) research on by the tranquilizer thalidomide and theconditions they may be subtly coerced orconditions particularly affecting prisoners Tuskeegee syphilis experiments, whichunduly influenced to engage in researchas a class (for example, vaccine trials and were not conducted using inmates, but didactivities, for which they would not other-other research on hepatitis which is much involve another vulnerable population:wise volunteer…. Respect for personsmore prevalent in prisons than elsewhere; black men in the U.S. rural south. By thewould then dictate that prisoners be pro-and research on social and psychological late 1970’s, legislation had been passedtected. Whether to allow prisoners to "vol-problems such as alcoholism, drug addic- preventing federal inmates from participat-unteer" or to "protect" them presents ation, and sexual assaults) provided that the ing in clinical trials and very few state juris-dilemma." study may proceed only after the Secretary dictions continued their clinical research [of the Department of Health and Human These passages accurately state the programs using inmates. Services] has consulted with appropriate equipoise that persists to this day regardingexperts including experts in penology, med- THE BELMONT REPORT AND prisoners as research subjects. How toicine, and ethics, and published notice, in 45 CFR 46 best balance between not "depriving" thethe Federal Register, of his intent to In response to the growing public concerninmate of an opportunity to participate andapprove such research; or (D) research on regarding abuses during clinical research,protecting the inmate from coercionpractices, both innovative and accepted, the National Research Act was signed intoremains the enduring challenge of thiswhich have the intent and reasonable prob- law on July 12, 1974. This federal law cre-issue with vocal advocates of each positionability of improving the health or well-being ated the National Commission for theweighing in. of the subject. In cases in which those Protection of Human Subjects of studies require the assignment of prisoners The federal legislation, published in the Biomedical and Behavioral Research, in a manner consistent with protocols Code of Federal Regulations, that deals hereafter referred to as "The Commission". approved by the IRB to control groups with the protection of human research sub- One of The Commission's charges was to which may not benefit from the research, jects is called Title 45 CFR Part 46 and is identify the basic ethical principles that commonly referred to as 45 CFR 46. It should underlie the conduct of biomedical Continued on page 3 September 2005 Vol. 8, Issue 9 visit IDCR online at www.IDCRonline.org 3

RESEARCHINCORRECTIONS... appropriate since life-saving treatment, notto resume research with prisoners, virtually (continued from page 2) available outside of clinical trials, becameno clinical trials using pharmaceutical the study may proceed only after theavailable to incarcerated patients withagents are being conducted in the state Secretary has consulted with appropriateAIDS. prison systems today. Behavioral, social, experts, including experts in penology, and psychological research continues to be medicine, and ethics, and published noticeIn 1998, one of the pharmaceutical manu-pursued by many institutions using prison- in the Federal Register, of the intent tofacturers of HIV medications implementeders as subjects. approve such research."6 a non-comparative trial of a combination of three nucleosides for the treatment of HIVCOMMENT According to 45 CFR 46, permissiblein prisoners only. Many prisoner advocatesIt has now been over 30 years since 45 research includes not only social, behav-became concerned that prisoners wereCFR 46 Subpart C has been enacted. ioral, and psychological research, but alsobeing exploited in the name of medicalWhether an inmate can ever act therapeutic trials using pharmaceuticalresearch since all of the pharmaceuticalautonomously and what the standard of agents in this trial were available outside ofminimal risk for an inmate remains agents for medical conditions that particu- 11 larly affect inmates (though the use ofclinical trials and there was already someunclear.Three issues are at the crux of question in 1998 if three nucleosides alonethis question. First, are prisoners and the placebos in this situation requires addition- 7 al safeguards.) The example given in thewere adequate therapy for HIV infection.general population well served by not hav- law specifically mentions hepatitis, but theToday we know that triple nucleoside thera-ing federal funding for clinical research health condition that came to the forefrontpy is inferior to either protease inhibitor-using pharmaceutical therapies in the as a condition particularly affecting prison-based or non-nucleoside reverse transcrip-incarcerated population; second, does the ers was HIV infection and AIDS. Undertase inhibitor-based potent combinationlaw serve its goal to protect a vulnerable pressure from patients and patient advoca-therapy and is not recommended as firstpopulation; and third, does the federal law cy groups, HIV clinical research movedline therapy for HIV infection. Subjectingimpact upon non-federally funded from the strictly academic setting to a vari-prisoners to the choice of receiving whatresearch? Secretary Tommy Thompson of ety of other patient sites including non-uni-might be inferior treatment seemed tothe DHHS has speculated that it is past versity affiliated hospitals, private physicianexceed the limit of minimal risk that 45 CFR time that Subpart C be evaluated again offices, and community consortiums. In the46 had set as a standard. The scientific(personal communication). To this end, the 1990s, when effective HIV treatment thera-research community was again faced withDHHS has asked the Institute of Medicine pies were under investigation in multiplethe difficult question of how best to protectof the National Academy of Sciences to clinical trials, HIV clinical trials at some aca-prisoners. investigate the impact of Subpart C, and to demic sites re-entered the prison setting. determine if there should be any change in As a result, a group of concerned correc- In this case, inclusion of prisoners was the current law. The Committee of Ethical tional clinicians organized a conference, often justified as a means to provide access Considerations for Revisions to the DHHS' "Clinical Trials in Corrections." Over 100 to cutting-edge therapies to persons living Regulations for Protection of Prisoners like-minded individuals and representatives with HIV who were incarcerated. At sever- Involved in Research was impaneled and from the Office of Human Research al major medical centers, HIV research was will examine whether the conclusions Protections attended this meeting, and pro- extended into correctional facilities. For reached by the National Commission for ceeds were published in 2001 in AIDS example, clinical trials being conducted at the Protection of Human Subjects of Reader.13What happened next had a chill- The University of Texas Medical Branch in Biomedical and Behavioral Research in the ing effect on pharmaceutical medical 12 Galveston and the University of Miami in 1970’s remain appropriate today.The research using prisoners as subjects. The Florida were offered to inmates in the Texas committee will hold five public meetings at IRBs at the University of Texas Medical Department of Criminal Justice and the which they will collect data from invited Branch, the University of Miami, Brown Florida Department of Corrections, respec- panelists who work or perform research in University, and Yale University were tively. Additionally, behavioral research the correctional setting and will also hold reviewed by the OHRP and received "let-two workshops to further inform the regarding AIDS in the incarcerated popula- 8 ters of determination"that the composition tion were being conducted by Yale and process. Three of the public meetings have of the IRBs and their procedures to ensure Brown Universities in their respective state been held: March 16, 2005, National the protection of prisoners were inade- jurisdictions. Not all of these studies fell Academies of Science, Washington, D.C., quate. Enrollment in clinic trials was sus- under the purview of 45 CFR 46, as these May 4, 2005, The National Academies of pended at the University of Texas MedicalScience, Washington, D.C., and July 18, regulations apply to federally funded stud- 9 Branch at Galvestonand the University of ies and some of these investigations were the Gladstone Institute, San Francisco, CA. Miami.10Although each of the Universities funded by pharmaceutical industry support. The committee's final report is expected in cited above eventually received permission Allowing prisoners to participate seemed March, 2006.

References: http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=50 1. Richardson T. Acres of Skin: human experiments at Holmesburg Prison, 8. Department of Health and Human Services. OHRP determination letters. a true story of abuse and exploitation in the name of medical science. Last accessed August 30, 2005 from Canadian Journal of History. 2001; 36(1):184-6. http://www.hhs.gov/ohrp/compliance/letters/index.html 2. Caelleigh As. Prisoners. Academic Medicine. 2000; 75(10):999. 9. Department of Health and Human Services. Letter of determination for 3. Hornblum Am. They were cheap and available: prisoners as research the University of Texas Medical Branch at Galveston. Last accessed subjects in twentieth century America. British Medical Journal. 1997; August 30, 2005 from http://www.hhs.gov/ohrp/detrm_letrs/jul00c.pdf 315(7120):1437-41. 10. Department of Health and Human Services. Letter of determination for 4. The Nuremberg Code. Last accessed August 30, 2005 from the University of Miami. Last accessed August 30, 2005 from http://ohsr.od.nih/gov/guidelines/nuremberg.html http://www.hhs.gov/ohrp/detrm_letrs/jul00l.pdf 5. The Belmont Report. Last accessed August 30, 2005 from 11. Stone TH. Discerning minimal risk in research involving prisoners as http://ohsr.od.nih.gov/guidelines/belmont.html human subjects. Journal of Law, Medicine & Ethics. 2004; 32(3):535-7. 6. 45 CFR 46. Last accessed August 30, 2005 from 12. Institute of Medicine. Ethical considerations for revisions to the DHHS http://ohsr.od.nih.gov/guidelines/45cfr46.html regulations for protection of prisoners involved in research. Last accessed 7. Department of Health and Human Services. Guidelines for the use of August 30, 2005 from http://iom.edu/project.asp?id=24594 antiretroviral agents in HIV-1-infected adults and adolescents. Last 13. DeGroot AS, et al. HIV in clinical trials: right or retrogressions? AIDS accessed August 30, 2005 from Reader. 2001; 11(1):34-40. September 2005 Vol. 8, Issue 9 visit IDCR online at www.IDCRonline.org 4

Faculty Disclosure In accordance with the Accreditation Council for LETTERFROMTHEEDITOR Continuing Medical Education Standards for Dear Colleagues, Commercial Support, the faculty for this activity have been asked to complete Conflict of Interest This issue is dedicated to clinical trials in corrections. Prior to 2000, several correctional practi-Disclosure forms. Disclosures are listed at the end of tioners and facilities were involved in clinical trials in order to permit the incarcerated population toarticles. All of the individual medications discussed gain the benefits of investigational drugs and other therapies that could only be obtained throughin this newsletter are approved for treatment of HIV trials. In 2000, the Office of Protection from Research Risks (currently named Office for Human and hepatitisunless otherwise indicated. For the Research Protections) investigated every clinical trial from every major university, correctional sys-treatment of HIV and hepatitis infection, many physi- cians opt to use combination antiretroviral therapy tem, and quality Institutional Review Board involved in prisoner research. That investigation which is not addressed by the FDA. caused most of the aforementioned programs to stop enrolling new patients and taper their exist- ing efforts. Associate Editors Rick Altice, MD Many of us involved in correctional healthcare felt that both society and our patients were Director of Clinical Research, inadequately served by this act. Although mostly minor violations were documented, the tone cre- Director, HIV in Prisons Program, ated by the investigation lead to irreparable damage to clinical trials in corrections. Universities Director, Community Health Care Van, decided it was not worth the effort and correctional administrators wanted no part of any potential Associate Professor of Medicine controversy. Yale University AIDS Program David Paar, MD The advantages of clinical trials in correctional populations, both for the inmates and society, and Associate Professor of Medicine, the advocacy for them, are phenomenal. There was a pervasive feeling that affording this benefit University of Texas, Medical Branch to our patients was going to be impossible, even though many of us continually brought the issue Karl Brown, MD, FACP of clinical trials in corrections to the highest levels of authority. Infectious Disease Supervisor PHS-Rikers Island In the last year of his position as Agency Head of the Department of Health and Human Services Ralf Jürgens (DHHS), Secretary Tommy Thompson personally determined that there might be real value to Consultant, inmates and society if the question of clinical trials within clinical settings were evaluated again. To HIV/AIDS, Human Rights, Drug Policy and that end, the DHHS asked the Institute of Medicine of the National Academy of Sciences to reeval- Prisons uate the pertinent parts of Federal law pertaining to prisoner inclusion in research. Joseph Paris, PhD, MD, FSCP, CCHP Medical Director, It should be our job to advocate for our patients in this area and to remind the committee of two Georgia Dept. of Corrections specific items: first - the effect of Federal law is far more reaching than the words of the statute Lester Wright, MD, MPH themselves and, second - the current situation discriminates against legitimate scientific inquiry Chief Medical Officer, and encourages unregulated research which may be performed solely for remuneration. New York State Dept. of Correctional Services After reading this issue, readers should be familiar with the history of research involving prisoners, Dean Rieger, MD 45 CFR 46, the Belmont Report and the requirements for conducting research involving prisoners. Medical Director, Readers should also be able to identify when research requires approval by an Institutional Review Indiana Dept. of Corrections Board. Neil Fisher, MD Medical Director, Chief Health Officer, Very truly yours, 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 *Nothing to Disclose Correctional Medical Institute, Correctional Medical Services Josiah Rich, MD Associate Professor of Medicine and Community Health Subscribe to IDCR Brown University School of Medicine, The Miriam Hospital Faxto 617-770-3339for any of the following:(please print clearly or type) Steven F. Scheibel, MD Regional Medical Director ____ Yes, I would like to add/update/correct (circle one) my contact information for my complimentary Prison Health Services, Inc subscription of IDCR fax/email newsletter. David A. Wohl, MD Associate Professor of Medicine ____ Yes, I would like to sign up the following colleague to receive a complimentary subscription of University of North Carolina IDCR fax/email newsletter. AIDS Clinical Research Unit Barry Zack, MPH ____ Yes, I would like my IDCR to be delivered in the future as an attached PDFfile in an Executive Director, Centerforce email (rather than have a fax). Michelle Gaseau The Corrections Connection NAME: FACILITY: Layout Kimberly Backlund-Lewis CHECK ONE: The Corrections Connection Distribution Physician Physician Assistant Nurse/Nurse Practitioner Nurse Administrator Screened Images Multimedia Pharmacist Medical Director/Administrator HIV Case Worker/Counselor Other Managing Editor ADDRESS: CITY: STATE:ZIP: Courtney E Colton IDCR FAX: PHONE:

EMAIL: 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?

NO, individuals are NOT living YES, individuals ARE living

NOT Human Subjects Research 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

NO YES Were/will the specimens/data be collected specifically for the proposed Human Subjects Research research through an interaction or intervention with living individuals?

NO YES Can the recipient link the specimens/data directly Human Subjects Research to identifiable living individuals?

NO YES Can the provider link the specimens/data, directly or Human Subjects Research indirectly, to identifiable living individuals?

NO YES NOTHuman 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 link- Human Subjects Research* ing them to identifiable living individuals?

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

STATELAWS101*

State Legislation California* Specific legislation including criminal penalties for failure to comply; requirement that all clinical investiga- tors - 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** 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*** Georgia has specific restrictions on cancer and THC research and surgical procedures under investigation. Kentucky^ Kentucky has a Cabinet for Health Services, which has specific requirements for research funded through the state. Maryland^^, Maryland and North Carolina have adopted the Federal statute for all state participants in research. North Carolina^^^ Wisconsin, Wisconsin, Pennsylvania, Texas, Ohio, and Virginia have all adopted the basic precepts of the Federal Pennsylvania, Texas,statute, but have made modifications by their legislatures. For instance, Ohio requires fully informed con- Ohio, Virginia sent even for proposals that have minimal risk. New Yorko New York has the most complex of the statutes, adopting both the Federal 45 CFR 46 and overlaying cer- tain 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). oNY Public Health Law 2444(3) (2004).

IDCR-o-gram...(continued from page 5) ** Examples of situations in which the recipient cannot link the Footnotes specimens/data to living individuals include: *All human subjects research must obtain institutional review - The key to deciper the code is destroyed before the research board (IRB) approval. Exceptions include when there is no effort begins to contribute to the general body of knowledge and the informa- - The investigators and the holder of the key to the code enter tion will be used only for risk management or internal modifica- into an agreement preventing the release of the key to investiga- tions of ones' own system or facility. tors under any circumstances All DHHS-supported human subjects research involving prisoners - There are IRB-approved written policies in place preventing as subjects must comply with all regulations set forth in 45 CFR release of the key under any circumstances 46 Subpart C. When prisoners are involved as subjects in - There are other legal requirements prohibiting the release of the research, composition of the IRB must satisfy the following key under any circumstances requirements: - A majority of the IRB (exclusive of prisoner members) shall Endnotes have no association with the prison(s) involved, apart from their Adapted from Office of Extramural Research. Research involving membership on the IRB. private information or biological specimens. (n.d.). Accessed - At least one member of the IRB must be a prisoner, or a prison- August 17, 2005 from er representative with appropriate background and experience to http://grants.nih.gov/grants/policy/hs/index.htm and serve in that capacity, except that where a particular research NIH. Office of Human Research Protections. Guidance on the project is reviewed by more than one IRB, only one IRB need involvement of prisoners as research. (n.d.). Accessed August satisfy this requirement. 17, 2005 from http://www.hhs.gov/ohrp/humansubjects/guid- Research involving prisoners (or other vulnerable populations) ance/prisoner.htm cannot receive expedited IRB approval. September 2005 Vol. 8, Issue 9 visit IDCR online at www.IDCRonline.org 7

Research 101: Types of Clinical Trials

Type of Trial Purpose Treatment Trials Test experimental treatments, new combinations of drugs, or new approaches to surgery or radia- tion therapy Prevention Trials 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, miner- als, or lifestyle changes. Diagnostic Trials Conducted to find better tests or procedures for diagnosing a particular disease or condition. Screening Trials Test the best way to detect certain diseases or health conditions. Quality of Life TrialsExplore ways to improve comfort and the quality of life for individuals with a chronic illness.

Clinical Trial Phases*

Phase I Phase II Phase III Phase IV DescriptionInitial studies Controlled clinicalExpanded controlled and uncontrolled trials Post-marketing studies after preliminary evidence of the drug has studies been obtained

Purpose Assess the safety,Evaluate clinical Gather additional information to evaluate the Detect any rare or tolerability, metab-efficacy of the overall benefit-risk relationship of the drug andlong-term adverse olism, and phar- therapy for a par-provide adequate basis for physician labeling;effects over a macologic actionsticular indication definitively assesses efficacy of the new thera-much larger of the therapy in or indications in py, especially in comparison with currently patient population humans and the patients with the available alternatives and timescale side effects asso-disease/condition than was possible ciated with under study; during the initial increasing doses determine the clinical trials; common short- delineate addition- term side effects al information, and risks including drugs' risks, benefits, and optimal use

Number 20-80 100-300 1,000-3,000 Varies of People Given Drug

Additional Conducted in The developmentDouble-blind randomized controlled trials; Phase IV studies Informationinpatient clinic, process for a newmost expensive, time-consuming phase to may be mandated where subject cantherapy often failsdesign and run; once a therapy has proven by regulatory be observed by at this phase due satisfactory over Phase III trials, the trial authorities or may full-time medical to the discovery ofresults are usually combined into a large docu-be undertaken by staff; not blinded;poor efficacy or ment containing a comprehensive description the sponsoring often no placebo toxic effects of the methods and results of human and ani- company for com- control mal studies, manufacturing procedures, formu-petitive or other lation details, and shelf life. This collection of reasons; adverse information is then submitted to the FDA for effects detected approval of the therapy. by Phase IV trials may result in the withdrawal or restriction of a therapy

*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 visit IDCR online at www.IDCRonline.org 8 SAVETHE NEWSANDLITERATUREREVIEWS DATES 24 vs 48 Weeks Pegasys/RBV for Co-infec- should not be used as an initial regimen in ARV tion: Which is Better? treatment-naïve patients and (2) lopinavir/riton- United States Conference on In a randomized, controlled trial, 128 patients co-avir can be dosed as one single daily dose (6 AIDS infected with HIV and HCV genotype 2 or 3capsules or 10mL - equivalent to 800mg September 28-October 2, 2005 received 180 mcg Pegasys sq once weekly inlopinavir/200mg ritonavir) in treatment-naïve Houston, Texas combination with 10.6-13.0 mg/kg/day ribavirinpatients. Once-daily dosing is not recommended Visit: www.nmac.org (RBV.) All patients with undetectable HCV RNAin treatment-experienced patients or in patients at 24 weeks after initiation of therapy were ran-receiving concomitant efavirenz, nevirapine, IDSA Conference domized at 28 weeks to either stop treatment oramprenavir, fosamprenavir or nelfinavir. October 6-9, 2005 continue treatment for 20 weeks, for a total of 48NIH. Antiretroviral treatment guidelines. (n.d.). San Francisco, CA weeks of treatment. A significantly lower relapseAccessed August 15, 2005 from Visit: www.idsociety.org rate was found in the patient group receiving 48http://aidsinfo.nih.gov/guidelines/default_db2.asp weeks of treatment compared to those receiving?id=50 National Conference on 24 weeks of treatment (11% vs 40%.) Study Correctional Health Care authors concluded that the optimal duration ofPancreatitis in HIV-Infected Adults (NCCHC) treatment in HCV genotype 2- and 3-infectedIn a cross-protocol analysis of 20 Adult AIDS October 8-12, 2005 patients co-infected with HIV is at least 48 weeks.Clinical Trials Group (AACTG) study sites, rates Denver, Colorado Zanini, Puoti, et al. Poster abstractof clinical and clinical/laboratory pancreatitis were Visit: www.ncchc.org MoPpLB0103. International AIDS Conference.relatively low. Seventeen of the 20 studies con- IDCR Pre-Conference Seminar Rio de Janeiro. July 25, 2005. sidered two definitions of pancreatitis: clinical at NCCHC pancreatitis and a combined definition of clinical "Infectious Diseases in Texas Mandates HIV Testing for All Inmates and/or laboratory pancreatitis, defined as grade 3 Corrections: An Integrated Texas Governor Rick Perry signed legislation onor 4 amylase and/or lipase elevation. The remain- Approach" June 21 implementing mandatory HIV testing foring three studies defined pancreatitis as elevated October 8, 2005 inmates pending release from Texas' prisons.serum amylase and a compatible clinical syn- Denver, Colorado The policy will be adopted in the Texasdrome of nausea, vomiting and/or abdominal Visit: www.ncchc.org Department of Criminal Justice by September 1,pain. Pancreatitis incident rates were calculated with the hope of preventing the spread of thebased on a Poisson distribution. Analysis of 17 Society of Correctional virus both within and outside of the Texas prisonstudies reflecting 4 arms yielded a relatively low Physicians Annual Meeting system and to inform inmates of their HIV status.overall clinical pancreatitis rate of 0.61 per 100 October 9, 2005 The University of Texas Medical Brach atperson-years (PYs) and a higher clinical/labora- Denver, Colorado Galveston, which administers healthcare to thetory pancreatitis rate of 2.23 per 100 PYs. Thus, Visit: www.corrdocs.org majority of Texas' correctional facilities, recentlythe clinical/laboratory pancreatitis definition yield- reported that HIV prevalence within the Texased a rate nearly four-fold higher than the clinical "Drug-drug Interactions and prison system is 2.1%. pancreatitis definition. Rates of pancreatitis in Metabolic Complications of West M. Daily Texan. Accessed June 21, 2005 didanosine (ddI) arms seemed to be dose depen- HIV" from www.dailytexanonline.com/ dent. Pancreatitis rates for ddI/stavudine (d4T) Satellite Broadcast media/paper410/news/2005/06/21/University/In trials were high at 4.16 per 100 PYs clinical and October 26, 2005 mates.To.Take.Hiv.Test.Before.Release-6.25 per 100 PYs clinical/laboratory. The highest 12:30-2:30pm EST Visit: 958334.shtml. rates were seen with the combination www.amc.edu/patient/hiv/hivconf/ indinavir/ddI/d4T. Study authors concluded that index.htm Updates to the Guidelines for Use of ARVs inthe combination of nucleoside reverse transcrip- HIV-1-Infected Adults/Adolescents tase inhibitors (NRTIs) and definition of pancre- APHA Meeting and Exposition The Panel on Clinical Practices for the Treatmentatitis has an impact on the incidence of pancre- November 5-9, 2005 of HIV Infection has issued the following supple-atitis. Further evaluation is needed to determine New Orleans, LA mental recommendations, effective immediately,how much of this pancreatitis is directly caused Visit: www.apha.org for the use of antiretroviral agents (ARVs) in HIV-by antiretroviral drugs and how much is attribut- 1-infected adults and adolescents: (1) a regimenable to preexisting comorbidities. American Association for the containing "tenofovir + didanosine + NNRTI"Reisler R, et al. JAIDS. 2005; 39(2):159-66. Study of Liver Diseases Meeting November 11-15, 2005 RESOURCES San Francisco, CA Visit: www.aasld.org NIH Clinical Trials Website http://www.clinicaltrials.gov/ct/info/whatis National Viral Hepatitis NIH Office of Extramural Research Human Subjects Website Prevention Conference http://grants.nih.gov/grants/policy/hs/index.htm December 5-9 Washington, DC DHHS Office for Human Research Protections (OHRP) Visit: www.cdc.gov/ncidod/ http://www.hhs.gov/ohrp/ diseases/hepatitis.conference.htm DHHS OHRP Guidance on the Involvement of Prisoners in Research http://www.hhs.gov/ohrp/humansubjects/guidance/prisoner.htm XVI International AIDS Conference The Belmont Report. Full report available at: August 13-18, 2006 http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm Toronto, Canada OHRP Human Subject Assurance Online Training Visit: www.aids2006.org http://ohrp-ed.od.nih.gov/CBTs/Assurance/login.asp September 2005 Vol. 8, Issue 9 visit IDCR online at www.IDCRonline.org 9

SELF-ASSESSMENTTESTFORCONTINUINGMEDICALEDUCATIONCREDIT 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:5. Research involving prisoners cannot received expedited IRB A. DHHS-supported research involving prisoners. approval. True or false? B. Research involving prisoners in which the information is A. True used solely for internal modifications of one's own B. False system/facility. C. Research that involves prisoners, in which data may indirectly be linked to identifiable participants of the study. D. A and B IDCR EVALUATION E. A and C 5 Excellent 4 Very Good 3 Fair 2 Poor 1 Very Poor 2. The following statement(s) regarding clinical trial phases is/are false: 1. Please evaluate the following sections with respect to: A. Phase II clinical trials are conducted to determine the short- and long-term side effects and risks of a new educational value clarity therapy/drug. Main Article5 4 3 2 1 5 4 3 2 1 B. Phase III clinical trials typically involve 300-3,000 In the News5 4 3 2 1 5 4 3 2 1 participants. Save the C. Phase I clinical trials assess the metabolism and safety of Dates 5 4 3 2 1 5 4 3 2 1 a therapy/drug and are blinded, controlled studies. D. None of the above statements are false. 2. Do you feel that IDCR helps you in your work? E. All of the above statements are false. Why or why not? 3. A prisoner or prisoner representative should be included on the IRB reviewing research involving prisoners, but is not neces- sary if a therapy/drug is not being given to prisoners during the study. True or false? A. True 3. What future topics should IDCR address? B. False

4. According to 45 CFR 46, permissible research involving pris- oners includes the following: A. The study of prisons as institutional entities, providing that 4. How can IDCR be made more useful to you? 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. 5. Do you have specific comments on this issue? D. None of the above research is permissible under 45 CFR 46. E. All of the above research is permissible under 45 CFR 46.

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