¹ See Casey, Denise & Stodolsky, Marvin, On The Shoulders of Giants: Private Sector Leverages HGP Successes, Human Genome News, Nov. 2000, at 2, 2Google Scholar.

² Healthcare programs comprise 10% of gross domestic product in Germany, France, and Switzerland, and 14% in the United States. See Health Insurance in the United States: an Industry in Transition, 2,3-16 (1998).

³ The Fda has primary responsibility for the regulation of new drugs, medical devices, “biologies” and other products, materials and therapies destined for medical use: See Federal Food, Drug and Cosmetics Act, 21 U.S.C. §§ 301-395 (1994); Public Health Service Act, 42 U.S.C. §§ 201-300aa-13 (1994) (originally Biologies Act of 1902); Food and Drug Administration Modernization Act of 1997 (“FDAMA”), 21 U.S.C. § 353 (1997). Under these sources of authority, FDA requires and regulates clinical trials for such advances to determine their efficacy and safety. See, e.g., 21 U.S.C. § 360e(c)(l)(A). A “biologic” has been defined as “Any virus, therapeutic serum … vaccine, blood, blood component or derivative, allergenic product, or analogous product … applicable to the prevention, treatment or cure of diseases, or injuries to man,” 42 U.S.C. § 262 (a). The agency has also enacted various policies, for example, that “all gene therapy products are regulated by the FDA.” FDA, Guidance for Human Somatic Cell Therapy and Gene Therapy (March 1998), available at http://www.fda.gov/cber/gdlns/somgene.pdf [hereinafter FDA Gene Therapy Guidance].

⁴ See Kean, Marcia, Managing Information on Clinical Trials Outcomes, 3 J. BlOLAW & Bus. 53, 53-55 (2000)Google Scholar.

⁵ See Gene Therapy: Is There Oversight for Patient Safety?: Hearing Before the Subcomm. on Public Health of the Senate Comm. on Health, Education, Labor and Pension, 106th Cong. 28, 31 (2000) (statement of Amy Patterson, Director of the Office of Biotechnology Activities, National Institutes of Health) (“Clinical research, including human gene therapy research, is not without risk. Research is, by definition, experimental—if the outcome were known, the study would not have to be conducted. Thus, the risks associated with the experimental treatment cannot always be predicted. For this reason, there exists a comprehensive system of Federal laws, regulations, and guidelines pertaining to the protection of human subjects in clinical trials.”) [hereinafter Patterson]. See also James T. O'Reilly, Elders, Surgeons, Regulators, Jurors: Are Medical Experimentation's Mistakes Too Easily Buried?, 31 Loy. U. Chi. L.J. 317, 324 (2000) (“Experimentation by its nature involves trial and error. Some drugs and devices will harm some patients in the process of perfecting the product. Society, however, benefits from the learning that comes with experimental failure, modification and replication.”).

⁶ Robin Blatt & Michael Malinowski, Clinical Trials: The Intersection Between Research and Medicine, 1 J. Biolaw & Bus. 3, 3 (1998).

⁷ See Jonathan M. Fishbein et al., Domestic and Multinational Clinical Trials: Issues in Design, Implementation, and Management for Biotechnology Research and Product Development, 1 J. Biolaw & Bus. 6, 10 (1998) (“The very nature of the therapeutic indication, its severity, the current standard of care, and the availability of test subjects all greatly influence how the development program will proceed. With these concepts in consideration, a clinical trial's design must maintain scientific integrity and produce credible data.”).

⁸ See generally Safety Management: The Challenge of Change (Andrew Hale & Michael Baram, eds., 1998) [hereinafter Safety Management],

⁹ See id. at 191.

¹⁰ See supra note 6; see also The Fruits of Genomics: Drug Pipelines Face Indigestion Until the New Biology Ripens (2001).

¹¹ See supra note 5.

¹² See id.

¹³ See id. From 1989 to January 2000, the FDA received 288 applications and over 800 amendments for gene therapy clinical testing, according to Dr. Jay Siegel, Director of FDA's Center for Biologic Evaluation and Research. See infra note 118.

¹⁴ See infra note 118.

¹⁵ See supra note 5; see also Michael Baram et al., Human Gene Therapy Research: Technological Temptations and Social Control, 1 The Genetic Resource 10, 12-13 (1993); Reinhard Kurth, Risk Potential of the Chromosonal Insertion of Foreign DNA, 772 Annals N.Y. Acad. Sci., 140, 140-51 (1995).

¹⁶ See Alice Dembner, Dangerous Dosage, Boston Globe, Feb. 18, 2001, at Al (reporting that drug trials “have killed at least eight children and subjected hundreds more to harmful side effects in the last seven years”).

¹⁷ See Diana L. Bush, Gene Therapy Trials: The Role of the National Institutes of Health and Conflicts of Interest, 19 Biotech. L. Rep. 576, 576-78 (2000).

¹⁸ See id. at 576, 578.

¹⁹ See Initiation of Disqualification Proceeding and Opportunity to Explain: FDA notice to Dr. James Wilson, Univ. Pennsylvania Institute for Human Gene Therapy (Nov. 30, 2000), available at http://www.fda.gov/foi/nidpoe/nl21.pdf (last visited Apr. 5, 2001) (summarizing violations of “regulations governing the proper conduct of clinical studies involving investigational new drugs”) [hereinafter FDA Notice].

²⁰ See University Sued Over Patient's Death Following Gene Therapy Clinical Trial, Toxic L. Rep. 1031 (Oct. 12, 2000). A confidential settlement was reached. See Family Settles Suit Over Patient's Death Following Gene Therapy Clinical Trials, Toxic L. Rep. 1227 (Nov. 30, 2000).

²¹ See Bush, supra note 17, at 576.

²² See Deborah Nelson & Rick Weiss, Gene Therapy Deaths Disclosed, Boston Globe, Nov. 3, 1999, atAlO.

²³ See id.; see also discussion infra Parts V.VI.VII.

²⁴ See Bush, supra note 17, at 586-588. The Cornell and Tufts researchers were found to hold equity interests in GenVac and Vascular Genetics, companies sponsoring their trials. See Richard Knox, Physicians Deny Deaths Unreported, Boston Globe, Nov. 4, 1999, at CI; see discussion infra Part VII.

²⁵ See Bush, supra note 17, at 587-588. See also Bernard Lo et al., Conflict-of-interest Policies for Investigators in Clinical Trials, 343 New Eng. J. Med. 1616, 1618-19 (2000) (examining the shortcomings of current conflict of interest policies at leading U.S. medical schools); S. Van McCrary et al., A National Survey of Policies on Disclosure of Conflicts of Interest in Biomedical Research, 343 New Eng. J. Med. 1621, 1624-25 (2000) (discussing the variation among policies on conflict of interest at research institutions and suggesting that the current standards of disclosure may be inadequate to maintain a high level of scientific integrity).

²⁶ See Liz Kowalczyk, New Steps Urged on University Research Bias, Boston Globe, Feb. 21, 2001, at Al.

²⁷ The Nuremberg Code, from Trials of War Criminals before the Nuremberg Military Tribunals Under Control Council Law No. 10, Nuremberg, Oct. 1946-Apr. 1949, Washington D.C.: U.S. G.P.O., 1949-1953, available at http://www.ushmm.org/research/doctros/Nurembreg_Code.htm.

²⁸ Id.

²⁹ Declaration of Helsinki, World Medical Association, June 1964, adopted by the 18th World Medical Assembly, Helsinki, Finland (“statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects”) [hereinafter Declaration of Helsinki].

³⁰ See id.

³¹ See id.

³² Id.

³³ See The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 44 Fed. Reg. 23,192, 23,192 (1979) (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Dept. of Health, Education and Welfare) [hereinafter The Belmont Report].

³⁴ See id.

³⁵ See id.

³⁶ See id.

³⁷ Id. at 23,194.

³⁸ Id.

³⁹ See Protection of Human Research Subjects and Creation of National Bioethics Advisory Commission, Exec. Order No. 12975, 60 Fed. Reg. 52,063 (Oct. 3, 1995).

⁴⁰ See Judith A. Cregan, Light, Fast, and Flexible: A New Approach to Regulation of Human Gene Therapy, 32 McGeorge L. Rev. 261, 261 (2000) (citing statement of Paul Gelsinger in Gene Therapy: Is There Oversight for Patient Safety; Hearings before the Subcomm. on Public Health of the Senate Comm. on Health, Education, Labor, and Pensions, 106^lh Cong. (2000)).

⁴¹ See generally, Fishbein, supra note 7; O'Reilly, supra note 5.

⁴² See supra note 5 and acccompanying text.

⁴³ See FDA Gene Therapy Guidance, supra note 3, § IC.

⁴⁴ The regulations apply to clinical research, whether privately or publicly funded, if the research methods and findings are intended to support an application for FDA approval of the sale, distribution and medical use of a product subject to its authority. See 21 C.F.R.§ 312 (2000) and other sections on drugs, devices and biologic products. Thus, prior to developing or doing clinical trials on such products, it is important for the potential applicant “to determine with the guidance of the FDA,” the applicability of FDA regulatory review and clinical testing requirements. See Fishbein, supra note 7, at 7.

⁴⁵ See Patterson, supra note 5, at 32.

⁴⁶ NIH requirements are set forth in its Guidelines, and apply to projects it supports, as well as other projects at institutions receiving NIH support for recombinant DNA work. See id. The requirements are set pursuant to the Public Health Service Act, 42 U.S.C. § 201-300. Under this mandate, NIH, the Department of Health and Human Services, and FDA have established a uniform regulation on informed consent, 45 C.F.R. § 46 (2000), and delineated the oversight responsibilities of Institutional Review Boards (“IRBs”), 21 C.F.R. § 56.101 (2000); 45 C.F.R. § 46.103 (2000).IRBs have been dubbed as “silent overseers who operate in the paper-laden netherworld of research institutions.” O'Reilly, supra note 5, at 331.

⁴⁷ See id.

⁴⁸ See generally Andrew Hale Et Al., After the Event: From Accident to Organizational Learning (1997) (discussing risk analysis and risk management in hazardous industries); Andrew Hale & Michael Baram, Safety Management: the Challenge of Change (1998).

⁴⁹ See Committee on Quality of Health Care in America, Institute of Medicine, to Err is Human: Building A Safer Health System 8-10 (Linda T. Krohn, et al. eds., 2000).

⁵⁰ See 21 C.F.R. § 312.32; see also Siegel, infra note 118. Investigational clinical trials in humans with gene therapy products are subject to FDA's requirements for drugs and biologies in 21 C.F.R. § 312 regarding the IND. As a product moves through Phase I, II and III trials, various regulations become applicable for biologies considered drugs, such as gene therapy products, and focus on safety, purity, potency, and efficacy. See 21 C.F.R. §§ 200.5-.200 (regarding Current Good Manufacturing Practices); 21 C.F.R. §§ 300-300.100 (regarding new drug applications); 21 C.F.R. §§ 600.3-.90 (regarding biologies establishment and licensing).

⁵¹ Drugs are defined as “usually synthetic, organic compounds with defined structures and physical and chemical characteristics…very stable and resistant to heat.” Fishbein, supra note 7, at 8.

⁵² See Fishbein, supra note 7, at 7-8.

⁵³ Id.

⁵⁴ Id.

⁵⁵ See id. The IND application must detail the product's composition and structure, proposed dosage and routes of administration, the investigative plan and research protocol, data on prior animal tests and human experience (including foreign data), information on any prior problems, and withdrawals from investigation or marketing. 21 C.F.R. § 312 (2000); FDA Gene Therapy Guidance, supra note 3 (for gene therapy products in particular). The Guidance calls for extensive data and information on: the type of cell to be used, donor selection criteria, cell culture quality control and banking procedures, materials used during manufacturing; the therapy product's potency, viability, purity, and safety test results (pursuant to 21 C.F.R. 610); the vectors to be used, their sources, characteristics, production and banking systems, routes of administration, potency, purity, safety, and replicability; pre-clinical studies defining safe doses, toxicity parameters for target organs; animal species selection and models of disease. See id.

⁵⁶ Phase I is closely monitored to establish an initial degree of confidence about safety of the product and dosage levels; Phase II is focused on efficacy for intended use as well as safety; and larger Phase III trials seek to gain statistical proof of safety and efficacy. Finally, a Phase IV trial may be conducted to confirm results and may extend, post-marketing, to study efficacy and safety in types of persons who were not subjects in the preceeding trials, such as children and the elderly. See Fishbein, supra note 7, at 9-10.

⁵⁷ See supra note 50.

⁵⁸ See id.

⁵⁹ See Fishbein, supra note 7, at 13-16; O'Reilly, supra note 5, at 349-350; Office of the Inspector General, U.S. Dept. of Health and Human Services, Institutional Review Boards: Promising Approaches, no. OEI-01-97-00191 (1998) [hereinafter OIG REPORT]. According to O'Reilly and the OIG Report, clinical research consumes an estimated $4 billion annually, with three-fourths being company-sponsored and increasingly out-sourced to Contract Research Organizations (CRO's) and Study Management Organizations (SMO's) to reduce research costs. See id. CRO's/SMO's are small new companies that are widely-scattered and can be difficult to hold accountable to FDA procedures. See also Kurt Eichenwald & Gina Kolata, A Doctor's Drug Studies Turn into Fraud, N.Y. Times, May 17, 1999, at Al.

⁶⁰ See 21 C.F.R. § 312.32(a)-(c) (2000).

⁶¹ See id.

⁶² See id.

⁶³ See id.

⁶⁴ See 21 C.F.R. §312.33.

⁶⁵ Prashanth Vishwanath, To Report or Not to Report: Fallacies in the Notification Requirements of Gene Therapy Trials, 5-6 (unpublished paper, Bioinformatics Dept., Boston University, May 2000) (on file with the author).

⁶⁶ “The reports submitted to the FDA are confidential and are not accessible to other investigators in the field as well. In general, the Freedom of Information Act requires Federal agencies to make their records available to the public upon request. However, this requirement does not apply to, among other things, “trade secrets and commercial or financial information that is obtained from a person and that is privileged or confidential.” Under 18 U.S.C. 1905, it is a criminal offense for an officer or employee of…any Federal department or agency to publish, divulge, disclose, or make known “in any manner or to any extent not authorized by law any information coming to him in the course of his employment or official duties or by reason of any examination or investigation made by, or return, report or record made to or filed with, such department or agency or officer or employee thereof, which information concerns or relates to the trade secrets, (or) processes…of any person, firm, partnership, corporation or association.” This [precludes FDA] from making the information public.” Id. at 5-7; see also FDA Handbook, infra note 73.

⁶⁷ See Siegel, infra note 118.

⁶⁸ NIH Guidelines for Research Involving Recombinant DNA Molecules, (Apr. 1998) at http://www4.od.nih.gov/oba/guidelines.html. These guidelines are constantly changing. Appendix M covers the design and submission of protocols for clinical trials involving human subjects. For description of the RAC and its functions, see Patterson, supra note 5.

⁶⁹ See id. at app. M-I-III.

⁷⁰ See id. at app. M-VI.

⁷¹ See id. at 84.

⁷² See id. at app. M-I-B-l.

⁷³ FDA, A Handbook for Requesting Information and Records from the FDA at http://www.fda.gove/opaconVbackgrounders/foiahand.html (last visited Jan. 9, 2001); 21 C.F.R. § 20 (1999).

⁷⁴ While NIH promotes public awareness, it recognizes the potential sensitivity of the materials involved in public review. Thus, it provides that while no submission may be designated confidential in its entirety, a trial sponsor may indicate that specific portions of the materials involved are proprietary or trade secret with appropriate explanation, so that NIH can determine whether to exclude such information from public review. See infra note 174.

⁷⁵ See NIH Guidelines, supra note 68, §§ I-D-l, I-D-2.

⁷⁶ See supra note 20

⁷⁷ NIH Guidelines, supra note 68, app. M-I-C-4; see also Patterson, supra note 5, at 29..

⁷⁸ Patterson, supra note 5, at 34.

⁷⁹ Researchers complain that the NIH requirement is burdensome, too broad to be useful and confounded by additional guidelines of other research funding agencies. For example, National Cancer Institute Guidelines define an adverse event as “any unfavorable or unintended sign (including an abnormal lab finding), symptom or disease temporally associated with the use of a medical treatment or procedure regardless of whether it is related to the medical treatment or procedure.” See Nci Guidelines: Adverse Event Reporting Requirements for Nci Investigational Agents §1.1 (Sept. 17, 1999). In addition, there is controversy over the confidentiality of information contained in adverse event reports sent to NIH. Accordingly, NIH has proposed changes to its Guidelines to lessen such concern by disallowing the inclusion of proprietary or patient identifying information, in such reports. See Recombinant DNA Research, 65 Fed. Reg. 77, 655, 77,656 (proposed Dec. 12, 2000).

⁸⁰ It can also suspend or terminate funds for all other rDNA research at the same institution. See id. at 36.

⁸¹ See Patterson, supra note 5 at 34.

⁸² See id.

⁸³ See id.

⁸⁴ See Dembner, supra note 16.

⁸⁵ See Patterson, supra note 5.

⁸⁶ See FDA Notice, supra note 19.

⁸⁷ Id. at 1. FDA's findings and charges against Dr. Wilson do not, however, seek to establish why Gelsinger's death occurred, nor do they attempt to blame Wilson for the death.

⁸⁸ Id. at 2-4.

⁸⁹ Id. at 5-8.

⁹⁰ Id. at 8-12.

⁹¹ Id. at 12-14.

⁹² See OIG Report, supra note 59; O'Reilly, supra note 5.

⁹³ See Bush, supra note 17, at 576 n.7 (citing Deborah Nelson & Rick Weiss, Earlier Gene Test Deaths Not Reported: NIH Was Unaware of Adverse Events, Wash. Post, Jan. 31, 2000, at A1).

⁹⁴ See id. at 582.

⁹⁵ See Knox, supra note 24, at CI; Nelson & Weiss, supra note 22, at A10.

⁹⁶ See Bush, supra note 17, at 581.

⁹⁷ See Patterson, supra note 5, at 35-36.

⁹⁸ See id. at 36.

⁹⁹ See Michael Baram Shame, Blame and Liability: Why Safety Management Suffers Organizational Learning Disabilities, in After the Event: From Accident to Organizational Learning 161, 196 (Andrew Hale et al., eds., 1997) (discussing that persons do not report errors for fear of self-incrimination and because it could be career threatening).

¹⁰⁰ See Bush, supra note 17, at 586; Joseph N. Distenfano, et al., Pennsylvania Biotechnology Researcher Negotiated Corporate Funding, K. Night-Ridder Tr1B. Bus. News, Feb. 27, 2000, available in 2000 WL 14922081.

¹⁰¹ See Distenfano, supra note 100

¹⁰² See Bush, supra note 17, at 586; Distenfano, supra note 100.

¹⁰³ See Bush, supra note 17, at 586 n.187; Distenfano, supra note 100.

¹⁰⁴ See Bush, supra note 17 at 587 n209, (citing and summarizing Rick Weiss & Deborah Nelson, Scientists Reminded to Report Deaths: FDA Responds to Gene Therapy Flap, Wash. Post, Nov. 6, 1999, at A15).

¹⁰⁵ See Bush, supra note 17, at 587.

¹⁰⁶ See Financial Disclosure of Clinical Investigators, 60 Fed. Reg. 5233, 5233 (1998). See discussion in Allan M. Green, Increased Industry-Academic Interactions Lead FDA to Require Financial Disclosure by Clinical Investigators, 3 J. Biolaw And Bus. 15 (2000). For further discussion of FDA disclosure policy, see text infra notes 139-141.

¹⁰⁷ See Bush, supra note 17, at 586-590; see also Lo, supra note 25; Van McCrary, supra note 25.

¹⁰⁸ Lo, supra note 25, at 1619.

¹⁰⁹ Id.

¹¹⁰ Van McCrary, supra note 25, at 1625.

¹¹¹ Id.

¹¹² See Medical Schools Offer Rules on Doctors' Conflicts of Interest, N.Y. Times, Feb. 8, 2001,atA23.

¹¹³ See Conflicts of Interests in Human Research: Risks and Pitfalls of “Easy Money” in Research Funding, 9 Health L. Rep. (BNA) 1378 (Aug. 31, 2000) (noting that the regulations require disclosure of certain financial arrangements but do not impose limits or other similar restrictions) [hereinafter Conflicts of Interest in Human Research].

¹¹⁴ Frances Miller, Trusting Doctors: Tricky Business When it Comes to Clinical Research (Feb. 13, 2001) (unpublished manuscript, on file with author).

¹¹⁵ See Bush, supra note 17, at 589.

¹¹⁶ See supra note 106.

¹¹⁷ See, for example, Larry R. Churchill, et al., Genetic Research as Therapy: Implications of ·Gene Therapy'for Informed Consent, 26 J.L. Med. & Ethics 38, 38-47 (1998).

¹¹⁸ See Carol Mason Spicer, Federal Oversight and Regulation of Human Subjects Research-An Update, 10 Kennedy Inst. of Ethics J., 261, 261-64 (2000). See also Gene Therapy: Promoting Saefty: Hearing Before the Subcomm. on Public Health of the Senate Comm. on Health, Education, Labor and Pensions, 106th Cong. (Feb. 2, 2000) (statement of Jay Siegel, FDA, DHHS); see Patterson, supra note 5.

¹¹⁹ Spicer, supra note 118, at 264.

¹²⁰ See Spicer, supra note 118; see also infra note 146.

¹²¹ See Spicer, supra note 118, at 262.

¹²² See id. at 264.

¹²³ See Siegel, supra note 118.

¹²⁴ Id.

¹²⁵ See FDA, Manual of Standard Operating Procedures and Policies, §§ 9101.1 (Notification of NIH/OBA of Changes in a Gene Therapy Protocol); 9101.2 (Notification of NIH/OBA of FDA's Receipt of Adverse Event Reports to Gene Therapy IND's) (Dec. 7, 1999), available at http://www.fda.gov/cber/regsopp/regsopp.htm (last visited May 17, 2001).

¹²⁶ See Siegel, supra note 118.

¹²⁷ See Biotechnology Industry Association, Oversight of Gene Therapy, at http://www.bio.org/issues/genetherapy-120799.html (last visited May 17, 2001).

¹²⁸ See id.

¹²⁹ See Cregan, supra note 40, at 284-87. But see O'Reilly, supra note 5, at 363: “As a safeguard for patients, a statutory or common law tort standard of strict liability to fully compensate test subjects for physical harm resulting from the experimentation [drug testing on elderly persons] seems particularly sensible.” For additional discussion of industry concerns over disclosures, see Marcia A. Kean, Managing Information on Clinical Trial Outcomes: Legal, Business and Scientific Implications, 3 J. BlOlaw And Bus., 53, 53-55 (2000).

¹³⁰ See 21 C.F.R. §312.21,312.40.

¹³¹ See 21 C.F.R. § 312.23. According to FDA's Gene Therapy Guidance, supra note 3, IND applications for gene therapies should follow the format described in 21 C.F.R. § 312.23.

¹³² Id. at (6)(i).

¹³³ Id. at(6)(ii).

¹³⁴ Id. at(7)(I).

¹³⁵ Id.

¹³⁶ Id. at (8).

¹³⁷ See FDA Gene Therapy Guidance, supra note 3, at 1.

¹³⁸ See Siegel, supra note 118. Note that NIH has announced “there is insufficient preclinical data to support the initiation of clinical trials involving pre-natal gene transfer” and cited 26 issues which need to be addressed. NIH, Conclusions: Gene Therapy Policy Conference, Pre-Natal Gene Transfer: Scientific. Medical, and Ethical Issues, (Jan. 7-8, 1999) at http://www4.od.nih.gov/oba/rac/gtpcconc.htm (last visited May 17, 2001). This action relates to highly controversial germ-line gene therapy. However, neither NIH nor FDA have taken such precautionary actions regarding clinical trials of somatic cell gene therapy, the subject of all gene therapy trials to date, even though a similar set of issues could be compiled.

¹³⁹ See supra notes 99-116 and accompanying text.

¹⁴⁰ See 21 C.F.R. §54(1998).

¹⁴¹ See FDA, Guidance for Industry: Financial Disclosure by Clinical Investigators, (March 20, 2001), at http://www.fda.gov/oc/guidance/financialdis.html.

¹⁴² See 21 C.F.R. § 312.21, 312.32, 312.33.

¹⁴³ See Donna Shalala, Editorial, 343 New Eng. J. Med. 808-10 (2000).

¹⁴⁴ See supra note 17.

¹⁴⁵ See supra note 121; see also DHHS, PHS Policy on Instruction in the Responsible Conduct of Research, (December 1, 2000), available at http://ori.dhhs.gov/html/programs/finalpolicy.asp (last visited May 17,2001).

¹⁴⁶ See Human Subjects Protections in VA Medical Research: Hearing Before the Subcomm. on Oversight and Investigations of the House Comm. on Veterans Affairs, 106th Cong. (Sept. 28, 2000) (statement of Dr. Greg Koski, Director, Office for Human Research Protections, DHHS) at http://veterans.house.gov/hearings/schedulel06/sept00/9-28-00/gkoski.htm.

¹⁴⁷ Id.

¹⁴⁸ Id.

¹⁴⁹ “The FDA has not proposed any new FDA review office or new requirements for biotechnology, stating that its current procedures were adequate for regulating biotechnology products” but has “published several documents called 'Point to Consider' that manufacturers 'might wish to consider' in their research and production of gene therapy products.” Cregan, supra note 40, at 271.

¹⁵⁰ See Sheryl Gay Stolberg, Experts Call for New Rules on Research, N.Y. Times, April 18, 2001, at A16 (regarding a proposed private accreditation system).

¹⁵¹ See Chemical Manufacturers Association, Responsible Care and Codes of Management Practices, at http://www.cmahq.com (last visited June 7, 2001). The program consists of a set of basic principles and six Codes of Management Practices for protecting worker and public health and the environment from accidents and pollutants, a system for evaluating and verifying continuing progress in implementing each Code, public reports on progress, and growing public involvement. In addition to chemical manufacturers, the program has been joined by chemical distributors and shippers, and has now been adopted by other chemical industry associations in over thirty nations. A company's failure to implement or to show continuing progress results in its exclusion from the relevant trade association. See Michael Baram, Corporate Management of Chemical Accident Risks, in Environmental Strategies for Industry 227 (K. Fischer, J. Schott, eds., 1993).

¹⁵² The author participated in the development of Responsible Care as a consultant to the Chemical Manufacturers Association (CMA), and in gaining its approval by CMA member companies. Many provisions in the Codes of Management Practices are intended to enable chemical manufacturers to improve their compliance with pollution control and accident prevention regulations, to manage their processes and product marketing so that harms and tort liabilities are minimized, and to enable their downstream industrial customers to also improve compliance and reduce harms and liabilities.

¹⁵³ See discussion of private certification in Bryan A. Liang, Kristopher Storti, Creating Problems as Part of the Solution: The JCAHO Sentinel Event Policy, Legal Issues and Patient Safety, 33 J. Health L. 263, 263-85 (2000). For prompting of new federal efforts, see Lucian Leape, Error in Medicine, 272 Jama 1851 (1994); To Err is Human, supra note 49.

¹⁵⁴ For a primer on hospital risk management and loss control, see Charles G. Benda, Fay A. Rosovsky, Managed Care and the Law: Liability and Risk Management, A Practical Guide (1996).

¹⁵⁵ See Michael D. Cabana, et al., Why Don 't Physicians Follow Clinical Practical Guidelines? A Framework for Improvement, 282 Jama 1458 (1999). See also Michael Baram, Medical Error and Responsibility in Managed Healthcare, in Safety in Medicine, (Charles Vincent & Bas de Mol, eds., 2000).

¹⁵⁶ See Marcos D. Jiminez & Dana Foster, The Importance of Compliance Programs for the Health Care Industry, 7 U. Miami Bus. L. Rev. 503 (1999) (discussing DHHS efforts to improve compliance management in the healthcare sector and the incentives for the targeted institutions).

¹⁵⁷ See Benda, supra note 154; and Wendy Mariner, Human Subjects Research, Law, Common Law of Human Experimentation, in Encyclopedia of Ethical, Legal and Policy Issues in Biotechnology 654 (2000).

¹⁵⁸ See Mariner, supra note 157; O'Reilly, supra note 5; Restatement (third) of Torts: Products Liability §6 (1998); Biomaterials Access Assistance Act, 21 U.S.C. § 1601 (1998).

¹⁵⁹ See Benda, supra note 154; O'Reilly, supra note 5.

¹⁶⁰ See EPA, Environmental Management Systems, at http://www.epa.gov/ems/index.htm (last visited May 17, 2001); Michael Baram, Improving Corporate Management of Risks to Health, Safety and Environment, a chapter in forthcoming book on HSE Regulations (Andrew Hale, ed. 2001) and presented at Symposium on HSE Regulation, Reimers Foundation and Technical University of Berlin, Bad Homburg, Germany (June 1999). See also Swiss Reinsurance Corp., Environmental Management Systems and Environmental Impairment Liability, (1998); John Voorhees, The Changing Environmental Management Scene: Federal Policy Impacts the Private and Public Sectors, 31 Envtl. L. Rep. 10079 (2001).

¹⁶¹ See EPA, Final Policy Statement on Incentives for Self-Policing, at http://www.epa.gov/fedrgstr/EPA-GENERALy2000/April/Day-ll/g8954.htm (last visited May 17, 2001); U.S. Dept. of Justice, Factors in Decisions on Criminal Prosecutions for Environmental Violations in the Context of Significant Voluntary Compliance or Disclosure Efforts by the Violator, (July 1, 1991), available at http://www.usdoj.gov/enrd/factors.htm (last visited May 17, 2001). See also U.S. Sentencing Commission, U.S. Sentencing Guidelines, § 8A1.2 (k)(l-7) (discussing consistent criteria applicable to sentencing criminal violators of federal regulations).

¹⁶² See id.; Baram, supra note 160; J. Alden Lincoln & Michael S. Baram, Environmental Management Systems: Best Management Practices, (Northeast Business Environmental Network 1997), available at http://www.nben.org/HTMLSrc/Forum/EMSMatrix.html (last visited May 17, 2001). The features are derived from analysis of EPA and DOJ policies and the Federal Sentencing Guidelines, supra note 161. See also Jiminez, supra note 156, for discussion of similar management models regarding compliance with healthcare regulations on Medicare, billing organizations, nursing and hospice facilities, clinical labs, etc. The DHHS Office of Inspector General has developed and promoted several of these management models, as discussed.

¹⁶³ See id.

¹⁶⁴ See Baram, supra note 160.

¹⁶⁵ Personal communications to the author by officials of companies belonging to the Northeast Business Environmental Network (e.g. John Bailey of Acushnet Rubber, Lee Wilmot of Hadco, etc., 1998-2001).

¹⁶⁶ See International Organization for Standardization, Management System Guidelines, ISO 9000 (Quality Management Systems), ISO 14000 (Environmental Management Systems) (1996 and subsequent amendments and additions), available at http://www.iso.ch/9000e/9kl4ke.htm.

¹⁶⁷ See supra note 151.

¹⁶⁸ See supra note 152.

¹⁶⁹ See After the Event: from Accident to Organizational Learning, (Andrew R. Hale, Bernard Wilpert, Matthias Freitag, eds., 1997); Chris Argyris, on Organizational Learning (1992); James T. Reason, Managing the Risks of Organizational Accidents (1997).

¹⁷⁰ See supra notes 60-68 and 77-83.

¹⁷¹ See id.

¹⁷² See supra notes 93-116.

¹⁷³ See Patterson, supra note 5; Siegel, supra note 118.

¹⁷⁴ See generally Office of Recombinant DNA Activities; Recombinant DNA Research: Proposed Actions Under the NIH Guidelines, 64 Fed. Reg. 63,827 (1999).

¹⁷⁵ See supra note 125, at SOPP 9101.2.

¹⁷⁶ Cregan, supra note 40 at 283.

¹⁷⁷ See Baram, Shame, Blame and Liability: Why Safety Management Suffers Organizational Learning Disabilities, in After the Event, supra note 169.

¹⁷⁸ Chemical Accident Prevention Provisions, 40 C.F.R. § 68.60 (1996); and Process Safety Management of Highly Hazardous Chemicals, 29 C.F.R. 1910.119 (1992).

¹⁷⁹ See Chemical Manufacturers Association, Process Safety Code of Management Practices, at http://www.cmahq.com (last visited June 11, 2001).

¹⁸⁰ American Institute of Chemical Engineers, Lessons Learned Database, at http://www.aiche.org/ccps/lldb.htm (last visited May 17, 2000). This ongoing project is intended “to pool process safety incident experience among participating companies so they can learn from the experience of others, while minimizing corporate liability.”

¹⁸¹ See generally lnt'1 Institute for Applied Systems Analysis, The Influence of Organization and Management on the Safety of NPPS and Other Complex Industrial Systems, Rpt. WP-91-028 (1991); available at http://iiasa.asc.at/cgi-bin/pubsrch7WP91028 (last visited May 17, 2001); G. E. Apostolakis, Organizational Factors and Nuclear Power Plant Safety in Nuclear Safety, A Human Factors Perspective (Jyuji Misumi, Bernard Wilpert, Rainer Miller, eds., 1999).

¹⁸² See discussion in TO ERR IS HUMAN, supra note 49.

¹⁸³ See id.

¹⁸⁴ See Baram, supra note 177; Isadore Rosenthal, “Major Event Analysis in the United States Chemical Industry: Organizational Learning vs. Liability,” in After the Event, supra note 169; Err is Human, supra note 49.

¹⁸⁵ See supra notes 169, 184.