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Page 1: Legal and ethical considerations for genetic clinical research

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Introduction

Pharmacogenomics is the science of under-standing how different genotypes produce

different responses to medications. Althoughpharmacogenomics promises great possibilitiesfor the future of medicine, it requires ethical andlegal questions to be considered. As stated in thepreamble of a new national regulation in theUnited States for the protection of individuallyidentifiable health information, ‘the absence ofprivacy protections for health informationendanger these efforts by creating a barrier ofdistrust and suspicion among consumers’ [5].

Genetic testing practices remain moreadvanced than the laws governing the appropriateuse of genetics. Although there is no specific fed-eral law governing DNA and genetic privacy, statelegislators concerned with the potential for dis-crimination by employers and insurers based on

Legal and Ethical Considerationsfor Genetic Clinical Research

Judith E. Beach1,* and William A. Goolsby2

1Quintiles Transnational Corp., 4709 Creekstone Drive, Suite 200, Riverbirch Building, Durham NC 27703,USA.2The University of North Carolina at Chapel Hill, Masters Candidate, School of Public Health, USA

Copyright © 2003 John Wiley & Sons, Ltd. Qual Assur J 2003; 77, 22–31.DOI: 10.1002/qaj.209

*Correspondence to: Judith E. Beach, Quintiles TransnationalCorp., 4709 Creekstone Drive, Suite 200, Riverbirch Building,Durham NC 27703, USAE-mail: [email protected]

Summary

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Page 2: Legal and ethical considerations for genetic clinical research

genetic test results have successfully passednumerous state laws. Professional associationsand private organizations have published manyguidelines and articles on genetic testing practices.

The purpose of this article is to provide a pic-ture of the legal and ethical ramifications of per-forming genetic testing. The genetic testing issuehas been broken down into several categories:federal policies and regulations, state laws includ-ing privacy protection, risks and benefits, sec-ondary use of samples, and access to genetic testresults, and examples of international policiesdealing with this issue.

Federal Laws, Regulations,and Policies

Although 63% of the 1000 participants in a 1997national survey said they would not take genetictests if insurers and employers could gain access tothe results [6], currently, no United States’ lawspecifically addresses genetic information andgenetic privacy. Nevertheless, throughout the pastseveral years, there have been many bills intro-duced specifically addressing genetic informationand privacy to ensure protection of rights.Discussed below are several laws and regulations inexistence that protect genetic information on thesame level as other confidential health information.

Health Insurance Portability andAccountability Act of 1996(HIPAA), issued 28 December2000 and the final amendmentissued on 14 August 2002

In accordance with HIPAA, the Department ofHealth and Human Services (HHS) issued pri-vacy standards governing protection of individu-ally identifiable health information by coveredentities, i.e. health-care providers, payment plansand health-care clearinghouses [7]. These standards, with a compliance date of 14 April2003, protect genetic information within the category of ‘individually identifiable health infor-mation,’ when it bears some identifying link to thesource individual, such as a name, address, or

social security number. Indeed, HHS notes theimportance of providing protection for genetic test-ing, quoting Senator Leahy’s comments on 10 March 1999 Introduction of the ‘MedicalInformation Privacy and Security Act,’ ‘In genetictesting studies at the National Institutes of Health,32% of eligible people who were offered a test for breast-cancer risk declined to take it, citing concerns about loss of privacy and the poten-tial for discrimination in health insurance’ [8].

The final HIPAA regulation supports the con-cept of de-identification to protect individuallyidentifiable health information; i.e. protectedhealth information (PHI) [9]. PHI includesgenetic information identifiable to an individual.The rule provides national standards for de-iden-tification of PHI: a safe harbor standard whereby18 specified direct and indirect identifiers areremoved and an alternative method where a stat-istician makes and documents a determinationthat the risk of re-identification of PHI is ‘verysmall’ [10].

Food and Drug Administration

FDA has regulatory authority over all clinicalinvestigations of drugs, biologics, and uses ofmedical devices to gain approval for marketing inthe US inclusive of genetic testing and clinicalresearch. Although not directly addressing genet-ics, the overall regulatory scheme is applicable.In addition to the FDA’s Center for DrugEvaluation and Research (CDER) and theCenter for Biologics Evaluation and Research(CBER), there is also the Center for Devices andRadiological Health (CDRH) for medical devices.The FDA’s regulations are found in the Code ofFederal Regulations (CFR) Title 21. Those provi-sions of particular applicability to the protectionof human subjects in clinical trials are the fol-lowing: Protection of Human Subjects – 21 CFRPart 50 and IRBs – 21 CFR Part 56.

21 CFR Part 50, Part B. InformedConsent

Adequate informed consent is critical in the case ofgenetic testing in research. The FDA’s regulation

Copyright © 2003 John Wiley & Sons, Ltd. Qual Assur J 2003; 77, 22–31.

Legal and Ethical Considerations 23

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on informed consent states researchers mustobtain legal informed consent before subjects’ par-ticipation in research. Informed consent is com-posed of several parts. It must describe researchobjectives, the duration of the research, any pro-cedures used, and identification of any experi-mental procedures. There is a requirement thatthe informed consent include a description ofrisks and potential benefits. Subjects must also beinformed of alternate procedures or othercourses of treatment that could be pursued. TheFDA may also look at any data, in full-identifiedform, obtained from the research.

21 CFR Part 56. InstitutionalReview Boards (IRBs)

This regulation describes the appropriateness ofIRB review, composition of IRBs, and oversightfunctions. IRBs serve to ensure that informedconsent is obtained from each study participant.The IRB ensures minimized research risk to sub-jects, determines the reasonableness of risks, andgenerally oversees investigations, including thoseinvolving genetics.

The Common Rule

Since no federal law addresses genetic testing in aresearch context, there is a federal policy knownas the ‘Common Rule,’ formally 45 CFR Part 46,including guidance concerning the practice ofgenetic testing in a research context. TheCommon Rule applies to all research involvinghuman subjects conducted, supported, or other-wise regulated by any of 16 federal departmentsor agencies, including HHS, the Department ofDefense, and the Department of Transportation.The FDA concurs with the scope of the CommonRule, but has not adopted it. Instead, FDA’s rulesfor the protection of human subjects are found in21 CFR Parts 50 and 56 for informed consent andIRBs, respectively, as noted above.

The relevant portion of the Common Rule isSubpart A: Federal Policy for the Protection ofHuman Subjects, which applies to all researchinvolving human subjects conducted, supported, orregulated by any Federal Department or Agency.

For an IRB to approve a research proposal, certaincriteria must be satisfied. The Common Rule listsseven requirements that include minimized risk,reasonable risks in relation to benefits, equitableselection of subjects, informed consent of the sub-jects, documentation showing informed consent,adequate provision for monitoring of data (includ-ing genetic data), and adequate provisions to pro-tect the privacy of the subjects and to maintain theconfidentiality of the data.

Belmont Report

The underlying justification for the protections ofParts 50 and 56 and the Common Rule, imple-mented by FDA and HHS, respectively, was theBelmont Report, issued by the NationalCommission for the Protection of HumanSubjects of Biomedical and Behavioral Research(NCPHSBBR), established in 1974 by theNational Research Act [11].

The Office of Inspector General(OIG)

In 1998, the Department of Health and HumanServices’ OIG released a report entitledInstitutional Review Boards: A Time for Reform[12]. The report describes flaws in the protectionof human subjects in clinical trials. Subsequently,it led to government action against numerousresearch institutions. In June of 2000, the OIGissued several reports: Recruiting HumanSubjects: Pressures in Industry-SponsoredClinical Research, and Recruiting HumanSubjects: Sample Guidelines for Practice, andFDA Oversight of Clinical Investigators. Thereports focused on recruitment of human sub-jects into industry-sponsored clinical trials that included genetic clinical trials. The OIGasserted that the investigation of IRBs was of crit-ical importance based upon rising industry commercialization and competitiveness, whichhave increased the difficulty in locating adequatenumbers of human subjects. The OIG expressed particular concerns regarding informed consent,patient confidentiality, and eligibility for trialenrollment. The OIG reported that oversight of

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recruitment methods is limited and opined thatFDA’s oversight does not provide day-to-dayoversight of clinical trials but provides a retro-spective review of the trials.

The FDA’s oversight focuses on data integrityconcerns more than human subject protectionand, according to the OIG, lacks clear and spe-cific guidelines. The OIG noted several con-cerns. First, the OIG was concerned about theimplementation of new guidance from HHS andFDA regarding informed consent and potentialconflicts of interest. Second, OIG recommendedthe formation of a group to assist Federal regu-latory authorities in developing guidelines onproper recruiting practices and financial incentives. Third, the OIG reported that IRBsand investigators should be sufficiently edu-cated about human subject protections. Fourth,the OIG recommended new initiatives to trainclinical investigators and members of IRBs incrucial patient protection principles. The fifthconcern advocated for clarification of FDA andIRB authorities and improved monitoring ofpatient safety by researchers, sponsors, andFDA.

Office of Human ResearchProtections (OHRP)

To help address these and other concerns relatingto the protection of human subjects, theSecretary of Health and Human Services estab-lished the Office of Human Research Protections(OHRP) within the Office of Human SubjectProtections in the Public Health and ScienceOffice of the Secretary, which is under the direc-tion of the Assistant Secretary for Health.

Human Research SubjectsProtection Act of 2002

In May 2002, US Representatives DeGette andGreenwood introduced the ‘Human ResearchSubjects Protection Act of 2002,’ providing moreprotections for human subjects such as stricterinformed consent and addressing some OIG con-cerns discussed above [13].

Certificates of Confidentiality

Certificates of Confidentiality are issued by theNational Institutes of Health (NIH) to protectidentifiable research information from forceddisclosure. They allow the investigator and otherswho have access to research records to refuse todisclose identifying information on research par-ticipants in any civil, criminal, administrative,legislative, or other proceeding, whether at thefederal, state, or local level. Certificates of confi-dentiality may be granted for studies collectinginformation that if disclosed could have adverseconsequences for subjects or damage their finan-cial standing, employability, insurability, or repu-tation. By protecting researchers and institutionsfrom being compelled to disclose information thatwould identify research subjects, Certificates ofConfidentiality help achieve the research objec-tives and promote participation in studies byassuring confidentiality and privacy to partici-pants. Certificates constitute an important tool toprotect the privacy of research study participants[14].

Recombinant AdvisoryCommittee (RAC)

The National Institutes of Health’s Office ofBiotechnology Activities, formerly ORDA, sup-ports the RAC, which monitors the progress inhuman genetics research. The committee alsooversees and registers federally funded researchinvolving recombinant DNA. The directive of theRAC is to develop and implement NIH policies ofhuman gene transfer; however, much of the over-sight authority of RAC has been curtailed.Oversight authority has increased some what primarily in response to the Gelsinger case, discussed later.

National Bioethics AdvisoryCommission Recommendations(Commission Expired October2001)

The National Bioethics Advisory Commission(NBAC) produced a report, Research Involving

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Legal and Ethical Considerations 25

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Human Biological Materials: Ethical Issues andPolicy Guidance, August 1999, with the intentionof addressing perceived difficulties in the

interpretation of existing federal regulations.NBAC made 23 recommendations, outlined inTable 1.

26 J. E. Beach and W. A. Goolsby

Copyright © 2003 John Wiley & Sons, Ltd. Qual Assur J 2003; 77, 22–31.

Table 1. Summarized NBAC recommendations

No. Topic Summary

1 Interpretation of Federal Policy Interpret 45 CFR Part 46 to regulate unlinked samples (eligible

for exemption) and coded or identified samples (not usually

eligible for exemption)

2 Interpretation of Federal Policy All minimal risk involving humans should be eligible for

expedited review

3 Use of unlinked samples An IRB may exempt research from IRB review if investigator has

unlinked samples effectively and unlinking will not reduce the

value of the research

4 Use of coded or identified Before releasing coded or identified information, a repository

Samples should require that the investigator provide documentation

that the research will be conducted in compliance with federal

regulations

5 Use of coded or identified Requirements of an investigator before IRB approval include

samples justification of research design, description of collection process,

plans to access medical records, and how confidentiality will be

protected

6 Informed consent Informed consent for research use should be obtained separately

from consent to clinical procedures

7 Informed consent Subjects must understand that refusal to consent to research will

not affect quality of clinical care

8 Informed consent General releases for research given in conjunction with clinical

care prior to publication of these recommendations should not

be presumed to cover all types of research over an indefinite

period. IRBs should review consent documents

9 Informed consent Consent forms should have a sufficient number of options – six

examples, one somewhat controversial

10 Waiver of consent Three criteria for minimal risk: adequate protection of confiden-

tiality, no inappropriate release of information, a plan for

revealing results to subjects

11 Waiver of consent Issues for IRB consideration before issuing a waiver of consent in-

clude state and federal law, customary practice; political, cultural,

or economic significance; and subject's community welfare

12 Waiver of consent If research presents minimal risk, IRBs may determine it would be

impracticable to meet the consent requirements in 45 CFR §

46.116 (d)(3) only if the sample was collected before these

recommendations were published

13 Waiver of consent OHRP should make clear that the fourth criterion for waiver of

consent in 45 CFR § 46.116 (d)(f) usually does not apply to

biological materials

14 Reporting results to subjects Disclosure of research results to subjects should occur only when

the findings are valid and accurate, have significant health

implications, and have an available treatment

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The Human Genome Project

The project formally began in 1990 with thegoal of mapping the entire human genetic struc-ture. The availability of this genetic informa-tion ‘creates tremendous new opportunities toidentify and present many of the leading causes ofdeath and disability in this country and aroundthe world’ [14]. Although acclaimed, a 1995national poll found that more than 85% of thosesurveyed were either ‘very concerned’ or ‘some-what concerned’ that insurers and employersmight gain access to and use genetic information[15]. Consequently, there have been a great num-ber of proposed bills concerning genetic privacywithin the last several years. The most notablehave been the proposed Genetic Privacy Act of1995 and the Genetic Privacy and Non-discrimination Acts, though neither have beensigned into law.

State Laws

Several states already have passed laws governingthe collection, analysis, and/or dissemination ofgenetic information. Most of the laws addressinformed consent and protection from discrimi-nation; however, several states have potentiallyproblematic laws for organizations conduct-ing genetic tests. Governing many aspects ofcollection, analysis, retention, and storage ofgenetic information, state statutes could signifi-cantly affect research studies. Current and pro-posed legislations fall into five primary categories.

Laws defining genetic information as the source individual’s personal property

The laws of several states include genetic infor-mation as personal property [16–18]. Although

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Legal and Ethical Considerations 27

Table 1. continued

No. Topic Summary

15 Reporting results to subjects Investigators should include in their research protocol

anticipated findings, circumstances that may lead to disclosure of

findings, and a plan for how to disclose findings

16 Reporting results to subjects When results are disclosed to subject, appropriate referrals to

medical professionals should be given

17 Potential harms to others Investigators should plan research to minimize harm to groups

and IRB review exemption should not be granted if research

poses significant risk of harm to a group.

18 Potential harms to others Potential harm to groups should be disclosed during informed

consent process.

19 Publication and dissemination Plans for disseminating results should include provisions to min-

of results imize potential harms to individuals or groups.

20 Publication and dissemination Journals should specify whether research was conducted in

of results compliance with the common rule

21 Professional and educational NIH, professional societies, and health care organizations

responsibilities should continue and expand efforts to train

investigators about ethical issues and regulations on human

biological materials

22 Professional and educational All research sponsors should make the resources needed to

responsibilities comply with these recommendations available

23 Use of medical records in State and federal legislators should seek to harmonize rules

research governing medical records and human biological materials.

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genetic information is given personal propertystatus in some states, the right of an individual todestroy one’s own genetic information is notalways established.

Laws directing the destructionof genetic information at thesource individual’s request

From state to state, exceptions to the right todestroy genetic information occur when subjectsgive informed consent to sample or informationretention [19, 20].

Laws guaranteeing access toown genetic test results

Some states require test results be providedto individuals upon request. In such states,human research subjects must expressly waive rights to test results or the researcherimplicitly grants access to the genetic information[21–24].

Laws limiting promulgation ofgenetic information

Researchers may use information obtained fromgenetic tests, however subject identity may not bedisclosed. Additionally, the information must bede-identified making the probability of patientre-identification low [25].

Laws addressing the appropri-ateness of circumstantialgenetic testing

In some states, genetic testing is legal only fordiagnostic and therapeutic purposes [26–28]. Theexception to this requirement relates to theperformance of research which permits genetictesting so long as the individual level patientinformation is not identifiable or anonymous test-ing is involved [29].

Although appearing problematic, in reality,many of these laws and regulations may be complied with through increased levels of

communication with research subjects andaltered wording of the informed consent discus-sion and document.

Civil Litigation

Because of young Jesse Gelsinger’s death inSeptember 1999 during his participation in a genetherapy study for the treatment of ornithine tran-scarbamylase (OTC) deficiency at the Universityof Pennsylvania, the Gelsinger family sued theUniversity of Pennsylvania alleging carelessnessand gross negligence. In addition to the lawsuitagainst the University, the Gelsinger family suedthe research team. Significantly, also named in thesuit initially was a bioethicist who assisted inwording the informed consent and was consultedon the ethical issues of the gene-therapy trial, butwho was later dismissed from the lawsuit prior tosettlement. A settlement with the University ofPennsylvania for an amount held confidentialbetween the parties was reached on 3 November2000. Although the head of the research teamresigned in July 2002 as head of the Institute forHuman Gene Therapy at University of Pennsy-lvania, it has been reported that his resignationhad nothing to do with the Gelsinger case (SandersE. Researcher Wilson to step down as IHGT head.The Daily Pennsylvanian, 23 April 2002).

International Laws andPolicies

A major international policy that presents guide-lines for research on human subjects, theDeclaration of Helsinki, provides basic ethicalprinciples and rules. Although these rules are ahuge improvement upon what was previously inplace, they are often seen as nonspecific. TheDeclaration of Helsinki does not address manytopics, including the collection, analysis, and dissemination of genetic information. However,two major international organizations, theHuman Genome Organization (HUGO) and theWorld Health Organization (WHO) have pub-lished guidelines and statements on genetic

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testing and genetic analysis. Although these poli-cies are not legally enforceable, they reflectthought and concern for the welfare of testingsubjects and following their direction should beconsidered as an ethical goal of a company. A fewcountries also have issued documents addressingconcerns of genetic testing in clinical trials.

Declaration of Helsinki

The Declaration of Helsinki was first adopted bythe World Medical Association (WMA) at the 18thWMA General Assembly held in Helsinki,Finland in June 1964. The Declaration, titled‘The Ethical Principles for Medical ResearchInvolving Human Subjects’ provides basic ethicalprinciples and rules, treating all information,including genetic data, as protected. The 2000Amendments were adopted by the 52nd GeneralAssembly of the WMA held in Edinburgh,Scotland in October 2000, and is the fifth amend-ment of the Declaration [30].

Human Genome Organization(HUGO)

The HUGO is an international organization ofscientists involved in the Human GenomeProject. The HUGO Statement on DNASampling: Control and Access and Statement onthe Principled Conduct of Genetics Research dis-cuss ethical considerations surrounding genetictesting, particularly confidentiality, consent, dis-closure, and security. HUGO promotes access toindividual’s genetic information by relatives butnot third parties. In addition to discouragingthird party access, HUGO advocates thatinformed consent should be accompanied by con-tinual review and oversight.

World Health Organization (WHO)

In 2002, WHO issued a report, Genomics andWorld Health which includes a section that examines the role that ethics should play ingenetic research and genetic medicine, particu-larly the planned development of large-scalegenetic databases [31].

United Nation Education,Scientific, and CulturalOrganization (UNESCO)

In 1997, the United Nations Education, Scientific,and Cultural Organization (UNESCO) issued aUniversal Declaration on the Human Genomeand Human Rights. Articles 5 and 7 are mostapplicable to genetic research issues. Article 5requires risk and benefit assessment informationbe provided before participation in geneticresearch, treatment, or diagnosis; calls forinformed consent; expresses that participantshave a right to know and understand the resultsof the genetic information; and requires review ofall research protocols. Article 7 mandates thatidentifiable genetic information must be held inthe strictest of confidentiality.

The European Union

The EU has for some years had in effect a broaddata protection ‘framework directive,’ the EUData Protection Directive, wherein the EU mem-ber states were directed to bring their national‘laws, regulations, and administrative provisions’into congruence by 25 October 1998 [32]. Thesenational data protection laws include a height-ened protection for ‘sensitive’ data such as healthinformation that is inclusive of genetic data.

United Kingdom

The UK’s Advisory Committee on Genetic Testing(ACGT) issued ‘Advice to Research EthicsCommittees’ in response to legal and ethicalquestions surrounding genetic testing. TheAdvisory Committee on Genetic testing publishedthis report after having received a large number ofinquiries from Research Ethics Committees (theUK’s version of IRBs) on the subject of genetictesting. These ‘Points to Consider’ were publishedin order to aid Research Ethics Committees in better identifying issues that should be discussedwith individual researchers. The recommenda-tions, or ‘Points to Consider,’ are in the form ofquestions that can be posed to individualresearchers by research ethics committees. The

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Legal and Ethical Considerations 29

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questions cover topics such as protocol, technique,and confidentiality. Recommendations of theACGT include non-identifiable or coded samplesand they advocate for specific consent beforerevealing test results to subjects and/or inclusionof the results in the individual’s medical record. Inaddition, the recommendation suggests that sub-jects should be informed of all consequencesrelated to the disclosure of their genetic informa-tion and that genetic samples should not be usedfor secondary studies unless the data are anony-mous or consent is obtained.

Canada

Section eight of Canada’s Tri-Council PolicyStatement, ‘Ethical Conduct for ResearchInvolving Humans,’ focuses on human geneticresearch. The statement discusses ethical consid-erations such as consent, confidentiality, risks,families, genetic counseling, gene alteration, DNAbanking, and commercial use of genetic informa-tion. As a condition of funding, researchers andtheir institutions must apply the ethical princi-ples and the articles of this policy. The PrivacyCommissioner of Canada has published the list ofrecommendations with the intent of strengtheningcurrent Canadian privacy laws. This statementaddresses discrimination, consent, and access toresults, confidentiality, and retention of geneticsamples.

Australia

The Australian ‘National Statement on EthicalConduct in Research Involving Humans’ guide-lines protect participants from potential harmand raise awareness of ethical considerationsinvolved in genetic research participation. Theguidelines recommend researchers considersocial and cultural consequences of theirresearch; advocates that research protocols mustspecify if genetic information will be stored andwhether the data is identified, potentially identi-fiable, or de-identified form; stresses that identi-fiable information not be released to others; andprohibits researchers from transferring genetic

information to another research group, exclusiveof special circumstances.

Conclusion

Highly publicized advances in genetic sciencesare heightening the public’s awareness of theimportance of genetic testing for the developmentof ‘personal medicines.’ At the same time, there is increasing concern by the public of the poten-tial for genetic discrimination, particularly byemployers and insurers, which has beenaddressed primarily in state laws. While no fed-eral or international law directly covers privacyconcerns related to genetic testing, several regula-tions protect identifiable health information, ingeneral, inclusive of genetic information. Also,there are numerous national and internationalguidelines that provide recommendations for theprotection of genetic information.

Acknowledgements

The authors greatly appreciate the contributiontowards the underlying research provided byTaylor Lea, a legal intern with the QuintilesTransnational Legal Department during the sum-mer of 2000 and also for the assistance of AndreaJackson, Executive Legal Assistant, also with theQuintiles Legal Department.

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6. Genetic Information and the Workplace. Department of Labor,

HHS, Equal Employment Opportunity Commission, January

20, 1998.

7. http://www.hhs.gov/ocr/hipaa/[June 2002].

8. 65 Fed Reg at 82466 and 67 Fed Reg 53,182–53,273 (August 14,

2002).

9. 67 Fed Reg 53,182–53,273.

10. 45 CFR §164.514.

11. National Research Act of 1974, Pub. L. No. 93-48, 45 CFR 46.

12. NHS, Office of Inspector General. Institutional Review Boards:

A Time for Reform. June 1998.

13. H.R. 4697, 107th Cong (2002).

14. 65 Fed Reg at 82,466.

15. See Harris Poll, 1995 #34.

16. COLO. REV. STAT. § 10-3-1104.7(l)(a) (2001).

17. GA. CODE ANN. § 33-54-1 (2001).

18. OR. REV. STAT. § 192.533(b) (2001).

19. NEV. REV. STAT. § 629.161 (2001).

20. OR. REV. STAT. § 192.537(4) (2001).

21. NEV. REV. STAT. § 629.141 (2001).

22. OR. REV. STAT. § 192.537(7) (2001).

23. TEX. CODE ANN. § 21.404 (2001).

24. H.R. 1537, 21st Leg. (Haw. 2001).

25. VA. CODE ANN. § 38.2-508.4(c) (Michie 2001).

26. COLO. REV. STAT. § 10-3-1104.7(5) (2001).

27. GA. CODE ANN. § 33-54-6 (2001).

28. MONT. CODE. ANN. § 33-18-904 (2001).

29. OR. REV. STAT. § 192.537(2)(a) (2001).

30. http://www.wma.net/e/policy/17-c_e.html

31. www.who.int/genomics. See Section 8. Ethical Issues in Genetic

Research, Screening and Testing, with Particular Reference to

Developing Countries.

32. Directive 95/46/EC of the European Parliament and of the

Council, 24 October 1995, effective 25 October 1998.

Copyright © 2003 John Wiley & Sons, Ltd. Qual Assur J 2003; 77, 22–31.

Legal and Ethical Considerations 31