Human Subjects ProtectionsSystem Discussion

Samuel J. Tilden

SACHRP

July 16, 2008

System Challenges for Human Subjects Protection Programs

• Oversight system entry

• Research information use and disclosure

• Effectiveness/accountability

HSP System Entry

1. Is it research?

2. Does it involve human subjects?

3. Is it exempt?

4. Is institution engaged in it?

• Mission creep

Public Law 93-348-July 12, 1974AN ACT

To amend the Public Health Service Act to establish a program of National Research Service Awards to assure the continued excellence of biomedical and behavioral research and to provide for the protection of human subjects involved in biomedical and behavioral research and for other purposes.

Be in enacted by the Senate and House of Representatives of the United States of America in Congress assembled,

Section 1. This Act may be cited as the “National Research Act”.

TITLE I – BIOMEDICAL AND BEHAVIORAL RESEARCH TRAINING

Short Title

Sec. 101. This title may be cited as the “National Research Service Award Act of 1974”.

Findings and Declaration of Purpose

Sec. 102.

(b) It is the purpose of this title to increase the capability of the institutes of the National Institutes of Health and the Alcohol, Drug Abuse, and Mental Health Administration to carry out their responsibility of maintaining a superior national program of research into the physical and mental diseases and impairment of man.

Public Law 93-348-July 12, 1974 [88 Stat. 352]

INSTITUTIONAL REVIEW BOARDS; ETHICS GUIDANCE PROGRAM

Sec. 212 (a) Park I of title IV of the Public Health Service Act as amended by section 103 of this Act, is amended by adding at the end the following new section:

“INSTITUTIONAL REVIEW BOARDS; ETHICS GUIDANCE PROGRAM”

“Sec. 474. (a) The Secretary shall by regulation require that each entity which applies for a grant or contract under this Act for any project or program which involves the conduct of biomedical or behavioral research involving human subjects submit in or with its application for such grant or contract assurances satisfactory to the Secretary that it has established (in accordance with regulations which the Secretary shall prescribe) a board (to be known as a “Institutional Review Board”) to review biomedical and behavioral research involving human subjects conducted at or sponsored by such entity in order to protect the rights of the human subjects of such research.

PUBLIC LAW 99-158-Nov. 20, 1985 [99 STAT. 820]

Public Law 99-158 99th Congress

An Act

To amend the Public Health Service Act to revise and extend the authorities under that Act relating to the National Institutes of Health and National Research Institutes, and for the purposes.

Be it enacted by the Senate and House of Representatives of the United States of America in Congress assembled,

SECTION 1. SHORT TITLE; REFERENCE TO ACT; AND TABLE OF CONTENTS

(a) Short Title – This Act may be cited as the “Health Research Extension Act of 1985”.

(b) Reference to Act. – Except as otherwise specifically provided, whenever in this Act an amendment or repeal is expressed in terms of an amendment to, or repeal of, a section or other provision, the reference shall be considered to be reference to a section or other provision of the Public Health Service Act.

PUBLIC LAW 99-158-Nov. 20, 1985 [99 STAT. 873]

“Part G – General Provisions”

“INSTITUTIONAL REVIEW BOARDS; ETHICS GUIDANCE PROGRAM”

“Sec. 491 (a) The Secretary shall by regulation require that each entity which applies for a grant, contract, or cooperative agreement under this Act for any project or program which involves the conduct of biomedical or behavioral research involving human subjects submit in or with its application for such grant, contract, or cooperative agreement assurances satisfactory to the Secretary that it has established (in accordance with regulations which the Secretary shall prescribe) a board (to be known as an “Institutional Review Board”) to review biomedical and behavioral research involving human subjects conducted at or supported by such entity in order to protect the rights of the human subjects or such research.

Federal Register, Vol. 39, No. 105 Thursday, May 30, 1974

Title 45 – Public Welfare

Subtitle A – Department of Health, Education, and Welfare, General Administration

Part 46 – Protection of Human Subjects

§ 46.1 Applicability

(a) The regulations in this part are applicable to all Department of Health, Education, and Welfare grants and contracts supporting research, development, and related activities in which human subjects are involved.

Effective date. This part shall become effective on July 1, 1974: Provided, however, That with respect to programs administered by the Office of Education and the National Institute of Education, this part shall become effective upon adoption or implementation in regulations issued by, respectively, the Commissioner of Education and the Director of the National Institute of Education, with the approval of the Secretary of Health, Education, and Welfare

Federal Register, Vol. 43, No. 231 – Thursday, November 30, 1978

DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE

Office of the Secretary

Protection of Human Subjects

Institutional Review Boards: Report and Recommendations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

Definitions. For purposes of this report:

1. Scientific research is a formal investigation designed to develop or contribute to generalizable knowledge.

Comment: A research project generally is described in a protocol that sets forth explicit objectives and formal procedures designed to reach those objectives. The protocol may include therapeutic and other activities intended to benefit the subjects, as well as procedures to evaluate such activities. Research objectives range from understanding normal and abnormal physiological or psychological functions or social phenomena, to evaluating diagnostic, therapeutic or preventative interventions; removal of body tissues or fluids; administration of chemical substances or forms of energy; modification of diet, daily routine or service delivery; alteration of environment; observation; administration of questionnaires or tests; randomization; review of records, etc.

Federal Register, Vol. 46, No. 16 – Monday, January 26, 1981DEPARTMENT OF HEALTH AND HUMAN SERVICES

Office of the Secretary45 CFR Part 46

Final Regulations Amending Basic HHS Policy for the Protection of Human Research Subjects

These amendments substantially reduce the scope of the existing HHS regulatory coverage by exempting broad categories of research which normally present little or no risk of harm to subjects. Specifically, the new regulations: (1) Exempt from coverage most social, economic and educational research in which the only involvement of human subjects will be in one or more of the following categories; (a) The use of survey and interview procedures; (b) the observation of public behavior; or (c) the study of data, documents, records and specimens.

* * *Although HHS found considerable merit to the suggestion that the regulations should define what is covered …, there might be other categories of research involving significant risk that would be inadvertently exempted from coverage. Nonetheless, HHS recognizes that it may have unintentionally included within its coverage description types of research which should be exempted and for this reasons § 46.101(e) of the final regulations provides for a waiver which can be used to remedy such situations.

Analysis of System Entry

• Definition of research is intended to be all inclusive of scientific research

• Failure to apply exemptions results in large amounts of no/low risk research to IRB review

•Exemption practice by IRBs largely a failure

• Practical Result - Any directed scholarly or investigative inquiry involving human subjects is subject to review

Research Information & Technology

• Electronic environment

• Genetic concerns

• National standards• HIPAA• GINA• FDAAA 2007, PL 110-161

• Common rule does not ensure confidentiality (GAO HEHS 99-55)

CR & Privacy45CFR46.102(f) Human subject means a living individual about whom an

investigator…obtains…1. Data through intervention or interaction with the individual, or2. Identifiable private information.

Private information includes information about behavior … in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) ….

45CFR46.111(a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied:

(7) When appropriate, there are adequate provisions to protect the privacy of subjects and confidentiality of data.

45CFR46.101(b)…following categories are exempt…

(3) Research involving the use of educational tests (…), etc. if (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained…

* * *

45CFR46.116(a) Basic elements of informed consent.

(5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;

* * *

45 CFR46.117(c) An IRB may waive the requirement for…a signed consent form…if it finds…

(1) That the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality.

CR & Confidentiality

HIPAA & Research

• Specific, comprehensive confidentiality provisions• Describes uses and disclosures by covered entities

for covered functions (45 CFR 160.103)• Generally permits use and disclosure by CE for

T,P,O without authorization• Research (other than some QA,QI) neither T,P,O

nor a covered function of a covered entity

HIPAA & Research

• Designed to transfer information from healthcare domain into research domain which is not subject to HIPAA provisions

• Institutions/IRBs seem to want to superimpose HIPAA confidentiality provisions over CR

Analysis on Information

• More specific privacy & confidentiality standards for research information desirable

• HIPAA supplies defacto standards despite not having been designed to do so

• Results - Research standards for privacy and confidentiality are feasible and necessary

Research Involving Human Subjects

Intervention

Interaction

No Intervention/ Interaction

> MR

MR

> MR

MR

Waiver of consent review

Research

Privacy

&

Confidentiality

Regs.

IRB Review

Expedited IRB review

IRB Review

Consent review

Approved HSR Project

Proportional Model of HSP Review

Effectiveness/Accountability

• National Commission recommended single Departmental office (i.e. OHRP equivalent) appropriately resourced Accredit IRBs Monitor IRB compliance Provide IRB education Focus on improving performance

• Presidential Commission recommended same

Effectiveness/Accountability

• OIG Recommendations Eliminate or lessen specific procedural

requirements that are of questionable value Require IRBs undergo regular performance-

focused evaluations More on-site visits, inspections, and

educational sessions Less reliance on assurances, incidents, and

complaints

Effectiveness/Accountability

• Compliance designed to prevent and detect harm with the emphasis on prevention

• Key steps involves iterative methodology Establish process identifying both key &

critical intermediate steps Assessment of outcome and intermediate

steps Correct, improve and simplify

• Accreditation not enough without OHRP

Total OHRP $*

4,735,615

4,447,7604,164,874

4,424,546

4,085,253

4,672,1034,100,000

3,946,286

0

1,000,000

2,000,000

3,000,000

4,000,000

5,000,000

FY2001

FY2002

FY2003

FY2004

FY2005

FY2006

FY2007

FY2008

* Not adjusted for inflation

Percent S&B $ vs. Non-S&B $

1317

252531

2418

26 8783

757569

757482

0%

20%

40%

60%

80%

100%

FY2001

FY2002

FY2003

FY2004

FY2005

FY2006

FY2007

FY2008

Non-S&B Salary/Benefit

OHRP FTEs*

39 3942 45 43

39 3839

28

39 393335 37

05

101520253035404550

FY 2001 FY 2002 FY 2003 FY 2004 FY 2005 FY 2006 FY 2007

FTE Authorized FTE Actual

* Includes 2 administrative support FTEs outside of OHRP

749,750

1,388,6881,466,990

900,000

1,406,148

1,450,097

1,817,495

600,000

800,000

1,000,000

1,200,000

1,400,000

1,600,000

1,800,000

2,000,000

FY2001

FY2002

FY2003

FY2004

FY2005

FY2006

FY2007

FY2008

Carryover Non-S&B

OHRP Non-S&B and Carryover $

SACHRP $*

0

100,000

200,000

300,000

400,000

500,000

2005 2006 2007

SACHRP Govworks $

* Does not include OHRP S&B

Unfunded or Under-funded Activities in 2008

Current Activities• Meetings of SACHRP or SACHRP subcommittee

• Further development and maintenance of a database for compliance information

• Not for cause compliance site visits (domestic and international)

• QA workshops

• International

• New ActivitiesEquivalent protection determinations (est. 5 FTEs)

The End